Efficacy and Safety of Efpeglenatide Versus Dulaglutide in Patients With Type 2 Diabetes Mellitus Inadequately Controlled With Metformin

NCT03684642 | Terminated Phase 3 Results DMC FDA Drug

• 3 other identifiers: EFC148292017-002956-10U1111-1205-3150
• Study Type: interventional
• Target: 908
• Locations: 4 countries
• Sites: 45

Brief Summary

Primary Objective: To demonstrate the non-inferiority of once weekly injection of efpeglenatide in comparison to once weekly injection of dulaglutide on glycated hemoglobin (HbA1c) change in participants with Type 2 diabetes mellitus (T2DM) inadequately controlled with metformin. Secondary Objectives:

• To demonstrate the superiority of once weekly injection of efpeglenatide with once weekly injection of dulaglutide on glycemic control.
• To demonstrate the superiority of once weekly injection of efpeglenatide with once weekly injection of dulaglutide on body weight.
• To evaluate the safety of once weekly injection of efpeglenatide and once weekly injection of dulaglutide.

Conditions

Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (1)

• Change From Baseline to Week 56 in HbA1c

  Adjusted Least square (LS) means and Standard errors (SE) were obtained from analysis of covariance (ANCOVA) model to account for missing data. Missing values were imputed by baseline observation carried forward (BOCF)-like multiple imputation method.

  Baseline to Week 56

Secondary Outcomes (5)

• Change From Baseline to Week 56 in Body Weight

  Baseline to Week 56

• Number of Participants With HbA1c < 7.0 %

  Week 56

• Change From Baseline to Week 56 in Fasting Plasma Glucose (FPG)

  Baseline to Week 56

• 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 56

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

  Baseline up to Week 56

Study Arms (3)

Efpeglenatide 4 mg

EXPERIMENTAL

Participants received Efpeglenatide subcutaneous (SC) injection once weekly up to Week 56 on top of metformin. Participants initiated dosing at 2 mg once weekly and increased every 2 weeks to the maximum of 4 mg once weekly for the treatment duration.

Drug: Efpeglenatide; Drug: Background therapy Metformin

Efpeglenatide 6 mg

EXPERIMENTAL

Participants received Efpeglenatide SC injection once weekly up to Week 56 on top of metformin. Participants initiated dosing at 2 mg once weekly and increased every 2 weeks to the maximum of 6 mg once weekly for the treatment duration.

Drug: Efpeglenatide; Drug: Background therapy Metformin

Dulaglutide 1.5 mg

ACTIVE COMPARATOR

Participants received Dulaglutide SC injection once weekly up to Week 56 on top of metformin. Participants initiated dosing at 0.75 mg once weekly and increased after 2 weeks to 1.5 mg once weekly for the treatment duration.

Drug: Dulaglutide; Drug: Background therapy Metformin

Interventions

Efpeglenatide DRUG

Pharmaceutical form: solution for injection; Route of administration: SC

Also known as: SAR439977

Efpeglenatide 4 mg; Efpeglenatide 6 mg

Dulaglutide DRUG

Pharmaceutical form: solution for injection; Route of administration: SC

Also known as: Trulicity™

Dulaglutide 1.5 mg

Background therapy Metformin DRUG

Pharmaceutical form: tablet; Route of administration: oral; Dose to be kept stable throughout the study.

Dulaglutide 1.5 mg; Efpeglenatide 4 mg; Efpeglenatide 6 mg

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 stable dose of at least 1500 milligram per day (mg/day) of metformin, or tolerated maximum dose, or as per country regulation if less, for at least 3 months prior to screening.
• HbA1c between 7.0 percent (%) and 10.0% (inclusive) measured by the central laboratory at screening.

You may not qualify if:

• 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 (GI) 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 had 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 predisposes to MTC (e.g., multiple endocrine neoplasia syndromes).
• Body weight change of greater than or equal to (\>=) 5 kilogram within the last 3 months prior to screening.
• Systolic blood pressure greater than (\>)180 millimeter of mercury (mmHg) and/or diastolic blood pressure \>100 mmHg at randomization.
• Severe renal disease as defined by estimated glomerular filtration rate (eGFR), by Modification of Diet in Renal Disease (MDRD)\] of less than (\<)30 mL/min/1.73 m\^2.
• Laboratory findings at the screening visit:
• Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>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).
• 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 (WOCBP) 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.
• The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Sponsors & Collaborators

• Hanmi Pharmaceutical Company Limited: collaborator
• Sanofi: lead

Study Sites (45)

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 8400054

Peoria, Arizona, 85381, 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 8400007

San Diego, California, 92120, 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 8400026

Van Nuys, California, 91405, United States

Location

Investigational Site Number 8400050

Waterbury, Connecticut, 06708, United States

Location

Investigational Site Number 8400055

Orlando, Florida, 32825, 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 8400060

Meridian, Idaho, 83642, United States

Location

Investigational Site Number 8400059

Skokie, Illinois, 60077, United States

Location

Investigational Site Number 8400044

Lexington, Kentucky, 40503, United States

Location

Investigational Site Number 8400061

Boston, Massachusetts, 02115, 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 8400028

Burlington, North Carolina, 27215, 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 8400014

Goose Creek, South Carolina, 29445, United States

Location

Investigational Site Number 8400030

Dallas, Texas, 75230, United States

Location

Investigational Site Number 8400020

San Antonio, Texas, 78218, United States

Location

Investigational Site Number 8400043

San Antonio, Texas, 78229, United States

Location

Investigational Site Number 8400053

San Antonio, Texas, 78258, United States

Location

Investigational Site Number 8400037

Layton, Utah, 84041, United States

Location

Investigational Site Number 8400049

Manassas, Virginia, 20110, United States

Location

Investigational Site Number 3480004

Budapest, 1036, Hungary

Location

Investigational Site Number 3480003

Debrecen, 4025, Hungary

Location

Investigational Site Number 3480001

Gyula, 5700, Hungary

Location

Investigational Site Number 3480005

Hatvan, 3000, Hungary

Location

Investigational Site Number 3480002

Nyíregyháza, 4400, Hungary

Location

Investigational Site Number 6160008

Gdansk, 80-382, Poland

Location

Investigational Site Number 6160004

Gdynia, 81-537, Poland

Location

Investigational Site Number 6160010

Katowice, 40-040, Poland

Location

Investigational Site Number 6160009

Poznan, 60-702, Poland

Location

Investigational Site Number 6160003

Warsaw, 01-192, Poland

Location

Investigational Site Number 6160001

Wroclaw, 50-381, Poland

Location

Investigational Site Number 8040003

Kyiv, 02002, Ukraine

Location

Investigational Site Number 8040001

Kyiv, 03037, Ukraine

Location

Investigational Site Number 8040002

Kyiv, 03049, Ukraine

Location

Investigational Site Number 8040004

Vinnytsia, 21050, Ukraine

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

efpeglenatide; dulaglutide

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, model-based efficacy analyses were performed in the mITT population instead of the ITT population originally planned and data was carefully considered given that the study was terminated early.

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: NONE
• Masking Details: The study was open-label for the tested versus comparator drug and double blind for the doses.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 24, 2018
• First Posted: September 26, 2018
• Study Start: September 26, 2018
• Primary Completion: October 13, 2020
• Study Completion: November 17, 2020
• Last Updated: November 1, 2021
• Results First Posted: November 1, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will not share

Locations

PL (6); HU (5); UA (4); US (30)