The goal of this clinical trial is designed to characterise the safety, tolerability, efficacy, and PK of Aom0304 across oHCM and nHCM populations and to inform dose selection for future Phase 3 development. The main questions it aims to answer are: 1. Which dose is safe and tolerant of Aom0304 in participants with HCM? 2. Which dose is effective of 12 weeks of Aom0304 treatment in participants with oHCM or nHCM? Researchers will compare different doses of Aom0304 to see which works best. All participants will receive Aom0304, but at different dose levels depending on which cohort they joined. Participants will: 1. Undergo screening up to 28 days before enrollment to confirm eligibility 2. Adjust dose every 2 weeks assessed by the Investigator according to predefined criteria at Titration Phase (Week 1 Day 1 to Week 8). 3. Continuation of the last tolerated and effective dose; no further escalation is permitted at Maintenance Phase (Week 8 to Week 12). 4. Study drug discontinued and follow up at Off-treatment Follow-up Period (at the end of Week 12 to Week 16).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
56
The first dose of Aom0304 is to be administered orally under supervision, the second dose it to be administered orally at home. Participants will be supplied with Aom0304 for BID dosing orally at home. During the treatment period of 12 weeks, participants will receive the assigned dosing according to cohort allocation and dose titration strategy. There will be a Dose titration phase and Maintenance phase from Day 2 to Week 12. The dose titration will be assessed by the Investigator every 2 weeks (ie, at Week 2, Week 4, Week 6, and Week 8) according to predefined safety and efficacy criteria. Dose adjustment for Aom0304 will follow the sequence of 60 mg, 120 mg, 240 mg, and a maximum of 360 mg BID.
The first dose of Aom0304 is to be administered orally under supervision, the second dose it to be administered orally at home. Participants will be supplied with Aom0304 for BID dosing orally at home. During the treatment period of 12 weeks, participants will receive the assigned dosing according to cohort allocation and dose titration strategy. There will be a Dose titration phase and Maintenance phase from Day 2 to Week 12. The dose titration will be assessed by the Investigator every 2 weeks (ie, at Week 2, Week 4, Week 6, and Week 8) according to predefined safety and efficacy criteria. Dose adjustment for Aom0304 will follow the sequence of 60 mg, 120 mg, 240 mg, and a maximum of 360 mg BID.
The first dose of Aom0304 is to be administered orally under supervision, the second dose it to be administered orally at home. Participants will be supplied with Aom0304 for BID dosing orally at home. During the treatment period of 12 weeks, participants will receive the assigned dosing according to cohort allocation and dose titration strategy. There will be a Dose titration phase and Maintenance phase from Day 2 to Week 12. The dose titration will be assessed by the Investigator every 2 weeks (ie, at Week 2, Week 4, Week 6, and Week 8) according to predefined safety and efficacy criteria. Dose adjustment for Aom0304 will follow the sequence of 120 mg, 240 mg, 360mg and a maximum of 480 mg BID.
The first dose of Aom0304 is to be administered orally under supervision, the second dose it to be administered orally at home. Participants will be supplied with Aom0304 for BID dosing orally at home. During the treatment period of 12 weeks, participants will receive the assigned dosing according to cohort allocation and dose titration strategy. There will be a Dose titration phase and Maintenance phase from Day 2 to Week 12. The dose titration will be assessed by the Investigator every 2 weeks (ie, at Week 2, Week 4, Week 6, and Week 8) according to predefined safety and efficacy criteria. Dose adjustment for Aom0304 will follow the sequence of 60 mg, 120 mg, 240 mg, and a maximum of 360 mg BID.
To evaluate the safety and tolerability of Aom0304 in participants with HCM
Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), with LVEF \< 50% with abnormal vital signs, abnormal laboratory tests results, abnormal electrocardiograms (ECGs) and with changes in LVEF.
Time frame: Baseline to week 12
Change from Baseline in Left Ventricular Outflow Tract Gradient (LVOT-G) at Rest and Post-Valsalva in Participants with oHCM
Change in LVOT-G (mmHg) measured by echocardiography at rest and after Valsalva maneuver.
Time frame: Baseline to week 12
Change from Baseline in Peak Oxygen Consumption (pVO2)
Change in pVO2 measured using cardiopulmonary exercise testing (CPET).
Time frame: Baseline to week 12
Change from Baseline in Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Summary Score (CSS)
The KCCQ is a 23-item, self-administered disease-specific questionnaire. The Clinical Summary Score combines the Physical Limitation and Symptom domains. Scores are transformed to a range of 0 to 100, where higher scores indicate better health status and fewer symptoms.
Time frame: Baseline to week 12
To assess the effects of 12 weeks of Aom0304 treatment on N-terminal pro B type natriuretic peptide (NT-proBNP)
Changes in NT-proBNP from Baseline
Time frame: Baseline to week 12
Proportion of participants achieving a LVOT-G response of resting LVOT-G < 30 mm Hg and post-Valsalva LVOT-Gs < 50 mm Hg
Proportion of participants with resting left ventricular outflow tract gradient (LVOT-G) \< 30 mmHg and post-Valsalva LVOT-Gs \< 50 mm Hg measured by echocardiography at Week 12.
Time frame: Baseline to week 12.
Proportion of Participants Achieving Post-Valsalva LVOT-G < 30 mmHg at Week 12
Proportion of participants with post-Valsalva left ventricular outflow tract gradient (LVOT-G) \< 30 mmHg measured by echocardiography at Week 12.
Time frame: Baseline to week 12.
Proportion of Participants Achieving ≥ 20 mmHg Reduction in Post-Valsalva LVOT-G at Week 12
Proportion of participants showing a reduction of ≥ 20 mmHg in post-Valsalva left ventricular outflow tract gradient (LVOT-G) from Baseline to Week 12, measured by echocardiography.
Time frame: Baseline to week 12.
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