A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase 2a Study to Evaluate the Effect of HT-4253 for the Prevention of Alzheimer's Disease in APOE4 Carriers

Plain English Summary

Study to Evaluate the Effect of HT-4253 for the Prevention of Alzheimer's Disease in APOE4 Carriers is a Phase 2 clinical trial sponsored by Halia Therapeutics, Inc. studying Alzheimers Disease. This study tests a new drug called HT-4253 to see if it can prevent Alzheimer's disease. It's for individuals aged 50-75 who carry a specific gene (APOE4) and show early signs of amyloid buildup in the brain, but do not have Alzheimer's or significant memory loss yet. Participants will receive either the study drug or a placebo for about a year, with regular check-ups and tests. Currently, there are no approved medications specifically for preventing Alzheimer's in this high-risk group. The trial aims to enroll 112 participants.

Official 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. You can join if you are between 50 and 75 years old, have a positive test for amyloid (a protein linked to Alzheimer's), and carry the APOE4 gene. You cannot join if you have been diagnosed with Alzheimer's or significant memory loss, have certain other medical conditions, or have recently used other investigational drugs for Alzheimer's. Participants must be in good general health, have a BMI between 18 and 32, and be able to comply with study procedures. This trial is studying Alzheimers Disease, so participants generally need a confirmed diagnosis.

What They're Measuring

The main goal is to see if HT-4253 can reduce the amount of amyloid in the brain, which is a key indicator of Alzheimer's risk, moving participants from a high-risk to a low-risk category. The specific primary outcome measures are: Primary Objective (48 weeks); Primary Endpoint (Week 48); Primary Endpoint (Week 48); Primary Endpoint (Week 48). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial addresses a critical need for preventative treatments for Alzheimer's disease by targeting individuals with a high genetic risk and early biological markers. Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Alzheimers Disease, where improved treatment options are needed.

Investor Insight

This trial represents an early-stage investment in a potentially significant market for Alzheimer's prevention, with HT-4253 aiming to fill a gap in the current treatment landscape. Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor if you have the APOE4 gene and a positive amyloid test, and if this trial is right for you. Participation involves regular visits for about a year, including blood tests, cognitive assessments, and receiving either the study drug or a placebo. You'll need to commit to attending all scheduled appointments and following study instructions carefully. The trial is being conducted at 1 site. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: CROSSOVER
• Masking: TRIPLE
• Enrollment: 112 participants

Interventions

• DRUG: HT-4253 — It is anticipated that 112 participants will be randomized to receive HT-4253 (56 in each study arm).
• OTHER: Placebo — It is anticipated that 112 participants will be randomized to receive placebo (56 in each study arm).

Primary Outcomes

• Primary Objective (48 weeks)
• Primary Endpoint (Week 48)
• Primary Endpoint (Week 48)
• Primary Endpoint (Week 48)

Secondary Outcomes

• 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)

Full Eligibility Criteria

Inclusion Criteria:

1. Participant must be 50-75 years of age, without previous AD diagnosis at the time of signing the informed consent.
2. Capable of giving signed informed consent.
3. Body mass index (BMI) between 18 and 32 kg/m2.
4. A positive amyloid probability score from PrecivityAD2™ test (≥ 47.5).
5. APOE4 carrier: homozygous (APOE4/APOE4) or heterozygous (APOE3/APOE4), confirmed using the Precivity-ApoE™ test.
6. Must be ambulatory.
7. Must be in good health, as determined by the PI, without clinically significant medical history.
8. Normal physical examination, 12-lead ECG, and vital signs, as determined by the PI.
9. Females must meet one of the following:

   * Postmenopausal
   * Surgically sterile
10. 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.
11. Female participants must have a negative serum pregnancy test (β-human chorionic gonadotropin \[β-hCG\]) at screening.
12. Able to comply with the study procedures in the view of the PI.

Exclusion Criteria:

1. Any medical or neurological condition that in the opinion of the PI may be supportive of dementia.
2. A history of subjective memory decline with gradual onset and slow progression over the 6 months prior to Screening.
3. Previous or current diagnosis of AD or mild cognitive decline: MoCA \< 26.
4. 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.
5. 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.
6. 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.
7. Prior treatment with an investigational LRRK2 inhibitor or any investigational AD therapy within the 6 months prior to Screening.
8. 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).
9. Transient ischemic attack or stroke or any unexplained loss of consciousness (e.g., fainting without a diagnosis) within 1 year prior to Screening.
10. Known cerebral or systemic vasculopathy.
11. 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).
12. 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.
13. 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).
14. History of unstable angina, myocardial infarction, and/or chronic heart failure.
15. Chronic, uncontrolled hypertension (systolic blood pressure ≥ 160 mmHg, diastolic blood pressure ≥ 95 mmHg).
16. Vaccinations within 10 days prior to Screening.
17. Use of any medications, including prescription, over the counter (OTC) medications, vitamins, herbal preparations, and supplements, that, in the opinion of the PI, may put the participant at higher risk for AEs, or impair the participant's ability to complete study procedures.
18. Use of other investigational drugs at the time of Screening or within 30 days or 5 half-lives prior to signing of the ICF, whichever is longer, or longer if required by local regulations.
19. History of heavy smoking (i.e., more than 10 cigarettes a day or the tobacco/nicotine equivalent) within 3 months of Screening or refuse to abstain from tobacco or nicotine-containing products throughout the duration of the study.
20. History of, or current substance use disorder, including heavy alcohol use.
21. Pregnant or breastfeeding.
22. Presence of any laboratory abnormalities at Screening.
23. Prolonged QT interval exclusions for QTcF \>450 ms for males and \>470 ms for females Note: Entry of any participant with an abnormal ECG must be approved and documented by signature of the PI or a medically qualified sub-investigator.
24. Impaired renal function with estimated glomerular filtration rate (eGFR) \< 60 mL/min/1.73 m2.

Trial Locations

• Cleveland Clinic Abu Dhabi, Abu Dhabi, United Arab Emirates

Frequently Asked Questions

Related Conditions

• Alzheimer's Disease
• Mild Cognitive Impairment
• Dementia
• Neurodegenerative Diseases
• Genetics of Alzheimer's Disease
• Amyloidosis
• Tauopathy
• Cognitive Decline
• Geriatrics
• Preventative Medicine

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