Research Study Investigating How Well NNC0174-0833 Works in People Suffering From Overweight or Obesity.

Obesity Clinical Trial

Official title:

Investigation of Safety and Efficacy of NNC0174-0833 for Weight Management - a Dose Finding Trial.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03856047
• Other study ID #: NN9838-4433
• Secondary ID: U1111-1214-04292
• Status: Completed
• Phase: Phase 2
• Start date: March 1, 2019
• Est. completion date: March 25, 2021

Study information

• Verified date: July 2023
• Source: Novo Nordisk A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will look at the change in body weight in people taking NNC0174-0833, liraglutide and "dummy" medicine, from the start to the end of the study. As well as taking the medicine, participants will have talks with study staff about healthy food choices, how to be more physically active and what participants can do to lose weight. Participants will either take NNC0174-0833, liraglutide or "dummy" medicine - which treatment participants get is decided by chance. Participants will need to take one injection once a week or once a day, depending on the treatment. The study medicine is injected with a thin needle in a skin fold in the stomach, thigh or upper arm. The study will last for about 8 months. Participants will have 12 clinic visits with the study doctor.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 706
• Est. completion date: March 25, 2021
• Est. primary completion date: March 2, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 18 years or older at the time of signing the informed consent.

• Female subject of non-childbearing potential or Male subject who is surgically sterilised (vasectomy) or who is willing to use adequate contraceptive methods (as required by local regulation or practice) throughout the trial (until 'end of trial').

• BMI equal to 30.0 kg/m^2 or greater or BMI equal to 27.0 kg/m^2 or greater with the presence of at least one of the following weight-related comorbidities (treated or untreated): hypertension or dyslipidaemia (to be assessed at the investigator's discretion).

Exclusion Criteria:

• HbA1c equal to 48 mmol/mol (6.5 percentage) or greater as measured by the central laboratory at screening.

• A self-reported change in body weight greater than 5 kg (11 lbs) within 90 days prior to screening irrespective of medical records.

Related Conditions & MeSH terms

• Obesity
• Overweight

Intervention

Drug:
• NNC0174-0833
Participants will get one dose of NNC0174-0833 once weekly. The medicine is injected with a thin needle in a skin fold in the stomach, thigh or upper arm using NovoPen® 4. Participants will gradually increase the dose until they reach the target dose, and will continue on the this dose once weekly up to 26 weeks.
• Placebo (NNC0174-0833)
Participants will get one dose of Placebo (NNC0174-0833) once weekly. The medicine is injected with a thin needle in a skin fold in the stomach, thigh or upper arm using NovoPen® 4. Participants will gradually increase the dose until they reach the target dose, and will continue on the this dose once weekly up to 26 weeks.
• Liraglutide 3.0 mg
Participants will get one dose of liraglutide 3.0 mg once daily. The medicine is injected with a thin needle in a skin fold in the stomach, thigh or upper arm using pre-filled PDS290 pen-injector. Participants will gradually increase their dose every week until they reach the target dose of 3.0 mg daily. The participants will continue on 3.0 mg of liraglutide, once daily up to 26 weeks.
• Placebo (Liraglutide 3.0 mg)
Participants will get one dose of Placebo (liraglutide 3.0 mg) once daily. The medicine is injected with a thin needle in a skin fold in the stomach, thigh or upper arm using pre-filled PDS290 pen-injector. Participants will gradually increase their dose every week until they reach the target dose of 3.0 mg. The participants will continue on Placebo (liraglutide 3.0 mg), once daily up to 26 weeks.

Locations

Country	Name	City	State
Canada	Novo Nordisk Investigational Site	Calgary	Alberta
Canada	Novo Nordisk Investigational Site	Calgary	Alberta
Canada	Novo Nordisk Investigational Site	Edmonton	Alberta
Canada	Novo Nordisk Investigational Site	Hamilton	Ontario
Canada	Novo Nordisk Investigational Site	Hamilton	Ontario
Denmark	Novo Nordisk Investigational Site	Aarhus N
Denmark	Novo Nordisk Investigational Site	Hvidovre
Finland	Novo Nordisk Investigational Site	Jyväskylä
Finland	Novo Nordisk Investigational Site	Kuopio
Finland	Novo Nordisk Investigational Site	Turku
Finland	Novo Nordisk Investigational Site	University Of Helsinki
Ireland	Novo Nordisk Investigational Site	Dublin
Japan	Novo Nordisk Investigational Site	Tokyo
Japan	Novo Nordisk Investigational Site	Tokyo
Japan	Novo Nordisk Investigational Site	Tokyo
Poland	Novo Nordisk Investigational Site	Bialystok
Poland	Novo Nordisk Investigational Site	Katowice
Poland	Novo Nordisk Investigational Site	Poznan
Serbia	Novo Nordisk Investigational Site	Belgrade
Serbia	Novo Nordisk Investigational Site	Novi Sad
South Africa	Novo Nordisk Investigational Site	Bloemfontein	Free State
South Africa	Novo Nordisk Investigational Site	Boksburg	Gauteng
South Africa	Novo Nordisk Investigational Site	Durban	KwaZulu-Natal
South Africa	Novo Nordisk Investigational Site	Durban	KwaZulu-Natal
South Africa	Novo Nordisk Investigational Site	Johannesburg	Gauteng
United Kingdom	Novo Nordisk Investigational Site	Bradford-on-Avon
United Kingdom	Novo Nordisk Investigational Site	Bristol
United Kingdom	Novo Nordisk Investigational Site	Coventry
United Kingdom	Novo Nordisk Investigational Site	Liverpool
United Kingdom	Novo Nordisk Investigational Site	London
United Kingdom	Novo Nordisk Investigational Site	London
United Kingdom	Novo Nordisk Investigational Site	Rotherham
United States	Novo Nordisk Investigational Site	Anaheim	California
United States	Novo Nordisk Investigational Site	Arlington	Virginia
United States	Novo Nordisk Investigational Site	Bristol	Tennessee
United States	Novo Nordisk Investigational Site	Charleston	South Carolina
United States	Novo Nordisk Investigational Site	Chicago	Illinois
United States	Novo Nordisk Investigational Site	Crystal River	Florida
United States	Novo Nordisk Investigational Site	Elkridge	Maryland
United States	Novo Nordisk Investigational Site	Franklin	Ohio
United States	Novo Nordisk Investigational Site	Gaffney	South Carolina
United States	Novo Nordisk Investigational Site	Greensboro	North Carolina
United States	Novo Nordisk Investigational Site	Jacksonville	Florida
United States	Novo Nordisk Investigational Site	Mason	Ohio
United States	Novo Nordisk Investigational Site	Norman	Oklahoma
United States	Novo Nordisk Investigational Site	North Dartmouth	Massachusetts
United States	Novo Nordisk Investigational Site	Pembroke Pines	Florida
United States	Novo Nordisk Investigational Site	Ponte Vedra	Florida
United States	Novo Nordisk Investigational Site	Richmond	Virginia
United States	Novo Nordisk Investigational Site	Rochester	New York
United States	Novo Nordisk Investigational Site	Round Rock	Texas
United States	Novo Nordisk Investigational Site	Spartanburg	South Carolina
United States	Novo Nordisk Investigational Site	Spring Valley	California
United States	Novo Nordisk Investigational Site	Wadsworth	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Countries where clinical trial is conducted

United States,  Canada,  Denmark,  Finland,  Ireland,  Japan,  Poland,  Serbia,  South Africa,  United Kingdom, 

References & Publications (1)

Lau DCW, Erichsen L, Francisco AM, Satylganova A, le Roux CW, McGowan B, Pedersen SD, Pietilainen KH, Rubino D, Batterham RL. Once-weekly cagrilintide for weight management in people with overweight and obesity: a multicentre, randomised, double-blind, pl — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Body Weight (%)	Change in body weight (%) from week 0 to week 26 is presented. For descriptive analysis and statistical analysis the endpoint was evaluated based on the data from in-trial period and treatment adherent period, respectively. In-trial period was defined as the uninterrupted time interval from date of randomisation to date of last contact with trial site. Follow-up time for positive antibodies was not included in the in-trial period. Treatment-adherent: a participant is treatment adherent until the first time of non-adherence defined as: participant has not been dosed with trial product within the prior 14 days; participant has received other weight management drug or bariatric surgery; participant has not reached target dose at a pre-specified week; After the pre-specified evaluation week for the target dose, the participant has not received the target dose ±10% within the prior 14 days.	From baseline (week 0) to week 26
Secondary	Percentage of Participants With Weight Loss of = 5% of Baseline Body Weight at 26 Weeks	Percentage of participants who achieved a weight loss of greater than or equal to (=) 5% of baseline (week 0) body weight at 26 weeks is presented. The numbers presented are predictions from a logistic regression model.	Week 26
Secondary	Percentage of Participants With Weight Loss of = 10% of Baseline Body Weight at 26 Weeks	Percentage of participants who achieved a weight loss = 10% of baseline (week 0) body weight at 26 weeks is presented. The numbers presented are predictions from a logistic regression model.	Week 26
Secondary	Change in Body Weight (Kg)	Change in body weight (Kg) from week 0 to week 26 is presented. The endpoint was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomisation to date of last contact with trial site. Follow-up time for positive antibodies was not included in the in-trial period.	From baseline (week 0) to week 26
Secondary	Change in Waist Circumference	Change in waist circumference from week 0 to week 26 is presented. The endpoint was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomisation to date of last contact with trial site. Follow-up time for positive antibodies was not included in the in-trial period.	From baseline (week 0) to week 26
Secondary	Change in Total Cholesterol	Change in total cholesterol from week 0 to week 26 is presented. The endpoint was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomisation to date of last contact with trial site. Follow-up time for positive antibodies was not included in the in-trial period.	From baseline (week 0) to week 26
Secondary	Change in High Density Lipoprotein (HDL) Cholesterol	Change in HDL cholesterol from week 0 to week 26 is presented. The endpoint was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomisation to date of last contact with trial site. Follow-up time for positive antibodies was not included in the in-trial period.	From baseline (week 0) to week 26
Secondary	Change in Low Density Lipoprotein (LDL) Cholesterol	Change in LDL cholesterol from week 0 to week 26 is presented. The endpoint was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomisation to date of last contact with trial site. Follow-up time for positive antibodies was not included in the in-trial period.	From baseline (week 0) to week 26
Secondary	Change in Very Low Density Lipoprotein (VLDL) Cholesterol	Change in VLDL cholesterol from week 0 to week 26 is presented. The endpoint was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomisation to date of last contact with trial site. Follow-up time for positive antibodies was not included in the in-trial period.	From baseline (week 0) to week 26
Secondary	Change in Triglycerides	Change in triglycerides from week 0 to week 26 is presented. The endpoint was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomisation to date of last contact with trial site. Follow-up time for positive antibodies was not included in the in-trial period.	From baseline (week 0) to week 26
Secondary	Change in Glycosylated Haemoglobin (HbA1c) (%-Point)	Change in HbA1c (measured as percentage point of HbA1c) from week 0 to week 26 is presented. The endpoint was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomisation to date of last contact with trial site. Follow-up time for positive antibodies was not included in the in-trial period.	From baseline (week 0) to week 26
Secondary	Change in HbA1c (mmol/Mol)	Change in HbA1c (measured as millimoles per mole (mmol/mol)) from week 0 to week 26 is presented. The endpoint was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomisation to date of last contact with trial site. Follow-up time for positive antibodies was not included in the in-trial period.	From baseline (week 0) to week 26
Secondary	Change in Fasting Plasma Glucose (FPG) (mmol/L)	Change in FPG (measured as mmol/L)) from week 0 to week 26 is presented. The endpoint was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomisation to date of last contact with trial site. Follow-up time for positive antibodies was not included in the in-trial period.	From baseline (week 0) to week 26
Secondary	Change in FPG (mg/dL)	Change in FPG (measured as milligrams per decilitre (mg/dL)) from week 0 to week 26 is presented. The endpoint was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomisation to date of last contact with trial site. Follow-up time for positive antibodies was not included in the in-trial period.	From baseline (week 0) to week 26
Secondary	Change in Fasting Insulin	In the below table, fasting insulin data at week 0 and at week 26 is presented. The endpoint was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomisation to date of last contact with trial site. Follow-up time for positive antibodies was not included in the in-trial period.	From baseline (week 0) to week 26
Secondary	Percentage Change in Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)	Percentage change in HOMA-IR from week 0 to week 26 is presented. Insulin resistance is a condition in which cells fail to respond to normal actions of hormone in body. HOMA-IR is calculated using a subject's fasting plasma insulin and glucose levels. HOMA-IR = fasting serum insulin (micro international units per milliliter (µU/ml)) × fasting plasma glucose (millimoles per liter (mmol/l)) / 22.5. HOMA-IR scores are classified as follows: less than 1.0: considered Insulin sensitive, 0.5-1.4: considered Healthy, Above 1.8: considered Early insulin resistance; Above 2.7 is considered significant insulin resistance. HOMA-IR score ranges from 0-infinity (no upper limit). Higher the score, higher the level of insulin resistance. Endpoint was evaluated based on data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomisation to date of last contact with trial site. Follow-up time for positive antibodies was not included in in-trial period.	From baseline (week 0) to week 26
Secondary	Change in Homeostatic Model Assessment of Beta-cell Function (HOMA-beta)	Change between the value of HOMA-beta cell function collected at Week 26 and HOMA-beta cell function collected at Week 0 is presented. The homeostatic model assessment estimates steady state beta cell function as a percentage of a normal reference population (%B). HOMA %B = 20 * insulin (micro international units per milliliter (µIU/mL)) / fasting plasma glucose (millimoles per liter (mmol/L)) - 3.5. HOMA-beta score ranges from minus infinity to infinity (no limits). The higher the score the better beta-cell function for HOMA-beta. The endpoint was evaluated based on the data from in-trial period. In-trial period was defined as the uninterrupted time interval from date of randomisation to date of last contact with trial site. Follow-up time for positive antibodies was not included in the in-trial period.	From baseline (week 0) to week 26
Secondary	Number of Treatment-emergent Adverse Events (TEAEs)	An adverse event (AE) was any untoward medical occurrence in a clinical trial participant administered or used a medicinal product, whether or not considered related to the medicinal product or usage. All AEs reported here are TEAEs. TEAE is defined as an event that had onset date during the on-treatment period. The endpoint was evaluated based on the data from on-treatment period which started from the date of first trial product administration to date of last trial product administration excluding potential off-treatment time intervals triggered by at least 6 consecutive missed doses for cagrilintide or 6 consecutive weeks of missed dosing with liraglutide.	From week 0 to week 32
Secondary	Number of Treatment-emergent Serious Adverse Events (TESAEs)	An AE was any untoward medical occurrence in a clinical trial participant administered or used a medicinal product, whether or not considered related to the medicinal product or usage. Serious AE is an AE that resulted in death, life threatening, persistent or significant incapacity or substantial disruption of ability to conduct normal life functions, hospitalization or prolongation of existing hospitalization, congenital anomaly or birth defect, important medical events that may not result in death, be life threatening, or require hospitalization. All SAEs reported in the below table are TESAEs. The endpoint was evaluated based on the data from on-treatment period which started from the date of first trial product administration to date of last trial product administration excluding potential off-treatment time intervals triggered by at least 6 consecutive missed doses for cagrilintide or 6 consecutive weeks of missed dosing with liraglutide.	From week 0 to week 32
Secondary	Number of Participants With Occurrence of Anti-drug Antibodies Towards Cagrilintide	Number of participants with occurrence of anti-drug antibodies towards cagrilintide from randomisation from week 0 to week 32 is presented. The endpoint was evaluated based on the data from in-trial period. The in-trial period was defined as the uninterrupted time interval from date of randomisation to date of last contact with trial site. Follow-up time for positive antibodies was not included in the in-trial period. This endpoint is applicable only for the cagrilintide treatment arms.	From week 0 to week 32
Secondary	Change in Diastolic Blood Pressure (DBP)	Blood pressure was measured in a sitting position after 5 minutes of rest. The end point is evaluated while the subject is treatment-adherent. A participant is treatment adherent until the first time of non-adherence defined as: a) the participant has not been dosed with trial product within the prior 14 days; b) the participant has received other weight management drug or bariatric surgery c) the participant has not reached target dose at a pre-specified week d) After the pre-specified evaluation week for the target dose, the participant has not received the target dose +/- 10 % within the prior 14 days. This endpoint is applicable only for the cagrilintide treatment arms.	From baseline (week 0) to week 26
Secondary	Change in Systolic Blood Pressure (SBP)	Blood pressure was measured in a sitting position after 5 minutes of rest. The end point is evaluated while the subject is treatment-adherent. A participant is treatment adherent until the first time of non-adherence defined as: a) the participant has not been dosed with trial product within the prior 14 days; b) the participant has received other weight management drug or bariatric surgery c) the participant has not reached target dose at a pre-specified week d) After the pre-specified evaluation week for the target dose, the participant has not received the target dose +/- 10 % within the prior 14 days. This endpoint is applicable only for the cagrilintide treatment arms.	From baseline (week 0) to week 26
Secondary	Change in Pulse	Change in pulse from week 0 to week 26 is presented. The endpoint was evaluated based on the data from on-treatment period which started from the date of first trial product administration to date of last trial product administration excluding potential off-treatment time intervals triggered by at least 6 consecutive missed doses for cagrilintide or 6 consecutive weeks of missed dosing with liraglutide.	From baseline (week 0) to week 26
Secondary	Change in High Sensitivity C-reactive Protein (hsCRP)	In the below table, hsCRP data at week 0 and at week 26 is presented. The endpoint was evaluated based on the data from on-treatment period which started from the date of first trial product administration to date of last trial product administration excluding potential off-treatment time intervals triggered by at least 6 consecutive missed doses for cagrilintide or 6 consecutive weeks of missed dosing with liraglutide.	From baseline (week 0) to week 26
Secondary	Change in Plasminogen Activator Inhibitor-1 (PAI-1) Activity	Due to the assay development issue faced by the laboratory, the Plasminogen Activator Inhibitor-1 (PAI-1) activity (mg/L) was not performed in the study.	From baseline (week 0) to week 26
Secondary	Change in Renin Activity	Change in renin activity from week 0 to week 26 is presented. The endpoint was evaluated based on the data from on-treatment period which started from the date of first trial product administration to date of last trial product administration excluding potential off-treatment time intervals triggered by at least 6 consecutive missed doses for cagrilintide or 6 consecutive weeks of missed dosing with liraglutide.	From baseline (week 0) to week 26
Secondary	Change in Aldosterone	Change in aldosterone from week 0 to week 26 is presented. The endpoint was evaluated based on the data from on-treatment period which started from the date of first trial product administration to date of last trial product administration excluding potential off-treatment time intervals triggered by at least 6 consecutive missed doses for cagrilintide or 6 consecutive weeks of missed dosing with liraglutide.	From baseline (week 0) to week 26