Comparison of SAR341402 to NovoLog in Adult Patients With Type 1 Diabetes Mellitus Also Using Insulin Glargine

NCT03874715 | Completed Phase 3 Results FDA Drug

• 3 other identifiers: EFC15178U1111-1197-7811136342
• Study Type: interventional
• Target: 210
• Locations: 1 country
• Sites: 33

Brief Summary

Primary Objective: To demonstrate similarity in pharmacokinetics (PK) of SAR341402 and NovoLog after 4x4-week periods of alternating administration of SAR341402 and NovoLog compared to 16-week continuous use of NovoLog in participants with Type 1 diabetes mellitus (T1DM) also using insulin glargine. Secondary Objectives:

• To compare the effects of alternating administration of SAR341402 and NovoLog with continuous use of NovoLog on immunogenicity.
• To evaluate the safety of alternating administration of SAR341402 and NovoLog versus continuous use of NovoLog.
• To compare other PK parameters between the two treatment arms (alternating administration of SAR341402 and NovoLog and continuous use of NovoLog).

Conditions

Type 1 Diabetes Mellitus

Outcome Measures

Primary Outcomes (3)

• Pharmacokinetics (PK): Area Under the Plasma Concentration Versus Time Curve From Time Zero to Last Measurable Timepoint (AUClast) of Insulin Aspart Following Administration of Either SAR341402 (Switching Arm) or NovoLog (Non-switching Arm)

  AUClast was defined as area under the plasma concentration versus time curve from time zero to last measurable timepoint. Insulin aspart was the active ingredient of SAR341402 and NovoLog.

  0 hour (hr)(Pre-dose), 10, 20, 30, 40 & 50 minutes (min), 1hr, 1hr-10, 20, 30, 40 & 50min, 2hr, 2hr-15, 30 & 45min, 3hr, 3hr-15, 30 & 45min, 4hr, 4hr-20 & 40min, 5hr, 5hr-20 & 40min, 6hr, 6hr-30min, 7hr, 7hr-30min & 8hr post-dose on Day 112

• Pharmacokinetics: Area Under the Plasma Concentration Versus Time Curve (AUC) of Insulin Aspart Following Administration of Either SAR341402 (Switching Arm) or NovoLog (Non-switching Arm)

  AUC was defined as area under the concentration versus time curve. Insulin aspart is the active ingredient of SAR341402 and NovoLog.

  0 hr (pre-dose), 10, 20, 30, 40 & 50 min, 1 hr, 1 hr-10, 20, 30, 40 & 50 min, 2 hr, 2 hr-15, 30 & 45 min, 3 hr, 3 hr-15, 30 & 45 min, 4 hr, 4 hr-20 & 40 min, 5 hr, 5 hr-20 & 40 min, 6 hr, 6 hr-30 min, 7 hr, 7 hr-30 min & 8 hr post-dose on Day 112

• Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) of Insulin Aspart Following Administration of Either SAR341402 (Switching Arm) or NovoLog (Non-switching Arm)

  Cmax was defined as the maximum observed plasma concentration. Insulin aspart is the active ingredient of SAR341402 and NovoLog.

  0 hr (pre-dose), 10, 20, 30, 40 & 50 min, 1 hr, 1 hr-10, 20, 30, 40 & 50 min, 2 hr, 2hr-15, 30 & 45 min, 3 hr, 3 hr-15, 30 & 45 min, 4 hr, 4 hr-20 & 40 min, 5 hr, 5 hr-20 & 40 min, 6 hr, 6 hr-30 min, 7 hr, 7 hr-30 min & 8 hr post-dose on Day 112

Secondary Outcomes (5)

• Number of Participants With Treatment-emergent Anti-Insulin Aspart Antibodies (AIAs)

  From first injection of IMP (Day 1) up to 1 day after the last injection of IMP (i.e., up to Day 113)

• Number of Participants With at Least One Hypoglycemic Event

  From first injection of IMP (Day 1) up to 1 day after the last injection of IMP (i.e., up to Day 113)

• Number of Hypoglycemic Events Per Participant-year

  From first injection of IMP (Day 1) up to 1 day after the last injection of IMP (i.e., up to Day 113)

• Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)

  From first injection of IMP (Day 1) up to 1 day after the last injection of IMP (i.e., up to Day 113)

• Pharmacokinetics: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Insulin Aspart Following Administration of Either SAR341402 (Switching Arm) or NovoLog (Non-switching Arm)

  0 hr (pre-dose), 10, 20, 30, 40 & 50 min, 1 hr, 1 hr-10, 20, 30, 40 & 50 min, 2 hr, 2hr-15, 30 & 45 min, 3 hr, 3 hr-15, 30 & 45 min, 4 hr, 4 hr-20 & 40 min, 5 hr, 5 hr-20 & 40 min, 6 hr, 6 hr-30 min, 7 hr, 7 hr-30 min & 8 hr post-dose on Day 112

Study Arms (2)

Switching: NovoLog/SAR341402

EXPERIMENTAL

Participants self-administered subcutaneous (SC) injection daily prior to the start of a meal during the 16-week treatment period, starting with NovoLog (100 units per milliliters \[U/mL\]) for the first 4 weeks, then SAR341402 (100 U/mL) for 4 weeks, followed by NovoLog (at same dose) for 4 weeks and then SAR341402 (at same dose) for the last 4 weeks on top of mandatory background therapy with Lantus (Insulin glargine, 100 U/mL) as basal insulin.

Drug: Insulin Aspart SAR341402; Drug: Insulin Aspart; Drug: Insulin glargine U100

Non-Switching: NovoLog

ACTIVE COMPARATOR

Participants self-administered SC injection of NovoLog (100 U/mL) daily prior to the start of a meal during the 16-week treatment period on top of mandatory background therapy with Lantus (Insulin glargine, 100 U/mL) as basal insulin.

Drug: Insulin Aspart; Drug: Insulin glargine U100

Interventions

Insulin Aspart SAR341402 DRUG

Pharmaceutical form: Solution for injection Route of administration: Subcutaneous

Switching: NovoLog/SAR341402

Insulin Aspart DRUG

Pharmaceutical form: Solution for injection Route of administration: Subcutaneous

Also known as: NovoLog

Non-Switching: NovoLog; Switching: NovoLog/SAR341402

Insulin glargine U100 DRUG

Pharmaceutical form: Solution for injection Route of administration: Subcutaneous

Also known as: Lantus

Non-Switching: NovoLog; Switching: NovoLog/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.
• Participants on continuous insulin treatment for at least 12 months prior to screening.
• Participants exclusively on a multiple (greater than or equal to 3) daily injection insulin analogue regimen using:
• NovoLog as mealtime insulin for at least 12 weeks prior to screening and
• Insulin glargine (100 units per milliliter \[U/mL\]) as basal insulin for at least 12 weeks prior to screening. Note: Participants not meeting this criterion could also qualify, provided that they completed the run-in period during which NovoLog and Lantus was administered so that, at the time of randomization, the participants had been on NovoLog and insulin glargine (100 U/mL) for at least 12 weeks (including any potential pre-screening administration).
• Glycated hemoglobin (HbA1c) less than or equal to 10 percent (%) (85.79 millimoles per mole) at screening.
• Body mass index less than or equal to 35 kilograms per meter square (kg/m\^2) at screening.

You may not qualify if:

• Pancreatectomy and/or islet cell transplantation.
• Clinically significant laboratory findings, as defined by the protocol.
• Known presence of factors that interfered with the HbA1c measurement.
• History of severe hypoglycemia required emergency room admission or hospitalization within 3 months prior to screening.
• Hospitalization for recurrent diabetic ketoacidosis within 3 months prior to screening.
• Retinopathy or maculopathy with one of the following treatments, either recent (within 3 months of screening) or planned: intravitreal injections or laser or vitrectomy surgery.
• Use of glucose lowering treatments other than the multiple dose injections and basal insulin regimen (including use of insulin pump therapy), within 12 weeks prior to screening.
• Participants had received systemic glucocorticoids for one week or more within 3 months prior to screening (topical, nasal spray, inhaled or intra-articular applications are allowed).
• Participants had received systemic immunosuppressive agents within 6 months prior to screening.
• The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Sponsors & Collaborators

• Sanofi: lead

Study Sites (33)

Investigational Site Number 8400014

Concord, California, 94520, United States

Location

Investigational Site Number 8400001

Temecula, California, 92591, United States

Location

Investigational Site Number 8400015

Ventura, California, 93003, United States

Location

Investigational Site Number 8400010

Aurora, Colorado, 80045, United States

Location

Investigational Site Number 8400029

Waterbury, Connecticut, 06708-3346, United States

Location

Investigational Site Number 8400038

Doral, Florida, 33166, United States

Location

Investigational Site Number 8400030

Miami, Florida, 33165, United States

Location

Investigational Site Number 8400032

New Port Richey, Florida, 34652, United States

Location

Investigational Site Number 8400026

Ocoee, Florida, 34761, United States

Location

Investigational Site Number 8400033

Palm Harbor, Florida, 34684, United States

Location

Investigational Site Number 8400012

Atlanta, Georgia, 30318, United States

Location

Investigational Site Number 8400005

Columbus, Georgia, 31904, United States

Location

Investigational Site Number 8400009

Roswell, Georgia, 30076, United States

Location

Investigational Site Number 8400019

Crystal Lake, Illinois, 60012, United States

Location

Investigational Site Number 8400028

Des Moines, Iowa, 50314, United States

Location

Investigational Site Number 8400018

Lexington, Kentucky, 40503, United States

Location

Investigational Site Number 8400023

Baltimore, Maryland, 21237, United States

Location

Investigational Site Number 8400003

Rockville, Maryland, 20852-4267, United States

Location

Investigational Site Number 8400013

Waltham, Massachusetts, 02453, United States

Location

Investigational Site Number 8400004

Flint, Michigan, 48532, United States

Location

Investigational Site Number 8400021

Kansas City, Missouri, 64111, United States

Location

Investigational Site Number 8400031

Washington, Missouri, 63090, United States

Location

Investigational Site Number 8400036

Omaha, Nebraska, 68114, United States

Location

Investigational Site Number 8400017

Las Vegas, Nevada, 89148, United States

Location

Investigational Site Number 8400007

New York, New York, 10001, United States

Location

Investigational Site Number 8400006

Morehead City, North Carolina, 28557, United States

Location

Investigational Site Number 8400035

Rocky Mount, North Carolina, 27804, United States

Location

Investigational Site Number 8400034

Jefferson City, Tennessee, 37760, United States

Location

Investigational Site Number 8400040

Dallas, Texas, 75235, United States

Location

Investigational Site Number 8400042

El Paso, Texas, 79935, United States

Location

Investigational Site Number 8400027

Houston, Texas, 77079, United States

Location

Investigational Site Number 8400016

Mesquite, Texas, 75149, United States

Location

Investigational Site Number 8400041

Waco, Texas, 76710, United States

Location

Related Publications (2)

• Shah VN, Al-Karadsheh A, Barnes C, Mandry J, Nakhle S, Wernicke-Panten K, Kramer D, Schmider W, Pierre S, Teichert L, Rotthaeuser B, Mukherjee B, Bailey TS. Pharmacokinetic similarity of switching SAR341402 insulin aspart biosimilar and NovoLog insulin aspart versus continuous use of NovoLog in adults with type 1 diabetes: The GEMELLI X trial. Diabetes Obes Metab. 2024 Feb;26(2):540-547. doi: 10.1111/dom.15341. Epub 2023 Oct 25.

  PMID: 37880868 RESULT

• Shah VN, Al-Karadsheh A, Barnes C, Mandry J, Nakhle S, Wernicke-Panten K, Kramer D, Schmider W, Pierre S, Teichert L, Rotthaeuser B, Mukherjee B, Bailey TS. Safety and Efficacy of Switching SAR341402 Insulin Aspart and Originator Insulin Aspart vs Continuous Use of Originator Insulin Aspart in Adults With Type 1 Diabetes: The GEMELLI X Trial. J Diabetes Sci Technol. 2025 Jul;19(4):1051-1059. doi: 10.1177/19322968241232709. Epub 2024 Feb 29.

  PMID: 38420944 RESULT

MeSH Terms

Conditions

Diabetes Mellitus, Type 1

Interventions

Insulin Aspart; Insulin Glargine

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

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: Sanofi aventis recherche & développement

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: March 12, 2019
• First Posted: March 14, 2019
• Study Start: March 11, 2019
• Primary Completion: July 8, 2020
• Study Completion: July 8, 2020
• Last Updated: April 17, 2024
• Results First Posted: July 21, 2023

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will share

Locations

US (33)