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

A 30-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 Metformin Alone or in Combination With Sulfonylurea

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.

Study Overview

• Status: Terminated
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Placebo; Drug: Efpeglenatide SAR439977; Drug: Background therapy: Metformin alone or in combination with SU

Detailed Description

Study duration per participant was approximately 39 weeks including an up to 3-week Screening Period, a 30-week Treatment Period, and a 6-week safety Follow-up Period.

• Study Type: Interventional
• Enrollment (Actual): 312
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Baotou, China, 014010
    • Investigational Site Number 1560005
  • Beijing, China, 101199
    • Investigational Site Number 1560042
  • Hangzhou, China, 310009
    • Investigational Site Number 1560053
  • Hefei, China, 210011
    • Investigational Site Number 1560051
  • Hunan, China, 411100
    • Investigational Site Number 1560011
  • Meihekou, China, 135000
    • Investigational Site Number 1560025
  • Nanchang, China, 330006
    • Investigational Site Number 1560055
  • Nanjing, China, 210011
    • Investigational Site Number 1560024
  • Pingxiang, China, 337055
    • Investigational Site Number 1560020
  • Shandong, China, 250013
    • Investigational Site Number 1560031
  • Shandong, China, 250031
    • Investigational Site Number 1560030
  • Shanghai, China, 200040
    • Investigational Site Number 1560012
  • Shanghai, China, 200040
    • Investigational Site Number 1560013
  • Shanghai, China, 200065
    • Investigational Site Number 1560004
  • Shanghai, China, 200090
    • Investigational Site Number 1560022
  • Tianjin, China, 300052
    • Investigational Site Number 1560041
  • Wenzhou, China, 325027
    • Investigational Site Number 1560010
  • Wuhu, China, 241001
    • Investigational Site Number 1560052
  • Wuxi, China, 214000
    • Investigational Site Number 1560034
  • Xuzhou, China, 221006
    • Investigational Site Number 1560026
  • Yichun, China, 336000
    • Investigational Site Number 1560044
  • Zhengzhou, China, 450003
    • Investigational Site Number 1560003
• Taiwan
  • Kaohsiung, Taiwan, 83301
    • Investigational Site Number 1580006
  • Taichung, Taiwan, 40705
    • Investigational Site Number 1580003
  • Taipei, Taiwan, 11217
    • Investigational Site Number 1580002
• 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
    • Mesa, Arizona, United States, 85206
      • Investigational Site Number 8400042
    • Phoenix, Arizona, United States, 85020
      • Investigational Site Number 8400051
    • Tucson, Arizona, United States, 85741
      • Investigational Site Number 8400056
  • California
    • Huntington Park, California, United States, 90255
      • Investigational Site Number 8400057
    • Los Angeles, California, United States, 90057
      • Investigational Site Number 8400009
    • Spring Valley, California, United States, 91978
      • Investigational Site Number 8400045
    • Tustin, California, United States, 92780
      • Investigational Site Number 8400040
  • Colorado
    • Colorado Springs, Colorado, United States, 80909
      • Investigational Site Number 8400047
  • Florida
    • Coral Gables, Florida, United States, 33134
      • Investigational Site Number 8400046
    • Pembroke Pines, Florida, United States, 33026
      • Investigational Site Number 8400041
  • Georgia
    • Lawrenceville, Georgia, United States, 30044
      • Investigational Site Number 8400025
  • Kentucky
    • Lexington, Kentucky, United States, 40503
      • Investigational Site Number 8400044
  • 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
    • Morehead City, North Carolina, United States, 28557
      • Investigational Site Number 8400036
  • Ohio
    • Maumee, Ohio, United States, 43537
      • Investigational Site Number 8400013
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73111
      • Investigational Site Number 8400048
  • Texas
    • Dallas, Texas, United States, 75230
      • Investigational Site Number 8400030
    • San Antonio, Texas, United States, 78229
      • Investigational Site Number 8400043
  • Utah
    • Layton, Utah, United States, 84041
      • Investigational Site Number 8400037

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 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.

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 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.

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
• Masking: QUADRUPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo; 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; Pharmaceutical form: solution for injection Route of administration: subcutaneous; Drug: Background therapy: Metformin alone or in combination with SU; Pharmaceutical form: tablet Route of administration: oral, administered as per investigator and in accordance with local labeling.
EXPERIMENTAL: Efpeglenatide 2 mg; 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; Pharmaceutical form: solution for injection Route of administration: subcutaneous; Drug: Background therapy: Metformin alone or in combination with SU; Pharmaceutical form: tablet Route of administration: oral, administered as per investigator and in accordance with local labeling.
EXPERIMENTAL: Efpeglenatide 4 mg; 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; Pharmaceutical form: solution for injection Route of administration: subcutaneous; Drug: Background therapy: Metformin alone or in combination with SU; Pharmaceutical form: tablet Route of administration: oral, administered as per investigator and in accordance with local labeling.
EXPERIMENTAL: Efpeglenatide 6 mg; 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; Pharmaceutical form: solution for injection Route of administration: subcutaneous; Drug: Background therapy: Metformin alone or in combination with SU; Pharmaceutical form: tablet Route of administration: oral, administered as per investigator and in accordance with local labeling.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Week 30 in HbA1c	This analysis included all Week 30 assessment values available.	Baseline to Week 30

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With HbA1c <7.0%	Participants who had no available assessment for HbA1c <7% at Week 30 were considered as non-responders.	Week 30
Change From Baseline to Week 30 in Fasting Plasma Glucose (FPG)	This analysis included all Week 30 assessment values available.	Baseline to Week 30
Change From Baseline to Week 30 in Body Weight	This analysis included all Week 30 assessment values available.	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)	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 30
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 30

Collaborators and Investigators

• Sponsor: Sanofi
• Collaborators: Hanmi Pharmaceutical Company Limited

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 1, 2019
• Primary Completion (ACTUAL): November 28, 2020
• Study Completion (ACTUAL): December 27, 2020

Study Registration Dates

• First Submitted: December 7, 2018
• First Submitted That Met QC Criteria: December 7, 2018
• First Posted (ACTUAL): December 10, 2018

Study Record Updates

• Last Update Posted (ACTUAL): December 2, 2021
• Last Update Submitted That Met QC Criteria: November 4, 2021
• Last Verified: November 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; Metformin; Efpeglenatide
• Other Study ID Numbers: EFC15337; U1111-1205-1291 (OTHER: 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
• product manufactured in and exported from the U.S.: No