Efficacy and Safety of Efpeglenatide Versus Placebo in Patients With Type 2 Diabetes Mellitus Inadequately Controlled With Basal Insulin Alone or in Combination With Oral Antidiabetic Drug(s)

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 type 2 diabetes mellitus (T2DM) inadequately controlled with basal insulin alone or in combination with oral antidiabetic drugs (OADs). 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 was approximately 64 weeks including an up to 2-week Screening Period, a 30-week Core Treatment Period, a 26-week Safety Extension Period, and a 6-week safety Follow-up Period.

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 Basal Insulin Alone or in Combination With Oral Antidiabetic Drug(s)

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Efpeglenatide SAR439977
* Drug: Placebo
* Drug: Background therapy


Participation Criteria
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Eligibility Criteria
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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 basal insulin regimen alone or in combination with OADs for at least 6 months prior to screening. HbA1c between 7.0 percent (%) 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. 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 millimetres of mercury (mmHg) and/or diastolic blood pressure >100 mmHg at randomization. End-stage renal disease as defined by estimated glomerular filtration rate (by Modification of Diet in Renal Disease) of less than 15 mL/min/1.73 m^2. Laboratory findings at the screening Visit: Alanine aminotransferase or aspartate aminotransferase >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 [pg/mL]). 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 were 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.

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 |
| --- | --- |
| Placebo Comparator: Placebo<br>Participants received placebo (matched to efpeglenatide) subcutaneous (SC) injection once weekly up to Week 56 on top of basal insulin alone or in combination with oral antidiabetic drugs (OADs). | Drug: Placebo<br>* Pharmaceutical form: solution for injection Route of administration: subcutaneous<br>Drug: Background therapy<br>* Lantus (Insulin Glargine), SC, once daily; OADs, administered as per investigator prescription and in accordance with local labeling.<br>|
| Experimental: Efpeglenatide 2 mg<br>Participants received Efpeglenatide 2 milligrams (mg) SC injection once weekly up to Week 56 on top of basal insulin alone or in combination with OADs. | Drug: Efpeglenatide SAR439977<br>* Pharmaceutical form: solution for injection Route of administration: subcutaneous<br>Drug: Background therapy<br>* Lantus (Insulin Glargine), SC, once daily; OADs, administered as per investigator prescription and in accordance with local labeling.<br>|
| Experimental: Efpeglenatide 4 mg<br>Participants received Efpeglenatide 4 mg SC injection once weekly up to Week 56 on top of basal insulin alone or in combination with OADs. Participants initiated dosing at 2 mg once weekly up to Week 1; which was up titrated to 4 mg and maintained at the 4 mg dose through-out the treatment duration up to Week 56. | Drug: Efpeglenatide SAR439977<br>* Pharmaceutical form: solution for injection Route of administration: subcutaneous<br>Drug: Background therapy<br>* Lantus (Insulin Glargine), SC, once daily; OADs, administered as per investigator prescription and in accordance with local labeling.<br>|
| Experimental: Efpeglenatide 6 mg<br>Participants received Efpeglenatide 6 mg SC injection once weekly up to Week 56 on top of basal insulin alone or in combination with OADs. Participants initiated dosing at 2 mg once weekly up to Week 1; which was up titrated to 4 mg until Week 4 and later up-titrated to 6 mg and maintained at the 6 mg dose through-out the treatment duration up to Week 56. | Drug: Efpeglenatide SAR439977<br>* Pharmaceutical form: solution for injection Route of administration: subcutaneous<br>Drug: Background therapy<br>* Lantus (Insulin Glargine), SC, once daily; OADs, administered as per investigator prescription and in accordance with local labeling.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 30 in HbA1c |  | Baseline to Week 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With HbA1c <7.0% at Week 30 | Participants who had no available assessment for HbA1c at Week 30 were considered as non-responders. | Week 30 | 
| Change From Baseline to Week 56 in HbA1c | This analysis included Week 56 assessment performed per protocol as well as premature end of treatment/study visit recorded as Week 56 due to early termination. | Baseline to Week 56 | 
| Change From Baseline to Week 30 in Fasting Plasma Glucose (FPG) |  | Baseline to Week 30 | 
| Change From Baseline to Week 30 and Week 56 in Body Weight | This analysis included Week 56 assessment performed per protocol as well as premature end of treatment/study visit recorded as Week 56 due to early termination. | Baseline to Week 30 and Week 56 | 
| Number of Participants With At Least One Hypoglycemic Events (Documented Symptomatic Hypoglycemia <3.0 mmol/L [<54 mg/dL], and Severe Hypoglycemia) | 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 | 
| 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 |