Clinical trial NCT03874715: Comparison of SAR341402 to NovoLog in Adult Patients With Type 1 Diabetes Mellitus Also Using Insulin Glargine
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Type 1 Diabetes Mellitus
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2019-03-14
Enrollment: 210
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 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).

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).

Eligibility criteria: Inclusion criteria:

* 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.

Exclusion criteria:

* 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.

Primary outcomes:
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)
timeFrame: 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
measure: 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)
timeFrame: 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
measure: Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) of Insulin Aspart Following Administration of Either SAR341402 (Switching Arm) or NovoLog (Non-switching Arm)
timeFrame: 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:
measure: Number of Participants With Treatment-emergent Anti-Insulin Aspart Antibodies (AIAs)
timeFrame: From first injection of IMP (Day 1) up to 1 day after the last injection of IMP (i.e., up to Day 113)
measure: Number of Participants With at Least One Hypoglycemic Event
timeFrame: From first injection of IMP (Day 1) up to 1 day after the last injection of IMP (i.e., up to Day 113)
measure: Number of Hypoglycemic Events Per Participant-year
timeFrame: From first injection of IMP (Day 1) up to 1 day after the last injection of IMP (i.e., up to Day 113)
measure: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
timeFrame: From first injection of IMP (Day 1) up to 1 day after the last injection of IMP (i.e., up to Day 113)
measure: Pharmacokinetics: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Insulin Aspart Following Administration of Either SAR341402 (Switching Arm) or NovoLog (Non-switching Arm)
timeFrame: 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
Other outcomes:
Locations:
city: Concord
country: United States
facility: Investigational Site Number 8400014
state: California
city: Temecula
country: United States
facility: Investigational Site Number 8400001
state: California
city: Ventura
country: United States
facility: Investigational Site Number 8400015
state: California
city: Aurora
country: United States
facility: Investigational Site Number 8400010
state: Colorado
city: Waterbury
country: United States
facility: Investigational Site Number 8400029
state: Connecticut
city: Doral
country: United States
facility: Investigational Site Number 8400038
state: Florida
city: Miami
country: United States
facility: Investigational Site Number 8400030
state: Florida
city: New Port Richey
country: United States
facility: Investigational Site Number 8400032
state: Florida
city: Ocoee
country: United States
facility: Investigational Site Number 8400026
state: Florida
city: Palm Harbor
country: United States
facility: Investigational Site Number 8400033
state: Florida
city: Atlanta
country: United States
facility: Investigational Site Number 8400012
state: Georgia
city: Columbus
country: United States
facility: Investigational Site Number 8400005
state: Georgia
city: Roswell
country: United States
facility: Investigational Site Number 8400009
state: Georgia
city: Crystal Lake
country: United States
facility: Investigational Site Number 8400019
state: Illinois
city: Des Moines
country: United States
facility: Investigational Site Number 8400028
state: Iowa
city: Lexington
country: United States
facility: Investigational Site Number 8400018
state: Kentucky
city: Baltimore
country: United States
facility: Investigational Site Number 8400023
state: Maryland
city: Rockville
country: United States
facility: Investigational Site Number 8400003
state: Maryland
city: Waltham
country: United States
facility: Investigational Site Number 8400013
state: Massachusetts
city: Flint
country: United States
facility: Investigational Site Number 8400004
state: Michigan
city: Kansas City
country: United States
facility: Investigational Site Number 8400021
state: Missouri
city: Washington
country: United States
facility: Investigational Site Number 8400031
state: Missouri
city: Omaha
country: United States
facility: Investigational Site Number 8400036
state: Nebraska
city: Las Vegas
country: United States
facility: Investigational Site Number 8400017
state: Nevada
city: New York
country: United States
facility: Investigational Site Number 8400007
state: New York
city: Morehead City
country: United States
facility: Investigational Site Number 8400006
state: North Carolina
city: Rocky Mount
country: United States
facility: Investigational Site Number 8400035
state: North Carolina
city: Jefferson City
country: United States
facility: Investigational Site Number 8400034
state: Tennessee
city: Dallas
country: United States
facility: Investigational Site Number 8400040
state: Texas
city: El Paso
country: United States
facility: Investigational Site Number 8400042
state: Texas
city: Houston
country: United States
facility: Investigational Site Number 8400027
state: Texas
city: Mesquite
country: United States
facility: Investigational Site Number 8400016
state: Texas
city: Waco
country: United States
facility: Investigational Site Number 8400041
state: Texas
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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. 2024 Feb 29:19322968241232709. doi: 10.1177/19322968241232709. Online ahead of print.