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

Type 1 Diabetes Mellitus Clinical Trial

— SORELLA1  

Official title:

Six-Month, Randomized, Open-Label, Parallel-group Comparison of SAR342434 to Humalog® in Adult Patients With Type 1 Diabetes Mellitus Also Using Insulin Glargine, With a 6-month Safety Extension Period

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02273180
• Other study ID #: EFC12619
• Secondary ID: 2013-002945-12U1
• Status: Completed
• Phase: Phase 3
• First received: October 21, 2014
• Last updated: December 20, 2017
• Start date: October 2014
• Est. completion date: July 2016

Study information

• Verified date: December 2017
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 507
• Est. completion date: July 2016
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion criteria:

• Participants with T1DM diagnosed for at least 12 months and had been treated with insulin glargine and Humalog or Novolog®/Novo Rapid® (at least 3 times daily before each meal) in the 6 months prior to the screening visit.

• Written informed consent.

Exclusion criteria:

• At screening visit, age under legal age of adulthood.

• HbA1c <7.0% or >10% at screening.

• Diabetes other than T1DM.

• Status post pancreatectomy.

• Status post pancreas and/or islet cell transplantation.

• Pregnancy and lactation.

• Women of childbearing potential not protected by highly effective contraceptive method of birth control.

• Less than 1 year on continuous insulin treatment.

• Use of insulin pump in the last 6 months before screening visit.

• Use of glucose lowering treatments other than insulin including non-insulin injectable peptides in the last 6 months prior to screening visit.

• Use of insulin other than insulin glargine and Humalog or Novolog/Novo Rapid as part of a multiple injection regimen (3 to 4 injections per day) in the last 6 months before screening visit. Liprolog® is a European Union approved insulin lispro and is allowed in those countries where it is marketed.

• Hospitalization for diabetic ketoacidosis in the last 6 months before screening visit.

• Unstable proliferative diabetic retinopathy or any other rapidly progressive diabetic retinopathy or macular edema likely to require treatment (eg, laser, surgical treatment, or injectable drugs) 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:
• SAR342434
SAR342434 100 U/mL (dose range of 1 Unit to 80 Units) self-administered by deep subcutaneous (SC) injection, immediately (within 5-10 minutes) before meal intake. Dose adjusted to achieve a 2-hour post prandial plasma glucose (PPG) in range of 6.7 to 8.9 mmol/L (120 to 160 mg/dL) while avoiding hypoglycemia.
• Humalog
Humalog 100 U/mL (dose range of 1 unit to 60 units) self-administered by deep SC injection, immediately (within 5-10 minutes) before meal intake. Dose adjusted to achieve a 2 hour PPG in range of 6.7 to 8.9 mmol/L (120 to 160 mg/dL) while avoiding hypoglycaemia.
• Insulin glargine HOE901
Insulin glargine 100 U/mL injected QD subcutaneously consistent with the local label. Doses adjusted to achieve glycemic target for fasting, preprandial plasma glucose (SMPG) between 4.4 to 7.2 mmol/L (80 to 130 mg/dL) without hypoglycemia.

Locations

Country	Name	City	State
France	Investigational Site Number 250002	Corbeil Essonnes
France	Investigational Site Number 250005	Mantes La Jolie
France	Investigational Site Number 250003	Montpellier Cedex 5
France	Investigational Site Number 250001	Vandoeuvre Les Nancy
Germany	Investigational Site Number 276001	Berlin
Germany	Investigational Site Number 276004	Dortmund
Germany	Investigational Site Number 276006	Hannover
Germany	Investigational Site Number 276002	Heidelberg
Germany	Investigational Site Number 276003	Neumünster
Germany	Investigational Site Number 276008	Pirna
Germany	Investigational Site Number 276007	Potsdam
Germany	Investigational Site Number 276005	Sulzbach-Rosenberg
Hungary	Investigational Site Number 348001	Budapest
Hungary	Investigational Site Number 348002	Budapest
Hungary	Investigational Site Number 348003	Budapest
Hungary	Investigational Site Number 348005	Budapest
Hungary	Investigational Site Number 348010	Budapest
Hungary	Investigational Site Number 348011	Budapest
Hungary	Investigational Site Number 348007	Debrecen
Japan	Investigational Site Number 392006	Chuo-Ku
Japan	Investigational Site Number 392003	Higashiosaka-Shi
Japan	Investigational Site Number 392004	Izumisano-Shi
Japan	Investigational Site Number 392005	Kamakura-Shi
Japan	Investigational Site Number 392001	Shinjuku-Ku
Japan	Investigational Site Number 392002	Yamato-Shi
Poland	Investigational Site Number 616005	Krakow
Poland	Investigational Site Number 616001	Poznan
Poland	Investigational Site Number 616003	Szczecin
Poland	Investigational Site Number 616002	Warszawa
Poland	Investigational Site Number 616004	Zabrze
Russian Federation	Investigational Site Number 643003	Moscow
Russian Federation	Investigational Site Number 643006	Samara
Russian Federation	Investigational Site Number 643002	Saratov
Russian Federation	Investigational Site Number 643001	St-Petersburg
Russian Federation	Investigational Site Number 643004	St-Petersburg
Russian Federation	Investigational Site Number 643005	St-Petersburg
Russian Federation	Investigational Site Number 643007	Tomsk
Spain	Investigational Site Number 724002	A Coruña
Spain	Investigational Site Number 724001	Cáceres
Spain	Investigational Site Number 724004	Lérida
Spain	Investigational Site Number 724005	Málaga
Spain	Investigational Site Number 724003	Sabadell
United States	Investigational Site Number 840015	Albuquerque	New Mexico
United States	Investigational Site Number 840054	Albuquerque	New Mexico
United States	Investigational Site Number 840036	Atlanta	Georgia
United States	Investigational Site Number 840038	Baltimore	Maryland
United States	Investigational Site Number 840016	Bell Gardens	California
United States	Investigational Site Number 840005	Bradenton	Florida
United States	Investigational Site Number 840030	Burlington	North Carolina
United States	Investigational Site Number 840011	Chesapeake	Virginia
United States	Investigational Site Number 840019	Chicago	Illinois
United States	Investigational Site Number 840033	Chicago	Illinois
United States	Investigational Site Number 840048	Chula Vista	California
United States	Investigational Site Number 840046	Concord	California
United States	Investigational Site Number 840007	Dakota Dunes	South Dakota
United States	Investigational Site Number 840029	Dallas	Texas
United States	Investigational Site Number 840034	Dallas	Texas
United States	Investigational Site Number 840041	Dallas	Texas
United States	Investigational Site Number 840003	Denver	Colorado
United States	Investigational Site Number 840037	Denver	Colorado
United States	Investigational Site Number 840004	Des Moines	Iowa
United States	Investigational Site Number 840039	Fresno	California
United States	Investigational Site Number 840018	Gallipolis	Ohio
United States	Investigational Site Number 840060	Great Falls	Montana
United States	Investigational Site Number 840051	Greenville	North Carolina
United States	Investigational Site Number 840002	Houston	Texas
United States	Investigational Site Number 840020	Idaho Falls	Idaho
United States	Investigational Site Number 840028	La Jolla	California
United States	Investigational Site Number 840043	Marrero	Louisiana
United States	Investigational Site Number 840012	McHenry	Illinois
United States	Investigational Site Number 840021	Metairie	Louisiana
United States	Investigational Site Number 840042	Miami	Florida
United States	Investigational Site Number 840050	Miami	Florida
United States	Investigational Site Number 840057	Miami Lakes	Florida
United States	Investigational Site Number 840061	Miami Lakes	Florida
United States	Investigational Site Number 840009	Milwaukee	Wisconsin
United States	Investigational Site Number 840059	Mineola	New York
United States	Investigational Site Number 840006	New Port Richey	Florida
United States	Investigational Site Number 840013	North Miami Beach	Florida
United States	Investigational Site Number 840026	Omaha	Nebraska
United States	Investigational Site Number 840040	Omaha	Nebraska
United States	Investigational Site Number 840031	Port Charlotte	Florida
United States	Investigational Site Number 840027	Rapid City	South Dakota
United States	Investigational Site Number 840014	Rockville	Maryland
United States	Investigational Site Number 840045	Roswell	Georgia
United States	Investigational Site Number 840023	Tacoma	Washington
United States	Investigational Site Number 840049	Tucson	Arizona
United States	Investigational Site Number 840022	Ventura	California
United States	Investigational Site Number 840062	Wilmington	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  France,  Germany,  Hungary,  Japan,  Poland,  Russian Federation,  Spain, 

References & Publications (1)

Garg SK, Wernicke-Panten K, Rojeski M, Pierre S, Kirchhein Y, Jedynasty K. Efficacy and Safety of Biosimilar SAR342434 Insulin Lispro in Adults with Type 1 Diabetes Also Using Insulin Glargine-SORELLA 1 Study. Diabetes Technol Ther. 2017 Sep;19(9):516-526. doi: 10.1089/dia.2017.0117. Epub 2017 Aug 30. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in Daily Insulin Dose From Baseline to Week 26 and Week 52	Change in daily insulin dose (basal, mealtime and total) was calculated by subtracting baseline value from Week 26 and Week 52 values respectively.	Baseline, Week 26, Week 52
Primary	Change in HbA1c From Baseline to 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.	Baseline, Week 26
Secondary	Percentage of Participants With HbA1c <7.0% at Week 26	Participants who had no available assessment for HbA1c at Week 26 were considered as non-responders.	Week 26
Secondary	Change in Fasting Plasma Glucose (FPG) From Baseline to 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.	Baseline, Week 26
Secondary	Change in Mean 24-Hour Plasma Glucose Concentration From Baseline to 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.	Baseline, Week 26
Secondary	Change in Post Prandial Plasma Glucose (PPG) Excursion From Baseline to 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.	Baseline, Week 26
Secondary	Number of Hypoglycemia Events (Any Hypoglycemia, Documented Symptomatic Hypoglycemia and Severe Hypoglycemia) Per Participant-Year	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.	First dose of study drug up to 1 day after the last dose administration (maximum treatment exposure: 400 days)
Secondary	Percentage of Participants With Hypersensitivity Reactions and Injection Site Reactions	Percentage of participants with hypersensitivity reactions and injection site reactions were reported.	First dose of study drug up to 1 day after the last dose administration (maximum treatment exposure: 400 days)
Secondary	Percentage of Participants With Treatment Emergent Anti-insulin Antibodies (AIAs)	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).	First dose of study drug up to 1 day after the last dose administration (maximum treatment exposure: 400 days)