NCT07217665 is a Phase 2 clinical trial evaluating AADvac1, a tau active immunotherapy vaccine, as a treatment for Progressive Supranuclear Palsy (PSP). This trial is part of the PSP Clinical Trial Platform (NCT07173803), a master protocol designed to efficiently evaluate multiple investigational products for PSP simultaneously[1].
AADvac1 targets pathological tau proteins through active immunization, stimulating the immune system to produce antibodies that bind and facilitate clearance of toxic tau species. This approach differs from passive antibody therapies by inducing long-lasting active immunity.
| Field | Value |
|---|---|
| NCT ID | NCT07217665 |
| Status | Not Yet Recruiting |
| Phase | Phase 2 |
| Sponsor | University of Pennsylvania |
| Study Type | Interventional |
| Allocation | Randomized |
| Intervention Model | Parallel Assignment |
| Blinding | Triple (Participant, Investigator, Outcomes Assessor) |
| Estimated Enrollment | ~200 participants |
| Start Date | 2024 |
| Estimated Completion | ~2028 |
AADvac1 is a first-in-class active tau vaccine developed by Axon Neuroscience SE[2]. The vaccine consists of a synthetic tau peptide conjugated to keyhole limpet hemocyanin (KLH), designed to provoke a robust immune response against pathological tau proteins[3][4].
Immunological mechanism:
AADvac1 targets patients with confirmed PSP based on the Movement Disorder Society (MDS) PSP criteria, specifically those with:
Active vaccination offers several advantages over passive antibody approaches[5]:
AADvac1 completed Phase 1 testing in healthy volunteers and patients with mild cognitive impairment/early Alzheimer's disease, demonstrating:
The AADvac1 Phase 2 trial in Alzheimer's disease (Zin万丈-1) provided key safety and biomarker data[3:1]:
The translation from AD to PSP is supported by:
NCT07217665 is conducted under the PSP Clinical Trial Platform (NCT07173803) master protocol[1:1]. Key design features:
Likely inclusion criteria for the AADvac1 regimen:
Likely exclusion criteria:
| Measure | Timepoint | Purpose |
|---|---|---|
| Clinical Global Impression of Change (CGI-C) | 52 weeks | Global clinical assessment |
| Montreal Cognitive Assessment (MoCA) | 52 weeks | Cognitive function |
| Timed Up and Go Test (TUG) | 52 weeks | Mobility/balance |
| MDS-UPDRS Part III | 52 weeks | Motor examination |
| 軁Quality of Life (PSP-QoL) | 52 weeks | Patient-reported outcome |
Comprehensive safety monitoring including:
An independent Data Safety Monitoring Board (DSMB) reviews:
| Agent | Type | Target | Trial Status | Notes |
|---|---|---|---|---|
| AADvac1 (NCT07217665) | Active vaccine | Tau aggregates | Not Yet Recruiting | Platform Regimen A |
| Tilavonemab (NCT02880956) | mAb | N-terminal tau | Failed Phase 2 | Did not meet primary endpoint |
| Gosuranemab (NCT02882456) | mAb | N-terminal tau | Failed Phase 2 | No efficacy signal |
| BIIB080 (NCT05348786) | ASO | MAPT mRNA | Recruiting | Tau-lowering approach |
| E2814 (NCT05615614 (DOES NOT EXIST)) | mAb | Microtubule binding region | Recruiting | Anti-aggregation |
| Bepranemab (NCT04838314) | mAb | Tau | Phase 2 | Different epitope |
PSP is a 4R-tauopathy characterized by:
Targeting tau pathology addresses the core disease mechanism:
Compared to passive monoclonal antibodies[6]:
As of early 2026, this trial is not yet recruiting. Updates will be tracked as enrollment begins.
| Milestone | Expected Timeframe |
|---|---|
| IRB approval and site activation | 2025-2026 |
| First patient enrolled | 2026 Q1-Q2 |
| Enrollment completion | 2027 Q4 |
| Primary endpoint readout | 2028 Q1 |
NCT07217665 - The Progressive Supranuclear Palsy Clinical Trial Platform - Regimen A: AADvac1. ↩︎ ↩︎
Kovacech B, et al. AADvac1 Active Tau Immunotherapy in Alzheimer's Disease: Phase 2 Results. Alzheimer's Research & Therapy. 2022. ↩︎ ↩︎
Novak P, et al. Tau Active Immunization with AADvac1 in Safety and Immunogenicity. Acta Neuropathologica Communications. 2019. ↩︎ ↩︎
Zilavec I, et al. AADvac1 peptide carrier KLH conjugate safety and immunogenicity profile. Frontiers in Immunology. 2021. ↩︎
Cummings J, et al. Alzheimer's disease drug development pipeline 2024. Alzheimer's & Dementia. 2024. ↩︎