Clinical trials
Trials in ε4/ε4 carriers
Trials run only in ε4 homozygotes or carriers, and major trials that report safety and results by genotype.
| Trial | Intervention | Who | Status and result | As of |
|---|---|---|---|---|
| APOLLOE4 | Valiltramiprosate (ALZ-801), oral | 325 ε4/ε4 with early Alzheimer’s (Phase 3) | Missed primary endpoint Prespecified MCI subgroup favored drug (nominal p-values). ARIA-E about 3% in both arms. In July 2026 the company reported a 53% net reduction in plasma p-tau217 versus placebo in the MCI subgroup. | Jul 2026 |
| Generation Study 1 | Umibecestat (BACE inhibitor) or CAD106 (amyloid vaccine) | Cognitively unimpaired ε4/ε4, aged 60–75 | Stopped 2019 Umibecestat arms stopped for mild cognitive worsening; CAD106 arm also halted. | Dec 2019 |
| Generation Study 2 | Umibecestat | Cognitively unimpaired ε4 carriers at high risk | Stopped 2019 Ended with the rest of the Generation Program. | 2019 |
| LX1001 | AAV gene therapy delivering APOE2 | ε4/ε4 with MCI or Alzheimer’s dementia (Phase 1/2) | Interim data 15 ε4/ε4 participants across four dose cohorts. Rising APOE2 in spinal fluid, tau PET reduction in 5 of 6 evaluated, no ARIA. FDA Fast Track. Small, open-label. | Jan 2026 |
| Clarity AD | Lecanemab | Early Alzheimer’s, all genotypes (Phase 3) | Positive Slowed decline; ARIA most frequent in ε4/ε4. | 2023 |
| TRAILBLAZER-ALZ 2 | Donanemab | Early Alzheimer’s, all genotypes (Phase 3) | Positive Slowed decline; ARIA most frequent in ε4/ε4. | 2023 |
| TRAILBLAZER-ALZ 6 | Donanemab, modified dose titration | Early Alzheimer’s (Phase 3b) | Reported ARIA-E 14% versus 24% with standard dosing; largest reduction in ε4/ε4. | 2025 |
| A4 Study | Solanezumab | Cognitively unimpaired with elevated amyloid | No benefit Rich natural-history data on ε4/ε4, including small bleeds over time. | 2023 |
| AHEAD 3-45 | Lecanemab | Preclinical Alzheimer’s (amyloid without symptoms) | Fully enrolled About 1,400 participants; primary completion expected December 2028. | Jun 2026 |
| HT-4253 | HT-4253, oral LRRK2 inhibitor (Halia Therapeutics) | Biomarker-positive ε4 carriers, prevention (Phase 2a) | Not yet recruiting 112 planned. Aims to lower an amyloid risk score in blood. | 2026 registry |
Trial status changes often. “As of” is the date of the result or status shown; check each registry entry for the latest. To find trials enrolling now, search ClinicalTrials.gov for APOE4.