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)

NCT03713684 | Terminated Phase 3 Results DMC FDA Drug

• 2 other identifiers: EFC14893U1111-1189-5009
• Study Type: interventional
• Target: 370
• Locations: 3 countries
• Sites: 47

Brief Summary

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.

Conditions

Type 2 Diabetes Mellitus

Outcome Measures

Primary Outcomes (1)

• Change From Baseline to Week 30 in HbA1c

  Baseline to Week 30

Secondary Outcomes (6)

• Number of Participants With HbA1c <7.0% at Week 30

  Week 30

• Change From Baseline to Week 56 in HbA1c

  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

  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)

  Baseline up to Week 56

Study Arms (4)

Placebo

PLACEBO COMPARATOR

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; Drug: Background therapy

Efpeglenatide 2 mg

EXPERIMENTAL

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; Drug: Background therapy

Efpeglenatide 4 mg

EXPERIMENTAL

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; Drug: Background therapy

Efpeglenatide 6 mg

EXPERIMENTAL

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; Drug: Background therapy

Interventions

Efpeglenatide SAR439977 DRUG

Pharmaceutical form: solution for injection Route of administration: subcutaneous

Efpeglenatide 2 mg; Efpeglenatide 4 mg; Efpeglenatide 6 mg

Placebo DRUG

Pharmaceutical form: solution for injection Route of administration: subcutaneous

Placebo

Background therapy DRUG

Lantus (Insulin Glargine), SC, once daily; OADs, administered as per investigator prescription and in accordance with local labeling.

Efpeglenatide 2 mg; Efpeglenatide 4 mg; Efpeglenatide 6 mg; Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead
• Hanmi Pharmaceutical Company Limited: collaborator

Study Sites (47)

Investigational Site Number 8400038

Birmingham, Alabama, 35211, United States

Location

Investigational Site Number 8400035

Chandler, Arizona, 85224, United States

Location

Investigational Site Number 8400005

Glendale, Arizona, 85306, United States

Location

Investigational Site Number 8400057

Huntington Park, California, 90255, United States

Location

Investigational Site Number 8400058

La Jolla, California, 92037, United States

Location

Investigational Site Number 8400009

Los Angeles, California, 90057, United States

Location

Investigational Site Number 8400045

Spring Valley, California, 91978, United States

Location

Investigational Site Number 8400040

Tustin, California, 92780, United States

Location

Investigational Site Number 8400026

Van Nuys, California, 91405, United States

Location

Investigational Site Number 8400055

Orlando, Florida, 32825, United States

Location

Investigational Site Number 8400041

Pembroke Pines, Florida, 33026, United States

Location

Investigational Site Number 8400025

Lawrenceville, Georgia, 30044, United States

Location

Investigational Site Number 8400052

West Des Moines, Iowa, 50265, United States

Location

Investigational Site Number 8400044

Lexington, Kentucky, 40503, United States

Location

Investigational Site Number 8400001

Bridgeton, New Jersey, 08302, United States

Location

Investigational Site Number 8400039

New Windsor, New York, 12553, United States

Location

Investigational Site Number 8400036

Morehead City, North Carolina, 28557, United States

Location

Investigational Site Number 8400013

Maumee, Ohio, 43537, United States

Location

Investigational Site Number 8400030

Dallas, Texas, 75230, United States

Location

Investigational Site Number 8400063

Dallas, Texas, 75390-9302, United States

Location

Investigational Site Number 8400043

San Antonio, Texas, 78229, United States

Location

Investigational Site Number 8400037

Layton, Utah, 84041, United States

Location

Investigational Site Number 1560005

Baotou, 014010, China

Location

Investigational Site Number 1560017

Beijing, 100730, China

Location

Investigational Site Number 1560006

Changsha, 410013, China

Location

Investigational Site Number 1560001

Chengdu, 610083, China

Location

Investigational Site Number 1560004

Shanghai, 014010, China

Location

Investigational Site Number 1560036

Shanghai, 200032, China

Location

Investigational Site Number 1560012

Shanghai, 200040, China

Location

Investigational Site Number 1560013

Shanghai, 200040, China

Location

Investigational Site Number 1560003

Zhengzhou, 450003, China

Location

Investigational Site Number 4100009

Busan, 49241, South Korea

Location

Investigational Site Number 4100001

Daejeon, 35233, South Korea

Location

Investigational Site Number 4100016

Gwangju, 501757, South Korea

Location

Investigational Site Number 4100010

Gwangju, 61453, South Korea

Location

Investigational Site Number 4100013

Gyeonggi-do, 11765, South Korea

Location

Investigational Site Number 4100015

Incheon, 21565, South Korea

Location

Investigational Site Number 4100014

Jeonju, 54907, South Korea

Location

Investigational Site Number 4100007

Seongnam-si, 13620, South Korea

Location

Investigational Site Number 4100008

Seoul, 02447, South Korea

Location

Investigational Site Number 4100002

Seoul, 03080, South Korea

Location

Investigational Site Number 4100005

Seoul, 03722, South Korea

Location

Investigational Site Number 4100004

Seoul, 05278, South Korea

Location

Investigational Site Number 4100003

Seoul, 06351, South Korea

Location

Investigational Site Number 4100011

Seoul, 07345, South Korea

Location

Investigational Site Number 4100006

Seoul, 14647, South Korea

Location

Investigational Site Number 4100012

Suwon, 16247, South Korea

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Limitations and Caveats

The study was terminated early by the Sponsor on 09 September 2020. Due to early termination of the study, few efficacy evaluations originally planned in the protocol were no longer considered to be relevant and were not performed. Primary, and secondary efficacy data were descriptively summarized and data were carefully considered given that the study was terminated early.

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi

Contact-US@sanofi.com

800-633-1610

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2018
• First Posted: October 22, 2018
• Study Start: November 9, 2018
• Primary Completion: November 20, 2020
• Study Completion: January 4, 2021
• Last Updated: December 2, 2021
• Results First Posted: December 2, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (22); CN (9); KR (16)