Comparison of the Safety and Efficacy of HOE901-U300 With Lantus in Children and Adolescents With Type 1 Diabetes Mellitus

Type 1 Diabetes Mellitus Clinical Trial

— EDITION JUNIOR  

Official title:

6-Month, Multicenter, Randomized, Open-label, 2-Arm, Parallel-group Study Comparing the Efficacy and Safety of a New Formulation of Insulin Glargine and Lantus® Injected Once Daily in Children and Adolescents Age 6 - 17 Years With Type 1 Diabetes Mellitus With a 6-month Safety Extension Period

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02735044
• Other study ID #: EFC13957
• Secondary ID: 2015-002084-42U1
• Status: Completed
• Phase: Phase 3
• Start date: April 14, 2016
• Est. completion date: December 20, 2018

Study information

• Verified date: March 2022
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Primary Objective: To compare the efficacy of a new formulation of insulin glargine (HOE901-U300) to Lantus in terms of change of HbA1c from baseline to endpoint (month 6) in children and adolescents with type 1 diabetes mellitus. . Secondary Objectives: To compare HOE901-U300 and Lantus in terms of: - Percentage of participants reaching target HbA1c and fasting plasma glucose (FPG). - To assess the safety of HOE901-U300 including analysis of events of hypoglycemia, events of hyperglycemia with ketosis, and development of anti-insulin-antibodies.

Description:

The study duration per participant was approximately 58 weeks that consisted of a 2 week screening period, a main 6-month comparative efficacy and safety treatment period, a 6-month comparative safety extension period, and a 4-week post treatment follow up period.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 463
• Est. completion date: December 20, 2018
• Est. primary completion date: May 31, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Years to 17 Years

Eligibility

Inclusion criteria :

• Children and adolescents with type 1 diabetes mellitus (T1DM) for at least 1 year confirmed by typical symptoms at diagnosis and/or by antibody testing [presence of anti-GAD (glutamic acid decarboxylase) or anti-IA2 (islet antigen 2/tyrosine phosphatase) or anti-islet cell antibodies] and/or clinical features (eg, history of ketoacidosis)].
• Signed written informed consent obtained from parent(s)/legal guardian and written or oral assent obtained from participant.

Exclusion criteria:

• Age <6 years and >=18 years at randomization.
• Less than 1 year on insulin treatment prior to screening visit.
• Less than 6 months on basal plus mealtime insulin and self-monitoring of blood glucose prior to screening visit.
• Participants using premix insulins in the last 3 months before screening visit or participants using human regular insulin as mealtime insulin in the last 3 months before screening visit.
• Use of an insulin pump in the last 6 months before screening visit or plans to switch to pump within the next 6 months after screening visit.
• Any contraindication to use of insulin glargine as defined in the national product label.
• No willingness to inject insulin glargine (Lantus or HOE901-U300) once daily.
• HbA1c <7.5% or >11% at screening.
• Initiation of any glucose-lowering medications in the last 3 months before screening visit.
• Hospitalization or care in the emergency ward for diabetic ketoacidosis or history of severe hypoglycemia (as defined by need for glucagon or IV glucose) and accompanied by seizure and/or unconsciousness and/or coma in the last 3 months prior to screening visit.
• Postmenarchal girls not protected by highly-effective method(s) of birth control and/or who were unwilling or unable to be tested for pregnancy. Abstinence from sexual intercourse was considered as an acceptable form of birth control.
• Pregnant or breast-feeding adolescents, or adolescents who intended to become pregnant during the study period, or who were at risk of getting pregnant due to any psychosocial reason during the study period. The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Type 1 Diabetes Mellitus

Intervention

Drug:
• Insulin glargine,300 U/mL
Subcutaneous injection in the morning or evening using a prefilled pen. Dose titration to achieve fasting self-monitored plasma glucose (SMPG) from 90 to 130 milligram/deciliter (mg/dL) (5.0 to 7.2 millimol per liter [mmol/L])
• Insulin glargine (100 units /mL)
Subcutaneous injection in the morning or evening using a prefilled pen. Dose titration to achieve fasting SMPG from 90 to 130 mg/dL (5.0 to 7.2 mmol/L)
• Background therapy
Fast-acting mealtime insulin analogs

Locations

Country	Name	City	State
Argentina	Investigational Site Number 0320001	Caba
Argentina	Investigational Site Number 0320003	Caba
Argentina	Investigational Site Number 0320002	Capital Federal
Argentina	Investigational Site Number 0320004	Capital Federal
Argentina	Investigational Site Number 0320006	Mendoza
Argentina	Investigational Site Number 0320005	Salta
Argentina	Investigational Site Number 0320007	San Miguel De Tucuman
Brazil	Investigational Site Number 0760005	Curitiba
Brazil	Investigational Site Number 0760004	Fortaleza
Brazil	Investigational Site Number 0760006	Fortaleza
Brazil	Investigational Site Number 0760003	Porto Alegre
Brazil	Investigational Site Number 0760001	Sao Paulo
Brazil	Investigational Site Number 0760002	Sao Paulo
Bulgaria	Investigational Site Number 1000001	Plovdiv
Bulgaria	Investigational Site Number 1000005	Sofia
Bulgaria	Investigational Site Number 1000004	Varna
Canada	Investigational Site Number 1240003	Halifax
Canada	Investigational Site Number 1240002	Montreal
Canada	Investigational Site Number 1240005	Montreal
Canada	Investigational Site Number 1240006	Sherbrooke
Chile	Investigational Site Number 1520002	Santiago
Chile	Investigational Site Number 1520004	Santiago
Chile	Investigational Site Number 1520006	Santiago
Chile	Investigational Site Number 1520007	Temuco
Chile	Investigational Site Number 1520003	Viña Del Mar
Czechia	Investigational Site Number 2030003	Hradec Kralove
Czechia	Investigational Site Number 2030005	Ostrava - Poruba
Czechia	Investigational Site Number 2030001	Praha 5 - Motol
Denmark	Investigational Site Number 2080001	Herlev
France	Investigational Site Number 2500003	Montpellier
France	Investigational Site Number 2500002	Toulouse
Germany	Investigational Site Number 2760002	Hannover
Germany	Investigational Site Number 2760001	Heidelberg
Germany	Investigational Site Number 2760004	Leipzig
Germany	Investigational Site Number 2760003	Münster
Hungary	Investigational Site Number 3480001	Budapest
Hungary	Investigational Site Number 3480003	Budapest
Hungary	Investigational Site Number 3480004	Budapest
Hungary	Investigational Site Number 3480005	Gyula
Hungary	Investigational Site Number 3480002	Miskolc
Hungary	Investigational Site Number 3480006	Pécs
Hungary	Investigational Site Number 3480007	Székesfehérvár
Israel	Investigational Site Number 3760003	Beer Sheva
Israel	Investigational Site Number 3760001	Haifa
Israel	Investigational Site Number 3760006	Holon
Israel	Investigational Site Number 3760002	Petach Tikva
Italy	Investigational Site Number 3800001	Firenze
Italy	Investigational Site Number 3800005	Roma
Italy	Investigational Site Number 3800004	Torino
Italy	Investigational Site Number 3800006	Varese
Italy	Investigational Site Number 3800003	Verona
Japan	Investigational Site Number 3920006	Chiyoda-Ku
Japan	Investigational Site Number 3920002	Fukuoka-Shi
Japan	Investigational Site Number 3920003	Hiroshima-Shi
Japan	Investigational Site Number 3920007	Kobe-Shi
Japan	Investigational Site Number 3920005	Osaka-Shi
Japan	Investigational Site Number 3920004	Shinjuku-Ku
Latvia	Investigational Site Number 4280002	Daugavpils
Latvia	Investigational Site Number 4280001	Riga
Mexico	Investigational Site Number 4840003	Durango
Mexico	Investigational Site Number 4840004	México
Mexico	Investigational Site Number 4840001	Monterrey
Mexico	Investigational Site Number 4840002	Puebla
Mexico	Investigational Site Number 4840005	Veracruz
North Macedonia	Investigational Site Number 8070001	Skopje
Poland	Investigational Site Number 6160005	Bielsko-Biala
Poland	Investigational Site Number 6160001	Gdansk
Poland	Investigational Site Number 6160006	Szczecin
Poland	Investigational Site Number 6160003	Warszawa
Poland	Investigational Site Number 6160004	Warszawa
Poland	Investigational Site Number 6160007	Warszawa
Romania	Investigational Site Number 6420005	Bucharest
Romania	Investigational Site Number 6420007	Constanta
Romania	Investigational Site Number 6420004	Craiova
Romania	Investigational Site Number 6420006	Sibiu
Romania	Investigational Site Number 6420003	Timisoara
Russian Federation	Investigational Site Number 6430001	Moscow
Russian Federation	Investigational Site Number 6430004	Smolensk
Russian Federation	Investigational Site Number 6430002	St-Petersburg
Russian Federation	Investigational Site Number 6430003	Ufa
Serbia	Investigational Site Number 6880002	Belgrade
Serbia	Investigational Site Number 6880003	Belgrade
Serbia	Investigational Site Number 6880004	Nis
Spain	Investigational Site Number 7240002	Barcelona
Spain	Investigational Site Number 7240005	Barcelona
Spain	Investigational Site Number 7240003	Esplugues De Llobregat
Spain	Investigational Site Number 7240004	Sabadell
Spain	Investigational Site Number 7240006	Santa Cruz De Tenerife
Spain	Investigational Site Number 7240001	Vitoria
Sweden	Investigational Site Number 7520002	Stockholm
United Kingdom	Investigational Site Number 8260005	Doncaster
United Kingdom	Investigational Site Number 8260001	Ipswich
United Kingdom	Investigational Site Number 8260004	Kettering
United Kingdom	Investigational Site Number 8260002	Salisbury
United States	Investigational Site Number 8400037	Atlanta	Georgia
United States	Investigational Site Number 8400015	Buffalo	New York
United States	Investigational Site Number 8400016	Chapel Hill	North Carolina
United States	Investigational Site Number 8400005	Dallas	Texas
United States	Investigational Site Number 8400021	Dallas	Texas
United States	Investigational Site Number 8400032	Indianapolis	Indiana
United States	Investigational Site Number 8400029	Lufkin	Texas
United States	Investigational Site Number 8400035	Morehead City	North Carolina
United States	Investigational Site Number 8400038	Oklahoma City	Oklahoma
United States	Investigational Site Number 8400030	Philadelphia	Pennsylvania
United States	Investigational Site Number 8400010	Rapid City	South Dakota
United States	Investigational Site Number 8400034	Seattle	Washington
United States	Investigational Site Number 8400008	Tucson	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  Bulgaria,  Canada,  Chile,  Czechia,  Denmark,  France,  Germany,  Hungary,  Israel,  Italy,  Japan,  Latvia,  Mexico,  North Macedonia,  Poland,  Romania,  Russian Federation,  Serbia,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change From Baseline in HbA1c to Month 6	Change in HbA1c was calculated by subtracting baseline value from Month 6 value. Adjusted least-square (LS) means and standard errors (SE) were obtained using analysis of covariance (ANCOVA) after multiple imputations of missing data using post-baseline HbA1c data available on the main 6-month randomized period.	Baseline to Month 6
Secondary	Change From Baseline in Fasting Plasma Glucose (FPG) to Month 6	Change in FPG was calculated by subtracting baseline value from Month 6 value. Adjusted LS means and SE were obtained using ANCOVA after multiple imputation to address missing data in the main 6 month randomized period.	Baseline to Month 6
Secondary	Percentage of Participants With HbA1c Values of <7.5% at Month 6	Participants without any available HbA1c assessment at month 6 and/or with a premature study discontinuation during the main 6-month randomized period were considered as a failure (non-responders) in the analysis. Analysis was performed using Cochran-Mantel-Haenszel (CMH) method with randomization strata of screening HbA1c (<8.5%; >=8.5%) and randomization strata of age at screening (<12 years, >=12 years).	Month 6
Secondary	Percentage of Participants With HbA1c Values of <7.5% Without Any Episode of Severe and/or Documented Self-Monitored Plasma Glucose ([SMPG] <54 mg/dL [3.0 mmol/L]) Symptomatic Hypoglycemia During the Last 3 Months of the Main 6-month Randomized Period	Participants without any available HbA1c assessment at month 6 and/or with a premature study discontinuation during the main 6-month randomized period were considered as a failure (non-responders) in the analysis. Analysis was performed using Cochran-Mantel-Haenszel (CMH) method with randomization strata of screening HbA1c (<8.5%; >=8.5%) and randomization strata of age at screening (<12 years, >=12 years).	upto Month 6
Secondary	Percentage of Participants With FPG of <=130 mg/dL (7.2 mmol/L) at Month 6	Participants without any available FPG assessment at month 6 and/or with a premature study discontinuation during the main 6-month randomized period were considered as a failure (non-responders) in the analysis. Analysis was performed using Cochran-Mantel-Haenszel (CMH) method with randomization strata of screening HbA1c (<8.5%; >=8.5%) and randomization strata of age at screening (<12 years, >=12 years).	Month 6
Secondary	Percentage of Participants With FPG of <=130 mg/dL (7.2 mmol/L) Without Any Episode of Severe and/or Documented (SMPG <54 mg/dL [3.0 mmol/L]) Symptomatic Hypoglycemia During the Last 3 Months of the Main 6-month Randomized Period	Participants without any available HbA1c assessment at month 6 and/or with a premature study discontinuation during the main 6-month randomized period were considered as a failure (non-responders) in the analysis. Analysis was performed using Cochran-Mantel-Haenszel (CMH) method with randomization strata of screening HbA1c (<8.5%; >=8.5%) and randomization strata of age at screening (<12 years, >=12 years).	upto Month 6
Secondary	Change From Baseline in 24-Hour Mean Plasma Glucose Based on 8-point SMPG Profiles to Month 6	8-point SMPG profiles were measured at the following 8 points: between 01:00 and 04:00 (clock time) at night, pre-breakfast, 2 hours after breakfast, pre-lunch, 2 hours after lunch, pre-dinner, 2 hours after dinner, and bedtime. Analysis was performed using a ANCOVA model including the fixed categorical effects of treatment group, randomization strata of screening HbA1c (<8.5%; >=8.5%), randomization strata of age at screening (<12 years, >=12 years) and the baseline 24-hour average 8-point profile SMPG.	Baseline to Month 6
Secondary	Change From Baseline in Variability of 24-Hour Mean Plasma Glucose Based on 8-point SMPG Profiles at Month 6	8-point SMPG profiles were measured at the following 8 points: between 01:00 and 04:00 (clock time) at night, pre-breakfast, 2 hours after breakfast, pre-lunch, 2 hours after lunch, pre-dinner, 2 hours after dinner, and bedtime. Variability was assessed by the coefficient of variation (standard deviation divided by mean) calculated over the 8-point SMPG. Analysis was performed using a ANCOVA model including the fixed categorical effects of treatment group, randomization strata of screening HbA1c (<8.5%; >=8.5%) and randomization strata of age at screening (<12 years, >=12 years).	Baseline, Month 6
Secondary	Change From Baseline to Month 6 in 8-Point SMPG Profile Per Time Point	8-point SMPG profiles were measured for following 8 time points at Baseline and Month 6: between 01:00 and 04:00 (clock time) at night, pre-breakfast, 2 hours after breakfast, pre-lunch, 2 hours after lunch, pre-dinner, 2 hours after dinner, and bedtime.	Baseline to Month 6
Secondary	Percentage of Participants With at Least One Hypoglycemic Events (Any Hypoglycemia, Severe Hypoglycemia, Documented Symptomatic, Probable Symptomatic, Asymptomatic Hypoglycemia, Pseudo-hypoglycemia and Severe and/or Confirmed Hypoglycemia) at Month 12	Severe hypoglycemia: an event in which the child/adolescent having altered mental status and cannot assist in their care, is semiconscious or unconscious, or in coma ± convulsions and may require parenteral therapy (glucagon or glucose). Documented symptomatic hypoglycemia: an event during which typical symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of <=70 mg/dL (3.9 mmol/L). Asymptomatic hypoglycemia: an event not accompanied by typical symptoms of hypoglycemia but with a measured plasma glucose concentration <=70 mg/dL. Probable symptomatic hypoglycemia: an event during which symptoms of hypoglycemia were not accompanied by plasma glucose determination but was presumably caused by a plasma glucose concentration <=70 mg/dL. Pseudo-hypoglycemia:an event with any of the typical symptoms of hypoglycaemia with plasma glucose concentration >70 mg/dL.	Month 12
Secondary	Percentage of Participants With Any Hyperglycemia With Ketosis at Month 12	Hyperglycemia with ketosis was defined as SMPG >=252 mg/dL (14 mmol/L) with accompanying self-measured blood ketones >=1.5 mmol/L.	Month 12