Healthy Subjects (HS)Phase 1NCT07581431
A Phase 1, Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of ISM8969
A Phase 1 study of Healthy Subjects (HS) and Obese Adult Participants at Risk of Cardiovascular Disease, run by InSilico Medicine Hong Kong Limited at 1 site in Australia.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Subjects (HS), Obese Adult Participants at Risk of Cardiovascular Disease
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 100 participants
- Where
- 1 siteAustralia
- Study dates
- 15 Jun 2026to 31 Mar 2027
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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:
- 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.
Show all 12Show fewer
- Inclusion criteria 5~9 are only for the obese participants at risk of cardiovascular disease in MAD study):
- Male or female, ≥18 and ≤65 years of age.
- 30.0 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.
Who cannot join
- 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.
Show all 10Show fewer
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Australia1 site, 1 recruiting
- Recruiting
Nucleus Network Pty Ltd.
Melbourne, Victoria
About this study
Official title: 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.
- Being tested
- ISM8969 tablets or placebo
- Keywords
- NLRP3 Inhibitor, ISM8969
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ISM8969 tablets or placeboDrug
Administration: Oral
ISM8969 tablets or placeboDrug
Administration: Oral
ISM8969 tablets or placeboDrug
Administration: Oral
| Study group | Role | What they receive |
|---|---|---|
| Healthy adults in SAD cohorts will receive ISM8969 or placebo orally up to 6 single-dose levels. | Experimental | Not described Receives: Drug: ISM8969 tablets or placebo |
| Healthy adults and elderly participants in MAD cohorts will receive ISM8969 or placebo up to14 days. | Experimental | Not described Receives: Drug: ISM8969 tablets or placebo |
| Obese adult participants will receive ISM8969 or placebo orally up to 14 days. | Experimental | Not described Receives: Drug: ISM8969 tablets or placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The incidence of Adverse Events (AEs) after single or multiple doses of ISM8969 tablets.
To evaluate the safety and tolerability of ISM8969.
Measured: 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.)
Measured: 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.
Measured: Up to 14 days after last dose.
Secondary outcomes (12)
Maximal observed plasma concentration (Cmax）.
To characterize plasma PK of ISM8969 after the first dose and at steady state.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Day 3 and Day 17 after dose.
Terminal elimination half-life(T½).
To characterize plasma PK of ISM8969 after single and multiple dose administration.
Measured: Day 3 and Day 17 after dose.
Apparent clearance (CL/F).
To characterize plasma PK of ISM8969 after single and multiple dose administration.
Measured: 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.
Measured: 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.
Measured: Day 14 after dose.
Minimal observed concentration at steady-state (Cmin,ss).
To characterize plasma PK of ISM8969.
Measured: Day 14 before the last dose.
Minimal observed cerebrospinal fluid(CSF) concentration at steady-state (Cmin,ss).
To characterize PK of ISM8969 in cerebrospinal fluid (CSF).
Measured: Day 14 before the last dose.
Accumulation ratio (Day 14 : Day 1) (Racc).
To characterize the PK of ISM8969.
Measured: 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.
Measured: Day 14 after dose.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 May 2026
- Study start15 Jun 2026
- Primary completion29 Jan 2027 (estimated)
- Study completion31 Mar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Healthy Subjects (HS)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- InSilico Medicine Hong Kong Limited
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07581431
- Sponsor's protocol ID
- ISM8969-101
- Status last verified
- Jun 2026
- First submitted
- 10 Apr 2026
- Last updated
- 22 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No