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

Phase 3

Completed

• Conditions: Type 1 Diabetes Mellitus
• Interventions: Drug: Insulin Aspart SAR341402; Drug: Insulin Aspart; Drug: Insulin glargine U100

• Registration Number: NCT03874715
• Lead Sponsor: Sanofi

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).

Study Timeline

• Study Start: 2019-03-11
• Study First Submitted: 2019-03-12
• Study First Submitted QC: 2019-03-12
• Study First Posted: 2019-03-14
• Primary Completion: 2020-07-08
• Study Completion: 2020-07-08
• Disposition First Submitted: 2021-07-05
• Disposition First Submitted QC: 2021-07-05
• Disposition First Posted: 2021-07-08
• Results First Submitted: 2023-06-28
• Results First Submitted QC: 2023-06-28
• Results First Posted: 2023-07-21
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-21
• Last Update Posted: 2024-04-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 210

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Switching: NovoLog/SAR341402	Insulin Aspart SAR341402	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.
Switching: NovoLog/SAR341402	Insulin glargine U100	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.
Non-Switching: NovoLog	Insulin glargine U100	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.
Switching: NovoLog/SAR341402	Insulin Aspart	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.
Non-Switching: NovoLog	Insulin Aspart	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.

Primary Outcome Measures

Name	Time	Method
Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) 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	Cmax was defined as the maximum observed plasma concentration. Insulin aspart is the active ingredient of SAR341402 and NovoLog.
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)	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	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.
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)	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	AUC was defined as area under the concentration versus time curve. Insulin aspart is the active ingredient of SAR341402 and NovoLog.

Secondary Outcome Measures

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

Trial Locations

Locations (33)

Investigational Site Number 8400014; 🇺🇸 Concord, California, United States

Investigational Site Number 8400038; 🇺🇸 Doral, Florida, United States

Investigational Site Number 8400027; 🇺🇸 Houston, Texas, United States

Investigational Site Number 8400030; 🇺🇸 Miami, Florida, United States

Investigational Site Number 8400001; 🇺🇸 Temecula, California, United States

Investigational Site Number 8400029; 🇺🇸 Waterbury, Connecticut, United States

Investigational Site Number 8400012; 🇺🇸 Atlanta, Georgia, United States

Investigational Site Number 8400015; 🇺🇸 Ventura, California, United States

Investigational Site Number 8400005; 🇺🇸 Columbus, Georgia, United States

Investigational Site Number 8400023; 🇺🇸 Baltimore, Maryland, United States

Investigational Site Number 8400009; 🇺🇸 Roswell, Georgia, United States

Investigational Site Number 8400028; 🇺🇸 Des Moines, Iowa, United States

Investigational Site Number 8400004; 🇺🇸 Flint, Michigan, United States

Investigational Site Number 8400019; 🇺🇸 Crystal Lake, Illinois, United States

Investigational Site Number 8400042; 🇺🇸 El Paso, Texas, United States

Investigational Site Number 8400003; 🇺🇸 Rockville, Maryland, United States

Investigational Site Number 8400034; 🇺🇸 Jefferson City, Tennessee, United States

Investigational Site Number 8400040; 🇺🇸 Dallas, Texas, United States

Investigational Site Number 8400007; 🇺🇸 New York, New York, United States

Investigational Site Number 8400021; 🇺🇸 Kansas City, Missouri, United States

Investigational Site Number 8400006; 🇺🇸 Morehead City, North Carolina, United States

Investigational Site Number 8400035; 🇺🇸 Rocky Mount, North Carolina, United States

Investigational Site Number 8400017; 🇺🇸 Las Vegas, Nevada, United States

Investigational Site Number 8400031; 🇺🇸 Washington, Missouri, United States

Investigational Site Number 8400016; 🇺🇸 Mesquite, Texas, United States

Investigational Site Number 8400041; 🇺🇸 Waco, Texas, United States

Investigational Site Number 8400010; 🇺🇸 Aurora, Colorado, United States

Investigational Site Number 8400036; 🇺🇸 Omaha, Nebraska, United States

Investigational Site Number 8400013; 🇺🇸 Waltham, Massachusetts, United States

Investigational Site Number 8400032; 🇺🇸 New Port Richey, Florida, United States

Investigational Site Number 8400026; 🇺🇸 Ocoee, Florida, United States

Investigational Site Number 8400033; 🇺🇸 Palm Harbor, Florida, United States

Investigational Site Number 8400018; 🇺🇸 Lexington, Kentucky, United States