Primary Objectives: To demonstrate that HT-4253 improves the amyloid risk profile by transitioning biomarker-positive APOE4 carriers from a positive, high risk APS2 score to a negative, low risk APS2 score. Secondary Objectives: * To assess the effects of HT-4253 on tau related blood biomarker progression over the study period. * To assess the effects of HT-4253 on amyloid related blood biomarker progression over the study period. * To assess the safety and tolerability of HT-4253 in the UAE population.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
TRIPLE
Enrollment
112
It is anticipated that 112 participants will be randomized to receive HT-4253 (56 in each study arm).
It is anticipated that 112 participants will be randomized to receive placebo (56 in each study arm).
Burjeel Medical City
Abu Dhabi, Abu Dhabi Emirate, United Arab Emirates
RECRUITINGSheikh Shakbout Medical City (SSMC)
Abu Dhabi, Abu Dhabi Emirate, United Arab Emirates
NOT_YET_RECRUITINGCleveland Clinic Abu Dhabi
Abu Dhabi, United Arab Emirates
NOT_YET_RECRUITINGPrimary Objective
To evaluate that HT-4253 improves the amyloid risk profile by transitioning biomarker-positive APOE4 carriers from a positive, high risk APS2 score to a negative, lower risk APS2 score
Time frame: 48 weeks
Primary Endpoint
Proportion of participants demonstrating improvement in amyloid risk profile, as defined by movement from high risk APS2 category (≥ 47.5) at baseline to a lower APS2 category (\< 47.5) at week 48, as measured by C2N Diagnostics' PrecivityAD2™ test\*
Time frame: Week 48
Primary Endpoint
\*C2N PrecivityAD2™ Amyloid Probability Score 2 (APS2) Categories: •Low Risk (\< 47.5): Low likelihood of amyloid plaques in the brain, consistent with a negative amyloid Positron Emission Tomography (PET) scan
Time frame: Week 48
Primary Endpoint
• High Risk (≥ 47.5): A score within this range suggests that the participant is likely to have amyloid plaques, requiring further diagnostic evaluation
Time frame: Week 48
Secondary Objectives
Secondary Objectives: To evaluate the effects of HT-4253 on tau related blood biomarker progression over the study period
Time frame: 12, 24, 36, 48 weeks
Secondary Endpoints
•Change in slope of p-tau217 over 48 weeks.
Time frame: 12, 24, 36, 48 weeks
Secondary Endpoints
•Change from baseline in plasma p-tau217 at weeks 12, 24, 36, 48.
Time frame: 12, 24, 36, 48 weeks
Secondary Endpoints
•Change from baseline in plasma p-tau181 at week 12, 24, 36, 48.
Time frame: 12, 24, 36, 48 weeks
Secondary Objectives
To evaluate the effects of HT-4253 on amyloid related blood biomarker progression over the study period.
Time frame: 12, 24, 36, 48 weeks
Secondary Endpoints
• Change from baseline in plasma Aβ42 at weeks 12, 24, 36, 48.
Time frame: 12, 24, 36, 48 Weeks
Secondary Endpoints
• Change from baseline in plasma Aβ40 at weeks 12, 24, 36, 48.
Time frame: 12, 24, 36, 48 Weeks
Secondary Endpoints
• Change from baseline in plasma Aβ42/ Aβ40 ratio at weeks 12, 24, 36, 48.
Time frame: 12, 24, 36, 48 Weeks
Secondary Objectives
To evaluate the safety and tolerability of HT-4253 in the UAE population.
Time frame: 12, 24, 36, 48 weeks
Secondary Endpoints
• Incidence and severity of treatment emergent adverse events (TEAEs).
Time frame: 12, 24, 36, 48 weeks
Secondary Endpoints
• Incidence of serious adverse events (SAEs).
Time frame: 12, 24, 36, 48 weeks
Secondary Endpoints
• Incidence and severity of treatment-related adverse events (TRAEs)
Time frame: 12, 24, 36, 48 weeks
Secondary Endpoints
• Incidence of discontinuations due to adverse events (AEs)
Time frame: 12, 24, 36, 48 weeks
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