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

Sanofi463 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

463

Conditions

Type 1 Diabetes Mellitus

Interventions

Eligibility

Sex: ALLMin age: 6 YearsMax age: 17 Years

Medical Language ↔ Plain English

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.

Locations (107)

Investigational Site Number 8400008

Tucson, Arizona, United States

Investigational Site Number 8400037

Atlanta, Georgia, United States

Investigational Site Number 8400032

Indianapolis, Indiana, United States

Investigational Site Number 8400015

Buffalo, New York, United States

Investigational Site Number 8400016

Chapel Hill, North Carolina, United States

Outcomes

Primary Outcomes

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.

Time frame: Baseline to Month 6

Secondary Outcomes

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.

Time frame: Baseline to Month 6

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).

Time frame: Month 6

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

Time frame: upto Month 6

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).

Time frame: Month 6

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

Time frame: upto Month 6

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.

Time frame: Baseline to Month 6

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).

Time frame: Baseline, Month 6

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.

Time frame: Baseline to Month 6

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.

Time frame: Month 12

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.

Time frame: Month 12