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

Phase 3

Completed

Conditions: Type 1 Diabetes Mellitus

Interventions: Drug: Insulin glargine (100 units /mL)
Drug: Insulin glargine,300 U/mL
Drug: Background therapy

Registration Number: NCT02735044

Lead Sponsor: Sanofi

Brief 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.

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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.

Detailed 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 & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 463

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Lantus	Insulin glargine (100 units /mL)	Lantus (Insulin glargine 100 U/mL) SC injection once daily for 12 months.
HOE901-U300	Background therapy	HOE901-U300 (Insulin glargine 300 Units/milliliter \[U/mL\]) Subcutaneous(SC) injection once daily for 12 months.
HOE901-U300	Insulin glargine,300 U/mL	HOE901-U300 (Insulin glargine 300 Units/milliliter \[U/mL\]) Subcutaneous(SC) injection once daily for 12 months.
Lantus	Background therapy	Lantus (Insulin glargine 100 U/mL) SC injection once daily for 12 months.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in HbA1c to Month 6	Baseline 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.

Secondary Outcome Measures

Name	Time	Method
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	upto 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).
Percentage of Participants With HbA1c Values of <7.5% at Month 6	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).
Change From Baseline in Fasting Plasma Glucose (FPG) to Month 6	Baseline 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.
Percentage of Participants With FPG of <=130 mg/dL (7.2 mmol/L) at Month 6	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).
Change From Baseline in 24-Hour Mean Plasma Glucose Based on 8-point SMPG Profiles to Month 6	Baseline 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.
Change From Baseline in Variability of 24-Hour Mean Plasma Glucose Based on 8-point SMPG Profiles at Month 6	Baseline, 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).
Change From Baseline to Month 6 in 8-Point SMPG Profile Per Time Point	Baseline to Month 6	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.
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	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.
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	upto 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).
Percentage of Participants With Any Hyperglycemia With Ketosis at Month 12	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.

Trial Locations

Locations (107): Investigational Site Number 8400008
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Tucson, Arizona, United States
Investigational Site Number 8400037
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Atlanta, Georgia, United States
Investigational Site Number 8400032
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Indianapolis, Indiana, United States
Investigational Site Number 8400015
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Buffalo, New York, United States
Investigational Site Number 8400016
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Chapel Hill, North Carolina, United States
Investigational Site Number 8400035
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Morehead City, North Carolina, United States
Investigational Site Number 8400038
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Oklahoma City, Oklahoma, United States
Investigational Site Number 8400030
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Philadelphia, Pennsylvania, United States
Investigational Site Number 8400010
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Rapid City, South Dakota, United States
Investigational Site Number 8400005
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Dallas, Texas, United States
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Investigational Site Number 8400008
🇺🇸Tucson, Arizona, United States