ZUPREME-5

RecruitingPhase 3

A Phase III Study to Evaluate the Efficacy and Safety of Petrelintide in Participants With Overweight or Obesity and Established Cardiovascular Disease

A Phase III, Randomized, Double-Blind, Placebo Controlled, Parallel Group Study to Evaluate the Efficacy and Safety of Once Weekly Petrelintide Vs. Placebo in Participants With Overweight Or Obesity And Established Cardiovascular Disease

Lead sponsor

Hoffmann-La Roche

Asset

Petrelintide

Subcutaneous · Amylin analog

Listed sites

Recruiting sites

Estimated enrollment

2,500

Study population

Cardiovascular disease, Obesity / overweight

Eligibility highlights

•BMI ≥27

Primary endpoint

•Body Weight

Registered trial locations

Locations reported to ClinicalTrials.gov for this trial snapshot. Site count is not enrollment count; per-site enrollment is not available from source.

Identifiers

Registered as

NCT IDNCT07843472

Org study IDCC46446

Secondary ID2026-526190-41-00

Timeline

Milestones

Study first posted2026-09-28actual

Study start2026-09-30actual

Last update posted2026-10-07actual

Primary completion2030-07-28estimated

Study completion2030-10-06estimated

Assets

Investigational agents

Petrelintide

Who this study enrolls

Cardiovascular diseaseObesity / overweight

Who can enroll

Minimum age40 Years

SexAll

Healthy volunteersNot accepted

Inclusion criteria

•Participants with BMI ≥ 27 kg/m² and established CVD

•History of at least one self-reported unsuccessful dietary effort to lose body weight

Exclusion criteria

•Known history of Type 1 diabetes mellitus

•Current or previous treatment with petrelintide or any other amylin analog

Endpoints (43)

What's being measured

Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.

Coverage by outcome category

Weight & body composition

Cardiometabolic biomarkers

Other (unclassified)

Glycemic / diabetes

Patient-reported / QoL

Safety / tolerability / PK

Weight & body composition

10 endpoints

Primary/protocol endpoint

Percentage Change in Body Weight from Baseline

Time frame:From Baseline to Week 64

percent change from baseline, improvement

Secondary/protocol endpoint

Proportion of Participants Achieving ≥ 5% Body Weight Loss from Baseline

Time frame:From Baseline to Week 64

threshold achievement, improvement

Secondary/protocol endpoint

Proportion of Participants Achieving ≥ 10% Body Weight Loss from Baseline

Time frame:From Baseline to Week 64

threshold achievement, improvement

Secondary/protocol endpoint

Proportion of Participants Achieving ≥ 15% Body Weight Loss from Baseline

Time frame:From Baseline to Week 64

threshold achievement, improvement

Secondary/protocol endpoint

Change from Baseline in Waist Circumference (cm)

Time frame:From Baseline to Week 64

change from baseline, improvement

Secondary/protocol endpoint

Change from Baseline in Impact of Weight on Quality of Life-Lite Clinical Trials (IWQoL-Lite-CT) Physical Functioning Composite Score

Time frame:From Baseline to Week 64

change from baseline, improvement

Secondary/protocol endpoint

Change from Baseline in Body Mass Index (BMI) (kg/m²)

Time frame:From Baseline to Week 64

change from baseline, improvement

Secondary/protocol endpoint

Change from Baseline in Body Weight (kg)

Time frame:From Baseline to Week 64

change from baseline, improvement

Secondary/protocol endpoint

Change from Baseline in Waist-to-Hip Ratio

Time frame:From Baseline to Week 64

change from baseline, improvement

Secondary/protocol endpoint

Change from Baseline in Waist-to-Height Ratio

Time frame:From Baseline to Week 64

change from baseline, improvement

Glycemic / diabetes

7 endpoints

Secondary/protocol endpoint

Change from Baseline in Fasting Insulin

Time frame:From Baseline to Week 64

change from baseline, improvement

Secondary/protocol endpoint

Change from Baseline in Fasting Glucose

Time frame:From Baseline to Week 64

change from baseline, improvement

Secondary/protocol endpoint

Change from Baseline in Hemoglobin A1c (HbA1c)

Time frame:From Baseline to Week 64

change from baseline, improvement

Secondary/protocol endpoint

Percentage of Participants with Type 2 Diabetes at Screening Achieving HbA1c of < 5.7%

Time frame:At Week 64

threshold achievement, improvement

Secondary/protocol endpoint

Percentage of Participants with Type 2 Diabetes at Screening Achieving HbA1c of < 6.5%

Time frame:At Week 64

threshold achievement, improvement

Secondary/protocol endpoint

Percentage of Participants with Type 2 Diabetes at Screening Achieving HbA1c of < 7%

Time frame:At Week 64

threshold achievement, improvement

Secondary/protocol endpoint

Percentage of Participants With Baseline Prediabetes Achieving HbA1c of < 5.7%

Time frame:At Week 64

threshold achievement, improvement

Cardiometabolic biomarkers

10 endpoints

Secondary/protocol endpoint

Change from Baseline in High-Sensitivity C-Reactive Protein (hsCRP)

Time frame:From Baseline to Week 64

change from baseline, improvement

Secondary/protocol endpoint

Change from Baseline in Triglycerides

Time frame:From Baseline to Week 64

change from baseline, improvement

Secondary/protocol endpoint

Change from Baseline in High-Density Lipoprotein (HDL) Cholesterol

Time frame:From Baseline to Week 64

change from baseline, improvement

Secondary/protocol endpoint

Change from Baseline in Very-Low-Density Lipoprotein (VLDL) Cholesterol

Time frame:From Baseline to Week 64

change from baseline, improvement

Secondary/protocol endpoint

Change from Baseline in Non-HDL Cholesterol

Time frame:From Baseline to Week 64

change from baseline, improvement

Secondary/protocol endpoint

Change from Baseline in Total Cholesterol

Time frame:From Baseline to Week 64

change from baseline, improvement

Secondary/protocol endpoint

Change from Baseline in Low-Density Lipoprotein (LDL) Cholesterol

Time frame:From Baseline to Week 64

change from baseline, improvement

Secondary/protocol endpoint

Change from Baseline in Free Fatty Acids

Time frame:From Baseline to Week 64

change from baseline, improvement

Secondary/protocol endpoint

Change from Baseline in Systolic Blood Pressure

Time frame:From Baseline to Week 64

change from baseline, improvement

Secondary/protocol endpoint

Change from Baseline in Diastolic Blood Pressure

Time frame:From Baseline to Week 64

change from baseline, improvement

Patient-reported / QoL

6 endpoints

Secondary/protocol endpoint

Change from Baseline in IWQoL-Lite-CT Physical Functioning Composite Score in Participants with Poor Physical Functioning at Baseline (as defined by Patient Global Impression of Severity/Status [PGI-S])

Time frame:From Baseline to Week 64

change from baseline, improvement

Secondary/protocol endpoint

Change from Baseline in Short Form (36) Health Survey Version 2 (SF-36v2) Acute Form Physical Functioning Domain Score

Time frame:From Baseline to Week 64

change from baseline, improvement

Secondary/protocol endpoint

Change from Baseline in SF-36v2 Acute Form Physical Functioning Domain Score in Participants with Poor Physical Functioning at Baseline (as defined by PGI-S)

Time frame:From Baseline to Week 64

change from baseline, improvement

Secondary/protocol endpoint

Change from Baseline in Health-Related Quality of Life (HRQoL) as assessed by SF-36v2 Acute Form Domain Scores and Component Summary Scores

Time frame:From Baseline to Week 64

change from baseline, improvement

Secondary/protocol endpoint

Proportion of Participants with ≥ 3.7-Point Increase from Baseline in SF36v2 Physical Functioning Score

Time frame:From Baseline to Week 64

threshold achievement, improvement

Secondary/protocol endpoint

Proportion of Participants with Baseline Poor Physical Functioning Achieving a ≥ 3.7-Point Increase in SF36v2 Physical Functioning Score

Time frame:From Baseline to Week 64

threshold achievement, improvement

Safety / tolerability / PK

2 endpoints

Secondary/protocol endpoint

Incidence and Severity of Adverse Events, with Severity Determined According to Mild/Moderate/Severe Criteria

Time frame:From Baseline to Week 64

descriptive

Secondary/protocol endpoint

Percentage of Participants with Baseline Anti-Drug Antibodies (ADAs) and Treatment-Emergent ADAs Against Petrelintide

Time frame:From Baseline to Week 64

threshold achievement, event

Other (unclassified)

8 endpoints

Secondary/protocol endpoint/low confidence

Change from Baseline in Mean Daily Food Craving Score

Time frame:From Baseline to Week 64

change from baseline, improvement

Secondary/protocol endpoint/low confidence

Change from Baseline in Mean Daily Peak Hunger Score

Time frame:From Baseline to Week 64

change from baseline, improvement

Secondary/protocol endpoint/low confidence

Change from Baseline in HRQoL as assessed by IWQoL-Lite-CT Domain Scores and Total Score

Time frame:From Baseline to Week 64

change from baseline, improvement

Secondary/protocol endpoint/low confidence

Proportion of Participants with ≥ 14.6-Point Increase from Baseline in IWQoL-Lite-CT Physical Function Score

Time frame:From Baseline to Week 64

threshold achievement, improvement

Secondary/protocol endpoint/low confidence

Proportion of Participants with Baseline Poor Physical Functioning Achieving ≥ 14.6-Point Increase in IWQoL-Lite-CT Physical Functioning Score

Time frame:From Baseline to Week 64

threshold achievement, improvement

Secondary/protocol endpoint/low confidence

Change from Baseline in Mean Daily Average Hunger Score

Time frame:From Baseline to Week 64

change from baseline, improvement

Secondary/protocol endpoint/low confidence

Change from Baseline in Mean Daily Average Satiety Score

Time frame:From Baseline to Week 64

change from baseline, improvement

Secondary/protocol endpoint/low confidence

Change from Baseline in Mean Daily Average Appetite Score

Time frame:From Baseline to Week 64

change from baseline, improvement

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2

Snapshot dateNovember 5, 2026

Endpoint classificationDelfa endpoint taxonomy v2 (May 13, 2026)

Results tableno registry results posted yet

Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the November 5, 2026 snapshot.