Phase 3 Study of KAI-9531 in Adults With Obesity or Overweight With Weight-Related Comorbidities Without Diabetes

The primary objective of this study is to determine the effects of weekly subcutaneous administration of KAI-9531 compared to placebo on the percent change in body weight in participants with obesity or overweight with weight-related comorbidities, excluding those with diabetes. This evaluation is clinically significant for assessing the efficacy of the investigational product in weight management.

Secondary objectives include:

• Evaluation of the effects of maintenance doses of KAI-9531 on body weight, waist circumference, systolic blood pressure, lipid parameters, and patient reported outcomes.
• Assessment of body weight changes in a subgroup of participants with a body mass index (BMI) ≥35 kg/m2.
• Evaluation of maintenance doses on diastolic blood pressure, additional lipid and glycemic parameters, and BMI.
• Assessment of the safety and tolerability of maintenance doses.
• Evaluation of the immunogenicity of KAI-9531.
• Characterization of the population pharmacokinetics and exploration of the relationships between drug concentration and measures of efficacy, safety, and tolerability.

This clinical trial involves a total of 1,188 participants diagnosed with obesity. The study population includes both male and female individuals, including vulnerable populations, within the age ranges specified by codes 3 and 4. Selection is based on a body mass index (BMI) of ≥30 kg/m², or a BMI of ≥27 kg/m² accompanied by a comorbid condition such as hypertension, dyslipidemia, obstructive sleep apnea, or cardiovascular disease. Eligible subjects must have a history of at least one self-reported unsuccessful attempt at weight reduction through diet and exercise within the previous six months. The primary objective is to evaluate the effects of KAI-9531 SC QW compared to a placebo on the percent change in body weight.

This Phase 3, randomized, double-blind, placebo-controlled study is designed to evaluate the efficacy and safety of KAI-9531 in participants living with obesity or overweight with weight-related comorbidities, excluding those with diabetes. The investigational product is administered via subcutaneous injection once weekly. The primary endpoint is the percent change in body weight from baseline at Week 76. Secondary endpoints include changes in waist circumference, absolute body weight, systolic and diastolic blood pressure, fasting lipid profiles, fasting insulin, fasting blood glucose, and various quality of life and physical function scores. Safety assessments involve monitoring treatment-emergent adverse events, clinical laboratory parameters, electrocardiograms, and vital signs. The study protocol includes a screening visit to assess eligibility based on body mass index and medical history, followed by treatment and follow-up assessments through the end-of-study period. The overall duration of participant involvement is expected to extend through Week 76. Early termination of study participation may occur based on clinical criteria or protocol requirements.

The experimental medication is KAI-9531, which consists of the active substance TYROSYL-2-AMINOISOBUTYRYL-GLUTAMYL-GLYCYL-THREONYL-PHENYLALANYLTHREONYL-SERYL-ASPARTATE-TYROSYL-SERYL-ISOLEUCYL-TYROSYL-LYSYL([2-[2- AMINOETHOXY]ETHOXY]ACETYL-[2-[2-AMINOETHOXY]ETHOXY]ACETYL-GAMMA-GLUTAMYL-EICOSANOYL)-GLUTAMYL-LYSYL-ISOLEUCYL-ALANYL-ALANYL-GLUTAMINE-GLUTAMYL-PHENYLALANYL-VALYL-ASPARAGINE-CHROMYL-LEUCYL-LEUCYL-ALANYL-GLYCYL-GLYCYL-PROLYL-SERYL-SERYL-GLYCYL-ALANYL-PROLYL-PROLYL-PROLYL-SERYL AMIDE. It is provided as a solution for injection intended for subcutaneous injection. The dosage is 00 mg administered once weekly.

The placebo is a formulation identical to the KAI-9531 solution for injection but without the active drug.

The primary efficacy endpoint is the percent change in body weight (kg) from baseline measured at Week 76. Secondary efficacy assessments include the following:

• Percent change in body weight (kg) from baseline at Week 76, specifically evaluated in the subgroup of participants with a body mass index (BMI) ≥35 kg/m2.
• The percentage of participants achieving a weight reduction of ≥5%, ≥10%, ≥15%, ≥20%, ≥25%, and ≥30% from baseline at Week 76.
• Changes in waist circumference (cm), absolute body weight (kg), BMI (kg/m2), systolic blood pressure (SBP) (mm Hg), and diastolic blood pressure (DBP) (mm Hg).
• Percent changes from baseline at Week 76 in fasting laboratory parameters, including triglycerides, HDL-cholesterol, non-HDL-cholesterol, total cholesterol, LDL-cholesterol, VLDL-cholesterol, fasting insulin (mIU/L), and fasting blood glucose (mg/dL).
• Changes in the IWQOL-Lite-CT physical function composite score and cardiovascular outcomes (COEQ).