Efficacy and Safety of Efpeglenatide Versus Placebo in Patients With Type 2 Diabetes Mellitus Inadequately Controlled With Metformin Alone or in Combination With Sulfonylurea

NCT03770728 | Terminated Phase 3 Results DMC FDA Drug

• 2 other identifiers: EFC15337U1111-1205-1291
• Study Type: interventional
• Target: 312
• Locations: 3 countries
• Sites: 48

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 metformin alone or in combination with sulfonylurea (SU). 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.

Conditions

Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (1)

• Change From Baseline to Week 30 in HbA1c

  This analysis included all Week 30 assessment values available.

  Baseline to Week 30

Secondary Outcomes (5)

• Number of Participants With HbA1c <7.0%

  Week 30

• Change From Baseline to Week 30 in Fasting Plasma Glucose (FPG)

  Baseline to Week 30

• Change From Baseline to Week 30 in Body Weight

  Baseline to Week 30

• Number of Participants With At Least One Hypoglycemic Events (Documented Symptomatic Hypoglycemia <3.0 mmol/L [<54 mg/dL], Severe Hypoglycemia)

  Baseline up to Week 30

• Number of Hypoglycemic Events (Documented Symptomatic Hypoglycemia <3.0 mmol/L [<54 mg/dL] and Severe Hypoglycemia) Per Participant-Year

  Baseline up to Week 30

Study Arms (4)

Placebo

PLACEBO COMPARATOR

Participants received placebo (matched to Efpeglenatide) subcutaneous (SC) injection once weekly up to Week 30 on top of metformin alone or in combination with SU.

Drug: Placebo; Drug: Background therapy: Metformin alone or in combination with SU

Efpeglenatide 2 mg

EXPERIMENTAL

Participants received Efpeglenatide 2 milligrams (mg) SC injection once weekly up to Week 30 on top of metformin alone or in combination with SU.

Drug: Efpeglenatide SAR439977; Drug: Background therapy: Metformin alone or in combination with SU

Efpeglenatide 4 mg

EXPERIMENTAL

Participants received Efpeglenatide 4 mg SC injection once weekly up to Week 30 on top of metformin alone or in combination with SU. Participants initiated dosing at 2 mg once weekly up to Week 1; which was up titrated to 4 mg and was maintained at the 4 mg dose through-out the treatment duration, up to Week 30.

Drug: Efpeglenatide SAR439977; Drug: Background therapy: Metformin alone or in combination with SU

Efpeglenatide 6 mg

EXPERIMENTAL

Participants received Efpeglenatide 6 mg SC injection once weekly up to Week 30 on top of metformin alone or in combination with SU. Participants initiated dosing at 2 mg once weekly up to Week 1; which was up titrated to 4 mg until Week 3 and later up-titrated to 6 mg and was maintained at the 6 mg dose through-out the treatment duration, up to Week 30.

Drug: Efpeglenatide SAR439977; Drug: Background therapy: Metformin alone or in combination with SU

Interventions

Efpeglenatide SAR439977 DRUG

Pharmaceutical form: solution for injection Route of administration: subcutaneous

Efpeglenatide 2 mg; Efpeglenatide 4 mg; Efpeglenatide 6 mg

Placebo DRUG

Pharmaceutical form: solution for injection Route of administration: subcutaneous

Placebo

Background therapy: Metformin alone or in combination with SU DRUG

Pharmaceutical form: tablet Route of administration: oral, administered as per investigator and in accordance with local labeling.

Efpeglenatide 2 mg; Efpeglenatide 4 mg; Efpeglenatide 6 mg; Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 metformin alone or in combination with SU, for at least 3 months prior to screening.
• Glycated hemoglobin between 7.0% and 10.0% (inclusive) measured by the central laboratory at screening.

You may not qualify if:

• 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 or history of surgery affecting gastric emptying.
• 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 millimeters of mercury (mmHg) and/or diastolic blood pressure \>100 mmHg at randomization.
• Severe renal disease as defined by estimated glomerular filtration rate (eGFR) of \<30 milliliters per minute per 1.73 square meter.
• Laboratory findings at the screening visit:
• Alanine aminotransferase or aspartate aminotransferase \>3\*upper limit of the normal (ULN) or total bilirubin \>1.5\*ULN (except in case of documented Gilbert's syndrome);
• Amylase and/or lipase: \>3\*ULN laboratory range;
• Calcitonin \>=5.9 picomoles per liter (20 picograms per milliliter).
• 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 are unwilling to be tested for pregnancy during the study period and for at least 5 weeks after the last dose of study intervention.

Sponsors & Collaborators

• Sanofi: lead
• Hanmi Pharmaceutical Company Limited: collaborator

Study Sites (48)

Investigational Site Number 8400038

Birmingham, Alabama, 35211, United States

Location

Investigational Site Number 8400035

Chandler, Arizona, 85224, United States

Location

Investigational Site Number 8400005

Glendale, Arizona, 85306, United States

Location

Investigational Site Number 8400042

Mesa, Arizona, 85206, United States

Location

Investigational Site Number 8400051

Phoenix, Arizona, 85020, United States

Location

Investigational Site Number 8400056

Tucson, Arizona, 85741, United States

Location

Investigational Site Number 8400057

Huntington Park, California, 90255, United States

Location

Investigational Site Number 8400009

Los Angeles, California, 90057, United States

Location

Investigational Site Number 8400045

Spring Valley, California, 91978, United States

Location

Investigational Site Number 8400040

Tustin, California, 92780, United States

Location

Investigational Site Number 8400047

Colorado Springs, Colorado, 80909, United States

Location

Investigational Site Number 8400046

Coral Gables, Florida, 33134, United States

Location

Investigational Site Number 8400041

Pembroke Pines, Florida, 33026, United States

Location

Investigational Site Number 8400025

Lawrenceville, Georgia, 30044, United States

Location

Investigational Site Number 8400044

Lexington, Kentucky, 40503, United States

Location

Investigational Site Number 8400001

Bridgeton, New Jersey, 08302, United States

Location

Investigational Site Number 8400039

New Windsor, New York, 12553, United States

Location

Investigational Site Number 8400036

Morehead City, North Carolina, 28557, United States

Location

Investigational Site Number 8400013

Maumee, Ohio, 43537, United States

Location

Investigational Site Number 8400048

Oklahoma City, Oklahoma, 73111, United States

Location

Investigational Site Number 8400030

Dallas, Texas, 75230, United States

Location

Investigational Site Number 8400043

San Antonio, Texas, 78229, United States

Location

Investigational Site Number 8400037

Layton, Utah, 84041, United States

Location

Investigational Site Number 1560005

Baotou, 014010, China

Location

Investigational Site Number 1560042

Beijing, 101199, China

Location

Investigational Site Number 1560053

Hangzhou, 310009, China

Location

Investigational Site Number 1560051

Hefei, 210011, China

Location

Investigational Site Number 1560011

Hunan, 411100, China

Location

Investigational Site Number 1560025

Meihekou, 135000, China

Location

Investigational Site Number 1560055

Nanchang, 330006, China

Location

Investigational Site Number 1560024

Nanjing, 210011, China

Location

Investigational Site Number 1560020

Pingxiang, 337055, China

Location

Investigational Site Number 1560031

Shandong, 250013, China

Location

Investigational Site Number 1560030

Shandong, 250031, China

Location

Investigational Site Number 1560012

Shanghai, 200040, China

Location

Investigational Site Number 1560013

Shanghai, 200040, China

Location

Investigational Site Number 1560004

Shanghai, 200065, China

Location

Investigational Site Number 1560022

Shanghai, 200090, China

Location

Investigational Site Number 1560041

Tianjin, 300052, China

Location

Investigational Site Number 1560010

Wenzhou, 325027, China

Location

Investigational Site Number 1560052

Wuhu, 241001, China

Location

Investigational Site Number 1560034

Wuxi, 214000, China

Location

Investigational Site Number 1560026

Xuzhou, 221006, China

Location

Investigational Site Number 1560044

Yichun, 336000, China

Location

Investigational Site Number 1560003

Zhengzhou, 450003, China

Location

Investigational Site Number 1580006

Kaohsiung City, 83301, Taiwan

Location

Investigational Site Number 1580003

Taichung, 40705, Taiwan

Location

Investigational Site Number 1580002

Taipei, 11217, Taiwan

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Limitations and Caveats

The study was terminated early by the Sponsor on 09 September 2020. Due to early termination of the study, few efficacy evaluations and analyses originally planned in the protocol were no longer considered to be applicable and were not performed. Primary, and secondary efficacy data were descriptively summarized.

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi

Contact-US@sanofi.com

800-633-1610

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 7, 2018
• First Posted: December 10, 2018
• Study Start: August 1, 2019
• Primary Completion: November 28, 2020
• Study Completion: December 27, 2020
• Last Updated: December 2, 2021
• Results First Posted: December 2, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (23); CN (22); TW (3)