Clinical trial NCT05925114: Safety and Efficacy Study of S-309309 in Obese Adults
Official title: A Phase 2, Multicenter, Randomized, Double-blind, Dose-ranging, Placebo-controlled Study to Assess the Safety and Efficacy of S-309309 in Obese Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Obesity
Keywords: Body Weight
Waist
Body Mass Index (BMI)
Lead sponsor: Shionogi Inc.
Sponsor class: INDUSTRY
First posted: 2023-06-29
Enrollment: 365
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: Key Inclusion Criteria:

1. 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)
2. Stable body weight (defined as ≤ 5 kg of self-reported change) within 90 days prior to study start
3. Lifetime history of at least 1 unsuccessful dietary effort to lose body weight
4. 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:

1. Obesity of known endocrine origin (eg, untreated hypothyroidism, Cushing's syndrome)
2. Medical history or characteristics suggestive of genetic obesity
3. Any lifetime history of a suicide attempt or history of any suicidal ideation within the past year before entry into the study
4. History of documented human immunodeficiency virus (HIV) infection
5. 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
6. History of inflammatory conditions and autoimmune diseases
7. 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
8. 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
9. 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.
10. 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
11. A Patient Health Questionnaire-9 (PHQ-9) score of ≥ 15 at the Screening Visit
12. History of an eating disorder (eg, bulimia or anorexia nervosa)
13. History of drug or alcohol abuse within 5 years of the Screening Visit
14. A self-reported change in body weight \> 5 kg (11 pounds \[lbs\]) within 90 days prior to the Screening Visit
15. Known history of treated or untreated diabetes
16. Baseline hemoglobin A1c (HbA1c) ≥ 6.5% at the Screening Visit
17. Alanine aminotransaminase (ALT) \> 3 × upper limit of normal (ULN) at the Screening Visit
18. Aspartate aminotransaminase (AST) \> 3 × ULN at the Screening Visit
19. 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
20. 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)
21. 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
22. Marijuana use within 90 days prior to the Screening Visit
23. Use of medications that the investigator considers to be associated with weight changes within 90 days prior to the Screening Visit
24. 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
25. History of or planned bariatric surgery or intra-abdominal balloon during study participation
26. Concomitant use of any dietary or herbal supplement that is indicated for weight management or maintenance of healthy weight
27. Use of drugs or substances known to be inducers or inhibitors of P-glycoprotein (P-gp) within 28 days prior to dosing
28. Received any investigational drug within 3 months of the Screening Visit
29. 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
30. Presence of HIV antibody at the Screening Visit or within 90 days prior to the Screening Visit
31. Regularly consumes excessive amounts of alcohol, defined as \> 3 glasses of alcoholic beverages per day
32. 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
33. Female study participants who have a positive urine pregnancy test at the Screening Visit
34. Female study participants who are breastfeeding
35. Poor venous access based on the investigator's judgement
36. Unable to swallow capsules
37. 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.

Primary outcomes:
measure: Percent Change From Baseline in Body Weight
timeFrame: Baseline, Week 24
Secondary outcomes:
measure: Percentage of Participants Achieving a Weight Loss of ≥ 5%
timeFrame: Baseline to Week 24
measure: Percentage of Participants Achieving a Weight Loss of ≥ 10%
timeFrame: Baseline to Week 24
measure: Percentage of Participants Achieving a Weight Loss of ≥ 15%
timeFrame: Baseline to Week 24
measure: Percentage of Participants Achieving a Weight Loss of ≥ 20%
timeFrame: Baseline to Week 24
measure: Change From Baseline in Waist Circumference
timeFrame: Baseline, Week 24
measure: Change From Baseline in Hip/Waist Ratio
timeFrame: Baseline, Week 24
measure: Change From Baseline in BMI
timeFrame: Baseline, Week 24
measure: Change From Baseline in Glucose Metabolism Parameters as Assessed by Hemoglobin A1c or Glycosylated Hemoglobin (HbA1c)
timeFrame: Baseline, Week 24
measure: Change From Baseline in Glucose Metabolism Parameters as Assessed by Fasting Plasma Glucose (FPG)
timeFrame: Baseline, Week 24
measure: Change From Baseline in Cardiovascular Risk Factors
timeFrame: Baseline, Week 24
measure: Change From Baseline in Body Composition: Total Fat Mass as Assessed by DEXA scan
timeFrame: Baseline, Week 24
measure: Change From Baseline in Body Composition: Lean Mass as Assessed by DEXA scan
timeFrame: Baseline, Week 24
measure: Change From Baseline in Body Composition: Visceral Fat Mass as Assessed by DEXA scan
timeFrame: Baseline, Week 24
measure: Plasma Concentration of S-309309
timeFrame: Up to 24 weeks
measure: Change From Baseline in Adiponectin
timeFrame: Baseline, Week 24
measure: Change From Baseline in High Sensitivity C-reactive Protein (hsCRP)
timeFrame: Baseline, Week 24
measure: Change From Baseline in Leptin
timeFrame: Baseline, Week 24
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Flourish Research - Birmingham - PPDS
state: Alabama
city: Birmingham
country: United States
facility: Synexus Clinical Research
state: Alabama
city: Phoenix
country: United States
facility: Foothills Research Center - CCT - PPDS
state: Arizona
city: Los Angeles
country: United States
facility: National Research Institute - ClinEdge - PPDS
state: California
city: Montclair
country: United States
facility: Catalina Research Institute
state: California
city: Sacramento
country: United States
facility: Northern California Research Corp
state: California
city: Spring Valley
country: United States
facility: Encompass Clinical Research - ClinEdge - PPDS
state: California
city: Waterbury
country: United States
facility: Chase Medical Research LLC
state: Connecticut
city: Hialeah
country: United States
facility: A G A Clininical Trials- HyperCore PPDS
state: Florida
city: Jacksonville
country: United States
facility: Westside Center for Clinical Research - ERN - PPDS
state: Florida
city: Lake Worth
country: United States
facility: 3Sync, LLC
state: Florida
city: Miami Lakes
country: United States
facility: Angels Clinical Research Institute-Miami
state: Florida
city: Miami
country: United States
facility: Suncoast Research Group LLC - Flourish - PPDS
state: Florida
city: Oviedo
country: United States
facility: Oviedo Medical Research - ClinEdge PPDs
state: Florida
city: Sunrise
country: United States
facility: Precision Clinical Research
state: Florida
city: Columbus
country: United States
facility: Endocrine Consultants Research - Columbus - Centricity Research - HyperCore - PPDS
state: Georgia
city: Fayetteville
country: United States
facility: Javara, Inc./Privia Medical Group Georgia, LLC - Fayetteville - Javara - PPDS
state: Georgia
city: Lilburn
country: United States
facility: Lifeline Primary Care - CCT-PPDS
state: Georgia
city: Chicago
country: United States
facility: Flourish Research - Ravenswood - PPDS
state: Illinois
city: Louisville
country: United States
facility: L MARC Research Center
state: Kentucky
city: Annapolis
country: United States
facility: Annapolis Internal Medicine, LLC
state: Maryland
city: Silver Spring
country: United States
facility: Privia Medical Group Mid-Atlantic - Javara - PPDS
state: Maryland
city: Boston
country: United States
facility: Boston Clinical Trials Inc. - Alcanza - HyperCore - PPDS
state: Massachusetts
city: Methuen
country: United States
facility: ActivMed Practices & Research, Inc. - Portsmouth - Alcanza - HyperCore - PPDS
state: Massachusetts
city: Lincoln
country: United States
facility: Be Well Clinical Studies LLC
state: Nebraska
city: Las Vegas
country: United States
facility: Palm Research Center, Inc
state: Nevada
city: Charlotte
country: United States
facility: Tryon Medical Practice - Ballantyne - Javara - PPDS
state: North Carolina
city: Hickory
country: United States
facility: Lucas Research - Hickory - HyperCore - PPDS
state: North Carolina
city: Akron
country: United States
facility: AES - DRS - Synexus Clinical Research US, Inc.
state: Ohio
city: Cincinnati
country: United States
facility: Velocity Clinical Research (Cincinnati - Ohio) - PPDS
state: Ohio
city: Oklahoma City
country: United States
facility: Lynn Institute of East Oklahoma - ERN PPDS
state: Oklahoma
city: Hatboro
country: United States
facility: Hatboro Medical Associates PC
state: Pennsylvania
city: Elizabethton
country: United States
facility: Medical Care, LLC
state: Tennessee
city: Dallas
country: United States
facility: Dallas Diabetes Research Center
state: Texas
city: Houston
country: United States
facility: Helios CR Ins Houston - PPDS
state: Texas
city: Houston
country: United States
facility: Juno Research LLC
state: Texas
city: Houston
country: United States
facility: Juno Research LLC
state: Texas
city: Houston
country: United States
facility: Edrocrine and Psychiatry Center
state: Texas
city: Keller
country: United States
facility: Helios CR, Inc. - Keller - PPDS
state: Texas
city: Kingwood
country: United States
facility: Vytalus Medical Group
state: Texas
city: San Antonio
country: United States
facility: Flourish Research
state: Texas
city: San Antonio
country: United States
facility: Diabetes and Gandular Disease Clinic, PA
state: Texas
city: San Antonio
country: United States
facility: Consano Clinical Research
state: Texas
city: Murray
country: United States
facility: AES - DRS - Synexus Clinical Research US, Inc
state: Utah
city: Roy
country: United States
facility: Ogden Clinic - Grand View
state: Utah
city: Salt Lake City
country: United States
facility: Olympus Family Medicine - CCT - PPDS
state: Utah
city: South Ogden
country: United States
facility: South Ogden Family Medicine
state: Utah
city: Charlottesville
country: United States
facility: Charlottesville Medical Research Center
state: Virginia
city: Manassas
country: United States
facility: Manasas Clinical Research Center
state: Virginia
Study officials:
affiliation: Shionogi
name: Medical Director
role: STUDY_DIRECTOR
References: