Efficacy and Safety of Maridebart Cafraglutide in Adults with Moderate to Severe Obstructive Sleep Apnea and Overweight or Obesity Receiving Positive Airway Pressure Therapy

The primary objective of this study is to evaluate the efficacy of maridebart cafraglutide in improving the Apnea-Hypopnea Index (AHI) in adults with obstructive sleep apnea. The secondary objectives include:

• Assessment of AHI through percent change, clinically meaningful reduction, and rates of remission or mild asymptomatic disease.
• Evaluation of body weight reduction, central adiposity, and neck circumference.
• Measurement of hypoxic burden and levels of inflammation.
• Monitoring of systolic blood pressure and diastolic blood pressure.
• Analysis of lipid parameters and metabolic parameters.
• Evaluation of patient-reported sleep-related impairment.
• Characterization of safety, tolerability, and pharmacokinetics.

The study involves 135 participants diagnosed with obstructive sleep apnea. The population consists of adults, including both males and females, with a history of overweight or obesity. Eligible individuals must have a body mass index of at least 27 kg/m2 and a documented apnea-hypopnea index of 15 or greater. Participants are required to have a history of at least one unsuccessful attempt at weight loss through diet and exercise. Additionally, subjects must have been using positive airway pressure therapy for a minimum of three consecutive months prior to screening and intend to maintain this treatment throughout the trial.

This Phase 3, randomized, double-blind, placebo-controlled study is designed to evaluate the efficacy, safety, and tolerability of maridebart cafraglutide in adults with obstructive sleep apnea and overweight or obesity who are utilizing positive airway pressure therapy. The primary objective is to demonstrate superiority over placebo regarding the change in the apnea-hypopnea index from baseline at week 52. The study includes a screening visit to confirm eligibility based on criteria such as a body mass index of at least 27 kg/m2 and a documented history of moderate-to-severe sleep apnea. Following randomization, participants will receive either the investigational product or a placebo via subcutaneous injection. The clinical assessment continues through follow-up visits to monitor secondary endpoints, including changes in hypoxic burden, body weight, and high sensitivity C-reactive protein levels. The expected duration of participant involvement is 52 weeks. Early termination of study participation may occur according to protocol-defined conditions.

Maridebart cafraglutide (AMG 133) is an experimental solution for injection. The administration is via subcutaneous use. The dosage is 00 mg.

The placebo for AMG 133 is utilized as a comparator in this study.

The primary efficacy endpoint is the change in the Apnea-Hypopnea Index (AHI) from baseline at week 52. Secondary efficacy parameters evaluated at week 52 include the percent change in AHI from baseline and the achievement of a reduction in AHI of at least 50% from baseline. Additional secondary assessments include achieving an AHI of less than 5, or an AHI between 5 and 14 combined with an Epworth Sleepiness Scale (ESS) score of 10 or less. The change in sleep apnea-specific hypoxic burden from baseline is also measured at week 52.

Further secondary endpoints assessed at week 52 involve the percent change in body weight from baseline, the change in high sensitivity C-reactive protein (hs-CRP), and the change in systolic blood pressure (SBP). Efficacy is also evaluated through changes in the Patient-Reported Outcomes Measurement Information System (PROMIS) Short Form v1.0 Sleep-Related Impairment 8a score from baseline.