Efficacy and Safety of Efpeglenatide Versus Dulaglutide in Patients With Type 2 Diabetes Mellitus Inadequately Controlled With Metformin (AMPLITUDE-D)

A 56-week, Multicenter, Open-label, Active-controlled, Randomized Study to Evaluate the Efficacy and Safety of Efpeglenatide Once Weekly Compared to Dulaglutide Once Weekly in Patients With Type 2 Diabetes Mellitus Inadequately Controlled With Metformin

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.

Study Overview

• Status: Terminated
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Efpeglenatide; Drug: Background therapy Metformin; Drug: Dulaglutide

Detailed Description

Study duration per participant was approximately 65 weeks including an up to 3-week Screening Period, a 56-week Treatment Period and a 6-week safety Follow-up Period.

• Study Type: Interventional
• Enrollment (Actual): 908
• Phase: Phase 3

Contacts and Locations

Study Locations

• Hungary
  • Budapest, Hungary, 1036
    • Investigational Site Number 3480004
  • Debrecen, Hungary, 4025
    • Investigational Site Number 3480003
  • Gyula, Hungary, 5700
    • Investigational Site Number 3480001
  • Hatvan, Hungary, 3000
    • Investigational Site Number 3480005
  • Nyíregyháza, Hungary, 4400
    • Investigational Site Number 3480002
• Poland
  • Gdansk, Poland, 80-382
    • Investigational Site Number 6160008
  • Gdynia, Poland, 81-537
    • Investigational Site Number 6160004
  • Katowice, Poland, 40-040
    • Investigational Site Number 6160010
  • Poznan, Poland, 60-702
    • Investigational Site Number 6160009
  • Warszawa, Poland, 01-192
    • Investigational Site Number 6160003
  • Wroclaw, Poland, 50-381
    • Investigational Site Number 6160001
• Ukraine
  • Kyiv, Ukraine, 02002
    • Investigational Site Number 8040003
  • Kyiv, Ukraine, 03037
    • Investigational Site Number 8040001
  • Kyiv, Ukraine, 03049
    • Investigational Site Number 8040002
  • Vinnytsia, Ukraine, 21050
    • Investigational Site Number 8040004
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35211
      • Investigational Site Number 8400038
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Investigational Site Number 8400035
    • Glendale, Arizona, United States, 85306
      • Investigational Site Number 8400005
    • Peoria, Arizona, United States, 85381
      • Investigational Site Number 8400054
  • California
    • Huntington Park, California, United States, 90255
      • Investigational Site Number 8400057
    • Los Angeles, California, United States, 90057
      • Investigational Site Number 8400009
    • San Diego, California, United States, 92120
      • Investigational Site Number 8400007
    • Spring Valley, California, United States, 91978
      • Investigational Site Number 8400045
    • Tustin, California, United States, 92780
      • Investigational Site Number 8400040
    • Van Nuys, California, United States, 91405
      • Investigational Site Number 8400026
  • Connecticut
    • Waterbury, Connecticut, United States, 06708
      • Investigational Site Number 8400050
  • Florida
    • Orlando, Florida, United States, 32825
      • Investigational Site Number 8400055
    • Pembroke Pines, Florida, United States, 33026
      • Investigational Site Number 8400041
  • Georgia
    • Lawrenceville, Georgia, United States, 30044
      • Investigational Site Number 8400025
  • Idaho
    • Meridian, Idaho, United States, 83642
      • Investigational Site Number 8400060
  • Illinois
    • Skokie, Illinois, United States, 60077
      • Investigational Site Number 8400059
  • Kentucky
    • Lexington, Kentucky, United States, 40503
      • Investigational Site Number 8400044
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Investigational Site Number 8400061
  • New Jersey
    • Bridgeton, New Jersey, United States, 08302
      • Investigational Site Number 8400001
  • New York
    • New Windsor, New York, United States, 12553
      • Investigational Site Number 8400039
  • North Carolina
    • Burlington, North Carolina, United States, 27215
      • Investigational Site Number 8400028
    • Morehead City, North Carolina, United States, 28557
      • Investigational Site Number 8400036
  • Ohio
    • Maumee, Ohio, United States, 43537
      • Investigational Site Number 8400013
  • South Carolina
    • Goose Creek, South Carolina, United States, 29445
      • Investigational Site Number 8400014
  • Texas
    • Dallas, Texas, United States, 75230
      • Investigational Site Number 8400030
    • San Antonio, Texas, United States, 78218
      • Investigational Site Number 8400020
    • San Antonio, Texas, United States, 78229
      • Investigational Site Number 8400043
    • San Antonio, Texas, United States, 78258
      • Investigational Site Number 8400053
  • Utah
    • Layton, Utah, United States, 84041
      • Investigational Site Number 8400037
  • Virginia
    • Manassas, Virginia, United States, 20110
      • Investigational Site Number 8400049

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:

• 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.

Exclusion criteria:

• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Efpeglenatide 4 mg; 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; Pharmaceutical form: solution for injection; Route of administration: SC; Other Names: SAR439977; Drug: Background therapy Metformin; Pharmaceutical form: tablet; Route of administration: oral; Dose to be kept stable throughout the study.
Experimental: Efpeglenatide 6 mg; 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; Pharmaceutical form: solution for injection; Route of administration: SC; Other Names: SAR439977; Drug: Background therapy Metformin; Pharmaceutical form: tablet; Route of administration: oral; Dose to be kept stable throughout the study.
Active Comparator: Dulaglutide 1.5 mg; 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: Background therapy Metformin; Pharmaceutical form: tablet; Route of administration: oral; Dose to be kept stable throughout the study.; Drug: Dulaglutide; Pharmaceutical form: solution for injection; Route of administration: SC; Other Names: Trulicity™

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Hypoglycemic Events (Documented Symptomatic Hypoglycemia <3.0 mmol/L [<54 mg/dL] and Severe Hypoglycemia) Per Participant-Year	Documented symptomatic hypoglycemia was an event during which typical symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of <54 mg/dL (<3.0 mmol/L). Severe hypoglycemia was an event requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions.	Baseline up to Week 56
Change From Baseline to Week 56 in Body Weight	Adjusted LS means and SE were obtained from ANCOVA model to account for missing data. Missing values were imputed by BOCF-like multiple imputation method.	Baseline to Week 56
Number of Participants With HbA1c < 7.0 %	Participants who had no available assessment for HbA1c at Week 56 were considered as non-responders.	Week 56
Change From Baseline to Week 56 in Fasting Plasma Glucose (FPG)	Adjusted LS means and SE were obtained from ANCOVA model to account for missing data. Missing values were imputed by BOCF-like multiple imputation method.	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)	Documented symptomatic hypoglycemia was an event during which typical symptoms of hypoglycemia were accompanied by a measured plasma glucose concentration of <54 milligrams per deciliter (mg/dL) (<3.0 mmol/L). Severe hypoglycemia was an event requiring assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions.	Baseline up to Week 56

Collaborators and Investigators

• Sponsor: Sanofi
• Collaborators: Hanmi Pharmaceutical Company Limited

Study record dates

Study Major Dates

• Study Start (Actual): September 26, 2018
• Primary Completion (Actual): October 13, 2020
• Study Completion (Actual): November 17, 2020

Study Registration Dates

• First Submitted: September 24, 2018
• First Submitted That Met QC Criteria: September 24, 2018
• First Posted (Actual): September 26, 2018

Study Record Updates

• Last Update Posted (Actual): November 1, 2021
• Last Update Submitted That Met QC Criteria: October 28, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Dulaglutide; Metformin; Efpeglenatide
• Other Study ID Numbers: EFC14829; 2017-002956-10 (EudraCT Number); U1111-1205-3150 (Other Identifier: UTN)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No plan to share individual participant data (IPD) by SANOFI: Product rights transferred to Hanmi Pharmaceutical.

Drug and device information, study documents

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