Study Evaluating ISM8969 in Healthy Adult and Elderly Participants and Obese Adult Participants at Risk of Cardiovascular Disease

NCT07581431 | Not Yet Recruiting Phase 1 FDA Drug

• 1 other identifier: ISM8969-101
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single center, phase 1, randomized, double-blind, placebo-controlled sequential study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple ascending oral doses of ISM8969 in healthy adults and elderly participants and obese adult participants at risk of cardiovascular disease.

Conditions

Healthy Subjects (HS); Elderly Participants; Obese Adult Participants at Risk of Cardiovascular Disease

Keywords

NLRP3 Inhibitor; ISM8969

Outcome Measures

Primary Outcomes (3)

• The incidence of Adverse Events (AEs) after single or multiple doses of ISM8969 tablets.

  To evaluate the safety and tolerability of ISM8969.

  Up to 14 days after last dose.

• Number of Participants with Clinical Laboratory Abnormalities, and Abnormalities in Vital Signs, Physical Examinations,12-lead ECG

  Vital signs (blood pressure, heart rate, respiratory rate, and oral temperature), physical examinations, 12-lead ECG(heart rate , PR interval, QT interval, RR interval, QTcF and QRS),and clinical laboratory tests (hematology, biochemistry, coagulation and urinalysis, etc.)

  Up to 14 days after last dose.

• C-SSRS Score(Type 1 to Type 5)

  The C-SSRS(Columbia Suicidality Severity Rating Scale) is a suicidal ideation and behavior rating scale to evaluate suicide risk, higher C-SSRS scores mean a worse outcome.

  Up to 14 days after last dose.

Secondary Outcomes (11)

• Maximal observed plasma concentration (Cmax）.

  Day 1 and Day 14 after dose.

• Time when the maximal concentration is observed (Tmax).

  Day 1 and day 14 after dose.

• Area under the concentration-time curve from time zero to the last observed concentration (AUC0-t).

  Day 3 and Day 17 after dose.

• Area under the concentration-time curve from time zero to infinity (extrapolated)(AUC0-inf).

  Day 3 and Day 17 after dose.

• Terminal elimination half-life(T½).

  Day 3 and Day 17 after dose.

Study Arms (3)

Healthy adults in SAD cohorts will receive ISM8969 or placebo orally up to 6 single-dose levels.

EXPERIMENTAL

Drug: ISM8969 tablets or placebo

Healthy adults and elderly participants in MAD cohorts will receive ISM8969 or placebo up to14 days.

EXPERIMENTAL

Drug: ISM8969 tablets or placebo

Obese adult participants will receive ISM8969 or placebo orally up to 14 days.

EXPERIMENTAL

Drug: ISM8969 tablets or placebo

Interventions

ISM8969 tablets or placebo DRUG

Administration: Oral

Obese adult participants will receive ISM8969 or placebo orally up to 14 days.

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants must meet all the following criteria to be included in the study:
• Male or female participants, including adult participants (≥18 and \<65 years of age) for the SAD cohorts 1-6 and MAD cohorts 1-3, and elderly participants (≥65 and ≤80 years of age) for MAD cohort 4.
• Body mass index (BMI) \>18.5 and \<30.0 kg/m2 and body weight ≥50.0 kg for males and ≥45.0 kg for females.
• Non-smokers (no use of tobacco or nicotine products within 1 month prior to screening).
• Healthy as defined the current protocol.
• Male or female, ≥18 and ≤65 years of age.
• kg/m2 ≤ BMI \< 42.0 kg/m2.
• No change in body weight or self-reported change of less than 5.0% within 3 months before screening.
• Presence of 1 or more risk factors for cardiovascular disease such as hypertension, hyperlipidemia. If present, must be controlled with stable medication dose/therapy (defined as a stable medication dose/therapy for 3 months or longer).
• hsCRP ≥3 mg/L.

You may not qualify if:

• Participants for whom any of the following applies will be excluded from the study:
• Columbia suicide severity rating scale (C-SSRS) score above Type 1 ideation.
• Positive serology test results for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, human immunodeficiency virus (HIV) antigen and antibody, treponema pallidum antibody or QuantiFERON®-TB test at screening.
• Positive pregnancy test or lactating female participant.
• History of any central nervous system (CNS) disorder or history of seizure of any cause.
• Clinically significant 12-lead ECG, physical examination, vital signs or laboratory abnormalities at screening, including but not limited to defined in the protocol.
• History of significant cardiovascular or cerebrovascular disease within 6 months before screening, including but not limited to defined in the protocol.
• History of an active or untreated malignancy or are in remission from a clinically significant malignancy (other than basal- or squamous-cell skin cancer, or in situ carcinomas of the cervix) for less than 5 years; or there is a potential malignancy during screening.
• Participation in a clinical research study involving the administration of an investigational or marketed drug or device within 30 days (or 5 half-lives, whichever is longer) prior to the first dosing, administration of a biological product in the context of a clinical research study within 90 days (or 5 half-lives, whichever is longer) prior to the first dosing, or concomitant participation in an investigational study involving no drug or device administration.
• Presence of contraindication to lumbar puncture or lumbar catheter as judged by Investigator.

Sponsors & Collaborators

• InSilico Medicine Hong Kong Limited: lead

Study Sites (1)

Nucleus Network Pty Ltd.

Melbourne, Victoria, Australia

Location

Central Study Contacts

Johnny Ju

CONTACT

+86 021-50831718; Insilico-Clinicaltrial@insilico.ai

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 10, 2026
• First Posted: May 12, 2026
• Study Start (Estimated): May 29, 2026
• Primary Completion (Estimated): January 29, 2027
• Study Completion (Estimated): March 31, 2027
• Last Updated: May 12, 2026

Record last verified: 2026-04

Locations

AU (1)