A Clinical Proof-of-principle Trial in Adult Subjects With Newly Diagnosed Type 1 Diabetes Mellitus Investigating the Effect of NNC0114-0006 and Liraglutide on Preservation of Beta-cell Function

Diabetes Clinical Trial

Official title:

A Randomised, Double-blind, Double-dummy, Placebo-controlled, Parallel-group Multi-centre Clinical Proof-of-principle Trial in Adult Subjects With Newly Diagnosed Type 1 Diabetes Mellitus Investigating the Effect of NNC0114-0006 and Liraglutide on Preservation of Beta-cell Function

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02443155
• Other study ID #: NN9828-4150
• Secondary ID: 2014-001215-39U1
• Status: Completed
• Phase: Phase 2
• Start date: November 10, 2015
• Est. completion date: February 27, 2019

Study information

• Verified date: March 2021
• Source: Novo Nordisk A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This trial is conducted globally. The aim of this trial is to assess the clinical proof-of-principle of NNC0114-0006 and liraglutide on preservation of beta-cell function in adult subjects with newly diagnosed type 1 diabetes mellitus.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 308
• Est. completion date: February 27, 2019
• Est. primary completion date: August 31, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

• Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial
• T1DM (type 1 diabetes mellitus) (as diagnosed clinically) for not more than 20 weeks prior to screening - Male or female, aged 18-45 (both inclusive) at the time of signing the informed consent form
• Non-fasting peak C-peptide higher or equal to 0.2 nmol/l at visit 2
• BMI (body mass index) higher or equal to 18.5 kg/m^2
• Presence of one or more islet specific auto antibodies (glutamic acid decarboxylase (GAD), islet antigen-2 (IA2) or zinc-transporter 8 (ZnT8)) at screening
• Insulin dependence unless in temporary spontaneous remission (honeymoon period)

Exclusion Criteria:

• Daily insulin usage above 1 U/kg per day at screening or use of continuous subcutaneous insulin infusion (CSII)
• History of recurrent (e.g. several times a year) of severe (e.g. pneumonia) or chronic infections or conditions predisposing to chronic infections (e.g., bronchiectasis and chronic osteomyelitis)
• History of severe systemic fungal infection within the past 12 months prior to screening unless treated and resolved with appropriate documented therapy
• Vaccination within 4 weeks before randomisation, Visit 3 (V3)
• Receipt of any other concomitant medications or herbal products that can influence the immune system within 90 days prior to screening (V1)
• History of pancreatitis (acute or chronic)
• Family or personal history of Multiple Endocrine Neoplasia Type 2 (MEN2) or Medullary Thyroid Carcinoma (MTC)
• Any past or current diagnosis of malignant neoplasms
• Known impairment of the immune system, except for T1DM, coeliac disease, alopecia, autoimmune antibodies not considered clinical important (e.g. thyroid antibodies without any clinically important thyroid disease), and vitiligo

Related Conditions & MeSH terms

• Diabetes
• Diabetes Mellitus
• Diabetes Mellitus, Type 1

Intervention

Drug:
• NNC0114-0006
NNC0114-0006 12 mg/kg administered i.v (intravenously) every 6 weeks. Subjects will continue their pre-trial insulin treatment
• liraglutide
Liraglutide 1.8 mg administered s.c. (subcutaneously) daily. Subjects will continue their pre-trial insulin treatment
• placebo
Placebo administered s.c (subcutaneously) or i.v ( intravenously). Subjects will continue their pre-trial insulin treatment

Locations

Country	Name	City	State
Austria	Novo Nordisk Investigational Site	Graz
Austria	Novo Nordisk Investigational Site	Innsbruck
Austria	Novo Nordisk Investigational Site	Salzburg
Austria	Novo Nordisk Investigational Site	Wien
Austria	Novo Nordisk Investigational Site	Wien
Belgium	Novo Nordisk Investigational Site	Brussel
Belgium	Novo Nordisk Investigational Site	Edegem
Belgium	Novo Nordisk Investigational Site	Leuven
Canada	Novo Nordisk Investigational Site	Edmonton	Alberta
Canada	Novo Nordisk Investigational Site	Halifax	Nova Scotia
Canada	Novo Nordisk Investigational Site	Kingston	Ontario
Canada	Novo Nordisk Investigational Site	Laval	Quebec
Canada	Novo Nordisk Investigational Site	Montreal	Quebec
Canada	Novo Nordisk Investigational Site	PQ	Quebec
Canada	Novo Nordisk Investigational Site	Sherbrooke	Quebec
Canada	Novo Nordisk Investigational Site	Toronto	Ontario
Canada	Novo Nordisk Investigational Site	Vancouver	British Columbia
Canada	Novo Nordisk Investigational Site	Winnipeg	Manitoba
Denmark	Novo Nordisk Investigational Site	Aarhus N
Denmark	Novo Nordisk Investigational Site	Esbjerg
Denmark	Novo Nordisk Investigational Site	Hellerup
Finland	Novo Nordisk Investigational Site	Helsinki
Finland	Novo Nordisk Investigational Site	Oulu
Finland	Novo Nordisk Investigational Site	Tampere
Ireland	Novo Nordisk Investigational Site	Dublin
Ireland	Novo Nordisk Investigational Site	Dublin
Ireland	Novo Nordisk Investigational Site	Galway
Israel	Novo Nordisk Investigational Site	Holon
Israel	Novo Nordisk Investigational Site	Jerusalem
Israel	Novo Nordisk Investigational Site	Petah Tikva
Israel	Novo Nordisk Investigational Site	Rehovot
Italy	Novo Nordisk Investigational Site	Bergamo
Italy	Novo Nordisk Investigational Site	Catanzaro
Italy	Novo Nordisk Investigational Site	Milano
Italy	Novo Nordisk Investigational Site	Siena
Norway	Novo Nordisk Investigational Site	Oslo
Norway	Novo Nordisk Investigational Site	Stavanger
Poland	Novo Nordisk Investigational Site	Gdansk
Poland	Novo Nordisk Investigational Site	Gdansk
Poland	Novo Nordisk Investigational Site	Warszawa
Poland	Novo Nordisk Investigational Site	Zabrze
Portugal	Novo Nordisk Investigational Site	Almada
Portugal	Novo Nordisk Investigational Site	Amadora
Portugal	Novo Nordisk Investigational Site	Braga
Portugal	Novo Nordisk Investigational Site	Matosinhos
Portugal	Novo Nordisk Investigational Site	Porto
Portugal	Novo Nordisk Investigational Site	Viana do Castelo
Russian Federation	Novo Nordisk Investigational Site	Arkhangelsk
Russian Federation	Novo Nordisk Investigational Site	Chelyabinsk
Russian Federation	Novo Nordisk Investigational Site	Dzerzhinskiy
Russian Federation	Novo Nordisk Investigational Site	Kazan
Russian Federation	Novo Nordisk Investigational Site	Moscow
Russian Federation	Novo Nordisk Investigational Site	Moscow
Russian Federation	Novo Nordisk Investigational Site	Novosibirsk
Russian Federation	Novo Nordisk Investigational Site	Penza
Russian Federation	Novo Nordisk Investigational Site	Saint-Petersburg
Russian Federation	Novo Nordisk Investigational Site	Saratov
Russian Federation	Novo Nordisk Investigational Site	Saratov
Russian Federation	Novo Nordisk Investigational Site	Syktyvkar
Russian Federation	Novo Nordisk Investigational Site	Ulianovsk
Russian Federation	Novo Nordisk Investigational Site	Yoshkar-Ola
Serbia	Novo Nordisk Investigational Site	Belgrade
Serbia	Novo Nordisk Investigational Site	Kragujevac
Spain	Novo Nordisk Investigational Site	Barcelona
Spain	Novo Nordisk Investigational Site	Girona
Spain	Novo Nordisk Investigational Site	Málaga
Spain	Novo Nordisk Investigational Site	Palma de Mallorca
Spain	Novo Nordisk Investigational Site	Sabadell
Spain	Novo Nordisk Investigational Site	Sevilla
Spain	Novo Nordisk Investigational Site	Sevilla
Spain	Novo Nordisk Investigational Site	Valencia
Sweden	Novo Nordisk Investigational Site	Göteborg
Sweden	Novo Nordisk Investigational Site	Karlstad
Sweden	Novo Nordisk Investigational Site	Lund
Sweden	Novo Nordisk Investigational Site	Stockholm
Ukraine	Novo Nordisk Investigational Site	Kyiv
Ukraine	Novo Nordisk Investigational Site	Kyiv
Ukraine	Novo Nordisk Investigational Site	Kyiv
Ukraine	Novo Nordisk Investigational Site	Kyiv
Ukraine	Novo Nordisk Investigational Site	Kyiv
Ukraine	Novo Nordisk Investigational Site	Vinnytsia
Ukraine	Novo Nordisk Investigational Site	Zhytomyr
United Kingdom	Novo Nordisk Investigational Site	Belfast
United Kingdom	Novo Nordisk Investigational Site	Blackburn
United Kingdom	Novo Nordisk Investigational Site	Bristol
United Kingdom	Novo Nordisk Investigational Site	Cardiff
United Kingdom	Novo Nordisk Investigational Site	Chester
United Kingdom	Novo Nordisk Investigational Site	Edgbaston, Birmingham
United Kingdom	Novo Nordisk Investigational Site	London
United Kingdom	Novo Nordisk Investigational Site	London
United Kingdom	Novo Nordisk Investigational Site	Newcastle upon Tyne
United Kingdom	Novo Nordisk Investigational Site	Plymouth
United Kingdom	Novo Nordisk Investigational Site	Sheffield
United Kingdom	Novo Nordisk Investigational Site	Stevenage
United Kingdom	Novo Nordisk Investigational Site	Swansea
United States	Novo Nordisk Investigational Site	Atlanta	Georgia
United States	Novo Nordisk Investigational Site	Aurora	Colorado
United States	Novo Nordisk Investigational Site	Chapel Hill	North Carolina
United States	Novo Nordisk Investigational Site	Houston	Texas
United States	Novo Nordisk Investigational Site	La Jolla	California
United States	Novo Nordisk Investigational Site	Las Vegas	Nevada
United States	Novo Nordisk Investigational Site	Lexington	Kentucky
United States	Novo Nordisk Investigational Site	Mesquite	Texas
United States	Novo Nordisk Investigational Site	Miami	Florida
United States	Novo Nordisk Investigational Site	Nashville	Tennessee
United States	Novo Nordisk Investigational Site	Northridge	California
United States	Novo Nordisk Investigational Site	Orlando	Florida
United States	Novo Nordisk Investigational Site	Teaneck	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Canada,  Denmark,  Finland,  Ireland,  Israel,  Italy,  Norway,  Poland,  Portugal,  Russian Federation,  Serbia,  Spain,  Sweden,  Ukraine,  United Kingdom, 

References & Publications (1)

von Herrath M, Bain SC, Bode B, Clausen JO, Coppieters K, Gaysina L, Gumprecht J, Hansen TK, Mathieu C, Morales C, Mosenzon O, Segel S, Tsoukas G, Pieber TR; Anti-IL-21-liraglutide Study Group investigators and contributors. Anti-interleukin-21 antibody a — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area Under the Concentration-time Curve (AUC) 0-4h of Mixed Meal Tolerance Test (MMTT) Stimulated C-peptide at Week 54 Relative to Baseline	Area under the concentration-time curve, from 0 to 4 hours (AUC0-4h) of a mixed meal tolerance test (MMTT) stimulated C-peptide at week 54 is presented as ratio to baseline. AUC of C-peptide was measured as Nano moles*hour per liter (nmol*h/L).	0 - 4 hours post-dose on week 0 and week 54
Secondary	AUC0-2h of C-peptide at Week 54 Relative to Baseline	Area under the concentration-time curve, from 0 to 2 hours (AUC0-2h) of a MMTT stimulated C-peptide at week 54 is presented as ratio to baseline. AUC of C-peptide was measured as 'nmol*h/L'.	0-2 hours post-dose on week 0 and week 54
Secondary	Cmax of C-peptide at Week 54 Relative to Baseline	Maximum observed concentration (Cmax) of a MMTT stimulated C-peptide at week 54 is presented as ratio to baseline. Cmax of C-peptide was measured as nanomoles per liter (nmol/L).	0-4 hours post-dose on week 0 and week 54
Secondary	AUC0-4h of Glucose at Week 54 Relative to Baseline	Area under the concentration-time curve, from 0 to 4 hours (AUC0-4h) of a MMTT stimulated glucose at week 54 is presented as ratio to baseline. AUC of glucose was measured as Milli moles*hour per liter (mmol*h/L).	0 - 4 hours post-dose on week 0 and week 54
Secondary	AUC0-2h of Glucose at Week 54 Relative to Baseline	Area under the concentration-time curve, from 0 to 2 hours (AUC0-2h) of a MMTT stimulated glucose at week 54 is presented as ratio to baseline. AUC of glucose is measured as 'mmol*h/L'.	0-2 hours post-dose on week 0 and week 54
Secondary	Cmax of Glucose at Week 54 Relative to Baseline	Maximum observed concentration (Cmax) of a MMTT stimulated glucose at week 54 is presented as ratio to baseline. Cmax of C-peptide was measured as 'mmol/L'.	0-4 hours post-dose on week 0 and week 54
Secondary	Number of Treatment Emergent Adverse Events	An adverse event was any untoward medical occurrence in a participants administered a product, and which did not necessarily have a causal relationship with this treatment. An adverse event was defined as treatment emergent if the onset of the adverse event occurs on or after the first day of trial product administration. Number of treatment emergent adverse events from first dose of trial product to week 54 and week 80 are presented. Results are based on the on-treatment and on-observation period.; On-treatment period: From the day of first trial product administration to the day of the visit at week 54. On-observation: From the day after the visit at week 54 to the day of the last visit.	Week 0-54; Week 54-80
Secondary	Number of Treatment Emergent Hyperglycaemic Episodes	Hyperglycaemic episodes were defined as treatment-emergent if the onset occurred on or after the first day of trial product administration. Number of treatment emergent episodes of hyperglycaemic episodes from first dose of trial product to week 54 and from week 54 to week 80 are presented. Results are based on the on-treatment and on-observation period.; On-treatment period: From the day of first trial product administration to the day of the visit at week 54. On-observation: From the day after the visit at week 54 to the day of the last visit.	Week 0-54; Week 54-80
Secondary	Number of Treatment Emergent Episodes of Diabetic Ketoacidosis	Diabetic ketoacidosis episodes were defined as treatment-emergent if the onset occurred on or after the first day of trial product administration. Number of treatment emergent episodes of hyperglycaemic episodes from first dose of trial product to week 54 and from week 54 to week 80 are presented. Results are based on the on-treatment and on-observation period.; On-treatment period: From the day of first trial product administration to the day of the visit at week 54. On-observation: From the day after the visit at week 54 to the day of the last visit.	Weeks 0-54; Weeks 54-80
Secondary	Number of Participants Experiencing Treatment Emergent Injection/Infusion Site Reactions Caused by NNC0114-0006/Liraglutide/Placebo Injection/Infusion	Injection/infusion site reactions episodes were defined as treatment-emergent if the onset occurred on or after the first day of trial product administration. Number of participants experiencing treatment emergent episodes of injection/infusion site reactions episodes from first dose of trial product to week 54 (treatment period) is presented.	Week 0-54
Secondary	Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association (ADA)	Hypoglycaemic episodes were defined as treatment-emergent if the onset of the episode occurred on or after the first day of trial product administration, and no later than 1 day after the date of last contact. Number of treatment-emergent hypoglycaemic episodes according to American Diabetes Association (ADA) classification from first dose of trial product to week 54 and from week 54 to week 80 are presented.; Results presented hypoglycaemia episodes were recorded as per ADA definition: Severe hypoglycaemia, Documented symptomatic hypoglycaemia, Asymptomatic hypoglycaemia, Probable symptomatic hypoglycaemia and Pseudo-hypoglycaemia.	Weeks 0-54; Weeks 54-80
Secondary	Number of Treatment Emergent Hypoglycaemic Episodes According to Novo Nordisk Definitions	Hypoglycaemia episodes were recorded as per Novo Nordisk definition: Symptomatic BG-confirmed: An episode that is blood glucose (BG) confirmed by plasma glucose (PG) value <3.1 mmol/L with symptoms consistent with hypoglycaemia. Asymptomatic BG-confirmed: An episode that is BG-confirmed by PG value <3.1 mmol/L without symptoms consistent with hypoglycaemia. Severe or BG-confirmed symptomatic: An episode that is severe according to the ISPAD classification or BG-confirmed by a PG value <3.1 mmol/L with symptoms consistent with hypoglycaemia. BG-confirmed: An episode that is BG-confirmed by a PG value <3.1 mmol/L with or without symptoms consistent with hypoglycaemia. Severe or BG-confirmed: An episode that is severe according to the International Society for Pediatric and Adolescent Diabetes (ISPAD) classification or BG-confirmed by a PG value <3.1 mmol/L with or without symptoms consistent with hypoglycaemia.	Weeks 0-54; Weeks 54-80
Secondary	Change in Body Weight (kg)	Change in body weight is measured at week 54 and week 80 respective to baseline. Body weight was measured in unit 'Kg'.	(Week 0, week 54) and (week 0, week 80)
Secondary	Diabetes Retinopathy	Number of participants evaluated for diabetic retinopathy at baseline (Day -28 to -14), week 54 and week 80 are presented as 'yes', 'no' or 'unknown'.	Baseline, week 54 and week 80
Secondary	Estimated Glomerular Filtration Rate (eGFR)- Ratio to Baseline	The eGFR was measured using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. Change in eGFR (measured in milliliters per minute per 1.73 square meters) from baseline (week 0) at week 54 and week 80 is presented as ratio to baseline.	(Week 0, week 54) and (week 0, week 80)
Secondary	Change in Haematology: Erythrocytes	Change in erythrocytes (measured in 10^12 cells per liter) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.	(Week 0, week 54) and (week 0, week 80)
Secondary	Change in Haematology: Haematocrit	Change in haematocrit (measured in percentage '%') from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.	(Week 0, week 54) and (week 0, week 80)
Secondary	Change in Haematology: Haemoglobin	Change in haemoglobin (measured in millimoles per liter 'mmol/L') from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.	(Week 0, week 54) and (week 0, week 80)
Secondary	Change in Haematology: Leukocytes	Change in leukocytes (measured in 10^9 cells/L) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.	(Week 0, week 54) and (week 0, week 80)
Secondary	Change in Haematology: Mean Corpuscular Hemoglobin	Change in mean Corpuscular hemoglobin (measured in femtomole 'fmol') from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.	(Week 0, week 54) and (week 0, week 80)
Secondary	Change in Haematology: Mean Corpuscular Hemoglobin Concentration	Change in mean corpuscular hemoglobin concentration (MCHC) (measured in gram per liter 'g/L') from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.	(Week 0, week 54) and (week 0, week 80)
Secondary	Change in Haematology: Mean Corpuscular Volume	Change in Mean Corpuscular volume (measured in femtoliter 'fL') from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.	(Week 0, week 54) and (week 0, week 80)
Secondary	Change in Haematology: Thrombocytes	Change in thrombocytes (measured in 10^9 cells per liter) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.	(Week 0, week 54) and (week 0, week 80)
Secondary	Change in Haematology: Eosinophil	Change in eosinophil (measured in percentage '%') from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.	(Week 0, week 54) and (week 0, week 80)
Secondary	Change in Haematology: Neutrophils	Change in neutrophils (measured in percentage '%') from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.	(Week 0, week 54) and (week 0, week 80)
Secondary	Change in Haematology: Basophils	Change in basophils (measured in percentage '%') from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.	(Week 0, week 54) and (week 0, week 80)
Secondary	Change in Haematology: Lymphocytes	Change in lymphocytes (measured in percentage '%') from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.	(Week 0, week 54) and (week 0, week 80)
Secondary	Change in Haematology: Monocytes	Change in monocytes (measured in percentage '%') from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.	(Week 0, week 54) and (week 0, week 80)
Secondary	Change in Biochemistry: Alanine Aminotransferase (ALAT)	Change in ALAT (measured in units per liter [U/L]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.	(Week 0, week 54) and (week 0, week 80)
Secondary	Change in Biochemistry: Albumin	Change in albumin (measured in gram per deciliter [g/dL]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.	(Week 0, week 54) and (week 0, week 80)
Secondary	Change in Biochemistry: Amylase	Change in amylase (measured in units per liter [U/L]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.	(Week 0, week 54) and (week 0, week 80)
Secondary	Change in Biochemistry: Alkaline Phosphatase (ALP)	Change in ALP (measured in units per liter [U/L]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.	(Week 0, week 54) and (week 0, week 80)
Secondary	Change in Biochemistry: Aspartate Aminotransferase (ASAT)	Change in ASAT (measured in units per liter [U/L]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.	(Week 0, week 54) and (week 0, week 80)
Secondary	Change in Biochemistry: Total Bilirubin	Change in Total bilirubin (measured in micromole per liter [umol/L]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.	(Week 0, week 54) and (week 0, week 80)
Secondary	Change in Biochemistry: Calcium Corrected	Change in calcium corrected (measured in millimole per liter [mmol/L]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.	(Week 0, week 54) and (week 0, week 80)
Secondary	Change in Biochemistry: Chloride	Change in chloride (measured in millimole per liter [mmol/L]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.	(Week 0, week 54) and (week 0, week 80)
Secondary	Change in Biochemistry: Creatine Kinase	Change in creatine kinase (measured in units per liter [U/L]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.	(Week 0, week 54) and (week 0, week 80)
Secondary	Change in Biochemistry: Creatinine	Change in creatinine (measured in micromole per liter [umol/L]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.	(Week 0, week 54) and (week 0, week 80)
Secondary	Change in Biochemistry: Gamma-glutamyl Transferase (GGT)	Change in GGT (measured in units per liter [U/L]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.	(Week 0, week 54) and (week 0, week 80)
Secondary	Change in Biochemistry: C-reactive Protein Serum	Change in C-reactive protein serum (measured in milligrams per liter [mg/L]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.	(Week 0, week 54) and (week 0, week 80)
Secondary	Change in Biochemistry: Lactate Dehydrogenase	Change in Lactate Dehydrogenase (measured in units per liter [U/L]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.	(Week 0, week 54) and (week 0, week 80)
Secondary	Change in Biochemistry: Lipase	Change in lipase (measured in units per liter [U/L]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.	(Week 0, week 54) and (week 0, week 80)
Secondary	Change in Biochemistry: Magnesium	Change in magnesium (measured in millimole per liter [mmol/L]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.	(Week 0, week 54) and (week 0, week 80)
Secondary	Change in Biochemistry: Phosphate	Change in phosphate (measured in millimole per liter [mmol/L]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.	(Week 0, week 54) and (week 0, week 80)
Secondary	Change in Biochemistry: Potassium	Change in potassium (measured in millimole per liter [mmol/L]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.	(Week 0, week 54) and (week 0, week 80)
Secondary	Change in Biochemistry: Sodium	Change in sodium (measured in millimole per liter [mmol/L]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.	(Week 0, week 54) and (week 0, week 80)
Secondary	Change in Biochemistry: Total Protein	Change in total protein (measured in gram per liter [g/dL]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.	(Week 0, week 54) and (week 0, week 80)
Secondary	Change in Biochemistry: Blood Urea Nitrogen Serum	Change in blood urea nitrogen serum (measured in milligram per deciliter [mg/dL]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.	(Week 0, week 54) and (week 0, week 80)
Secondary	Change in Biochemistry: Uric Acid	Change in Uric Acid (measured in milligram per deciliter [mg/dL]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.	(Week 0, week 54) and (week 0, week 80)
Secondary	Change in International Normalised Ratio (INR)	Change in INR (measured in ratio]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.	(Week 0, week 54) and (week 0, week 80)
Secondary	Change in D-Dimer	Change in D-Dimer (measured in mg/L) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.	(Week 0, week 54) and (week 0, week 80)
Secondary	Change in Lipids: Total Cholesterol (Ratio to Baseline)	Change in total cholesterol (measured in mmol/L) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.	(Week 0, week 54) and (week 0, week 80)
Secondary	Change in Lipids: Free Fatty Acids (Ratio to Baseline)	Change in total free fatty acids (measured in mmol/L) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.	(Week 0, week 54) and (week 0, week 80)
Secondary	Change in Lipids: HDL Cholesterol (Ratio to Baseline)	Change in HDL cholesterol (measured in mmol/L) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.	(Week 0, week 54) and (week 0, week 80)
Secondary	Change in Lipids: LDL Cholesterol (Ratio to Baseline)	Change in LDL cholesterol (measured in mmol/L) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.	(Week 0, week 54) and (week 0, week 80)
Secondary	Change in Lipids: Triglycerides (TG) (Ratio to Baseline)	Change in Triglycerides (measured in mmol/L) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.	(Week 0, week 54) and (week 0, week 80)
Secondary	Change in Total Immunoglobulin E (IgE)	Change in IgE (measured in kilo international units per liter [kIU/L]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.	(Week 0, week 54) and (week 0, week 80)
Secondary	Change in Urinalysis: Urine Dipsticks	Urinalysis was performed by urine dipsticks for protein, glucose, erythrocytes, ketones leukocytes, nitrite, pH and specific gravity and categorised as normal, abnormal not clinically significant (NCS) and abnormal clinially significant (CS). Number of participants in each category at baseline (week 0), week 54 and 80 are presented.	Week 0, week 54 and week 80
Secondary	Change in Cytokines: Interleukin (IL)-6	IL-6 levels at baseline (week 0), weeks 54 and 80 are evaluated and presented.	Week 0, week 54 and week 80
Secondary	Change in Cytokines- Interleukin (IL)-10	IL-10 levels at baseline (week 0), weeks 54 and 80 are evaluated and presented.	Week 0, week 54 and week 80
Secondary	Change in Cytokines: Interleukin (IL)-17	IL-17 levels at baseline (week 0), weeks 54 and 80 are evaluated and presented.	Week 0, week 54 and week 80
Secondary	Change in Cytokines: Interferon (IFN) Gamma	IFN gamma levels at baseline (week 0), weeks 54 and 80 are evaluated and presented.	Week 0, week 54 and week 80
Secondary	Change in Cytokines: TNF-alpha	TNF-alpha levels at baseline (week 0), weeks 54 and 80 are evaluated and presented.	Week 0, week 54 and week 80
Secondary	Change in Hormone Level: Thyroid Stimulating Hormone (TSH)	Change in TSH (measured in milli international units per liter [mIU/L]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.	(Week 0, week 54) and (week 0, week 80)
Secondary	Change in Hormone Level: Calcitonin	Change in Calcitonin (measured in nanogram per liter [ng/L]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.	(Week 0, week 54) and (week 0, week 80)
Secondary	Change in Systolic and Diastolic Blood Pressure	Change in systolic blood pressure (SBP) and diastolic blood pressure (DBP) are evaluated from baseline (week 0) to weeks 54 and 80.	(Week 0, week 54) and (week 0, week 80)
Secondary	Change in Pulse	Change in pulse is evaluated from baseline (week 0) to weeks 54 and 80	(Week 0, week 54) and (week 0, week 80)
Secondary	Change in Body Temperature	Change in body temperature is evaluated from baseline (week 0) to weeks 54 and 80.	Week 0, week 54) and (week 0, week 80)
Secondary	Change in Respiratory Rate	Change in respiratory rate is evaluated from baseline (week 0) to weeks 54 and 80.	(Week 0, week 54) and (week 0, week 80)
Secondary	Change in Electrocardiogram (ECG)	The ECG was assessed by the investigator at baseline (week 0), week 54 and week 80 and categorised as normal, abnormal NCS or abnormal CS. Number of participants in each ECG category at baseline, week 54 and week 80 are presented.	Week 0, week 54 and week 80
Secondary	Change in Eye-examination	Dilated fundoscopy or fundus photography was performed by the investigator at week 0, week 54 and week 80. The results of the examination were interpreted for each eye (left/right) are categorised as normal, abnormal NCS or abnormal CS. Number of participants in each category at week 0, week 54 and week 80 are presented.	Week 0, week 54 and week 80
Secondary	Change in Physical Examination	Physical examination parameters are categorised as general appearance; head, ears, eyes, nose, throat, neck; respiratory system;cardiovascular system; gastrointestinal system including mouth; musculoskeletal system; central and peripheral nervous system; skin; lymph node palpation and thyroid gland. Investigator assessed the participants with normal, abnormal not clinically significant (NCS) and abnormal clinically significant (CS) findings at week 0, week 54 and week 80 are presented.	Week 0, week 54 and week 80
Secondary	Occurrence of Anti-NNC0114-0006 Antibodies	This outcome measure was applicable for NNC0114-0006 + Liraglutide treatment arm and NNC0114-0006 treatment arm. Participants was assessed for anti-NNC0114-0006 antibodies. Participant who reported anti-NNC0114-0006 antibodies were further analyzed for cross-reactivity. Number of participants who measured with anti-NNC0114-0006 antibodies at week 54 and week 80 are presented.	Week 0, week 54 and week 80
Secondary	Occurrence of Anti-liraglutide Antibodies	This outcome measure is applicable for NNC0114-0006 + Liraglutide treatment arm and Liraglutide treatment arm. Participants was assessed for anti-liraglutide antibodies. Participant who reported anti-liraglutide antibodies were further analyzed for cross-reactivity. Number of participants who measured with anti-liraglutide antibodies at week 54 and week 80 are presented.	Week 0, week 54 and week 80
Secondary	Change in Insulin Dose	The total daily insulin dose was derived as the average of the doses reported on the three days prior to the visit. Change in daily total insulin dose from baseline (week 0) after 54 weeks of treatment and week 80 are presented.	(Week 0, week 54) and (week 0, week 80)
Secondary	Change in Number of Insulin Injections	The number of insulin injections was derived as the average of the reported number on the three days prior to the visit. The change in number of insulin injections per day (count) from baseline (week 0) after 54 weeks of treatment and week 80 are presented.	(Week 0, week 54) and (week 0, week 80)
Secondary	Number of Weeks Off Bolus Insulin	The number of weeks off bolus insulin after 54 weeks of treatment and week 80 are presented.	(Week 0 to week 54) and (week 0 to week 80)
Secondary	Change in HbA1c	Change in glycosylated haemoglobin (HbA1c) is evaluated from baseline (week 0) to weeks 54 and 80.	(Week 0, week 54) and (week 0, week 80)
Secondary	Change in Fasting Plasma Glucose	Change in fasting plasma glucose is evaluated from baseline (week 0) to weeks 54 and 80.	(Week 0, week 54) and (week 0, week 80)
Secondary	Change in Fasting C-peptide- Ratio to Baseline	Change in fasting C-peptide (measured in nanomole per liter [nmol/L]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.	(Week 0, week 54) and (week 0, week 80)
Secondary	Change in Fasting Glucagon- Ratio to Baseline	Change in fasting glucagon (measured in picogram per milliliter [pg/mL]) from baseline (week 0) to weeks 54 and 80 is presented as ratio to baseline.	(Week 0, week 54) and (week 0, week 80)
Secondary	7-point SMPG Profiles	Participants measured plasma glucose values using the blood glucose meter at 7 time points: before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after start of dinner, bedtime. 7-point SMPG profile values are presented for week 54 and week 80.	Week 54 and Week 80
Secondary	Change in 7- Points Self-measured Plasma Glucose (SMPG) Postprandial Glucose /Prandial Increment: Breakfast, Lunch, Dinner	Participants measured plasma glucose values using the blood glucose meter at 7 time points: before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after start of dinner and at bedtime. Change from baseline (week 0) to week 54 and week 80 in 7-point SMPG postprandial glucose /prandial increment (breakfast, lunch and dinner) value are presented.	(Week 0, week 54) and (week 0, week 80)
Secondary	Change in 7- Points Self-measured Plasma Glucose (SMPG) Postprandial Glucose /Prandial Increment (Average Over the Three Meals)	Participants measured plasma glucose values using the blood glucose meter at 7 time points: before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after start of dinner, bedtime. Change from baseline (week 0) to week 54 and week 80 in 7-point self-measured plasma glucose (SMPG) postprandial glucose /prandial increment (average over the three meals) value is presented.	(Week 0, week 54) and (week 0, week 80)
Secondary	Change in Mean of 7-point Profiles	Participants measured plasma glucose values using the blood glucose meter at 7 time points: before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after start of dinner, bedtime. Change from baseline (week 0) to week 54 and week 80 in mean of 7-point profiles value is presented.	(Week 0, week 54) and (week 0, week 80)
Secondary	Before Breakfast 7- Points Self Measured Plasma Glucose (SMPG)	Participants measured plasma glucose values using the blood glucose meter at 7 time points: before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after start of dinner and at bedtime. Before breakfast 7-point self-measured plasma glucose (SMPG) profile values are presented at week 54 and week 80.	Week 54 and week 80
Secondary	Area Under the NNC0114-0006 Concentration-time Curve Over a Dosing Interval at Steady State (AUCtau, NNC0114-0006)	AUCtau, NNC0114-0006 was derived as the area under the concentration-time curve using the linear trapezoidal technique based on observed values and actual measurement times between 0 and 6 weeks (after the last dose). This outcome measure was applicable for NNC0114-0006 + Liraglutide and NNC0114-0006 treatment arms.	Pre-dose and 1 hour post-dose during week 48 to week 54
Secondary	Terminal Half-life (t½) After Last Dose of NNC0114-0006	Terminal half life was calculated as log(2)/?z. The terminal rate constant ?z was determined through linear regression with the logarithm to concentration as the response variable and actual measurement time as the explanatory variable. Valid observations from the terminal part of the curve, which is approximately linear, were used for the determination. This outcome measure was applicable for NNC0114-0006 + Liraglutide and NNC0114-0006 treatment arms.	Pre-dose and 1 hour post-dose during week 48 to week 80
Secondary	Apparent Volume of Distribution of NNC0114-0006 at Steadystate (Vss, NNC0114-0006)	The apparent volume of distribution of NNC0114-0006 at steady-state was calculated as mean residence time of (MRT) of NNC0114-0006 multiplied by clearance of NNC0114-0006 at steady state. This outcome measure was applicable for NNC0114-0006 + Liraglutide and NNC0114-0006 treatment arms.	Pre-dose and 1 hour post-dose during week 48 to week 80
Secondary	Clearance of NNC0114-0006 at Steady State (CLss, NNC0114-0006)	Clearance of NNC0114-0006 at steady state was calculated as dose/AUCtau, NNC0114-0006. This outcome measure was applicable for NNC0114-0006 + Liraglutide and NNC0114-0006 treatment arms.	Pre-dose and 1 hour post-dose during week 48 to week 54
Secondary	Mean Residence Time of NNC0114-0006 (MRT, NNC0114-0006)	This outcome measure was applicable for NNC0114-0006 + Liraglutide and NNC0114-0006 treatment arms. Mean residence time of NNC0114-0006 is presented.	Pre-dose and 1 hour post-dose during week 48 to week 80
Secondary	Accumulation Ratio of NNC114-0006 (RA,AUC, NNC0114-0006)	Accumulation ratio of NNC114-0006 was defined as AUC48-54 weeks/AUC0-6 weeks. This outcome measure was applicable for NNC0114-0006 + Liraglutide and NNC0114-0006 treatment arms.	Pre-dose and 1 hour post-dose during (week 0 to week 6) and (week 48 to week 54)
Secondary	Observed NNC0114-0006 Concentration Prior to Dosing of NNC0114-0006 at Steady State (Ctrough, NNC0114-0006)	Ctrough of NNC0114-0006 was defined as concentration prior to dosing of NNC0114-0006 at steady state. This outcome measure was applicable for NNC0114-0006 + Liraglutide and NNC0114-0006 treatment arms.	Week 48 (predose)
Secondary	Observed NNC0114-0006 Concentration 1 Hour After Dosing of NNC0114-0006 at Steady State (C1h, NNC0114-0006)	C1h, NNC0114-0006 was defined as concentration of NNC0114-0006 at 1 hour after dosing of NNC0114-0006 at steady state. This outcome measure was applicable for NNC0114-0006 + Liraglutide and NNC0114-0006 treatment arms.	Week 48 (1 hour post-dose)
Secondary	Liraglutide Concentration at Steady State (C Liraglutide)	C liraglutide was defined as the liraglutide concentration at steady state. This outcome measure was applicable for NNC0114-0006 + Liraglutide and Liraglutide treatment arms.	Week 54 (post-dose)
Secondary	Change in Biomarker: Immune Phenotyping- B Cell Panel	B cell panel is evaluated by Immune phenotyping of peripheral blood mononuclear cells (PBMC) at baseline (week 0), week 54 and week 80.; In below table CD refer to Cluster of Differentiation; IgMNeg refers to Immunoglobulin M negative; IgDNeg refers to Immunoglobulin D negative.	Week 0, week 54 and week 80
Secondary	Change in Biomarker: Immune Phenotyping- Natural Killer (NK) Cell Panel	NK cell panel is evaluated by Immune phenotyping of peripheral blood mononuclear cells (PBMC) at baseline (week 0), week 54 and week 80.; In below table ADCC refer to Antibody-dependent cellular cytotoxicity; CD refer to Cluster of Differentiation.	Week 0, week 54 and week 80
Secondary	Change in Biomarker: Immune Phenotyping- T Cell Panel	T cell panel is evaluated by Immune phenotyping of peripheral blood mononuclear cells (PBMC) at baseline (week 0), week 54 and week 80.; In below table CD refer to Cluster of Differentiation; TEMRA refers to terminally differentiated effector memory cells re-expressing CD45RA; CCR refers to C-C chemokine receptor; TREG refers to Regulatory T cells.	Week 0, week 54 and week 80
Secondary	Change in Biomarker: Immune Phenotyping- T Follicular Helper (TfH) Cell Panel	TfH cell panel is evaluated by Immune phenotyping of peripheral blood mononuclear cells (PBMC) at baseline (week 0), week 54 and week 80.; In below table CTFH refer to Circulating T follicular helper; ICOS refers to inducible T-cell co-stimulator; PD refers to Programmed cell death protein; CCR refers to C-C chemokine receptor; CXCR refers to C-X-C chemokine receptor; CD refer to Cluster of Differentiation; CM refers to central memory; EM refers to effector memory, TIGIT refers to T cell immunoreceptor with Ig and ITIM domains.	Week 0, week 54 and week 80
Secondary	Change in Biomarker: Immune Phenotyping- Myeloid Cell Panel	Myeloid panel is evaluated by Immune phenotyping of peripheral blood mononuclear cells (PBMC) at baseline (week 0), week 54 and week 80.; In below table HLA refers to Human Leukocyte Antigen; MDSC refers to myeloid-derived suppressor cell; DC refers to Dendritic cells; MYDC refers to Myeloid Dendritic Cells; IMMYE_MDSC refers to Immature myeloid cells & a subset of myeloid suppressor cells within the CD14-HLA class II- myeloid cell population.	Week 0, week 54 and week 80
Secondary	Autoantibodies Against Glutamic Acid Decarboxylase (GAD)	Participants were analyzed for autoantibodies against Glutamic acid decarboxylase (GAD) and were categorized as negative and positive.	Week 0, week 54 and week 80
Secondary	Autoantibodies Against Zinc-transporter 8 (ZnT8)	Participants were analyzed for autoantibodies against Zinc-transporter 8 (ZnT8) and were categorized as negative and positive.	Week 0, week 54 and week 80
Secondary	Autoantibodies Against Islet Antigen-2 (IA2)	Participants were analyzed for autoantibodies against Islet antigen-2 (IA2) and were categorized as negative and positive.	Week 0, week 54 and week 80
Secondary	Autoantibodies Against Insulin Autoantibodies (IAA)	Participants were analyzed for autoantibodies against Insulin autoantibodies (IAA) and were categorized as negative and positive.	Week 0, week 54 and week 80
Secondary	Change in Biomarker: Total Interleukin-21 (IL-21)	IL-21 is evaluated at baseline (week 0), week 54 and week 80.	Week 0, week 54 and week 80
Secondary	Change in Biomarker: Serum Vitamin D (1,25 Dehydroxy-calciferol)	Serum vitamin D is evaluated at baseline (week 0), week 54 and week 80.	Week 0, week 54 and week 80
Secondary	Change in Short Form 36 Health Survey (SF-36)	SF-36v2™ questionnaire measured the HRQoL on 8 domains (Bodily Pain, General Health, Mental Health, Physical Functioning, Role Emotion, Physical Health, Social Functioning and Vitality) on individual scale ranges. The scores 0-100 (where higher scores indicated a better HRQoL) from the SF-36 were converted to norm-based scores to enable a direct interpretation in relation to the distribution of the scores in the 2009 U.S. general population. Change from baseline (week 0) to week 54 and week 80 in SF-36 score is presented.The MCS measure is derived from domain scales of vitality, social functioning, role emotional and mental health. The PCS measure is derived from domain scales of physical functioning, role-physical, bodily pain, and general health. A norm-based score of 50 corresponds to the mean score and 10 corresponds to the standard deviation of the 2009 U.S. general population. A positive change score indicate an improvement since baseline.	(Week 0, week 54) and (week 0, week 80)
Secondary	Change in Experience of Treatment Benefits and Barriers (ETBB)	Treatment Benefits and Barriers (ETBB) questionnaire measured diabetes-specific health beliefs on 2 categories: Total Score for Perceived Barriers and Perceived Benefits. The measurement of perceived benefits of, and barriers to, treatment was achieved by creating a pool 28 statements each with a 7-point scale ranging from strongly agree (6) to strongly disagree (0). ETBB benefits score was calculated using the responses from questions 1, 4, 7, 8, 10, and 12 and ETBB barriers score was calculated using the responses from questions 2, 3, 5, 6, 9, and 11. Both was calculated as the sum of responses divided by number of responses received multiplied by the maximum number of responses. Based on the responses used the maximum responses available was 6. The higher score indicates more perceived benefits or more perceived barrier.	(Week 0, week 54) and (week 0, week 80)
Secondary	Change in Diabetes Treatment Satisfaction Questionnaire (DTSQ)	Change from baseline (week 0) in DTSQ is evaluated at week 54 and 80. The DTSQs items are scored on a 7-point graded response scale ranging from 6 to 0. Higher score indicates a higher level of glycaemia/treatment satisfaction.	(Week 0, week 54) and (week 0, week 80)
Secondary	Area Under the Concentration-time Curve (AUC) 0-4h of Mixed Meal Tolerance Test (MMTT) Stimulated C-peptide at Week 80 Relative to Baseline	Area under the concentration-time curve, from 0 to 4 hours (AUC0-4h) of a mixed meal tolerance test (MMTT) stimulated C-peptide at week 80 is presented as ratio to baseline. AUC of C-peptide was measured as Nano moles*hour per liter (nmol*h/L).	0 - 4 hours post-dose on week 0 and week 80
Secondary	AUC0-2h of C-peptide at Week 80 Relative to Baseline	Area under the concentration-time curve, from 0 to 2 hours (AUC0-2h) of a MMTT stimulated C-peptide at week 80 is presented as ratio to baseline. AUC of C-peptide was measured as 'nmol*h/L'.	0-2 hours post-dose on week 0 and week 80
Secondary	Cmax of C-peptide at Week 80 Relative to Baseline	Maximum observed concentration (Cmax) of a MMTT stimulated C-peptide at week 80 is presented as ratio to baseline. Cmax of C-peptide was measured as nanomoles per liter (nmol/L).	0-4 hours post-dose on week 0 and week 80
Secondary	AUC0-4h of Glucose at Week 80 Relative to Baseline	Area under the concentration-time curve, from 0 to 4 hours (AUC0-4h) of a MMTT stimulated glucose at week 80 is presented as ratio to baseline. AUC of glucose was measured as Milli moles*hour per liter (mmol*h/L).	0 - 4 hours post-dose on week 0 and week 80
Secondary	AUC0-2h of Glucose at Week 80 Relative to Baseline	Area under the concentration-time curve, from 0 to 2 hours (AUC0-2h) of a MMTT stimulated glucose at week 80 is presented as ratio to baseline. AUC of glucose was measured as 'mmol*h/L'.	0-2 hours post-dose on week 0 and week 80
Secondary	Cmax of Glucose at Week 80 Relative to Baseline	Maximum observed concentration (Cmax) of a MMTT stimulated glucose at week 80 is presented as ratio to baseline. Cmax of C-peptide was measured as 'mmol/L'.	0-4 hours post-dose on week 0 and week 80

External Links

•   Clinical Trials at Novo Nordisk