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
- Are there results?
- Not yet: the study is under way
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.
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- 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.
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- 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
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT07581431
- Acronym / sponsor ID
- ISM8969-101
- Keywords
- NLRP3 Inhibitor, ISM8969
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- InSilico Medicine Hong Kong LimitedIndustry (pharma, biotech, devices)
- Study start
- 15 Jun 2026 (actual)
- Primary completion
- 29 Jan 2027 (estimated)
- Study completion
- 31 Mar 2027 (estimated)
- First posted
- 12 May 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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.
- Inclusion criteria 5~9 are only for the obese participants at risk of cardiovascular disease in MAD study):
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ISM8969 tablets or placeboAdministration: Oral | Drug | Obese adult participants will receive ISM8969 or placebo orally up to 14 days. |
| ISM8969 tablets or placeboAdministration: Oral | Drug | Healthy adults and elderly participants in MAD cohorts will receive ISM8969 or placebo up to14 days. |
| ISM8969 tablets or placeboAdministration: Oral | Drug | Healthy adults in SAD cohorts will receive ISM8969 or placebo orally up to 6 single-dose levels. |
Primary outcome
The incidence of Adverse Events (AEs) after single or multiple doses of ISM8969 tablets.
Time frame: Up to 14 days after last dose.
To evaluate the safety and tolerability of ISM8969.
Number of Participants with Clinical Laboratory Abnormalities, and Abnormalities in Vital Signs, Physical Examinations,12-lead ECG
Time frame: Up to 14 days after last dose.
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.)
C-SSRS Score(Type 1 to Type 5)
Time frame: Up to 14 days after last dose.
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.
12 secondary outcomes
Maximal observed plasma concentration (Cmax）.
Time frame: Day 1 and Day 14 after dose.
Time when the maximal concentration is observed (Tmax).
Time frame: Day 1 and day 14 after dose.
Area under the concentration-time curve from time zero to the last observed concentration (AUC0-t).
Time frame: Day 3 and Day 17 after dose.
Area under the concentration-time curve from time zero to infinity (extrapolated)(AUC0-inf).
Time frame: Day 3 and Day 17 after dose.
Terminal elimination half-life(T½).
Time frame: Day 3 and Day 17 after dose.
Apparent clearance (CL/F).
Time frame: Day 1 and Day 14 after dose.
Apparent volume of distribution (V/F).
Time frame: Day 1 and day 14 after dose.
Maximal observed cerebrospinal fluid(CSF) concentration (Cmax,csf).
Time frame: Day 14 after dose.
Minimal observed concentration at steady-state (Cmin,ss).
Time frame: Day 14 before the last dose.
Minimal observed cerebrospinal fluid(CSF) concentration at steady-state (Cmin,ss).
Time frame: Day 14 before the last dose.
Accumulation ratio (Day 14 : Day 1) (Racc).
Time frame: Day 14 after dose.
Change from baseline in the concentration of blood high sensitivity C-reactive protein(hsCRP).
Time frame: Day 14 after dose.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
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.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 22 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Johnny Ju (+86 021-50831718, Insilico-Clinicaltrial@insilico.ai), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The incidence of Adverse Events (AEs) after single or multiple doses of ISM8969 tablets. (time frame: Up to 14 days after last dose.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jun 2026.