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

A Phase 1, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Ascending Oral Doses of ISM8969 in Healthy Adult and Elderly Participants and Obese Adult Participants at Risk of Cardiovascular Disease

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Healthy Subjects (HS); Elderly Participants; Obese Adult Participants at Risk of Cardiovascular Disease
• Intervention / Treatment: Drug: ISM8969 tablets or placebo

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Johnny Ju; Phone Number: +86 021-50831718; Email: Insilico-Clinicaltrial@insilico.ai

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia
      • Nucleus Network Pty Ltd.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

Participants must meet all the following criteria to be included in the study:

Inclusion criteria 1~4 are only for the healthy participants in the SAD and MAD study:

1. 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.
2. 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.
3. Non-smokers (no use of tobacco or nicotine products within 1 month prior to screening).

4. Healthy as defined the current protocol.

   Inclusion criteria 5~9 are only for the obese participants at risk of cardiovascular disease in MAD study):

5. Male or female, ≥18 and ≤65 years of age.
6. 30.0 kg/m2 ≤ BMI < 42.0 kg/m2.
7. No change in body weight or self-reported change of less than 5.0% within 3 months before screening.
8. 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).
9. hsCRP ≥3 mg/L.

Exclusion Criteria:

Participants for whom any of the following applies will be excluded from the study:

1. Columbia suicide severity rating scale (C-SSRS) score above Type 1 ideation.
2. 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.
3. Positive pregnancy test or lactating female participant.
4. History of any central nervous system (CNS) disorder or history of seizure of any cause.
5. Clinically significant 12-lead ECG, physical examination, vital signs or laboratory abnormalities at screening, including but not limited to defined in the protocol.
6. History of significant cardiovascular or cerebrovascular disease within 6 months before screening, including but not limited to defined in the protocol.
7. 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.
8. 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.
9. Presence of contraindication to lumbar puncture or lumbar catheter as judged by Investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Healthy adults in SAD cohorts will receive ISM8969 or placebo orally up to 6 single-dose levels.	Drug: ISM8969 tablets or placebo; Administration: Oral
Experimental: Healthy adults and elderly participants in MAD cohorts will receive ISM8969 or placebo up to14 days.	Drug: ISM8969 tablets or placebo; Administration: Oral
Experimental: Obese adult participants will receive ISM8969 or placebo orally up to 14 days.	Drug: ISM8969 tablets or placebo; Administration: Oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximal observed plasma concentration (Cmax）.	To characterize plasma PK of ISM8969 after the first dose and at steady state.	Day 1 and Day 14 after dose.
Time when the maximal concentration is observed (Tmax).	To characterize plasma PK of ISM8969 after the first dose and at steady state.	Day 1 and day 14 after dose.
Area under the concentration-time curve from time zero to the last observed concentration (AUC0-t).	To characterize plasma PK of ISM8969 after the first dose and at steady state.	Day 3 and Day 17 after dose.
Area under the concentration-time curve from time zero to infinity (extrapolated)(AUC0-inf).	To characterize plasma PK of ISM8969 after single and multiple dose administration.	Day 3 and Day 17 after dose.
Terminal elimination half-life(T½).	To characterize plasma PK of ISM8969 after single and multiple dose administration.	Day 3 and Day 17 after dose.
Apparent clearance (CL/F).	To characterize plasma PK of ISM8969 after single and multiple dose administration.	Day 1 and Day 14 after dose.
Apparent volume of distribution (V/F).	To characterize plasma PK of ISM8969 after single and multiple dose administration.	Day 1 and day 14 after dose.
Maximal observed cerebrospinal fluid(CSF) concentration (Cmax,csf).	To characterize cerebrospinal fluid(CSF) PK of ISM8969 at steady state.	Day 14 after dose.
Minimal observed concentration at steady-state (Cmin,ss).	To characterize plasma PK of ISM8969.; To characterize PK of ISM8969 in cerebrospinal fluid (CSF).	Day 14 before the last dose.
Accumulation ratio (Day 14 : Day 1) (Racc).	To characterize the PK of ISM8969.	Day 14 after dose.
Change from baseline in the concentration of blood high sensitivity C-reactive protein(hsCRP).	Concentration of hsCRP will be measured and reported.	Day 14 after dose.

Collaborators and Investigators

• Sponsor: InSilico Medicine Hong Kong Limited

Study record dates

Study Major Dates

• Study Start (Estimated): May 29, 2026
• Primary Completion (Estimated): January 29, 2027
• Study Completion (Estimated): March 31, 2027

Study Registration Dates

• First Submitted: April 10, 2026
• First Submitted That Met QC Criteria: May 6, 2026
• First Posted (Actual): May 12, 2026

Study Record Updates

• Last Update Posted (Actual): May 12, 2026
• Last Update Submitted That Met QC Criteria: May 6, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: NLRP3 Inhibitor; ISM8969
• Other Study ID Numbers: ISM8969-101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No