A Clinical Study Testing Enicepatide in Participants Living With Overweight or Obesity and Cardiovascular Disease (Enith-MACE)

A Phase III, Randomized, Double-Blind, Placebo-controlled, Trial to Evaluate the Efficacy and Safety of Enicepatide in Participants With Overweight or Obesity and Cardiovascular Disease

The purpose of this study is to evaluate the efficacy and safety of enicepatide, a dual glucagon-like peptide-1 (GLP-1)/glucose-dependent insulinotropic polypeptide (GIP) receptor agonist (RA), as a therapy to reduce the risk of major adverse cardiovascular events (MACE) in adults living with overweight or obesity and established cardiovascular disease (CVD), with or without type 2 diabetes mellitus (T2DM).

Study Overview

• Status: Not yet recruiting
• Conditions: Obesity; Cardiovascular Disease; Overweight
• Intervention / Treatment: Combination product: Placebo; Combination product: Enicepatide

• Study Type: Interventional
• Enrollment (Estimated): 8200
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Fastest response: use the inquiry form https://www.gene.com/contact-us/submit-medical-inquiry
• Study Contact Backup: Name: Reference Study ID Number: WC46385 https://forpatients.roche.com/ No attachments to email below; Phone Number: 888-662-6728 (U.S. Only); Email: global-roche-genentech-trials@gene.com

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:

• Body Mass Index (BMI) ≥25.0 kilograms per meter square (kg/m2)
• Have established and stable cardiovascular disease (CVD)
• Participants should be treated with stable (per investigator judgment) background therapy for CVD, such as hyperlipidemia and T2DM (if relevant), as per local and international guidelines, excluding use of GLP-1 RA-based therapies
• For participants with T2DM: HbA1c ≤10% based on central laboratory assessment at Screening

Exclusion Criteria:

• History of type 1 diabetes mellitus, or any lifetime history of ketoacidosis or hyperosmolar state/coma within 12 months prior to Screening
• Any serious medical condition or abnormality in clinical laboratory tests that precludes an individual's safe participation in and completion of the study per investigator judgment
• Any preplanned major medical procedure or surgery at the time of Screening including planning to have a surgical, endoscopic, or device treatment for obesity
• Known clinically significant gastric emptying abnormality (e.g., severe gastroparesis or gastric outlet obstruction)
• Chronic dialysis (e.g., chronic hemodialysis, chronic peritoneal dialysis)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Arm 1: Placebo; Participants will receive volume-matched placebo.	Combination product: Placebo; Participants will receive volume-matched placebo as per the schedule described in the protocol.
Experimental: Arm 2: Enicepatide; Participants will receive enicepatide.	Combination product: Enicepatide; Participants will receive enicepatide as per the schedule described in the protocol.; Other Names: RO7795068; RG6640; CT-388

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to First Occurrence of Any Component of 5-point (5P) MACE	The components of this composite 5P MACE endpoint consist of cardiovascular (CV) death, non-fatal myocardial infarction (MI), non-fatal stroke, hospitalization for heart failure (HHF) or urgent heart failure (HF) visit, or urgent coronary revascularization.	From randomization up to 4.2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to First Occurrence of Any Component of 3-point (3P) MACE	The components of this composite 3P MACE endpoint consist of CV death, non-fatal MI or non-fatal stroke.	From randomization up to 4.2 years
Time to New-Onset T2DM		From randomization up to 4.2 years
Total Occurrence of All-Cause Hospitalization		From randomization up to 4.2 years
Time to Death From Any Cause		From randomization up to 4.2 years
Time to CV Death		From randomization up to 4.2 years
Incidence and Severity of Adverse Events		From baseline up to 4.2 years
Time to First Occurrence of Any Component of 4-point (4P) MACE	The components of this composite 4P MACE endpoint consist of CV death, non-fatal MI, non-fatal stroke, or HHF or urgent HF visit.	From randomization up to 4.2 years
Time to First Occurrence of HHF, Urgent HF Visit, or CV Death		From randomization up to 4.2 years
Time to First Occurrence of HHF, Urgent HF Visit, or All-Cause Mortality		From randomization up to 4.2 years
Change From Baseline in Health-Related Quality of Life (HRQoL) as Assessed by the Short Form 36 Health Survey Version 2.0 (SF-36 V2) Acute Form Physical Functioning Domain Score		From baseline through Week 48
Change From Baseline in HRQoL as Assessed by the SF-36 V2 Acute Form Role-Physical Domain Score		From baseline through Week 48
Change From Baseline in HRQoL as Assessed by the SF-36 V2 Acute Form Bodily Pain Domain Score		From baseline through Week 48
Change From Baseline in HRQoL as Assessed by the SF-36 V2 Acute Form General Health Domain Score		From baseline through Week 48
Change From Baseline in HRQoL as Assessed by the SF-36 V2 Acute Form Vitality Domain Score		From baseline through Week 48
Change From Baseline in HRQoL as Assessed by the SF-36 V2 Acute Form Social Functioning Domain Score		From baseline through Week 48
Change From Baseline in HRQoL as Assessed by the SF-36 V2 Acute Form Role-Emotional Domain Score		From baseline through Week 48
Change From Baseline in HRQoL as Assessed by the SF-36 V2 Acute Form Mental Health Domain Score		From baseline through Week 48
Change From Baseline in HRQoL as Assessed by the SF-36 V2 Acute Form Physical Component Summary Score		From baseline through Week 48
Change From Baseline in HRQoL as Assessed by the SF-36 V2 Acute Form Mental Component Summary Score		From baseline through Week 48
Change From Baseline in Health Status as Assessed by the EuroQol-5 Dimensions 5-Level (EQ-5D-5L) Score		From baseline through Week 48
Time To First Occurrence of Sustained ≥40% Estimated Glomerular Filtration Rate (eGFR) Decline From Baseline, End Stage Kidney Disease (ESKD), or Renal Death		From randomization up to 4.2 years
Change From Baseline in Body Weight		From baseline through the end of study (up to 4.2 years)
Change From Baseline in Waist Circumference		From baseline through the end of study (up to 4.2 years)
Change From Baseline in Waist-to-Height Ratio		From baseline through the end of study (up to 4.2 years)
Change From Baseline in Systolic Blood Pressure		From baseline through the end of study (up to 4.2 years)
Change From Baseline in Diastolic Blood Pressure		From baseline through the end of study (up to 4.2 years)
Change From Baseline in Heart Rate		From baseline through the end of study (up to 4.2 years)
Change From Baseline in Double Product	Double product is defined as heart rate multiplied by systolic blood pressure.	From baseline through the end of study (up to 4.2 years)
Change From Baseline in Pulse Pressure		From baseline through the end of study (up to 4.2 years)
Change From Baseline in Mean Arterial Pressure		From baseline through the end of study (up to 4.2 years)
Change From Baseline in Total Cholesterol		From baseline through the end of study (up to 4.2 years)
Change From Baseline in Non-High-Density Lipoprotein (HDL)		From baseline through the end of study (up to 4.2 years)
Change From Baseline in Low-Density Lipoprotein (LDL)		From baseline through the end of study (up to 4.2 years)
Change From Baseline in HDL		From baseline through the end of study (up to 4.2 years)
Change From Baseline in Triglycerides (TG)		From baseline through the end of study (up to 4.2 years)
Change From Baseline in Very-low-Density Lipoprotein (vLDL)		From baseline through the end of study (up to 4.2 years)
Change From Baseline in Hemoglobin A1c (HbA1c)		From baseline through the end of study (up to 4.2 years)
Change From Baseline in High-Sensitivity C-Reactive Protein (hs-CRP)		From baseline through the end of study (up to 4.2 years)
Change From Baseline in N-Terminal pro-B-Type Natriuretic Peptide (NT-proBNP)		From baseline through the end of study (up to 4.2 years)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Collaborators: Chugai Pharmaceutical
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Publications and helpful links

Helpful Links

• <p>Please use this form to submit your questions for a faster response: https://www.gene.com/contact-us/submit-medical-inquiry. Do not include or attach any medical records when emailing or completing the form. A nurse will respond within 24 business hours.</p>

Study record dates

Study Major Dates

• Study Start (Estimated): January 6, 2027
• Primary Completion (Estimated): March 20, 2031
• Study Completion (Estimated): April 17, 2031

Study Registration Dates

• First Submitted: November 2, 2026
• First Submitted That Met QC Criteria: November 2, 2026
• First Posted (Actual): November 5, 2026

Study Record Updates

• Last Update Posted (Actual): November 5, 2026
• Last Update Submitted That Met QC Criteria: November 2, 2026
• Last Verified: October 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Overweight; Obesity; Cardiovascular Diseases
• Other Study ID Numbers: WC46385; 2026-526958-14-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No