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Trial record 1 of 1 for:    EFC14828
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Effect of Efpeglenatide on Cardiovascular Outcomes (AMPLITUDE-O)

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ClinicalTrials.gov Identifier: NCT03496298
Recruitment Status : Terminated (Sponsor decision to cancel TRIAL, not related to safety concern)
First Posted : April 12, 2018
Results First Posted : October 15, 2021
Last Update Posted : October 15, 2021
Sponsor:
Collaborator:
Hanmi Pharmaceutical Company Limited
Information provided by (Responsible Party):
Sanofi

Study Description
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Brief Summary:

Primary Objective:

To demonstrate that efpeglenatide 4 and 6 mg was noninferior to placebo on 3-point major adverse cardiac events (MACE) in Type 2 diabetes mellitus (T2DM) participants at high cardiovascular (CV) risk.

Secondary Objectives:

To demonstrate that efpeglenatide 4 and 6 mg was superior to placebo in T2DM participants with high CV risk on the following parameters:

  • 3-point MACE.
  • Expanded CV outcome.
  • Composite outcome of new or worsening nephropathy.

To assess the safety and tolerability of efpeglenatide 4 and 6 mg, both added to standard of care in T2DM participants at high CV risk.


Condition or disease Intervention/treatment Phase
Type 2 Diabetes Mellitus Drug: Efpeglenatide (SAR439977) Drug: Placebo Phase 3

Detailed Description:
The study duration per participant was up to approximately 36 months.
Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 4076 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study to Evaluate the Effect of Efpeglenatide on Cardiovascular Outcomes in Type 2 Diabetes Patients at High Cardiovascular Risk
Actual Study Start Date : April 27, 2018
Actual Primary Completion Date : December 10, 2020
Actual Study Completion Date : December 10, 2020

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Placebo Comparator: Placebo
Participants received placebo (matched to Efpeglenatide) as subcutaneous (SC) injection once weekly up to end of treatment.
 Drug: Placebo

Pharmaceutical form: Solution for injection

Route of administration: SC
Experimental: Efpeglenatide 4 mg
Participants received Efpeglenatide as SC injection 2 milligrams (mg) per week for 4 weeks then 4 mg per week up to end of treatment.
 Drug: Efpeglenatide (SAR439977)

Pharmaceutical form: Solution for injection,

Route of administration: SC
Experimental: Efpeglenatide 6 mg
Participants received Efpeglenatide as SC injection 2 mg per week for 4 weeks, then 4 mg per week for 4 weeks and then 6 mg per week up to end of treatment.
 Drug: Efpeglenatide (SAR439977)

Pharmaceutical form: Solution for injection,

Route of administration: SC


Outcome Measures
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Primary Outcome Measures :
  1. Time to First Occurrence of Major Adverse Cardiovascular Events (MACE): Event Rate Per 100 Participant-years for First Occurrence of Major Cardiovascular (CV) Event - Non-Inferiority Analysis [ Time Frame: From Day 1 until the date of first adjudicated and confirmed occurrence of major CV event (maximum duration: up to 31.5 months) ]
    All MACE positively adjudicated by the clinical endpoint committee (CEC) were used in the analysis of the composite outcome of first occurrence to CV death, non-fatal myocardial infarction (MI), and non-fatal stroke. Kaplan-Meier curves of the cumulative event rate by treatment groups were used to depict the first occurrence of MACE over time. The event rate per 100 participant-years (calculated by 100*number of participants with events/sum of time at risk (days) over all participants/365.25) measured in terms of number of events per 100 participant-years was reported.


Secondary Outcome Measures :
  1. Time to First Occurrence of Major Adverse Cardiovascular Events: Event Rate Per 100 Participant-years for First Occurrence of Major Cardiovascular Event - Superiority Analysis [ Time Frame: From Day 1 until the date of first adjudicated and confirmed occurrence of major CV event (maximum duration: up to 31.5 months) ]
    All MACE positively adjudicated by the CEC were used in the analysis of the composite outcome of first occurrence to CV death, non-fatal MI, and non-fatal stroke. Kaplan-Meier curves of the cumulative event rate by treatment groups were used to depict the first occurrence of MACE over time. The event rate per 100 participant-years (calculated by 100*number of participants with events/sum of time at risk (days) over all participants/365.25) measured in terms of number of events per 100 participant-years was reported.

  2. Time to First Occurrence of the Expanded Major Adverse Cardiovascular Events Composite Events: Event Rate Per 100 Participant-years for First Occurrence of Expanded Major Cardiovascular Event [ Time Frame: From Day 1 until the date of first adjudicated and confirmed occurrence of major CV event (maximum duration: up to 31.5 months) ]
    All MACE positively adjudicated by the CEC were used in the analysis of the expanded outcome of first occurrence to CV death (including fatal MI and fatal stroke), non-fatal MI, non-fatal stroke, coronary revascularization or hospitalization for unstable angina. Kaplan-Meier curves of the cumulative event rate by treatment groups were used to depict the first occurrence of MACE over time. The event rate per 100 participant-years (calculated by 100*number of participants with events/sum of time at risk (days) over all participants/365.25) measured in terms of number of events per 100 participant-years was reported. Data analysis was also performed independently by external steering committee for the publication.

  3. Time to First Occurrence of Composite Renal Endpoint: Event Rate Per 100 Participant-years for First Occurrence of Composite Renal Endpoint [ Time Frame: From Day 1 until the confirmed occurrence of composite renal endpoint (maximum duration: up to 31.5 months) ]
    Composite renal endpoint included the following: incident macroalbuminuria (defined as urinary albumin-to-creatinine ratio of greater than (>) 300, as measured in mg of albumin to grams of creatinine, or >33.9, as measured in mg of albumin to millimoles of creatinine), plus an increase in urinary albumin-to-creatinine ratio of at least 30% from baseline, a sustained decrease in estimated glomerular filtration rate (eGFR) of at least 40% for 30 days or more, renal-replacement therapy for 90 days or more, and a sustained eGFR of less than 15 ml per minute per 1.73 m^2 for 30 days or more. Kaplan-Meier curves of the cumulative event rate by treatment groups were used to depict the first occurrence of renal endpoint over time. The event rate per 100 participant-years (calculated by 100*number of participants with events/sum of time at risk (days) over all participants/365.25) measured in terms of number of events per 100 participant-years was reported.


Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

  • T2DM with glycosylated hemoglobin (HbA1c) greater than (>) 7 percentage.
  • Age 18 years or older who met at least one of the cardiovascular disease criteria or age 50 years (male), 55 years (female) or older with glomerular filtration rate greater than or equal to 25 and less than 60 milliliters per minute and at least had one cardiovascular risk factor.
  • Female participants agreed to follow contraceptive guidance.
  • Signed written informed consent.

Exclusion criteria:

  • Clinically relevant history of gastrointestinal disease associated with prolonged nausea and vomiting.
  • History of chronic pancreatitis or acute idiopathic pancreatitis or diagnosis of any type of acute pancreatitis within 3 months prior to screening.
  • Personal or family history of medullary thyroid cancer.
  • Hypertension (with a systolic blood pressure >180 millimeters of Mercury [mmHg] and/or diastolic blood pressure >100 mmHg).
  • Hospitalization for hypertensive emergency within 3 months prior to randomization.
  • Planned coronary procedure or surgery after randomization.
  • No documented ophthalmologic exam with fundoscopy within 6 months prior to randomization.
  • Retinopathy or maculopathy with treatment, either recent (3 months prior to randomization) or planned during the study.
  • Treated with any glucagon-like peptide-1 receptor agonist product alone (eg, exenatide, liraglutide, lixisenatide, albiglutide, dulaglutide, semaglutide) or in combination within 3 months prior to screening.
  • Use of any Dipeptidyl peptidase 4 inhibitor within 3 months prior to screening.
  • Antihyperglycemic treatment had not been stable within 3 months prior to screening.

The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03496298


Locations
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Sponsors and Collaborators
Sanofi
Hanmi Pharmaceutical Company Limited
Investigators
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Study Director: Clinical Sciences & Operations Sanofi
  Study Documents (Full-Text)

Documents provided by Sanofi:
Study Protocol  [PDF] July 30, 2018
Statistical Analysis Plan  [PDF] August 12, 2020

More Information
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Publications of Results:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT03496298    
Other Study ID Numbers: EFC14828
2017-002954-35 ( EudraCT Number )
U1111-1186-2533 ( Other Identifier: UTN )
First Posted: April 12, 2018    Key Record Dates
Results First Posted: October 15, 2021
Last Update Posted: October 15, 2021
Last Verified: August 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: No plan to share individual participant data (IPD) by Sanofi: product rights transferred to Hanmi pharmaceutical.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Diabetes Mellitus, Type 2
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
 Endocrine System Diseases
Efpeglenatide
Hypoglycemic Agents
Physiological Effects of Drugs