Safety Assessment of SAR341402 and NovoLog® Used in Continuous Subcutaneous Insulin Infusion for Type 1 Diabetes Mellitus Patients

Safety Assessment of SAR341402 and NovoLog® Used in Continuous Subcutaneous Insulin Infusion (CSII) in Adult Patients With Type 1 Diabetes Mellitus (T1DM)

Primary Objective:

- To assess the safety of SAR341402 and NovoLog® when used in external insulin pumps in terms of the number of patients with infusion set occlusions.

Secondary Objectives:

• To assess the safety of SAR341402 and NovoLog® when used in external pumps in terms of unexplained hyperglycemia.
• To assess the safety of SAR341402 and NovoLog® when used in external pumps in terms of:
• Intervals for infusion set changes.
• Number of patients with insulin pump for "non-delivery" alarm.
• Patient observation of infusion set occlusion.
• Adverse events and serious adverse events.
• Number of patients with hypoglycemic events [according to ADA (American Diabetes Association) Workgroup on hypoglycemia].

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes Mellitus
• Intervention / Treatment: Drug: Insulin aspart SAR341402; Drug: Insulin aspart

Detailed Description

The study duration for each patient will be approximately 10 weeks, including a 2-week screening period, 2 treatment periods of 4 weeks each, and 1-day post-treatment safety follow-up period.

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72211
      • Investigational Site Number 8400001
  • Colorado
    • Denver, Colorado, United States, 80262
      • Investigational Site Number 8400002
  • Iowa
    • West Des Moines, Iowa, United States, 50265
      • Investigational Site Number 8400003

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Male and female patients with Type 1 diabetes mellitus (T1DM).
• Age greater than or equal to 18 at the screening visit.
• Diabetes diagnosed at least 12 months before screening visit.
• At least 1 year of insulin treatment with at least 6 months of CSII (Continuous Subcutaneous Insulin Infusion) treatment with an external insulin pump.
• Demonstration of successful use of insulin pump and performing of a minimum of 4 blood glucose checks per day during screening.
• Laboratory parameters within the normal range (or defined screening threshold for the Investigator site), unless the Investigator considers an abnormality to be clinically irrelevant for T1DM patients.
• Signed written informed consent.

Exclusion criteria:

• Hemoglobin A1c (HbA1c) ≥8.5% at screening.
• Diabetes other than T1DM.
• History of infection at the infusion site within 3 months prior to the screening visit (Visit 1).
• Use of oral glucose-lowering agents or any injectable glucose-lowering agents other than insulin during the 3 months before screening visit.
• Hospitalization for recurrent diabetic ketoacidosis (DKA) in the last 6 months before screening visit.
• History of severe hypoglycemia requiring emergency room admission or hospitalization in the last 6 months before screening visit.
• Hypoglycemic unawareness as judged by the Investigator in the last 6 months before the screening visit.
• Any clinically significant abnormality identified on physical examination, laboratory tests, or vital signs at the time of screening that in the judgment of the investigator or any sub investigator would preclude safe completion of the study.
• Known history of illegal drug or alcohol abuse within 6 months prior to the time of screening.
• Use of investigational drug(s) within 3 months or 5 half-lives, whichever is longer, prior to the screening visit.
• Patients who had previously received SAR341402 in any other clinical trial.
• Any contraindication to the use of NovoLog® as defined in the national product labels; history of hypersensitivity to NovoLog® or to any of the excipients.
• Pregnancy and lactation.
• If female, pregnancy [defined as positive β-HCG (Human Chorionic Gonadotropin) in blood or in urine], breast-feeding.
• Patient is an employee or relative of an employee of the sponsor.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: SAR341402/NovoLog; SAR341402 will be self-administered via continuous subcutaneous insulin infusion via an insulin pump. The dose will be individually titrated and administered in a basal and bolus fashion. After 4 weeks of SAR341402 as treatment, patient will switch with NovoLog® as treatment.	Drug: Insulin aspart SAR341402; Pharmaceutical form: Solution Route of administration: Subcutaneous
EXPERIMENTAL: NovoLog/SAR341402; Novolog will be self-administered via continuous subcutaneous insulin infusion via an insulin pump. The dose will be individually titrated and administered in a basal and bolus fashion. After 4 weeks of NovoLog® as treatment, patient will switch with SAR341402 as treatment.	Drug: Insulin aspart; Pharmaceutical form: Solution Route of administration: Subcutaneous

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Infusion set occlusions	Number of patients with infusion set occlusions. Infusions set occlusions are defined as infusion set change due to failure to correct hyperglycemia (plasma glucose ≥ 250 mg/dL [13.9 mmol/L]) by insulin bolus via the insulin pump.	At week 4 from baseline of each treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Unexplained hyperglycemia	Number of patients with unexplained hyperglycemia. Unexplained hyperglycemia is defined as plasma glucose equal or above 250 mg/dL (13.9 mmol/L) whether or not corrected by a bolus through the insulin pump with no apparent material defects, medical, dietary, insulin dosing or pump failure. This will include infusion set occlusion as defined in the primary endpoint.	At week 4 from baseline of each treatment
Intervals for infusion set changes	Intervals for infusion set changes will be derived as number of days in the treatment period divided by the number of infusion set changes in the treatment period.	At week 4 from baseline of each treatment
Number of patients with insulin pump alarms for "non-delivery"	Number of patients with insulin pump "non-delivery" alarms (independent of confirmation of occlusion by hyperglycemia and failure to correct hyperglycemia by insulin bolus via the insulin pump).	At week 4 from baseline of each treatment
Patient observation of infusion set occlusion	Patient observation of infusion set occlusion (independent of confirmation of occlusion by hyperglycemia and failure to correct hyperglycemia by insulin bolus via the insulin pump).	Up to 10 weeks
Adverse events and serious adverse events	Number patients with adverse events and/or serious adverse events, including bruising at the infusion site and injection site, and hypersensitivity reactions.	Up to 10 weeks
Number of patients with hypoglycemic events	Number of patients with hypoglycemic events.	At week 4 from baseline of each treatment

Collaborators and Investigators

• Sponsor: Sanofi

Publications and helpful links

General Publications

• Thrasher J, Polsky S, Hovsepian L, Nowotny I, Pierre S, Bois De Fer B, Bhargava A, Mukherjee B, Garg SK. Safety and Tolerability of Insulin Aspart Biosimilar SAR341402 Versus Originator Insulin Aspart (NovoLog) When Used in Insulin Pumps in Adults with Type 1 Diabetes: A Randomized, Open-Label Clinical Trial. Diabetes Technol Ther. 2020 Sep;22(9):666-673. doi: 10.1089/dia.2019.0446. Epub 2020 Jan 28.

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 10, 2018
• Primary Completion (ACTUAL): October 6, 2018
• Study Completion (ACTUAL): October 6, 2018

Study Registration Dates

• First Submitted: February 12, 2018
• First Submitted That Met QC Criteria: February 12, 2018
• First Posted (ACTUAL): February 19, 2018

Study Record Updates

• Last Update Posted (ACTUAL): April 25, 2022
• Last Update Submitted That Met QC Criteria: April 21, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc; Insulin Aspart; Insulin, Long-Acting; Insulin degludec, insulin aspart drug combination
• Other Study ID Numbers: PDY15083; U1111-1200-1241 (OTHER: UTN)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: 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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No