Efficacy and Safety of Efpeglenatide Versus Placebo in Patients With Type 2 Diabetes Mellitus Inadequately Controlled With Basal Insulin Alone or in Combination With Oral Antidiabetic Drug(s)

NCT ID: NCT03713684

Last Updated: 2021-12-02

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 370 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-11-09
• Study Completion Date: 2021-01-04

Brief Summary

Primary Objective:

To demonstrate the superiority of once weekly injection of efpeglenatide in comparison to placebo in glycated hemoglobin (HbA1c) change in participants with type 2 diabetes mellitus (T2DM) inadequately controlled with basal insulin alone or in combination with oral antidiabetic drugs (OADs).

Secondary Objectives:

• To demonstrate the superiority of once weekly injection of efpeglenatide in comparison to placebo on glycemic control.
• To demonstrate the superiority of once weekly injection of efpeglenatide in comparison to placebo on body weight.
• To evaluate the safety of once weekly injection of efpeglenatide.

Detailed Description

Study duration per participant was approximately 64 weeks including an up to 2-week Screening Period, a 30-week Core Treatment Period, a 26-week Safety Extension Period, and a 6-week safety Follow-up Period.

Conditions

Type 2 Diabetes Mellitus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

Participants received placebo (matched to efpeglenatide) subcutaneous (SC) injection once weekly up to Week 56 on top of basal insulin alone or in combination with oral antidiabetic drugs (OADs).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Pharmaceutical form: solution for injection Route of administration: subcutaneous

Background therapy

Intervention Type: DRUG

Lantus (Insulin Glargine), SC, once daily; OADs, administered as per investigator prescription and in accordance with local labeling.

Efpeglenatide 2 mg

Participants received Efpeglenatide 2 milligrams (mg) SC injection once weekly up to Week 56 on top of basal insulin alone or in combination with OADs.

Group Type: EXPERIMENTAL

Efpeglenatide SAR439977

Intervention Type: DRUG

Pharmaceutical form: solution for injection Route of administration: subcutaneous

Background therapy

Intervention Type: DRUG

Lantus (Insulin Glargine), SC, once daily; OADs, administered as per investigator prescription and in accordance with local labeling.

Efpeglenatide 4 mg

Participants received Efpeglenatide 4 mg SC injection once weekly up to Week 56 on top of basal insulin alone or in combination with OADs. Participants initiated dosing at 2 mg once weekly up to Week 1; which was up titrated to 4 mg and maintained at the 4 mg dose through-out the treatment duration up to Week 56.

Group Type: EXPERIMENTAL

Efpeglenatide SAR439977

Intervention Type: DRUG

Pharmaceutical form: solution for injection Route of administration: subcutaneous

Background therapy

Intervention Type: DRUG

Lantus (Insulin Glargine), SC, once daily; OADs, administered as per investigator prescription and in accordance with local labeling.

Efpeglenatide 6 mg

Participants received Efpeglenatide 6 mg SC injection once weekly up to Week 56 on top of basal insulin alone or in combination with OADs. Participants initiated dosing at 2 mg once weekly up to Week 1; which was up titrated to 4 mg until Week 4 and later up-titrated to 6 mg and maintained at the 6 mg dose through-out the treatment duration up to Week 56.

Group Type: EXPERIMENTAL

Efpeglenatide SAR439977

Intervention Type: DRUG

Pharmaceutical form: solution for injection Route of administration: subcutaneous

Background therapy

Intervention Type: DRUG

Lantus (Insulin Glargine), SC, once daily; OADs, administered as per investigator prescription and in accordance with local labeling.

Interventions

Efpeglenatide SAR439977

Pharmaceutical form: solution for injection Route of administration: subcutaneous

Intervention Type: DRUG

Placebo

Pharmaceutical form: solution for injection Route of administration: subcutaneous

Intervention Type: DRUG

Background therapy

Lantus (Insulin Glargine), SC, once daily; OADs, administered as per investigator prescription and in accordance with local labeling.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Participant must be greater than or equal to (>=)18 years of age at the time of signing the informed consent.
• Participants with T2DM.
• Diabetes diagnosed at least 1 year before screening.
• Participants on basal insulin regimen alone or in combination with OADs for at least 6 months prior to screening.
• HbA1c between 7.0 percent (%) and 10.0% (inclusive) measured by the central laboratory at screening.

Exclusion Criteria

• History of severe hypoglycemia requiring emergency room admission or hospitalization within 3 months prior to screening.
• Retinopathy or maculopathy with one of the following treatments, either recent (within 3 months prior to screening) or planned: intravitreal injections or laser or vitrectomy surgery.
• Clinically relevant history of gastrointestinal disease associated with prolonged nausea and vomiting, including (but not limited to) gastroparesis, unstable and not controlled gastroesophageal reflux disease requiring medical treatment within 6 months prior to screening.
• History of pancreatitis (unless pancreatitis was related to gallstones and cholecystectomy has been performed), pancreatitis during previous treatment with incretin therapies, chronic pancreatitis, pancreatectomy.
• Personal or family history of medullary thyroid cancer (MTC) or genetic conditions that predispose to MTC (e.g., multiple endocrine neoplasia syndromes).
• Body weight change of >=5 kilograms within the last 3 months prior to screening.
• Systolic blood pressure greater than (>)180 millimetres of mercury (mmHg) and/or diastolic blood pressure >100 mmHg at randomization.
• End-stage renal disease as defined by estimated glomerular filtration rate (by Modification of Diet in Renal Disease) of less than 15 mL/min/1.73 m^2.
• Laboratory findings at the screening Visit:

• Alanine aminotransferase or aspartate aminotransferase >3 * upper limit of normal (ULN) or total bilirubin >1.5*ULN (except in case of documented Gilbert's syndrome);
• Amylase and/or lipase: >3*ULN;
• Calcitonin >=5.9 picomoles per liter (pmol/L) (20 picograms per milliliter [pg/mL]).
• Gastric surgery or other gastric procedures intended for weight loss within 2 years prior to screening, or planned during study period.
• Pregnant (confirmed by serum pregnancy test at screening) or breast-feeding women.
• Women of childbearing potential not willing to use highly effective method(s) of birth control or who were unwilling to be tested for pregnancy during the study period and for at least 5 weeks after the last dose of study intervention.

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hanmi Pharmaceutical Company Limited

INDUSTRY

Sponsor Role: collaborator

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Sciences & Operations

Role: STUDY_DIRECTOR

Sanofi

Locations

Investigational Site Number 8400038

Birmingham, Alabama, United States

Investigational Site Number 8400035

Chandler, Arizona, United States

Investigational Site Number 8400005

Glendale, Arizona, United States

Investigational Site Number 8400057

Huntington Park, California, United States

Investigational Site Number 8400058

La Jolla, California, United States

Investigational Site Number 8400009

Los Angeles, California, United States

Investigational Site Number 8400045

Spring Valley, California, United States

Investigational Site Number 8400040

Tustin, California, United States

Investigational Site Number 8400026

Van Nuys, California, United States

Investigational Site Number 8400055

Orlando, Florida, United States

Investigational Site Number 8400041

Pembroke Pines, Florida, United States

Investigational Site Number 8400025

Lawrenceville, Georgia, United States

Investigational Site Number 8400052

West Des Moines, Iowa, United States

Investigational Site Number 8400044

Lexington, Kentucky, United States

Investigational Site Number 8400001

Bridgeton, New Jersey, United States

Investigational Site Number 8400039

New Windsor, New York, United States

Investigational Site Number 8400036

Morehead City, North Carolina, United States

Investigational Site Number 8400013

Maumee, Ohio, United States

Investigational Site Number 8400030

Dallas, Texas, United States

Investigational Site Number 8400063

Dallas, Texas, United States

Investigational Site Number 8400043

San Antonio, Texas, United States

Investigational Site Number 8400037

Layton, Utah, United States

Investigational Site Number 1560005

Baotou, , China

Investigational Site Number 1560017

Beijing, , China

Investigational Site Number 1560006

Changsha, , China

Investigational Site Number 1560001

Chengdu, , China

Investigational Site Number 1560004

Shanghai, , China

Investigational Site Number 1560036

Shanghai, , China

Investigational Site Number 1560012

Shanghai, , China

Investigational Site Number 1560013

Shanghai, , China

Investigational Site Number 1560003

Zhengzhou, , China

Investigational Site Number 4100009

Busan, , South Korea

Investigational Site Number 4100001

Daejeon, , South Korea

Investigational Site Number 4100016

Gwangju, , South Korea

Investigational Site Number 4100010

Gwangju, , South Korea

Investigational Site Number 4100013

Gyeonggi-do, , South Korea

Investigational Site Number 4100015

Incheon, , South Korea

Investigational Site Number 4100014

Jeonju, , South Korea

Investigational Site Number 4100007

Seongnam-si, , South Korea

Investigational Site Number 4100008

Seoul, , South Korea

Investigational Site Number 4100002

Seoul, , South Korea

Investigational Site Number 4100005

Seoul, , South Korea

Investigational Site Number 4100004

Seoul, , South Korea

Investigational Site Number 4100003

Seoul, , South Korea

Investigational Site Number 4100011

Seoul, , South Korea

Investigational Site Number 4100006

Seoul, , South Korea

Investigational Site Number 4100012

Suwon, , South Korea

Countries

United States; China; South Korea

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

U1111-1189-5009

Identifier Type: OTHER

Identifier Source: secondary_id

EFC14893

Identifier Type: -

Identifier Source: org_study_id