Efficacy and Safety of Efpeglenatide Versus Placebo in Patients With Type 2 Diabetes Mellitus Inadequately Controlled With Diet and Exercise

Study Overview
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Brief Summary
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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

Detailed Description
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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.

Official Title
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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

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: efpeglenatide (SAR439977)
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 |