A Study Comparing the Efficacy and Safety of the Morning Injection of Toujeo Versus Lantus in Patients With Type 1 Diabetes Mellitus

Study Overview
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Brief Summary
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Primary Objective: To demonstrate that morning injection of Toujeo (HOE901-U300) compared to Lantus provides better glycemic control evaluated by Continuous Glucose Monitoring (CGM) in adult participants with type 1 diabetes mellitus. Secondary Objective: To demonstrate that treatment with HOE901-U300 compared to Lantus provides: Lower incidence rate of nocturnal symptomatic hypoglycemia; Better glucose control coverage during the last hours of CGM before next basal-insulin dosing; Less variability in CGM profile.

Detailed Description
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The maximum study duration per participant was to be of approximately 20 weeks that consisted of an up to a 4-week screening and CGM training period including a 1-2 week baseline (blinded) CGM performance (allowed for re-training), a 14-week open-label, comparative treatment period allowing for dose titration in both basal and meal-time insulin and including a 1-2 week end-of treatment blinded CGM collection with fixed dose of HOE901-U300 and Lantus, and a 2 day post treatment follow-up period.

Official Title
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A Randomized, Active-controlled, Parallel Group, 16-Week Open Label Study Comparing the Efficacy and Safety of the Morning Injection of Toujeo (Insulin Glargine-U300) Versus Lantus in Patients With Type 1 Diabetes Mellitus

Conditions
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Type 1 Diabetes Mellitus

Intervention / Treatment
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* Drug: HOE901-U300 (Insulin Glargine 300 U/ml)
* Drug: Lantus (Insulin Glargine 100 U/ml)
* Drug: Mandated back ground therapy


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Adult participants (male and female) with type 1 diabetes mellitus (T1DM). Signed written informed consent. Exclusion criteria: Age <18 years or >70 years. Fasting c-peptide ≥0.3 nmol/L as per source document or central lab test at Visit 1. Glycated hemoglobin (HbA1c) ≤ 6.5 % or ≥ 10.0% via central lab test at Visit 1. Participants who experienced none of episode of documented symptomatic and/or severe hypoglycemia (as per the American Diabetes Association (ADA) classification) during the past month prior to screening. Participants who experienced >1 episode of severe hypoglycemia resulting in coma/seizures during the last 12 months before screening. Participants received less than 1 year treatment with basal plus mealtime insulin. Used any basal insulins other than long-acting insulin analogs (ie, Lantus, Toujeo, Levemir, and Tresiba) in the past 3 months before screening. Required >80 U/day basal insulin analogs or not on stable dose (±20% total dose) within 30 days prior to screening. Used fewer than 2 injections of rapid-acting insulin analog per day within 30 days prior to screening. Used human regular insulin as mealtime insulin within 30 days prior to screening. Used an insulin pump during the last 6 months before screening. History of unstable proliferative diabetic retinopathy or any other rapidly progressive diabetic retinopathy or macular edema likely to required treatment (e.g., laser, surgical treatment, or injectable drugs) during the study period. Pregnant or breast-feeding women or planned pregnancy during the duration of the study. Use of any other investigational drug(s) within 1 month or 5 half-lives, whichever was longer prior to screening. Inappropriate CGM use during screening period evidenced by failure to obtain a minimum of 4 days of usable records by the end of screening. Noncompliance with self-monitored plasma glucose (SMPG) performance evidenced by failure to demonstrate at least 5 days of 5 point SMPG records by the end of screening. The above information is not intended to contain all considerations relevant to a participants's potential participation in a clinical trial.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HOE901-U300<br>HOE901-U300 (Insulin glargine, 300 U/mL) once daily for 16 weeks on top of mealtime insulins analogs. Basal insulin doses were individually titrated (until the end of Week 14) to reach fasting self-measured plasma glucose (SMPG) levels of 80 to 100 mg/dL, while mitigating hypoglycemia. | Drug: HOE901-U300 (Insulin Glargine 300 U/ml)<br>* Self-administered by subcutaneous (SC) injection in the morning (between waking up and breakfast) using a pre-filled pen.<br>* Other names: Toujeo;Drug: Mandated back ground therapy<br>* Rapid insulin analogs: e.g., insulin glulisine, insulin lispro or insulin aspart, used by participant at least 30 days before screening. Mealtime insulin was to be continued during the study and titrated towards protocol specified postprandial glucose targets (130-180 mg/dL).<br>|
| Active Comparator: Lantus<br>Lantus (Insulin glargine, 100 U/mL) once daily for 16 weeks on top of mealtime insulins analogs. Basal insulin doses were individually titrated (until the end of Week 14) to reach fasting SMPG levels of 80 to 100 mg/dL, while mitigating hypoglycemia. | Drug: Lantus (Insulin Glargine 100 U/ml)<br>* Self-administered by subcutaneous (SC) injection in the morning (between waking up and breakfast using a pre-filled pen.<br>* Other names: HOE901-U100;Drug: Mandated back ground therapy<br>* Rapid insulin analogs: e.g., insulin glulisine, insulin lispro or insulin aspart, used by participant at least 30 days before screening. Mealtime insulin was to be continued during the study and titrated towards protocol specified postprandial glucose targets (130-180 mg/dL).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Time of Mean Glucose Concentration Within the Target Range of 70-180 mg/dL as Obtained From CGM | The CGM system combined frequent interstitial glucose measurements (every 5 minutes) with ability to analyze glucose levels in real time. Adjusted least square (LS) means and standard error (SE) were obtained from a generalized linear model with identity link including post baseline CGM assessment during Week 15 (and/or Week 16). | During Week 15 and/or 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Documented Symptomatic Nocturnal Hypoglycemia | Documented symptomatic nocturnal hypoglycemia was defined as an event with typical symptoms of hypoglycemia accompanied by SMPG <=70 mg/dL that occurred between 00:00 and 05:59 hours as reported on the hypoglycemia electronic case report form (eCRF). | Baseline up to Week 16 | 
| Documented Symptomatic Nocturnal Hypoglycemia Event Rate Per Participant-Year | Documented symptomatic nocturnal hypoglycemia was defined as an event with typical symptoms of hypoglycemia accompanied by SMPG <=70 mg/dL that occurred between 00:00 and 05:59 hours as reported on the hypoglycemia eCRF. | Baseline up to Week 16 | 
| Mean Change From Baseline in Glucose Level During Last 4 Hours of CGM Data Collection Prior to the Next Day Basal Insulin Injection During Week 15 and/or Week 16 | Adjusted LS means and SE were obtained from mixed model including post baseline CGM assessment during the last 4 hours prior to the next day's basal insulin injection during Week 15 (and/or Week 16). | Baseline, during Week 15 and/or Week 16 | 
| Percentage of Time Glucose Concentrations Within the Target Range of 70 to 140 mg/dL During Last 4 Hours of CGM Data Collection Prior to Next Day Basal Insulin Injection | Adjusted LS means and SE were obtained from mixed model including post baseline CGM assessment during the last 4 hours prior to the next day's basal insulin injection during Week 15 (and/or Week 16). | During Week 15 and/or Week 16 | 
| Coefficient of Variation (CV%) in Mean CGM Glucose | CV% was a measure of spread of variability relative to mean of population. For CGM glucose values over 24 hours, CV% was measure of glycemic variability across 24-hour day and calculated for each period (total, within day and between days) as ratio of standard deviation of glucose values to mean of glucose values. | During Week 15 and/or Week 16 |