Study to Evaluate the Effect of HT-4253 for the Prevention of Alzheimer's Disease in APOE4 Carriers

NCT07399171 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: HT-4253-APOE-002
• Study Type: interventional
• Target: 112
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Alzheimers Disease

Outcome Measures

Primary Outcomes (4)

• Primary 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

  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\*

  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

  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

  Week 48

Secondary Outcomes (13)

• Secondary Objectives

  12, 24, 36, 48 weeks

• Secondary Endpoints

  12, 24, 36, 48 weeks

• Secondary Endpoints

  12, 24, 36, 48 weeks

• Secondary Endpoints

  12, 24, 36, 48 weeks

• Secondary Objectives

  12, 24, 36, 48 weeks

Study Arms (2)

Study Arm HT-4253

ACTIVE COMPARATOR

Arm HT-4253: HT-4253 (300 mg): dosed once a day, orally (PO QD)

Drug: HT-4253

Study Arm Placebo

PLACEBO COMPARATOR

Arm Placebo: Placebo: Dosed once a day, orally (PO QD). Participants in this group will switch over to active treatment at week 24.

Other: Placebo

Interventions

HT-4253 DRUG

It is anticipated that 112 participants will be randomized to receive HT-4253 (56 in each study arm).

Study Arm HT-4253

Placebo OTHER

It is anticipated that 112 participants will be randomized to receive placebo (56 in each study arm).

Study Arm Placebo

Eligibility Criteria

• Age: 50 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant must be 50-75 years of age, without previous AD diagnosis at the time of signing the informed consent.
• Capable of giving signed informed consent.
• Body mass index (BMI) between 18 and 32 kg/m2.
• A positive amyloid probability score from PrecivityAD2™ test (≥ 47.5).
• APOE4 carrier: homozygous (APOE4/APOE4) or heterozygous (APOE3/APOE4), confirmed using the Precivity-ApoE™ test.
• Must be ambulatory.
• Must be in good health, as determined by the PI, without clinically significant medical history.
• Normal physical examination, 12-lead ECG, and vital signs, as determined by the PI.
• Females must meet one of the following:
• Postmenopausal
• Surgically sterile
• Male participants who are sexually active with a woman of childbearing potential must agree to use a double contraception during the study and for 30 days after the last dose of HT-4253.
• Female participants must have a negative serum pregnancy test (β-human chorionic gonadotropin \[β-hCG\]) at screening.
• Able to comply with the study procedures in the view of the PI.

You may not qualify if:

• Any medical or neurological condition that in the opinion of the PI may be supportive of dementia.
• A history of subjective memory decline with gradual onset and slow progression over the 6 months prior to Screening.
• Previous or current diagnosis of AD or mild cognitive decline: MoCA \< 26.
• Any clinically significant CNS, cardiac, pulmonary, renal, gastrointestinal, endocrinological, respiratory, or metabolic conditions (or history), or other pathological or physiological conditions, that might interfere with the study results in the PI's opinion.
• Any condition which, in the PI's opinion, puts the participant at significant risk, could confound the study results, or may interfere significantly with the participant's participation in the study.
• History of clinically significant unstable psychiatric illness at the PI's discretion (e.g., uncontrolled major depression, uncontrolled schizophrenia, uncontrolled bipolar affective disorder) Note: Well-controlled and stable major depressive disorder or anxiety is permitted.
• Prior treatment with an investigational LRRK2 inhibitor or any investigational AD therapy within the 6 months prior to Screening.
• Concomitant use of prescription medications primarily indicated for psychiatric disorders or neurodegenerative disease (e.g., antipsychotics, mood stabilizers, investigational agents) within 30 days prior to first dose of study drug (Study Day 1).
• Transient ischemic attack or stroke or any unexplained loss of consciousness (e.g., fainting without a diagnosis) within 1 year prior to Screening.
• Known cerebral or systemic vasculopathy.
• History of seizure or convulsion within 3 years prior to Screening or progressive neurologic disease (Parkinson's with dementia, epilepsy with breakthrough seizures, normal pressure hydrocephalus, multiple sclerosis with recent relapse).
• Have donated blood or had loss of blood of more than a single unit of blood within 8 weeks before Screening or intend to donate blood during the course of the study.
• Poorly controlled diabetes mellitus, as defined by having dosage adjustment of diabetic medication within 3 months prior to first dose of study drug (Study Day 1).
• History of unstable angina, myocardial infarction, and/or chronic heart failure.
• Chronic, uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg, diastolic blood pressure ≥ 95 mmHg).

Sponsors & Collaborators

• Halia Therapeutics, Inc.: lead

Study Sites (1)

Cleveland Clinic Abu Dhabi

Abu Dhabi, United Arab Emirates

Location

MeSH Terms

Conditions

Alzheimer Disease

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Central Study Contacts

Medical Monitor

CONTACT

385-355-4315; monitor@haliatx.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 24, 2025
• First Posted: February 10, 2026
• Study Start: April 3, 2026
• Primary Completion (Estimated): May 20, 2027
• Study Completion (Estimated): August 20, 2027
• Last Updated: April 17, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

AE (1)