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

NCT03211858 | Completed Phase 3 Results FDA Drug

• 3 other identifiers: EFC150812017-000091-28U1111-1191-5775
• Study Type: interventional
• Target: 597
• Locations: 7 countries
• Sites: 82

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.

Conditions

Type 1 Diabetes Mellitus-Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (1)

• Change in Glycated Hemoglobin A1c (HbA1c) From Baseline to Week 26

  All values up to Week 26 were taken into account in the analysis, regardless of adherence to treatment. Change in HbA1c was calculated by subtracting baseline value from Week 26 value. Missing changes at Week 26 were imputed using a retrieved dropout multiple imputation method (separately for participants who prematurely discontinued or completed treatment). Adjusted least square (LS) means and standard errors (SE) were obtained using an analysis of covariance (ANCOVA) model on data obtained from the multiple imputations (results were combined using Rubin's formulae).

  Baseline, Week 26

Secondary Outcomes (11)

• Change in HbA1c From Baseline to Week 52

  Baseline, Week 52

• Percentage of Participants With HbA1c <7% at Week 26 and Week 52

  Week 26 and Week 52

• Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26 and Week 52

  Baseline, Week 26, and Week 52

• Change in the Mean 24-hour Plasma Glucose Concentration From Baseline to Week 26 and Week 52

  Baseline, Week 26, and Week 52

• Change in Postprandial Plasma Glucose (PPG) Excursion From Baseline to Week 26 and Week 52

  Baseline, Week 26, and Week 52

Other Outcomes (5)

• Change in Glycated Hemoglobin A1c From Baseline to Week 26 and Week 52: Subgroup Analysis by Prior Use of NovoLog/NovoRapid or Humalog/Liprolog

  Baseline, Week 26 and Week 52

• Number of Participants With at Least One Hypoglycemic Event: Subgroup Analysis by Prior Use of NovoLog/NovoRapid or Humalog/Liprolog

  From first injection of IMP up to Week 26 or up to 1 day after last injection of IMP, whichever comes earlier, for Week 26 analysis, and from first injection of IMP up to 1 day after last injection of IMP for Week 52

• Number of Participants With Adverse Events: Subgroup Analysis by Prior Use of NovoLog/NovoRapid or Humalog/Liprolog

  From first injection of IMP up to Week 26 or up to 1 day after last injection of IMP, whichever comes earlier for Week 26 analysis, and from first injection of IMP up to 1 day after last injection of IMP for Week 52

Study Arms (2)

SAR341402

EXPERIMENTAL

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

Drug: Insulin aspart; Drug: Insulin glargine (HOE901)

NovoLog/NovoRapid

ACTIVE COMPARATOR

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

Drug: NovoLog/NovoRapid; Drug: Insulin glargine (HOE901)

Interventions

Insulin aspart 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.

SAR341402

NovoLog/NovoRapid 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.

Also known as: Insulin aspart

NovoLog/NovoRapid

Insulin glargine (HOE901) 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.

Also known as: Lantus

NovoLog/NovoRapid; SAR341402

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (82)

Investigational Site Number 8400040

Little Rock, Arkansas, 72211, United States

Location

Investigational Site Number 8400012

Concord, California, 94520, United States

Location

Investigational Site Number 8400002

Escondido, California, 92025, United States

Location

Investigational Site Number 8400030

Fresno, California, 93720, United States

Location

Investigational Site Number 8400004

Greenbrae, California, 94904, United States

Location

Investigational Site Number 8400014

La Jolla, California, 92037, United States

Location

Investigational Site Number 8400043

Los Angeles, California, 90057, United States

Location

Investigational Site Number 8400036

Pomona, California, 91766, United States

Location

Investigational Site Number 8400011

Santa Barbara, California, 93105, United States

Location

Investigational Site Number 8400013

Ventura, California, 93003, United States

Location

Investigational Site Number 8400037

Aurora, Colorado, 80045, United States

Location

Investigational Site Number 8400018

Englewood, Colorado, 80113, United States

Location

Investigational Site Number 8400031

New Port Richey, Florida, 34652, United States

Location

Investigational Site Number 8400027

Ocoee, Florida, 34761, United States

Location

Investigational Site Number 8400007

Atlanta, Georgia, 30318, United States

Location

Investigational Site Number 8400022

Columbus, Georgia, 31904, United States

Location

Investigational Site Number 8400032

Roswell, Georgia, 30076, United States

Location

Investigational Site Number 8400038

Arlington Heights, Illinois, 60005, United States

Location

Investigational Site Number 8400005

Des Moines, Iowa, 50314, United States

Location

Investigational Site Number 8400041

Metairie, Louisiana, 70006, United States

Location

Investigational Site Number 8400015

Rockville, Maryland, 20852-4267, United States

Location

Investigational Site Number 8400042

Waltham, Massachusetts, 02453, United States

Location

Investigational Site Number 8400019

Flint, Michigan, 48532-3447, United States

Location

Investigational Site Number 8400003

Omaha, Nebraska, 68131, United States

Location

Investigational Site Number 8400024

Henderson, Nevada, 89052, United States

Location

Investigational Site Number 8400028

New York, New York, 10001, United States

Location

Investigational Site Number 8400025

Morehead City, North Carolina, 28557, United States

Location

Investigational Site Number 8400010

Wilmington, North Carolina, 28401, United States

Location

Investigational Site Number 8400023

Fargo, North Dakota, 58104, United States

Location

Investigational Site Number 8400029

Bend, Oregon, 97701, United States

Location

Investigational Site Number 8400033

Chattanooga, Tennessee, 37404, United States

Location

Investigational Site Number 8400044

Austin, Texas, 78731, United States

Location

Investigational Site Number 8400009

Dallas, Texas, 75230, United States

Location

Investigational Site Number 8400035

Dallas, Texas, 75230, United States

Location

Investigational Site Number 8400021

Dallas, Texas, 75246, United States

Location

Investigational Site Number 8400017

Houston, Texas, 77043, United States

Location

Investigational Site Number 8400001

Houston, Texas, 77079, United States

Location

Investigational Site Number 8400020

Houston, Texas, 77089, United States

Location

Investigational Site Number 8400016

Mesquite, Texas, 75149, United States

Location

Investigational Site Number 8400034

Salt Lake City, Utah, 84102, United States

Location

Investigational Site Number 8400008

Renton, Washington, 98057, United States

Location

Investigational Site Number 8400039

Bridgeport, West Virginia, 26330, United States

Location

Investigational Site Number 2460006

Jyväskylä, 40100, Finland

Location

Investigational Site Number 2460002

Kuopio, 70100, Finland

Location

Investigational Site Number 2460004

Pori, 28500, Finland

Location

Investigational Site Number 2460003

Seinäjoki, 60100, Finland

Location

Investigational Site Number 2760001

Berlin, 10115, Germany

Location

Investigational Site Number 2760006

Essen, 45136, Germany

Location

Investigational Site Number 2760004

Heidelberg, 69115, Germany

Location

Investigational Site Number 2760005

Oldenburg in Holstein, 23758, Germany

Location

Investigational Site Number 2760002

Pirna, 01796, Germany

Location

Investigational Site Number 3480012

Balatonfüred, 8230, Hungary

Location

Investigational Site Number 3480011

Budapest, 1036, Hungary

Location

Investigational Site Number 3480008

Budapest, 1042, Hungary

Location

Investigational Site Number 3480001

Budapest, 1062, Hungary

Location

Investigational Site Number 3480005

Budapest, 1062, Hungary

Location

Investigational Site Number 3480004

Budapest, 1139, Hungary

Location

Investigational Site Number 3480007

Debrecen, 4031, Hungary

Location

Investigational Site Number 3480003

Nagykanizsa, 8800, Hungary

Location

Investigational Site Number 3480010

Nyíregyháza, 4400, Hungary

Location

Investigational Site Number 3480009

Szentendre, 2000, Hungary

Location

Investigational Site Number 3920009

Fukuyama-Shi, Japan

Location

Investigational Site Number 3920008

Higashiosaka-Shi, Japan

Location

Investigational Site Number 3920007

Kashiwara-Shi, Japan

Location

Investigational Site Number 3920001

Koriyama-Shi, Japan

Location

Investigational Site Number 3920005

Kumamoto, Japan

Location

Investigational Site Number 3920003

Mito, Japan

Location

Investigational Site Number 3920010

Osaka, Japan

Location

Investigational Site Number 3920002

Sagamihara-Shi, Japan

Location

Investigational Site Number 3920004

Shinjuku-Ku, Japan

Location

Investigational Site Number 3920006

Ushiku-Shi, Japan

Location

Investigational Site Number 6160004

Bialystok, 15-435, Poland

Location

Investigational Site Number 6160003

Krakow, 31-501, Poland

Location

Investigational Site Number 6160005

Krakow, 31-548, Poland

Location

Investigational Site Number 6160007

Lublin, 20-538, Poland

Location

Investigational Site Number 6160006

Nowy Sącz, 33-300, Poland

Location

Investigational Site Number 6160001

Poznan, 60-834, Poland

Location

Investigational Site Number 6160002

Warsaw, 02-507, Poland

Location

Investigational Site Number 6430001

Saint Petersburg, 194358, Russia

Location

Investigational Site Number 6430002

Samara, 443041, Russia

Location

Investigational Site Number 6430003

Saratov, 410030, Russia

Location

Investigational Site Number 6430004

Tomsk, 634050, Russia

Location

Related Publications (3)

• 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.

  PMID: 31804851 BACKGROUND

• 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.

  PMID: 32068436 BACKGROUND

• 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.

  PMID: 33432547 DERIVED

MeSH Terms

Interventions

Insulin Aspart; Insulin Glargine

Intervention Hierarchy (Ancestors)

Insulin, Short-Acting; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Insulin, Long-Acting

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Trial Transparency Team

Contact-US@sanofi.com

800-633-1610

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 6, 2017
• First Posted: July 7, 2017
• Study Start: August 2, 2017
• Primary Completion: July 16, 2018
• Study Completion: January 12, 2019
• Last Updated: March 28, 2022
• Results First Posted: August 8, 2019

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will share

Locations

DE (5); HU (10); JP (10); FI (4); PL (7); RU (4); US (42)