A Phase 3 Study to Compare the Efficacy and Safety of KAI-9531 Versus Semaglutide in Participants Living with Obesity Without Diabetes

The primary objective is to demonstrate the superiority of KAI-9531 administered once weekly via subcutaneous injection compared to semaglutide and placebo in terms of the percent change in body weight in participants with obesity. Secondary objectives include evaluating the effects of the investigational product on waist circumference, body mass index (BMI), systolic blood pressure (SBP), and lipid parameters. The study further assesses patient-reported outcomes using the Impact of Weight on Quality of Life-Lite Clinical Trial (IWQOL-Lite-CT), the Eating Control Questionnaire (CoEQ), and the Food Nesting Questionnaire (FNQ). Additionally, the trial evaluates safety, tolerability, and immunogenicity, while characterizing the population pharmacokinetics and investigating the relationship between drug concentration and clinical outcomes.

The study involves a total of 932 patients consisting of both male and female participants. The population is comprised of individuals diagnosed with obesity within specific age ranges. Selection is based on a body mass index of 35 kg/m² or greater and a documented history of unsuccessful weight loss attempts through diet and exercise within the previous six months.

This Phase 3, randomized, active-controlled, placebo-controlled, and partially-blinded study is designed to evaluate the efficacy and safety of KAI-9531 compared to semaglutide and placebo in individuals living with obesity who do not have diabetes. The primary objective is to demonstrate the superiority of weekly subcutaneous injection of KAI-9531 over both semaglutide and placebo regarding the percent change in body weight from baseline at Week 76. The study methodology involves a sequence of visits beginning with a screening period to assess eligibility based on body mass index and weight loss history. Participants will undergo regular monitoring throughout the 76-week treatment period to evaluate secondary endpoints, including changes in waist circumference, triglycerides, and various metabolic and appetite-related scores. The trial is expected to conclude following the end-of-study visit after the final assessment period. Early termination from the study may occur based on predefined clinical conditions or safety protocols.

KAI-9531 is an experimental solution for injection. The administration route is subcutaneous injection on a once weekly schedule.

Semaglutide is used as a comparator treatment. It is administered as a solution for injection via subcutaneous injection. The available pharmaceutical forms include Wegovy FlexTouch pre-filled pens in doses of 0.25 mg, 0.5 mg, 1 mg, 1.7 mg, and 2.4 mg.

The primary efficacy endpoint is the percent change in body weight (kg) from baseline at Week 76. Secondary efficacy parameters, assessed at Week 76, include the percentage of participants achieving weight reductions of ≥5%, ≥10%, ≥15%, ≥20%, and ≥25% from baseline, as well as the change in absolute body weight (kg) and waist circumference (cm). Additional secondary measures include changes in systolic blood pressure (SBP), triglycerides (mg/dL), HDL-cholesterol (mg/dL), and non-HDL-cholesterol (mg/dL), alongside the WQOL-LiteCT Physical function composite score.

Further assessments at Week 76 involve the percentage of participants with a ≥30% reduction in body weight, changes in Body Mass Index (BMI) (kg/m2), and variations in several patient-reported metrics: CoEQ Craving Control score, Positive Mood score, Craving for Sweets score, Craving for Savory food score, Hunger score, Satiety score, Combined score, and the FNQ score. The evaluation also includes the number of treatment-emergent adverse events (TEAEs), anti-drug antibodies (ADA NAb), and concentrations of KAI-9531.