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

Zealand Pharma

Status and phase: Active, not recruiting; Phase 2

Conditions: Obesity

Treatments: Drug: Petrelintide; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT06662539

2024-512549-18 (EudraCT Number)

ZP8396-23094

Details and patient eligibility

About

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.

Full 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.

Enrollment: 494 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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494 participants in 6 patient groups, including a placebo group

Petrelintide Dose 1

Experimental group

Description:

Participants will self-inject petrelintide dose 1 subcutaneously once a week.

Treatment:

Drug: Petrelintide

Petrelintide Dose 2

Experimental group

Description:

Participants will self-inject petrelintide dose 2 subcutaneously once a week.

Treatment:

Drug: Petrelintide

Petrelintide Dose 3

Experimental group

Description:

Participants will self-inject petrelintide dose 3 subcutaneously once a week.

Treatment:

Drug: Petrelintide

Petrelintide Dose 4

Experimental group

Description:

Participants will self-inject petrelintide dose 4 subcutaneously once a week.

Treatment:

Drug: Petrelintide

Petrelintide Dose 5

Experimental group

Description:

Participants will self-inject petrelintide dose 5 subcutaneously once a week.

Treatment:

Drug: Petrelintide

Placebo

Placebo Comparator group

Description:

Participants will self-inject matching placebo to petrelintide subcutaneously once a week.

Treatment:

Drug: Placebo