Comparison of SAR341402 to NovoLog/NovoRapid in Adult Patients With Diabetes Mellitus Also Using Insulin Glargine

NCT ID: NCT03211858

Last Updated: 2022-03-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 597 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-08-02
• Study Completion Date: 2019-01-12

Brief Summary

Primary Objective:

To demonstrate non-inferiority of SAR341402 versus NovoLog/NovoRapid in glycated hemoglobin A1c (HbA1c) change from baseline to Week 26 in participants with type 1 or type 2 diabetes mellitus (T1DM or T2DM) also using Lantus®.

Secondary Objectives:

• To assess the immunogenicity of SAR341402 and NovoLog/NovoRapid in terms of positive/negative status and anti-insulin antibody (AIA) titers during the course of the study.
• To assess the relationship of AIAs with efficacy and safety.
• To assess the efficacy of SAR341402 and NovoLog/NovoRapid in terms of proportion of participants reaching HbA1c lesser than (<) 7.0% and change in HbA1c, fasting plasma glucose (FPG), and self-measured plasma glucose (SMPG) profiles from baseline to Week 26 and Week 52 (only Week 52 for HbA1c).
• To assess safety of SAR341402 and NovoLog/NovoRapid.

Detailed Description

The study consisted of a 2-week screening period, a 26-week treatment period, a 26-week comparative safety extension period, and a 1-day follow-up period. The maximum study duration was 54 weeks per participant and a 1 day safety follow-up.

Conditions

Type 1 Diabetes Mellitus-Type 2 Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

SAR341402

SAR341402 subcutaneous (SC), before meals intake on top of once daily (QD) Insulin Glargine, up to Week 52.

Group Type: EXPERIMENTAL

Insulin aspart

Intervention Type: DRUG

SAR341402 100 units per milliliters (U/mL) (dose range of 1 unit to 80 units) self-administered by SC injection, immediately (within 5-10 minutes) before meal intake. Dose adjusted to achieve a 2-hour postprandial plasma glucose (PPG \<10 millimoles/liter \[mmol/L\] \[\<180 milligram/deciliter {mg/dL}\]) while avoiding hypoglycemia.

Insulin glargine (HOE901)

Intervention Type: DRUG

Insulin glargine 100 U/mL injected QD subcutaneously consistent with the local label. Doses adjusted to achieve glycemic target for fasting, preprandial plasma glucose between 4.4 to 7.2 mmol/L (80 to 130 mg/dL) without hypoglycemia.

NovoLog/NovoRapid

NovoLog/NovoRapid SC, before meals intake on top of QD Insulin Glargine, up to Week 52.

Group Type: ACTIVE_COMPARATOR

NovoLog/NovoRapid

Intervention Type: DRUG

NovoLog/NovoRapid 100 U/mL (dose range of 1 unit to 60 units) self-administered by SC injection, immediately (within 5-10 minutes) before meal intake. Dose adjusted to achieve a 2-hour postprandial plasma glucose (PPG \<10 mmol/L \[\<180 mg/dL\]) while avoiding hypoglycemia.

Insulin glargine (HOE901)

Intervention Type: DRUG

Insulin glargine 100 U/mL injected QD subcutaneously consistent with the local label. Doses adjusted to achieve glycemic target for fasting, preprandial plasma glucose between 4.4 to 7.2 mmol/L (80 to 130 mg/dL) without hypoglycemia.

Interventions

Insulin aspart

SAR341402 100 units per milliliters (U/mL) (dose range of 1 unit to 80 units) self-administered by SC injection, immediately (within 5-10 minutes) before meal intake. Dose adjusted to achieve a 2-hour postprandial plasma glucose (PPG \<10 millimoles/liter \[mmol/L\] \[\<180 milligram/deciliter {mg/dL}\]) while avoiding hypoglycemia.

Intervention Type: DRUG

NovoLog/NovoRapid

NovoLog/NovoRapid 100 U/mL (dose range of 1 unit to 60 units) self-administered by SC injection, immediately (within 5-10 minutes) before meal intake. Dose adjusted to achieve a 2-hour postprandial plasma glucose (PPG \<10 mmol/L \[\<180 mg/dL\]) while avoiding hypoglycemia.

Intervention Type: DRUG

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 between 4.4 to 7.2 mmol/L (80 to 130 mg/dL) without hypoglycemia.

Intervention Type: DRUG

Other Intervention Names

Insulin aspart; Lantus

Eligibility Criteria

Inclusion Criteria

• Participants with T1DM or T2DM (T2DM US only) diagnosed for at least 12 months, who have been treated with a multiple daily injection regimen with
• NovoLog/NovoRapid or insulin lispro (100 U/mL) in the last 6 months prior to screening visit AND
• insulin glargine (100 U/mL) in the last 6 months prior to screening visit OR insulin detemir (Levemir®) in the last 12 months prior to screening visit.

Exclusion Criteria

• At screening visit, age under legal age of adulthood.
• HbA1c <7.0% or greater than (>) 10% at screening.
• Less than 1 year on continuous insulin treatment.
• Use of insulin pump in the last 3 months before screening visit.
• Participants with incomplete baseline 7-point SMPG profile, defined as participants who do not have 7-point profiles with at least 5 points on at least 2 days in the week before randomization Visit 3.
• Participants with T1DM: Use of glucose lowering agents other than insulin including use of non-insulin injectable peptides in the last 3 months prior to screening.
• Participants with T2DM:

• Use of glucagon-like peptide-1 (GLP-1) receptor agonists in the last 3 months before screening visit.
• Use of oral antidiabetic drugs (OADs) not on stable dose in the last 3 months before screening visit (sulfonylureas was discontinued at baseline).
• At screening visit, body mass index (BMI) greater than or equal to (>=) 35 kilogram per meter square (kg/m^2) in participants with T1DM and >=40 kg/m^2 in participants with T2DM.
• Use of insulin other than:

• insulin glargine 100 U/mL and NovoLog/NovoRapid or insulin lispro 100 U/mL as part of a multiple injection regimen in the last 6 months before screening visit, OR
• insulin detemir 100 U/mL in the 12 months before screening visit and NovoLog/NovoRapid or insulin lispro 100 U/mL in the last 6 months before screening visit as part of a multiple injection regimen.
• Status post pancreatectomy.
• Status post pancreas and/or islet cell transplantation.
• Hospitalization for recurrent diabetic ketoacidosis in the last 3 months before screening visit.
• History of severe hypoglycemia requiring Emergency Room admission or hospitalization in the last 3 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.
• Pregnant or breastfeeding women.
• Women of childbearing potential not protected by highly effective method(s) of birth control.

The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Investigational Site Number 8400040

Little Rock, Arkansas, United States

Investigational Site Number 8400012

Concord, California, United States

Investigational Site Number 8400002

Escondido, California, United States

Investigational Site Number 8400030

Fresno, California, United States

Investigational Site Number 8400004

Greenbrae, California, United States

Investigational Site Number 8400014

La Jolla, California, United States

Investigational Site Number 8400043

Los Angeles, California, United States

Investigational Site Number 8400036

Pomona, California, United States

Investigational Site Number 8400011

Santa Barbara, California, United States

Investigational Site Number 8400013

Ventura, California, United States

Investigational Site Number 8400037

Aurora, Colorado, United States

Investigational Site Number 8400018

Englewood, Colorado, United States

Investigational Site Number 8400031

New Port Richey, Florida, United States

Investigational Site Number 8400027

Ocoee, Florida, United States

Investigational Site Number 8400007

Atlanta, Georgia, United States

Investigational Site Number 8400022

Columbus, Georgia, United States

Investigational Site Number 8400032

Roswell, Georgia, United States

Investigational Site Number 8400038

Arlington Heights, Illinois, United States

Investigational Site Number 8400005

Des Moines, Iowa, United States

Investigational Site Number 8400041

Metairie, Louisiana, United States

Investigational Site Number 8400015

Rockville, Maryland, United States

Investigational Site Number 8400042

Waltham, Massachusetts, United States

Investigational Site Number 8400019

Flint, Michigan, United States

Investigational Site Number 8400003

Omaha, Nebraska, United States

Investigational Site Number 8400024

Henderson, Nevada, United States

Investigational Site Number 8400028

New York, New York, United States

Investigational Site Number 8400025

Morehead City, North Carolina, United States

Investigational Site Number 8400010

Wilmington, North Carolina, United States

Investigational Site Number 8400023

Fargo, North Dakota, United States

Investigational Site Number 8400029

Bend, Oregon, United States

Investigational Site Number 8400033

Chattanooga, Tennessee, United States

Investigational Site Number 8400044

Austin, Texas, United States

Investigational Site Number 8400009

Dallas, Texas, United States

Investigational Site Number 8400035

Dallas, Texas, United States

Investigational Site Number 8400021

Dallas, Texas, United States

Investigational Site Number 8400017

Houston, Texas, United States

Investigational Site Number 8400001

Houston, Texas, United States

Investigational Site Number 8400020

Houston, Texas, United States

Investigational Site Number 8400016

Mesquite, Texas, United States

Investigational Site Number 8400034

Salt Lake City, Utah, United States

Investigational Site Number 8400008

Renton, Washington, United States

Investigational Site Number 8400039

Bridgeport, West Virginia, United States

Investigational Site Number 2460006

Jyväskylä, , Finland

Investigational Site Number 2460002

Kuopio, , Finland

Investigational Site Number 2460004

Pori, , Finland

Investigational Site Number 2460003

Seinäjoki, , Finland

Investigational Site Number 2760001

Berlin, , Germany

Investigational Site Number 2760006

Essen, , Germany

Investigational Site Number 2760004

Heidelberg, , Germany

Investigational Site Number 2760005

Oldenburg in Holstein, , Germany

Investigational Site Number 2760002

Pirna, , Germany

Investigational Site Number 3480012

Balatonfüred, , Hungary

Investigational Site Number 3480011

Budapest, , Hungary

Investigational Site Number 3480008

Budapest, , Hungary

Investigational Site Number 3480001

Budapest, , Hungary

Investigational Site Number 3480005

Budapest, , Hungary

Investigational Site Number 3480004

Budapest, , Hungary

Investigational Site Number 3480007

Debrecen, , Hungary

Investigational Site Number 3480003

Nagykanizsa, , Hungary

Investigational Site Number 3480010

Nyíregyháza, , Hungary

Investigational Site Number 3480009

Szentendre, , Hungary

Investigational Site Number 3920009

Fukuyama-Shi, , Japan

Investigational Site Number 3920008

Higashiosaka-Shi, , Japan

Investigational Site Number 3920007

Kashiwara-Shi, , Japan

Investigational Site Number 3920001

Koriyama-Shi, , Japan

Investigational Site Number 3920005

Kumamoto, , Japan

Investigational Site Number 3920003

Mito, , Japan

Investigational Site Number 3920010

Osaka, , Japan

Investigational Site Number 3920002

Sagamihara-Shi, , Japan

Investigational Site Number 3920004

Shinjuku-Ku, , Japan

Investigational Site Number 3920006

Ushiku-Shi, , Japan

Investigational Site Number 6160004

Bialystok, , Poland

Investigational Site Number 6160003

Krakow, , Poland

Investigational Site Number 6160005

Krakow, , Poland

Investigational Site Number 6160007

Lublin, , Poland

Investigational Site Number 6160006

Nowy Sącz, , Poland

Investigational Site Number 6160001

Poznan, , Poland

Investigational Site Number 6160002

Warsaw, , Poland

Investigational Site Number 6430001

Saint Petersburg, , Russia

Investigational Site Number 6430002

Samara, , Russia

Investigational Site Number 6430003

Saratov, , Russia

Investigational Site Number 6430004

Tomsk, , Russia

Countries

United States; Finland; Germany; Hungary; Japan; Poland; Russia

References

Garg SK, Wernicke-Panten K, Wardecki M, Kramer D, Delalande F, Franek E, Sadeharju K, Monchamp T, Mukherjee B, Shah VN. Efficacy and Safety of Insulin Aspart Biosimilar SAR341402 Versus Originator Insulin Aspart in People with Diabetes Treated for 26 Weeks with Multiple Daily Injections in Combination with Insulin Glargine: A Randomized Open-Label Trial (GEMELLI 1). Diabetes Technol Ther. 2020 Feb;22(2):85-95. doi: 10.1089/dia.2019.0382.

Reference Type: BACKGROUND

PMID: 31804851 (View on PubMed)

Garg SK, Wernicke-Panten K, Wardecki M, Kramer D, Delalande F, Franek E, Sadeharju K, Monchamp T, Miossec P, Mukherjee B, Shah VN. Safety, Immunogenicity, and Glycemic Control of Insulin Aspart Biosimilar SAR341402 Versus Originator Insulin Aspart in People with Diabetes Also Using Insulin Glargine: 12-Month Results from the GEMELLI 1 Trial. Diabetes Technol Ther. 2020 Jul;22(7):516-526. doi: 10.1089/dia.2020.0008. Epub 2020 Mar 31.

Reference Type: BACKGROUND

PMID: 32068436 (View on PubMed)

Shah VN, Franek E, Wernicke-Panten K, Pierre S, Mukherjee B, Sadeharju K. Efficacy, Safety, and Immunogenicity of Insulin Aspart Biosimilar SAR341402 Compared with Originator Insulin Aspart in Adults with Diabetes (GEMELLI 1): A Subgroup Analysis by Prior Type of Mealtime Insulin. Diabetes Ther. 2021 Feb;12(2):557-568. doi: 10.1007/s13300-020-00992-x. Epub 2021 Jan 11.

Reference Type: DERIVED

PMID: 33432547 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2017-000091-28

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

U1111-1191-5775

Identifier Type: OTHER

Identifier Source: secondary_id

EFC15081

Identifier Type: -

Identifier Source: org_study_id