Safety and Efficacy Study of S-309309 in Obese Adults

Study Overview
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Brief Summary
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The primary objective of this study is to understand the efficacy of S-309309 on the body weight of obese adults.

Official Title
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A Phase 2, Multicenter, Randomized, Double-blind, Dose-ranging, Placebo-controlled Study to Assess the Safety and Efficacy of S-309309 in Obese Adults

Conditions
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Obesity

Intervention / Treatment
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* Drug: S-309309
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: BMI of ≥ 30 kg/m^2 (obese) with or without comorbidities. An online BMI calculator is available at Calculate Your BMI - Standard BMI Calculator (nih.gov) Stable body weight (defined as ≤ 5 kg of self-reported change) within 90 days prior to study start Lifetime history of at least 1 unsuccessful dietary effort to lose body weight Is a participant of non-childbearing potential (PONCBP) OR Is a participant of childbearing potential (POCBP) and using a contraceptive method that is highly effective as specified in the protocol. A POCBP must have a negative highly sensitive pregnancy test (urine or serum) before a first dose of study intervention as per protocol. Key Exclusion Criteria: Obesity of known endocrine origin (eg, untreated hypothyroidism, Cushing's syndrome) Medical history or characteristics suggestive of genetic obesity Any lifetime history of a suicide attempt or history of any suicidal ideation within the past year before entry into the study History of documented human immunodeficiency virus (HIV) infection History of or current cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrinological, hematological, or neurological disorders capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention; or interfering with the interpretation of data History of inflammatory conditions and autoimmune diseases Males: a QT interval corrected using Fridericia's formula (QTcF) interval of > 450 msec at the Screening Visit; females: a QTcF interval > 470 msec at the Screening Visit Active malignancy or history of malignancy (other than nonmelanoma skin cancer or any grade intraepithelial cervical neoplasia that has been surgically treated) within 5 years of enrollment in this study A severe psychiatric condition, such as schizophrenia, bipolar disorder, or major depression in the previous 2 years before the Screening Visit, or history of treatment with antipsychotics, antidepressants, or mood stabilizers in the previous 2 years before the Screening Visit. Suicidal ideation corresponding to type 4 or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS) within the past 30 days prior to the Screening Visit A Patient Health Questionnaire-9 (PHQ-9) score of ≥ 15 at the Screening Visit History of an eating disorder (eg, bulimia or anorexia nervosa) History of drug or alcohol abuse within 5 years of the Screening Visit A self-reported change in body weight > 5 kg (11 pounds [lbs]) within 90 days prior to the Screening Visit Known history of treated or untreated diabetes Baseline hemoglobin A1c (HbA1c) ≥ 6.5% at the Screening Visit Alanine aminotransaminase (ALT) > 3 × upper limit of normal (ULN) at the Screening Visit Aspartate aminotransaminase (AST) > 3 × ULN at the Screening Visit Estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m^2 according to the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) at the Screening Visit Chronic history of or current liver disease or known hepatic or biliary abnormalities (with the exception of nonalcoholic fatty liver disease, nonalcoholic steatohepatitis, Gilbert's syndrome or gallstones) Any underlying lens opacity that affects the BCVA, or any posterior subcapsular opacity ≥ P1 based on the LOCS III, even if not impacting the BCVA Marijuana use within 90 days prior to the Screening Visit Use of medications that the investigator considers to be associated with weight changes within 90 days prior to the Screening Visit Concomitant or previous steroid treatments (including eye-drops, inhalers, and nebulizers) for a total of ≥ 15 days during the 24 weeks prior to the Screening Visit; dermatological preparations of steroids will be allowed History of or planned bariatric surgery or intra-abdominal balloon during study participation Concomitant use of any dietary or herbal supplement that is indicated for weight management or maintenance of healthy weight Use of drugs or substances known to be inducers or inhibitors of P-glycoprotein (P-gp) within 28 days prior to dosing Received any investigational drug within 3 months of the Screening Visit History of coronavirus disease 2019 (COVID-19) infection within 14 days prior to the Screening Visit or close contact with a COVID-19 patient in the 14 days prior to the Screening Visit as reported by the participant and the participant's medical history Presence of HIV antibody at the Screening Visit or within 90 days prior to the Screening Visit Regularly consumes excessive amounts of alcohol, defined as > 3 glasses of alcoholic beverages per day Sensitivity to any of the study interventions, or components thereof, or drug or other allergy, that, in the opinion of the investigator or medical monitor, contraindicates participation in the study Female study participants who have a positive urine pregnancy test at the Screening Visit Female study participants who are breastfeeding Poor venous access based on the investigator's judgement Unable to swallow capsules Hemoglobinopathy, hemolytic anemia, or chronic anemia (hemoglobin concentration < 11.5 g/dL for males, < 10.5 g/dL for females) at the Screening Visit or any other condition known to interfere with interpretation of HbA1c measurement Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Level 1: S-309309<br>Participants will receive S-309309 (low dose) once daily for 24 weeks | Drug: S-309309<br>* Administered as oral capsules<br>|
| Experimental: Dose Level 2: S-309309<br>Participants will receive S-309309 (middle dose) once daily for 24 weeks | Drug: S-309309<br>* Administered as oral capsules<br>|
| Experimental: Dose Level 3: S-309309<br>Participants will receive S-309309 (high dose) once daily for 24 weeks | Drug: S-309309<br>* Administered as oral capsules<br>|
| Placebo Comparator: Placebo<br>Participants will receive placebo once daily for 24 weeks | Drug: Placebo<br>* Administered as an oral capsule that looks identical to S-309309 capsule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percent Change From Baseline in Body Weight |  | Baseline, Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving a Weight Loss of ≥ 5% |  | Baseline to Week 24 | 
| Percentage of Participants Achieving a Weight Loss of ≥ 10% |  | Baseline to Week 24 | 
| Percentage of Participants Achieving a Weight Loss of ≥ 15% |  | Baseline to Week 24 | 
| Percentage of Participants Achieving a Weight Loss of ≥ 20% |  | Baseline to Week 24 | 
| Change From Baseline in Waist Circumference |  | Baseline, Week 24 | 
| Change From Baseline in Hip/Waist Ratio |  | Baseline, Week 24 | 
| Change From Baseline in BMI |  | Baseline, Week 24 | 
| Change From Baseline in Glucose Metabolism Parameters as Assessed by Hemoglobin A1c or Glycosylated Hemoglobin (HbA1c) |  | Baseline, Week 24 | 
| Change From Baseline in Glucose Metabolism Parameters as Assessed by Fasting Plasma Glucose (FPG) |  | Baseline, Week 24 | 
| Change From Baseline in Cardiovascular Risk Factors |  | Baseline, Week 24 | 
| Change From Baseline in Body Composition: Total Fat Mass as Assessed by DEXA scan |  | Baseline, Week 24 | 
| Change From Baseline in Body Composition: Lean Mass as Assessed by DEXA scan |  | Baseline, Week 24 | 
| Change From Baseline in Body Composition: Visceral Fat Mass as Assessed by DEXA scan |  | Baseline, Week 24 | 
| Plasma Concentration of S-309309 |  | Up to 24 weeks | 
| Change From Baseline in Adiponectin |  | Baseline, Week 24 | 
| Change From Baseline in High Sensitivity C-reactive Protein (hsCRP) |  | Baseline, Week 24 | 
| Change From Baseline in Leptin |  | Baseline, Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Body Weight, Waist, Body Mass Index (BMI)