Once-weekly Petrelintide Versus Placebo for Obesity or Overweight With Co-morbidities (ZUPREME)

A Randomized, Double-blind, Phase 2, Dose-finding Trial of Once Weekly Petrelintide Compared With Placebo in Participants With Obesity or Overweight With Weight Related Comorbidities

The main purpose of this study is to compare dose levels of petrelintide versus placebo with regards to effect on body weight, safety, and tolerability.

Study Overview

• Status: Completed
• Conditions: Obesity
• Intervention / Treatment: Drug: Petrelintide; Drug: Placebo

Detailed Description

Obesity is a chronic disease with a rapidly increasing prevalence associated with significant comorbidities. Petrelintide is a long-acting amylin analog in development for weight management.

This is a randomized, double-blind, placebo-controlled, parallel-group, multinational, multicenter, dose-finding, Phase 2 clinical trial. The trial will compare 5 doses of once-weekly (OW) subcutaneously administered petrelintide with placebo.

This study consists of 3 periods:

1. A screening period of 2-3 weeks
2. A treatment period of 42 weeks
3. A safety follow-up period of 9 weeks.

• Study Type: Interventional
• Enrollment (Actual): 493
• Phase: Phase 2

Contacts and Locations

Study Locations

• Poland
  • Lesser Poland Voivodeship
    • Krakow, Lesser Poland Voivodeship, Poland, 31-501
      • Krakowskie Centrum MedyczneSp.z o.o
  • Masovian Voivodeship
    • Siedlce, Masovian Voivodeship, Poland, 08-110
      • ETG Siedlce
    • Warsaw, Masovian Voivodeship, Poland, 00-215
      • FutureMeds Warszawa Centrum
    • Warsaw, Masovian Voivodeship, Poland, 02-507
      • Panstwowy Instytut Medyczny Ministerstwa Spraw Wewnetrznych i Administracji
    • Warsaw, Masovian Voivodeship, Poland, 02-677
      • ETG Warszawa
    • Warsaw, Masovian Voivodeship, Poland, 03-291
      • FutureMeds Targowek
  • Warmian-Masurian Voivodeship
    • Olsztyn, Warmian-Masurian Voivodeship, Poland, 10-165
      • FutureMeds Olsztyn
• Romania
  • Bucharest, Romania, 022328
    • Institutul Clinic Fundeni
  • Bucharest, Romania, 011863
    • Institutul National de Endocrinologie C I Parhon
  • Bucharest, Romania, 030303
    • Fundatia Dr Victor Babes
  • Bucharest, Romania, 050159
    • Institutul de Pneumoftiziologie Marius Nasta
  • Constanța, Romania, 900591
    • Spitalul Clinic Judetean de Urgenta Sf Apostol Andrei Constanta
  • Dolj
    • Craiova, Dolj, Romania, 200515
      • Top Diabet
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • Florida
    • Boca Raton, Florida, United States, 33434
      • Excel Medical Clinical Trials, LLC
    • Clearwater, Florida, United States, 33756
      • Innovative Research of West Florida, Inc.
    • Miami, Florida, United States, 33155
      • Century Research LLC
    • Pompano Beach, Florida, United States, 33060-6977
      • Clinical Research Center Of Florida
    • West Palm Beach, Florida, United States, 33409
      • Palm Beach Research Center
  • Illinois
    • Chicago, Illinois, United States, 60640
      • Great Lakes Clinical Trials LLC dba Flourish Research
  • Kansas
    • Wichita, Kansas, United States, 67226
      • AMR Wichita East
  • Kentucky
    • Lexington, Kentucky, United States, 40509
      • Alliance for Multispecialty Research, LLC
  • Montana
    • Butte, Montana, United States, 59701
      • Mercury Street Medical Group, PLLC
  • New York
    • The Bronx, New York, United States, 10455
      • CHEAR Center LLC
  • North Carolina
    • Charlotte, North Carolina, United States, 28210
      • Javara Inc
    • Greensboro, North Carolina, United States, 27408
      • PharmQuest Life Sciences, LLC
    • New Bern, North Carolina, United States, 28562
      • Lucas Research, Inc.
  • Oklahoma
    • Norman, Oklahoma, United States, 73069
      • AMR Norman
  • Pennsylvania
    • Duncansville, Pennsylvania, United States, 16635
      • Altoona Center for Clinical Research - Research
  • Tennessee
    • Knoxville, Tennessee, United States, 37909
      • Alliance for Multispecialty Research
  • Texas
    • San Antonio, Texas, United States, 78229
      • Clinical Trials of Texas, LLC., dba Flourish Research
  • Virginia
    • Manassas, Virginia, United States, 20110
      • Manaasas Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female participants having body mass index (BMI) ≥30.0 kg/m2 or BMI ≥27.0 kg/m2 with the presence of at least one of the following comorbidities: hypertension or dyslipidemia (treated or untreated).

• A female participant is eligible to participate if she is:

  • A woman of nonchildbearing potential. OR
  • A woman of childbearing potential (WOCBP) who is not pregnant, does not intend to be pregnant, not lactating and is willing to use highly effective contraceptive methods (as required by local regulation or practice) throughout the trial and for 10 weeks after the last injection of the investigational medicinal product (IMP).
• Ability to comply with the protocol requirements including self-administration of IMP with vial and syringe.

Exclusion Criteria:

• Glycated hemoglobin (HbA1c) ≥48 mmol/mol (6.5%), as measured at screening.
• History of type 1 or type 2 diabetes mellitus.
• Treatment with glucose lowering agent(s) within 90 days prior to screening.
• A self-reported change in body weight >5% within 90 days prior to screening.
• Treatment with any medication (prescribed or over-the-counter) or alternative remedies (herbal or nutritional supplements) intended to promote weight loss within 6 months prior to screening.
• Previous or planned (during the trial period) obesity treatment with surgery or a body weight loss device. However, liposuction or surgical removal of fat depots more than 1 year prior to screening or device-based interventions (e.g. sleeve, banding or similar) that have been removed more than 6 months prior to screening, are allowed.
• Uncontrolled thyroid disease defined as thyroid stimulating hormone >4.20 mIU/L or <0.27 mIU/L as measured by the central laboratory at screening.
• Lifetime history of a suicidal attempt.
• History of major depressive disorder or other severe psychiatric disorders (e.g. schizophrenia or bipolar disorder).
• Estimated glomerular filtration rate value <60.0 mL/min/1.73m2, calculated by the Chronic Kidney Disease-Epidemiology (CKD-EPI) Creatinine Equation17, measured at screening.
• Impaired liver function, defined as alanine aminotransferase and/or aspartate aminotransferase ≥2.0 times or bilirubin >1.5 times upper normal limit, measured at screening.
• Presence or history of acute or chronic pancreatitis.
• Known clinically significant gastric emptying abnormality (for example, severe gastroparesis or gastric outlet obstruction) or chronic treatment that affects gastrointestinal (GI) motility.
• Presence or history of cardiovascular disease including stable and unstable angina pectoris, myocardial infarction, transient ischemic attack, stroke, cardiac decompensation.
• Presence or history of clinically significant arrhythmias or clinically significant conduction disorders.
• Known or suspected hypersensitivity to amylin analogs or related products.
• History of malignant neoplasms (except for basal or squamous cell skin cancer) within 5 years prior to screening.
• Known or suspected abuse of alcohol or recreational drugs.
• Participant previously treated with petrelintide or any other amylin analog.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Petrelintide Dose 1; Participants will self-inject petrelintide dose 1 subcutaneously once a week.	Drug: Petrelintide; Petrelintide will be taken by participants once weekly as a self-administered subcutaneous injection.; Other Names: ZP8396
Experimental: Petrelintide Dose 2; Participants will self-inject petrelintide dose 2 subcutaneously once a week.	Drug: Petrelintide; Petrelintide will be taken by participants once weekly as a self-administered subcutaneous injection.; Other Names: ZP8396
Experimental: Petrelintide Dose 3; Participants will self-inject petrelintide dose 3 subcutaneously once a week.	Drug: Petrelintide; Petrelintide will be taken by participants once weekly as a self-administered subcutaneous injection.; Other Names: ZP8396
Experimental: Petrelintide Dose 4; Participants will self-inject petrelintide dose 4 subcutaneously once a week.	Drug: Petrelintide; Petrelintide will be taken by participants once weekly as a self-administered subcutaneous injection.; Other Names: ZP8396
Experimental: Petrelintide Dose 5; Participants will self-inject petrelintide dose 5 subcutaneously once a week.	Drug: Petrelintide; Petrelintide will be taken by participants once weekly as a self-administered subcutaneous injection.; Other Names: ZP8396
Placebo Comparator: Placebo; Participants will self-inject matching placebo to petrelintide subcutaneously once a week.	Drug: Placebo; Matching placebo to petrelintide will be taken by participants once weekly as a self-administered subcutaneous injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent change from baseline in body weight to Week 28	To compare the dose-response of increasing doses of petrelintide versus placebo on body weight, when added as an adjunct to a reduced-calorie diet and increased physical activity after 28 weeks of exposure.	From Baseline (Day 1) to Week 28

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants achieving ≥5% Body Weight Loss at Weeks 28 and 42	To compare the efficacy of petrelintide versus placebo on body weight, when added as an adjunct to a reduced-calorie diet and increased physical activity.	From Baseline (Day 1) to Weeks 28 and 42
Percentage of Participants achieving ≥10% Body Weight Loss at Weeks 28 and 42	To compare the efficacy of petrelintide versus placebo on body weight, when added as an adjunct to a reduced-calorie diet and increased physical activity.	From Baseline (Day 1) to Weeks 28 and 42
Change from baseline in body weight to Weeks 28 and 42	To compare the efficacy of petrelintide versus placebo on body weight, when added as an adjunct to a reduced-calorie diet and increased physical activity.	From Baseline (Day 1) to Weeks 28 and 42
Change from baseline in waist circumference to Weeks 28 and 42	To compare the efficacy of petrelintide versus placebo on waist circumference, when added as an adjunct to a reduced-calorie diet and increased physical activity.	From Baseline (Day 1) to Weeks 28 and 42
Percent change from baseline in body weight to Week 42	To compare the efficacy of petrelintide versus placebo on body weight, when added as an adjunct to a reduced-calorie diet and increased physical activity.	From Baseline (Day 1) to Week 42
Change from baseline in hemoglobin A1c (HbA1c) to Week 42	To compare the efficacy of petrelintide versus placebo on HbA1c, when added as an adjunct to a reduced-calorie diet and increased physical activity.	From Baseline (Day 1) to Week 42
Change from baseline in fasting glucose to Week 42	To compare the efficacy of petrelintide versus placebo on fasting glucose, when added as an adjunct to a reduced-calorie diet and increased physical activity.	From Baseline (Day 1) to Week 42
Change from baseline in high-sensitivity C-reactive protein (hsCRP) to Week 42	To compare the efficacy of petrelintide versus placebo on hsCRP, when added as an adjunct to a reduced-calorie diet and increased physical activity.	From Baseline (Day 1) to Week 42
Change from baseline in fasting lipids to Week 42	To compare the efficacy of petrelintide versus placebo on fasting lipids, when added as an adjunct to a reduced-calorie diet and increased physical activity.	From Baseline (Day 1) to Week 42
Number of treatment emergent adverse events (TEAEs)	To compare the safety and tolerability of petrelintide versus placebo when added as an adjunct to a reduced-calorie diet and increased physical activity.	From Baseline (Day 1) to Week 51
Occurrences of anti-drug antibodies (ADAs) to petrelintide	To compare the safety and tolerability of petrelintide versus placebo when added as an adjunct to a reduced-calorie diet and increased physical activity.	From Baseline (Day 1) to Week 51

Collaborators and Investigators

• Sponsor: Zealand Pharma
• Collaborators: Parexel

Study record dates

Study Major Dates

• Study Start (Actual): December 9, 2024
• Primary Completion (Actual): September 30, 2025
• Study Completion (Actual): March 7, 2026

Study Registration Dates

• First Submitted: October 25, 2024
• First Submitted That Met QC Criteria: October 25, 2024
• First Posted (Actual): October 29, 2024

Study Record Updates

• Last Update Posted (Actual): March 23, 2026
• Last Update Submitted That Met QC Criteria: March 18, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Weight management; Amylin analog
• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Overweight; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Obesity
• Other Study ID Numbers: ZP8396-23094; 2024-512549-18 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No