Clinical trial NCT03211858: Comparison of SAR341402 to NovoLog/NovoRapid in Adult Patients With Diabetes Mellitus Also Using Insulin Glargine
Official title: Six-month, Randomized, Open-label, Parallel-group Comparison of SAR341402 to NovoLog®/NovoRapid® in Adult Patients With Diabetes Mellitus Also Using Insulin Glargine, With a 6-month Safety Extension Period
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 1 Diabetes Mellitus-Type 2 Diabetes Mellitus
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2017-07-07
Enrollment: 597
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Change in Glycated Hemoglobin A1c (HbA1c) From Baseline to Week 26
timeFrame: Baseline, Week 26
Secondary outcomes:
measure: Change in HbA1c From Baseline to Week 52
timeFrame: Baseline, Week 52
measure: Percentage of Participants With HbA1c <7% at Week 26 and Week 52
timeFrame: Week 26 and Week 52
measure: Change in Fasting Plasma Glucose (FPG) From Baseline to Week 26 and Week 52
timeFrame: Baseline, Week 26, and Week 52
measure: Change in the Mean 24-hour Plasma Glucose Concentration From Baseline to Week 26 and Week 52
timeFrame: Baseline, Week 26, and Week 52
measure: Change in Postprandial Plasma Glucose (PPG) Excursion From Baseline to Week 26 and Week 52
timeFrame: Baseline, Week 26, and Week 52
measure: Change in 7-Point SMPG Profiles From Baseline to Week 26 and Week 52 Per Time Point
timeFrame: Baseline, Week 26, and Week 52
measure: Number of Participants With at Least One Hypoglycemic Event
timeFrame: From first injection of investigational medicinal product (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
measure: Number of Hypoglycemia Events Per Participant-Year
timeFrame: From first injection of investigational medicinal product (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
measure: Percentage of Participants With Hypersensitivity Reactions and Injection Site Reactions
timeFrame: 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
measure: Percentage of Participants With at Least One Positive Anti-Insulin Aspart Antibodies (AIA) Sample
timeFrame: 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
measure: Percentage of Participants With Treatment-Induced, Treatment-Boosted and Treatment-Emergent Anti-insulin Aspart Antibodies (AIAs)
timeFrame: 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
Other outcomes:
measure: Change in Glycated Hemoglobin A1c From Baseline to Week 26 and Week 52: Subgroup Analysis by Prior Use of NovoLog/NovoRapid or Humalog/Liprolog
timeFrame: Baseline, Week 26 and Week 52
measure: Number of Participants With at Least One Hypoglycemic Event: Subgroup Analysis by Prior Use of NovoLog/NovoRapid or Humalog/Liprolog
timeFrame: 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
measure: Number of Participants With Adverse Events: Subgroup Analysis by Prior Use of NovoLog/NovoRapid or Humalog/Liprolog
timeFrame: 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
measure: Percentage of Participants With Treatment-Induced, Treatment-Boosted and Treatment-Emergent Anti-insulin Aspart Antibodies (AIAs): Subgroup Analysis by Prior Use of NovoLog/NovoRapid or Humalog/Liprolog
timeFrame: 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
measure: Change in Daily Insulin Dose From Baseline to Day 1, Week 26 and Week 52
timeFrame: Baseline, Day 1, Week 26 and Week 52
Locations:
city: Little Rock
country: United States
facility: Investigational Site Number 8400040
state: Arkansas
city: Concord
country: United States
facility: Investigational Site Number 8400012
state: California
city: Escondido
country: United States
facility: Investigational Site Number 8400002
state: California
city: Fresno
country: United States
facility: Investigational Site Number 8400030
state: California
city: Greenbrae
country: United States
facility: Investigational Site Number 8400004
state: California
city: La Jolla
country: United States
facility: Investigational Site Number 8400014
state: California
city: Los Angeles
country: United States
facility: Investigational Site Number 8400043
state: California
city: Pomona
country: United States
facility: Investigational Site Number 8400036
state: California
city: Santa Barbara
country: United States
facility: Investigational Site Number 8400011
state: California
city: Ventura
country: United States
facility: Investigational Site Number 8400013
state: California
city: Aurora
country: United States
facility: Investigational Site Number 8400037
state: Colorado
city: Englewood
country: United States
facility: Investigational Site Number 8400018
state: Colorado
city: New Port Richey
country: United States
facility: Investigational Site Number 8400031
state: Florida
city: Ocoee
country: United States
facility: Investigational Site Number 8400027
state: Florida
city: Atlanta
country: United States
facility: Investigational Site Number 8400007
state: Georgia
city: Columbus
country: United States
facility: Investigational Site Number 8400022
state: Georgia
city: Roswell
country: United States
facility: Investigational Site Number 8400032
state: Georgia
city: Arlington Heights
country: United States
facility: Investigational Site Number 8400038
state: Illinois
city: Des Moines
country: United States
facility: Investigational Site Number 8400005
state: Iowa
city: Metairie
country: United States
facility: Investigational Site Number 8400041
state: Louisiana
city: Rockville
country: United States
facility: Investigational Site Number 8400015
state: Maryland
city: Waltham
country: United States
facility: Investigational Site Number 8400042
state: Massachusetts
city: Flint
country: United States
facility: Investigational Site Number 8400019
state: Michigan
city: Omaha
country: United States
facility: Investigational Site Number 8400003
state: Nebraska
city: Henderson
country: United States
facility: Investigational Site Number 8400024
state: Nevada
city: New York
country: United States
facility: Investigational Site Number 8400028
state: New York
city: Morehead City
country: United States
facility: Investigational Site Number 8400025
state: North Carolina
city: Wilmington
country: United States
facility: Investigational Site Number 8400010
state: North Carolina
city: Fargo
country: United States
facility: Investigational Site Number 8400023
state: North Dakota
city: Bend
country: United States
facility: Investigational Site Number 8400029
state: Oregon
city: Chattanooga
country: United States
facility: Investigational Site Number 8400033
state: Tennessee
city: Austin
country: United States
facility: Investigational Site Number 8400044
state: Texas
city: Dallas
country: United States
facility: Investigational Site Number 8400009
state: Texas
city: Dallas
country: United States
facility: Investigational Site Number 8400035
state: Texas
city: Dallas
country: United States
facility: Investigational Site Number 8400021
state: Texas
city: Houston
country: United States
facility: Investigational Site Number 8400017
state: Texas
city: Houston
country: United States
facility: Investigational Site Number 8400001
state: Texas
city: Houston
country: United States
facility: Investigational Site Number 8400020
state: Texas
city: Mesquite
country: United States
facility: Investigational Site Number 8400016
state: Texas
city: Salt Lake City
country: United States
facility: Investigational Site Number 8400034
state: Utah
city: Renton
country: United States
facility: Investigational Site Number 8400008
state: Washington
city: Bridgeport
country: United States
facility: Investigational Site Number 8400039
state: West Virginia
city: Jyväskylä
country: Finland
facility: Investigational Site Number 2460006
city: Kuopio
country: Finland
facility: Investigational Site Number 2460002
city: Pori
country: Finland
facility: Investigational Site Number 2460004
city: Seinäjoki
country: Finland
facility: Investigational Site Number 2460003
city: Berlin
country: Germany
facility: Investigational Site Number 2760001
city: Essen
country: Germany
facility: Investigational Site Number 2760006
city: Heidelberg
country: Germany
facility: Investigational Site Number 2760004
city: Oldenburg In Holstein
country: Germany
facility: Investigational Site Number 2760005
city: Pirna
country: Germany
facility: Investigational Site Number 2760002
city: Balatonfüred
country: Hungary
facility: Investigational Site Number 3480012
city: Budapest
country: Hungary
facility: Investigational Site Number 3480011
city: Budapest
country: Hungary
facility: Investigational Site Number 3480008
city: Budapest
country: Hungary
facility: Investigational Site Number 3480001
city: Budapest
country: Hungary
facility: Investigational Site Number 3480005
city: Budapest
country: Hungary
facility: Investigational Site Number 3480004
city: Debrecen
country: Hungary
facility: Investigational Site Number 3480007
city: Nagykanizsa
country: Hungary
facility: Investigational Site Number 3480003
city: Nyíregyháza
country: Hungary
facility: Investigational Site Number 3480010
city: Szentendre
country: Hungary
facility: Investigational Site Number 3480009
city: Fukuyama-Shi
country: Japan
facility: Investigational Site Number 3920009
city: Higashiosaka-Shi
country: Japan
facility: Investigational Site Number 3920008
city: Kashiwara-Shi
country: Japan
facility: Investigational Site Number 3920007
city: Koriyama-Shi
country: Japan
facility: Investigational Site Number 3920001
city: Kumamoto-Shi
country: Japan
facility: Investigational Site Number 3920005
city: Mito-Shi
country: Japan
facility: Investigational Site Number 3920003
city: Osaka-Shi
country: Japan
facility: Investigational Site Number 3920010
city: Sagamihara-Shi
country: Japan
facility: Investigational Site Number 3920002
city: Shinjuku-Ku
country: Japan
facility: Investigational Site Number 3920004
city: Ushiku-Shi
country: Japan
facility: Investigational Site Number 3920006
city: Bialystok
country: Poland
facility: Investigational Site Number 6160004
city: Krakow
country: Poland
facility: Investigational Site Number 6160003
city: Krakow
country: Poland
facility: Investigational Site Number 6160005
city: Lublin
country: Poland
facility: Investigational Site Number 6160007
city: Nowy Sacz
country: Poland
facility: Investigational Site Number 6160006
city: Poznan
country: Poland
facility: Investigational Site Number 6160001
city: Warszawa
country: Poland
facility: Investigational Site Number 6160002
city: Samara
country: Russian Federation
facility: Investigational Site Number 6430002
city: Saratov
country: Russian Federation
facility: Investigational Site Number 6430003
city: St. Petersburg
country: Russian Federation
facility: Investigational Site Number 6430001
city: Tomsk
country: Russian Federation
facility: Investigational Site Number 6430004
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.