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Type 1 Diabetes MellitusPhase 3GEMELLI XNCT03874715

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

A Phase 3 study testing Insulin Aspart SAR341402, Insulin Aspart and Insulin glargine U100 in people with Type 1 Diabetes Mellitus, run by Sanofi at 33 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Type 1 Diabetes Mellitus
What is being tested?
Insulin Aspart SAR341402, Insulin Aspart and Insulin glargine U100
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
210 participants
Where
33 sitesUnited States
Study dates
11 Mar 2019to 8 Jul 2020
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
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  • 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.

Trial locations and contacts

33 sites in 1 country.

33 sites in 1 country

United States33 sites

  • Investigational Site Number 8400012

    Atlanta, Georgia, 30318

  • Investigational Site Number 8400010

    Aurora, Colorado, 80045

  • Investigational Site Number 8400023

    Baltimore, Maryland, 21237

  • Investigational Site Number 8400005

    Columbus, Georgia, 31904

  • Investigational Site Number 8400014

    Concord, California, 94520

  • Investigational Site Number 8400019

    Crystal Lake, Illinois, 60012

  • Investigational Site Number 8400040

    Dallas, Texas, 75235

  • Investigational Site Number 8400028

    Des Moines, Iowa, 50314

  • Investigational Site Number 8400038

    Doral, Florida, 33166

  • Investigational Site Number 8400042

    El Paso, Texas, 79935

  • Investigational Site Number 8400004

    Flint, Michigan, 48532

  • Investigational Site Number 8400027

    Houston, Texas, 77079

  • Investigational Site Number 8400034

    Jefferson City, Tennessee, 37760

  • Investigational Site Number 8400021

    Kansas City, Missouri, 64111

  • Investigational Site Number 8400017

    Las Vegas, Nevada, 89148

  • Investigational Site Number 8400018

    Lexington, Kentucky, 40503

  • Investigational Site Number 8400016

    Mesquite, Texas, 75149

  • Investigational Site Number 8400030

    Miami, Florida, 33165

  • Investigational Site Number 8400006

    Morehead City, North Carolina, 28557

  • Investigational Site Number 8400032

    New Port Richey, Florida, 34652

  • Investigational Site Number 8400007

    New York, New York, 10001

  • Investigational Site Number 8400026

    Ocoee, Florida, 34761

  • Investigational Site Number 8400036

    Omaha, Nebraska, 68114

  • Investigational Site Number 8400033

    Palm Harbor, Florida, 34684

  • Investigational Site Number 8400003

    Rockville, Maryland, 20852-4267

  • Investigational Site Number 8400035

    Rocky Mount, North Carolina, 27804

  • Investigational Site Number 8400009

    Roswell, Georgia, 30076

  • Investigational Site Number 8400001

    Temecula, California, 92591

  • Investigational Site Number 8400015

    Ventura, California, 93003

  • Investigational Site Number 8400041

    Waco, Texas, 76710

  • Investigational Site Number 8400013

    Waltham, Massachusetts, 02453

  • Investigational Site Number 8400031

    Washington, Missouri, 63090

  • Investigational Site Number 8400029

    Waterbury, Connecticut, 06708-3346

Other trials in United States

About this study

Official title: Randomized, Open Label, Parallel-group Study Comparing the Pharmacokinetics and Immunogenicity of Alternating Use of SAR341402 and NovoLog® Versus Continuous Use of NovoLog in Participants With Type 1 Diabetes Mellitus Also Using Insulin Glargine

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.

Read more

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).
Read the detailed description

The study duration per participant was less than 19 weeks (for participants who did not require the run-in period) and less than 31 weeks (for participants who require the run-in period).

Being tested
Insulin Aspart SAR341402, Insulin Aspart, Insulin glargine U100
Medical subject headings
Diabetes Mellitus, Type 1

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Insulin Aspart SAR341402Drug

    Pharmaceutical form: Solution for injection Route of administration: Subcutaneous

  • Insulin AspartDrug

    Also called NovoLog

    Pharmaceutical form: Solution for injection Route of administration: Subcutaneous

  • Insulin glargine U100Drug

    Also called Lantus

    Pharmaceutical form: Solution for injection Route of administration: Subcutaneous

Study groups in NCT03874715
Study groupRoleWhat they receive
Switching: NovoLog/SAR341402ExperimentalParticipants 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.
Receives: Drug: Insulin Aspart SAR341402; Drug: Insulin Aspart; Drug: Insulin glargine U100
Non-Switching: NovoLogActive comparatorParticipants 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.
Receives: Drug: Insulin Aspart; Drug: Insulin glargine U100

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 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

  2. 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.

    Measured: 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

  3. 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.

    Measured: 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)

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

    AIA was categorized as: treatment-induced AIA, treatment-boosted AIA, and treatment-emergent AIA. Treatment-induced AIAs: participants who developed AIA following investigational medicinal product (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). Treatment-boosted AIAs: participants 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). Participants with treatment-emergent AIA were defined as participants with treatment-induced, or treatment-boosted AIAs. On-treatment period was defined as the time from the first injection of IMP up to the last injection of IMP + 1 day.

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

  2. Number of Participants With at Least One Hypoglycemic Event

    Severe hypoglycemia: event in which participant required assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions, because participant was not capable of helping self. Documented symptomatic hypoglycemia: event in which typical symptoms of hypoglycemia (SOH) were accompanied by measured plasma glucose concentration (PGC) less than or equal to (<=) 3.9 millimoles per liter (mmol/L)(<70 milligrams per deciliter [mg/dL]) or <3.0 mmol/L(<54 mg/dL). Asymptomatic hypoglycemia: event without SOH and with measured PGC of <=3.9 mmol/L (<70 mg/dL) or <3.0 mmol/L (<54 mg/dL). Probable symptomatic hypoglycemia: event with SOH not accompanied by plasma glucose determination but was presumably caused by PGC <=3.9 mmol/L (70 mg/dL). Relative hypoglycemia: event with SOH but with measured PGC greater than (>) 3.9 mmol/L (70 mg/dL).

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

  3. Number of Hypoglycemic Events Per Participant-year

    Number of hypoglycemia events (any, severe, documented [both threshold], asymptomatic [both threshold], probable symptomatic and relative) per participant-year of exposure were reported. Severe hypoglycemia: event in which participant required assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions, because participant wasn't capable of helping self. Documented symptomatic hypoglycemia: event in which typical SOH were accompanied by measured PGC of <=3.9 mmol/L (<70 mg/dL) or <3.0 mmol/L(<54 mg/dL). Asymptomatic hypoglycemia: event without SOH and measured PGC of <=3.9 mmol/L (<70 mg/dL) or <3.0 mmol/L(<54 mg/dL). Probable symptomatic hypoglycemia: event with SOH not accompanied by plasma glucose determination but was presumably caused by PGC <=3.9 mmol/L (70 mg/dL). Relative hypoglycemia: event with SOH but with measured PGC >3.9 mmol/L (70 mg/dL).

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

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

    An Adverse Event (AE) was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily have to have a causal relationship with the treatment. Serious adverse events (SAEs) were defined as any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/ incapacity, was a congenital anomaly/birth defect, was a medically important event. TEAEs were defined as AEs that developed, worsened or became serious during the on-treatment period (from first injection of IMP up to 1 day after the last injection of IMP).

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

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

    Tmax was defined as the time taken to reach the maximum observed plasma concentration. Insulin aspart is the active ingredient of SAR341402 and NovoLog.

    Measured: 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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Mar 2019
  2. Study start11 Mar 2019
  3. Primary completion8 Jul 2020
  4. Study completion8 Jul 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
210 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03874715
Sponsor's protocol ID
EFC15178
Other IDs
U1111-1197-7811, 136342
Acronym
GEMELLI X
Status last verified
Mar 2024
First submitted
12 Mar 2019
Last updated
17 Apr 2024
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Publications

  • 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.

    PubMed 37880868

  • 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.

    PubMed 38420944

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Insulin Aspart SAR341402, Insulin Aspart and Insulin glargine U100 in people with Type 1 Diabetes Mellitus, run by Sanofi at 33 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 33 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 Jul 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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) (time frame: 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). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03874715, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Apr 2024.

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