Comparison of SAR342434 to Humalog as the Rapid Acting Insulin in Adult Patients With Type 1 Diabetes Mellitus Also Using Insulin Glargine

Phase 3

Completed

• Conditions: Type 1 Diabetes Mellitus
• Interventions: Drug: SAR342434; Drug: Humalog; Drug: Insulin glargine HOE901

• Registration Number: NCT02273180
• Lead Sponsor: Sanofi

Brief Summary

Primary Objective:

To demonstrate non-inferiority of SAR342434 versus Humalog in glycated haemoglobin A1c (HbA1c) change from baseline to Week 26 in participants with type 1 diabetes mellitus (T1DM) also using insulin glargine.

Secondary Objectives:

To assess the immunogenicity of SAR342434 and Humalog in terms of positive/negative status and antibody titers at baseline and during the course of the study.

To assess the relationship of anti-insulin antibodies with efficacy and safety including during the safety extension.

To assess the efficacy of SAR342434 and Humalog in terms of proportion of participants reaching target HbA1c (\<7%), Fasting plasma glucose (FPG), self-measured plasma glucose (SMPG) profiles, and insulin dose.

To assess safety of SAR342434 and Humalog.

Detailed Description

The study consisted of a:

* Up to 2 weeks screening period

* 26-week treatment period

* 26-week comparative safety extension period

* 1-day follow-up period

* The maximum study duration would be 54 weeks per participant and a 1-day safety follow-up

Study Timeline

• Study Start: 2014-10
• Study First Submitted: 2014-10-21
• Study First Submitted QC: 2014-10-22
• Study First Posted: 2014-10-23
• Primary Completion: 2015-12
• Study Completion: 2016-07
• Disposition First Submitted: 2016-12-20
• Disposition First Submitted QC: 2016-12-20
• Disposition First Posted: 2016-12-21
• Status Verified: 2017-12
• Results First Submitted: 2017-12-20
• Results First Submitted QC: 2017-12-20
• Last Update Submitted: 2017-12-20
• Results First Posted: 2018-01-18
• Last Update Posted: 2018-01-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 507

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
SAR342434	SAR342434	SAR342434 before meals intake on top of once daily (QD) Insulin Glargine, up to Week 52.
SAR342434	Insulin glargine HOE901	SAR342434 before meals intake on top of once daily (QD) Insulin Glargine, up to Week 52.
Humalog	Insulin glargine HOE901	Humalog before meals intake on top of QD Insulin Glargine, up to Week 52.
Humalog	Humalog	Humalog before meals intake on top of QD Insulin Glargine, up to Week 52.

Primary Outcome Measures

Name	Time	Method
Change in HbA1c From Baseline to Week 26	Baseline, Week 26	Change in HbA1c was calculated by subtracting baseline value from Week 26 value. Adjusted least square means and standard errors were obtained from a mixed-effect model with repeated measures (MMRM) to account for missing data, using all post-baseline HbA1c data available during the main 6-month period and adequate contrasts at Week 26.

Secondary Outcome Measures

Name	Time	Method
Change in Mean 24-Hour Plasma Glucose Concentration From Baseline to Week 26	Baseline, Week 26	Mean 24-hour plasma glucose concentration was calculated based on 7-point self-measured plasma glucose (SMPG) profiles with plasma glucose measurements before and 2-hours after each main meal and at bedtime. Mean 24-hour plasma glucose concentration was calculated for each profile and then averaged across profiles performed in week before a visit. Change in mean 24-hour plasma glucose concentration was calculated by subtracting baseline value from Week 26 value. Adjusted least squares means and standard errors were obtained from a MMRM to account for missing data, using all post-baseline data available during the main 6-month period and adequate contrasts at Week 26.
Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26	Baseline, Week 26	Change in FPG was calculated by subtracting baseline value from Week 26 value. Adjusted least squares means and standard errors were obtained from a MMRM approach to account for missing data, using all post-baseline FPG data available during the main 6-month period and adequate contrasts at Week 26.
Change in Post Prandial Plasma Glucose (PPG) Excursion From Baseline to Week 26	Baseline, Week 26	Plasma glucose excursions were calculated at breakfast, lunch and dinner for each 7-point SMPG profile, as 2-hour PPG minus plasma glucose value obtained 30 minutes prior to start of the meal. Values of plasma glucose excursions at each visit were then calculated as average across the profiles performed in the week before the visit. Change in PPG excursions was calculated by subtracting baseline value from Week 26 value. Adjusted least squares means and standard errors were obtained from a MMRM to account for missing data, using all post-baseline data available during the main 6-month period and adequate contrasts at Week 26.
Percentage of Participants With Hypersensitivity Reactions and Injection Site Reactions	First dose of study drug up to 1 day after the last dose administration (maximum treatment exposure: 400 days)	Percentage of participants with hypersensitivity reactions and injection site reactions were reported.
Percentage of Participants With HbA1c <7.0% at Week 26	Week 26	Participants who had no available assessment for HbA1c at Week 26 were considered as non-responders.
Number of Hypoglycemia Events (Any Hypoglycemia, Documented Symptomatic Hypoglycemia and Severe Hypoglycemia) Per Participant-Year	First dose of study drug up to 1 day after the last dose administration (maximum treatment exposure: 400 days)	Number of treatment-emergent hypoglycemia events per participant-year of exposure were reported. Severe hypoglycemia was an event in which the participant required the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. Documented symptomatic hypoglycemia was an event during which typical symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of \<=70 mg/dL (3.9 mmol/L). Hypoglycemic episodes with plasma glucose of 54 mg/dL (\<3.0 mmol/L) were also analyzed.
Percentage of Participants With Treatment Emergent Anti-insulin Antibodies (AIAs)	First dose of study drug up to 1 day after the last dose administration (maximum treatment exposure: 400 days)	Participants with treatment-emergent AIA (incidence) were reported (as participants with treatment-boosted or treatment-induced AIAs). Participants with treatment-induced AIAs were those who developed AIA following IMP administration (participants with at least one positive AIA sample at any time during on-treatment period, in those participants without pre-existing AIA or with missing baseline sample). Participants with treatment-boosted AIAs were those with pre-existing AIAs that were boosted to a significant higher titer following IMP administration (participants with at least one AIA sample with at least a 4-fold increase in titers compared to baseline value at any time during on-treatment period, in those participants with pre-existing AIA).

Trial Locations

Locations (89)

Investigational Site Number 348003; 🇭🇺 Budapest, Hungary

Investigational Site Number 348011; 🇭🇺 Budapest, Hungary

Investigational Site Number 616002; 🇵🇱 Warszawa, Poland

Investigational Site Number 616004; 🇵🇱 Zabrze, Poland

Investigational Site Number 724005; 🇪🇸 Málaga, Spain

Investigational Site Number 643002; 🇷🇺 Saratov, Russian Federation

Investigational Site Number 643004; 🇷🇺 St-Petersburg, Russian Federation

Investigational Site Number 724001; 🇪🇸 Cáceres, Spain

Investigational Site Number 643006; 🇷🇺 Samara, Russian Federation

Investigational Site Number 724003; 🇪🇸 Sabadell, Spain

Investigational Site Number 724004; 🇪🇸 Lérida, Spain

Investigational Site Number 643001; 🇷🇺 St-Petersburg, Russian Federation

Investigational Site Number 724002; 🇪🇸 A Coruña, Spain

Investigational Site Number 840039; 🇺🇸 Fresno, California, United States

Investigational Site Number 840005; 🇺🇸 Bradenton, Florida, United States

Investigational Site Number 840042; 🇺🇸 Miami, Florida, United States

Investigational Site Number 840031; 🇺🇸 Port Charlotte, Florida, United States

Investigational Site Number 840020; 🇺🇸 Idaho Falls, Idaho, United States

Investigational Site Number 840038; 🇺🇸 Baltimore, Maryland, United States

Investigational Site Number 840060; 🇺🇸 Great Falls, Montana, United States

Investigational Site Number 840051; 🇺🇸 Greenville, North Carolina, United States

Investigational Site Number 840041; 🇺🇸 Dallas, Texas, United States

Investigational Site Number 840061; 🇺🇸 Miami Lakes, Florida, United States

Investigational Site Number 840029; 🇺🇸 Dallas, Texas, United States

Investigational Site Number 840034; 🇺🇸 Dallas, Texas, United States

Investigational Site Number 840049; 🇺🇸 Tucson, Arizona, United States

Investigational Site Number 840048; 🇺🇸 Chula Vista, California, United States

Investigational Site Number 840016; 🇺🇸 Bell Gardens, California, United States

Investigational Site Number 840046; 🇺🇸 Concord, California, United States

Investigational Site Number 840028; 🇺🇸 La Jolla, California, United States

Investigational Site Number 840022; 🇺🇸 Ventura, California, United States

Investigational Site Number 840003; 🇺🇸 Denver, Colorado, United States

Investigational Site Number 840037; 🇺🇸 Denver, Colorado, United States

Investigational Site Number 840057; 🇺🇸 Miami Lakes, Florida, United States

Investigational Site Number 840050; 🇺🇸 Miami, Florida, United States

Investigational Site Number 840036; 🇺🇸 Atlanta, Georgia, United States

Investigational Site Number 840013; 🇺🇸 North Miami Beach, Florida, United States

Investigational Site Number 840019; 🇺🇸 Chicago, Illinois, United States

Investigational Site Number 840045; 🇺🇸 Roswell, Georgia, United States

Investigational Site Number 840033; 🇺🇸 Chicago, Illinois, United States

Investigational Site Number 840004; 🇺🇸 Des Moines, Iowa, United States

Investigational Site Number 840012; 🇺🇸 McHenry, Illinois, United States

Investigational Site Number 840043; 🇺🇸 Marrero, Louisiana, United States

Investigational Site Number 840021; 🇺🇸 Metairie, Louisiana, United States

Investigational Site Number 840014; 🇺🇸 Rockville, Maryland, United States

Investigational Site Number 840026; 🇺🇸 Omaha, Nebraska, United States

Investigational Site Number 840040; 🇺🇸 Omaha, Nebraska, United States

Investigational Site Number 840015; 🇺🇸 Albuquerque, New Mexico, United States

Investigational Site Number 840059; 🇺🇸 Mineola, New York, United States

Investigational Site Number 840054; 🇺🇸 Albuquerque, New Mexico, United States

Investigational Site Number 840030; 🇺🇸 Burlington, North Carolina, United States

Investigational Site Number 840062; 🇺🇸 Wilmington, North Carolina, United States

Investigational Site Number 840007; 🇺🇸 Dakota Dunes, South Dakota, United States

Investigational Site Number 840027; 🇺🇸 Rapid City, South Dakota, United States

Investigational Site Number 840018; 🇺🇸 Gallipolis, Ohio, United States

Investigational Site Number 840002; 🇺🇸 Houston, Texas, United States

Investigational Site Number 840011; 🇺🇸 Chesapeake, Virginia, United States

Investigational Site Number 840023; 🇺🇸 Tacoma, Washington, United States

Investigational Site Number 250002; 🇫🇷 Corbeil Essonnes, France

Investigational Site Number 250003; 🇫🇷 Montpellier Cedex 5, France

Investigational Site Number 250001; 🇫🇷 Vandoeuvre Les Nancy, France

Investigational Site Number 250005; 🇫🇷 Mantes La Jolie, France

Investigational Site Number 276001; 🇩🇪 Berlin, Germany

Investigational Site Number 276006; 🇩🇪 Hannover, Germany

Investigational Site Number 276004; 🇩🇪 Dortmund, Germany

Investigational Site Number 276002; 🇩🇪 Heidelberg, Germany

Investigational Site Number 276003; 🇩🇪 Neumünster, Germany

Investigational Site Number 276007; 🇩🇪 Potsdam, Germany

Investigational Site Number 348002; 🇭🇺 Budapest, Hungary

Investigational Site Number 276005; 🇩🇪 Sulzbach-Rosenberg, Germany

Investigational Site Number 348005; 🇭🇺 Budapest, Hungary

Investigational Site Number 392003; 🇯🇵 Higashiosaka-Shi, Japan

Investigational Site Number 392004; 🇯🇵 Izumisano-Shi, Japan

Investigational Site Number 348007; 🇭🇺 Debrecen, Hungary

Investigational Site Number 348010; 🇭🇺 Budapest, Hungary

Investigational Site Number 392006; 🇯🇵 Chuo-Ku, Japan

Investigational Site Number 392005; 🇯🇵 Kamakura-Shi, Japan

Investigational Site Number 348001; 🇭🇺 Budapest, Hungary

Investigational Site Number 616001; 🇵🇱 Poznan, Poland

Investigational Site Number 392001; 🇯🇵 Shinjuku-Ku, Japan

Investigational Site Number 616005; 🇵🇱 Krakow, Poland

Investigational Site Number 392002; 🇯🇵 Yamato-Shi, Japan

Investigational Site Number 616003; 🇵🇱 Szczecin, Poland

Investigational Site Number 643003; 🇷🇺 Moscow, Russian Federation

Investigational Site Number 643005; 🇷🇺 St-Petersburg, Russian Federation

Investigational Site Number 643007; 🇷🇺 Tomsk, Russian Federation

Investigational Site Number 840009; 🇺🇸 Milwaukee, Wisconsin, United States

Investigational Site Number 840006; 🇺🇸 New Port Richey, Florida, United States

Investigational Site Number 276008; 🇩🇪 Pirna, Germany