Clinical trial NCT07022977: A Study of MET233 in Individuals With Obesity or Overweight
Official title: A Randomized, Double-blind, Single and Multiple Ascending Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of MET233 in Otherwise Healthy Adult Participants With Obesity or Overweight
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Obesity and Overweight
Lead sponsor: Metsera
Sponsor class: INDUSTRY
First posted: 2025-06-15
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Part A (40 participants), Part B (40 participants), Part C (40 participants)
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to assess the safety, tolerability, pharmacokinetics, and pharmacodynamics of once-weekly subcutaneous injections of MET233 in otherwise healthy adults with overweight or obesity.

The trial will be conducted in three parts. Part A consists of single ascending dose (SAD) cohorts of MET233 or placebo. Part B consists of multiple ascending dose (MAD) cohorts, with participants treated with five once-weekly doses of MET233 or placebo. In Part C, participants will receive once-weekly doses of MET233 or placebo for 12 weeks, followed by a single higher, potential monthly dose.

Detailed description: This is a randomized, placebo-controlled, double-blind study designed to investigate the safety, tolerability, PK and pharmacodynamic (PD) of single and multiple ascending subcutaneous (SC) doses of MET233 in otherwise healthy adult participants with obesity or overweight (body mass index \[BMI\] 27.0 kg/m2 to 38.0 kg/m2, inclusive).

In Part A, approximately 40 participants will receive a single dose of MET233 at up to 5 dose levels. In Part B, approximately 40 participants will receive five weekly doses of MET233 at up to 4 dose levels. In Part C, up to 4 cohorts of 10 participants each will receive 12 weekly doses. These doses may include titration. For all cohorts in Part C, the 13th dose of MET233 administered on Day 85 may be a monthly-equivalent dose to allow evaluation of a potential to switch to a monthly dosing regimen.

Eligibility criteria: Inclusion Criteria:

* Adult (≥18 to ≤70 years) male and female participants with obesity or overweight (BMI 27.0 kg/m2 to 38.0 kg/m2, inclusive) but otherwise healthy.

Exclusion Criteria:

* Female who is lactating or who is pregnant according to the pregnancy test at the Screening visit or prior to the first study drug administration
* Seated blood pressure higher than 160/95 mmHg at the Screening visit
* Elevated resting pulse greater than 100 beats per minute at Screening visit
* Presence of clinically significant ECG abnormalities
* Diagnosis of diabetes (type 1 or type 2)
* Participation in a weight loss program with or without pharmacotherapy during the 3 months prior to study administration
* Obesity induced by endocrinologic disorders (e.g., Cushing's syndrome) or diagnosed monogenetic or syndromic forms of obesity (e.g., Melanocortin 4 Receptor deficiency or Prader-Willi Syndrome).

Primary outcomes:
measure: Occurrence of Treatment Emergent Adverse Events
timeFrame: Part A - Baseline (Day 0) to Day 89 Part B - Baseline (Day 0) to Day 113 Part C - Baseline (Day 0) to Day 162
Secondary outcomes:
measure: Area under the concentration versus time curve during the dosing interval (AUC(0-τ))
timeFrame: Part A: Baseline (Day 0) to Day 85 Part B: Baseline (Day 0) to Day 113 Part C: Baseline (Day 0) to Day 162
measure: Maximum observed concentration (Cmax)
timeFrame: Part A: Baseline (Day 0) to Day 85 Part B: Baseline (Day 0) to Day 113 Part C: Baseline (Day 0) to Day 162
measure: Time to maximum observed concentration (Tmax)
timeFrame: Part A: Baseline (Day 0) to Day 85 Part B: Baseline (Day 0) to Day 113 Part C: Baseline (Day 0) to Day 162
measure: Elimination half-life (t1/2)
timeFrame: Part A: Baseline (Day 0) to Day 85 Part B: Baseline (Day 0) to Day 113 Part C: Baseline (Day 0) to Day 162
measure: Percent change from baseline in body weight at the protocol-specified weekly post-baseline measurements
timeFrame: Part A: Baseline (Day 0) to Day 85 Part B: Baseline (Day 0) to Day 113 Part C: Baseline (Day 0) to Day 162
Other outcomes:
Locations:
city: Cypress
country: United States
facility: MET233 Research Site 001
state: California
Study officials:
References: