Efficacy and Safety of Efpeglenatide Versus Placebo in Patients With Type 2 Diabetes Mellitus Inadequately Controlled With Diet and Exercise (AMPLITUDE-M)

A 56-week, Multicenter, Double-blind, Placebo-controlled, Randomized Study to Evaluate the Efficacy and Safety of Efpeglenatide Once Weekly in Patients With Type 2 Diabetes Mellitus Inadequately Controlled With Diet and Exercise

Primary Objective:

To demonstrate the superiority of once weekly injection of efpeglenatide in comparison to placebo in glycated hemoglobin (HbA1c) change in participants with T2DM (Type 2 Diabetes Mellitus) inadequately controlled with diet and exercise.

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

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: efpeglenatide (SAR439977); Drug: placebo

Detailed Description

Study duration per participant is approximately 65 weeks, including a 3-week screening period, 30 weeks core treatment period, 26 weeks extension treatment period, and 6 weeks safety follow up.

• Study Type: Interventional
• Enrollment (Actual): 406
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 12627
    • Investigational Site Number 2760005
  • Frankfurt Am Main, Germany, 60313
    • Investigational Site Number 2760003
  • Leipzig, Germany, 04103
    • Investigational Site Number 2760001
• Poland
  • Gdansk, Poland, 80-382
    • Investigational Site Number 6160005
  • Gdynia, Poland, 81-537
    • Investigational Site Number 6160004
  • Katowice, Poland, 40-040
    • Investigational Site Number 6160007
  • Krakow, Poland, 31-501
    • Investigational Site Number 6160002
  • Poznan, Poland, 60-702
    • Investigational Site Number 6160006
  • 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
  • Vinnitsa, Ukraine, 21009
    • Investigational Site Number 8040004
• United Kingdom
  • Birmingham, United Kingdom, B15 2SQ
    • Investigational Site Number 8260005
  • Cardiff, United Kingdom, CF15 9SS
    • Investigational Site Number 8260004
  • Chorley, United Kingdom, PR7 7NA
    • Investigational Site Number 8260007
  • Glasgow, United Kingdom, G20 0SP
    • Investigational Site Number 8260008
  • Hexham, United Kingdom, NE46 1QJ
    • Investigational Site Number 8260001
  • Liverpool, United Kingdom, L22 0LG
    • Investigational Site Number 8260003
  • Manchester, United Kingdom, M15 6SX
    • Investigational Site Number 8260006
  • Reading, United Kingdom, RG2 0TG
    • Investigational Site Number 8260002
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35205
      • Investigational Site Number 8400004
  • Arizona
    • Glendale, Arizona, United States, 85306
      • Investigational Site Number 8400005
  • California
    • Canoga Park, California, United States, 91303
      • Investigational Site Number 8400003
    • Chula Vista, California, United States, 91911
      • Investigational Site Number 8400007
    • La Mesa, California, United States, 91942
      • Investigational Site Number 8400011
    • Los Angeles, California, United States, 90057
      • Investigational Site Number 8400009
    • Pomona, California, United States, 91767
      • Investigational Site Number 8400029
    • Tarzana, California, United States, 91356
      • Investigational Site Number 8400024
    • Van Nuys, California, United States, 91405
      • Investigational Site Number 8400026
  • Florida
    • DeLand, Florida, United States, 32720
      • Investigational Site Number 8400010
    • Hialeah, Florida, United States, 33012
      • Investigational Site Number 8400006
    • West Palm Beach, Florida, United States, 33409
      • Investigational Site Number 8400032
  • Georgia
    • Lawrenceville, Georgia, United States, 30044
      • Investigational Site Number 8400025
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Investigational Site Number 8400034
  • Missouri
    • Kansas City, Missouri, United States, 64128
      • Investigational Site Number 8400033
  • Nebraska
    • Lincoln, Nebraska, United States, 68503
      • Investigational Site Number 8400018
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Investigational Site Number 8400062
    • Las Vegas, Nevada, United States, 89109
      • Investigational Site Number 8400021
  • New Jersey
    • Bridgeton, New Jersey, United States, 08302
      • Investigational Site Number 8400001
  • North Carolina
    • Burlington, North Carolina, United States, 27215
      • Investigational Site Number 8400028
    • Wilmington, North Carolina, United States, 28401
      • Investigational Site Number 8400031
  • Ohio
    • Maumee, Ohio, United States, 43537
      • Investigational Site Number 8400013
  • Pennsylvania
    • Hatboro, Pennsylvania, United States, 19040
      • Investigational Site Number 8400008
  • Texas
    • Carrollton, Texas, United States, 75010
      • Investigational Site Number 8400017
    • Dallas, Texas, United States, 75230
      • Investigational Site Number 8400030
    • Houston, Texas, United States, 77074
      • Investigational Site Number 8400015
    • Plano, Texas, United States, 75024
      • Investigational Site Number 8400019
    • San Antonio, Texas, United States, 78218
      • Investigational Site Number 8400020
    • San Antonio, Texas, United States, 78229
      • Investigational Site Number 8400016
    • San Antonio, Texas, United States, 78229
      • Investigational Site Number 8400027
    • Schertz, Texas, United States, 78154
      • Investigational Site Number 8400023
  • Utah
    • Holladay, Utah, United States, 84117-7054
      • Investigational Site Number 8400002

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria:

• Participants must be at least 18 years of age at the time of signing the informed consent.
• Participants with T2DM, and treated with diet and exercise.
• Hemoglobin A1c between 7.0% and 10.0% (inclusive) measured by the central laboratory at Screening.

Exclusion criteria:

• 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 within 6 months prior to Screening or history of surgery affecting gastric emptying.
• History of pancreatitis (unless pancreatitis was related to gallstone and cholecystectomy has been performed) and pancreatitis during previous treatment with incretin therapies, chronic pancreatitis, and pancreatectomy.
• Personal or family history of Medullary Thyroidian Cancer (MTC) or genetic conditions that predisposes to MTC (eg multiple endocrine neoplasia syndromes).
• Retinopathy or maculopathy with one of the following treatments, either recent (within 3 months of screening) or planned: intravitreal injections or laser or vitrectomy surgery.
• Body weight change of ≥5 kg within the last 3 months prior to Screening.
• Systolic blood pressure >180 mmHg and/or diastolic blood pressure >100 mmHg at Randomization.
• End-stage renal disease as defined by estimated glomerular filtration rate (eGFR , by Modification of Diet in Renal Disease [MDRD]) of <15 mL/min/1.73 m2.
• Laboratory findings at the Screening Visit:
• Alanine aminotransferase (ALT ) or aspartate aminotransferase (AST ) >3 times the upper limit of the normal (ULN ) or total bilirubin >1.5 times the ULN (except in case of documented Gilbert's syndrome).
• Amylase and/or lipase: >3 times the ULN laboratory range.
• Calcitonin ≥5.9 pmol/L (20 pg/mL).
• Gastric surgery or other gastric procedures intended for weight loss within 2 years prior to Screening, or planned during study period.
• History of drug or alcohol abuse within 6 months prior to the time of Screening.
• Pregnant (demonstrated 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 during the study period and for at least 5 weeks after the last dose of study intervention.

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: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Efpeglenatide 2mg; Efpeglenatide low dose (Prefilled syringe) administered once weekly for 56 weeks	Drug: efpeglenatide (SAR439977); Pharmaceutical form: solution for injection Route of administration: subcutaneous
Experimental: Efpeglenatide 4 mg; Efpeglenatide middle dose (Prefilled syringe) administered once weekly for 56 weeks (including titration period)	Drug: efpeglenatide (SAR439977); Pharmaceutical form: solution for injection Route of administration: subcutaneous
Experimental: Efpeglenatide 6 mg; Efpeglenatide high dose (Prefilled syringe) administered once weekly for 56 weeks (including titration period)	Drug: efpeglenatide (SAR439977); Pharmaceutical form: solution for injection Route of administration: subcutaneous
Placebo Comparator: Placebo; Matching placebo (Prefilled syringe) administered once weekly for 56 weeks	Drug: placebo; Pharmaceutical form: solution for injection Route of administration: subcutaneous

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Glycated Hemoglobin (HbA1c) (%)	Change from Baseline to Week 30 in HbA1c	Baseline to Week 30

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in HbA1c (%)	Change from Baseline to Week 56 in HbA1c	Baseline to Week 56
Change in Fasting Plasma Glucose (FPG)	Change from Baseline to Week 30 in FPG	Baseline to Week 30
HbA1c <7%	Number of participants with HbA1c <7.0% at Week 30	Week 30
Change in Body Weight at Week 30	Change from Baseline to Week 30 in body weight	Baseline to Week 30
Change in Body Weight at Week 56	Change from Baseline to Week 56 in body weight	Baseline to Week 56
Hypoglycemic Participants	Number of participants with at least 1 hypoglycemic event during treatment period	Baseline to Week 56
Hypoglycemic Events	Number of hypoglycemic events	Baseline to Week 56
Treatment Emergent Adverse Events (TEAEs)	Number of participants with TEAEs	Baseline to Week 56

Collaborators and Investigators

• Sponsor: Hanmi Pharmaceutical Company Limited
• Collaborators: Sanofi

Publications and helpful links

General Publications

• Frias JP, Choi J, Rosenstock J, Popescu L, Niemoeller E, Muehlen-Bartmer I, Baek S. Efficacy and Safety of Once-Weekly Efpeglenatide Monotherapy Versus Placebo in Type 2 Diabetes: The AMPLITUDE-M Randomized Controlled Trial. Diabetes Care. 2022 Jul 7;45(7):1592-1600. doi: 10.2337/dc21-2656.

Study record dates

Study Major Dates

• Study Start (Actual): December 5, 2017
• Primary Completion (Actual): January 29, 2020
• Study Completion (Actual): September 7, 2020

Study Registration Dates

• First Submitted: November 21, 2017
• First Submitted That Met QC Criteria: November 21, 2017
• First Posted (Actual): November 27, 2017

Study Record Updates

• Last Update Posted (Actual): January 18, 2022
• Last Update Submitted That Met QC Criteria: January 11, 2022
• Last Verified: January 1, 2022

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; Efpeglenatide
• Other Study ID Numbers: EFC14822; 2016-001857-42; U1111-1182-1806 (Other Identifier: UTN)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No