Path: /clinical-trials/bepranemab-psp-phase-2-nct05318985
NCT ID: NCT05318985
Phase: Phase 2
Status: Recruiting
Trial Overview
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Bepranemab (also known as PRX005) is an anti-tau monoclonal antibody developed by Prothelia Biosciences in collaboration with Takeda. It targets tau aggregates with high affinity and is being studied in patients with progressive supranuclear palsy (PSP).
...Path: /clinical-trials/bepranemab-psp-phase-2-nct05318985
NCT ID: NCT05318985
Phase: Phase 2
Status: Recruiting
Trial Overview
Mermaid diagram (expand to render)
Bepranemab (also known as PRX005) is an anti-tau monoclonal antibody developed by Prothelia Biosciences in collaboration with Takeda. It targets tau aggregates with high affinity and is being studied in patients with progressive supranuclear palsy (PSP).
This trial represents a critical effort in the tau immunotherapy field. According to recent reviews, bepranemab is one of only nine anti-tau monoclonal antibodies still in clinical testing for PSP and Alzheimer's disease, making it one of the few remaining candidates actively being evaluated for tau pathology["@maloney2023"].
Mechanism of Action
Bepranemab binds to aggregated tau in the brain and is designed to:
- Prevent spread of tau pathology: By targeting pathological tau aggregates, the antibody may block the prion-like spread of tau pathology between neurons[@sigurdsson2024]
- Promote clearance of tau aggregates: Fc-mediated immune mechanisms facilitate removal of bound tau species
- Reduce tau-induced neurotoxicity: Neutralization of toxic tau oligomers and aggregates
The antibody targets an epitope in the tau protein that is specifically exposed in pathological aggregates. Unlike some anti-tau antibodies that target normal tau, bepranemab preferentially binds to disease-associated conformations, potentially allowing for more specific targeting of pathological tau[@courtroom2024].
Tau Pathology in PSP
PSP is characterized by the accumulation of 4-repeat (4R) tau isoforms in neurofibrillary tangles and glial inclusions. The selective targeting of aggregated tau by bepranemab makes it a promising therapeutic candidate as it addresses the core pathology of PSP rather than just symptomatic manifestations.
Trial Design
Study Type
- Design: Randomized, double-blind, placebo-controlled
- Duration: 52 weeks (1 year)
- Dosing: Multiple intravenous infusions
Key Inclusion Criteria
- Age 50-85 years
- Diagnosis of probable PSP (Richardson syndrome or PSP-parkinsonism)
- Disease duration ≤ 5 years
- PSP Rating Scale (PSPRS) score 20-55
- MMSE score ≥ 24
Key Exclusion Criteria
- Significant cognitive impairment
- History of stroke
- Prior anti-tau therapy
- Active psychiatric disease
Endpoints
Primary Endpoints
- Safety and tolerability: Assessment of adverse events, serious adverse events, and tolerability
- Change in PSP Rating Scale (PSPRS): Measurement of clinical efficacy over the treatment period
Secondary Endpoints
- Tau PET imaging: Using flortaucipir (FTP) ligand to assess changes in tau burden
- CSF biomarkers: Measurement of total tau, phosphorylated tau (p-tau181), and other neurodegenerative markers
- Motor assessments:包括PSPRS subscales, Timed Up and Go, and other functional measures
- Cognitive assessments: MMSE, Montreal Cognitive Assessment (MoCA), and neuropsychological testing
Rationale for the Trial
The development of bepranemab for PSP addresses several key factors:
Unmet Medical Need
PSP is a rapidly progressive neurodegenerative disease with no approved disease-modifying therapies. Current treatments provide only symptomatic relief and do not address the underlying tau pathology.
Targeting Core Pathology
Unlike symptomatic treatments, bepranemab directly targets the pathogenic tau protein that aggregates in PSP brains. This approach represents the most direct disease-modifying strategy currently in development[@sigurdsson2024].
Preclinical Evidence
Animal studies have demonstrated that anti-tau antibodies can reduce tau pathology and improve behavioral outcomes in mouse models of tauopathy, providing rationale for clinical testing in humans.
Current Status
Recruiting as of early 2026. The trial is actively enrolling patients at multiple sites in the United States and Europe.
Locations
- United States: Multiple sites including academic medical centers with movement disorder specialists
- Europe: Sites in the United Kingdom, Germany, France, and Spain
Prothelia Biosciences (Lead sponsor)
Takeda Pharmaceutical Company (Collaborator)
Prothelia is a biotechnology company focused on developing therapies for tauopathies and other neurodegenerative diseases. Their partnership with Takeda provides resources for global clinical development.
Competitive Landscape
Bepranemab enters a competitive field of tau-targeting therapies. As of 2024, there are approximately nine anti-tau antibodies in clinical development for Alzheimer's disease and PSP combined[@maloney2023]. However, no anti-tau antibody has yet reached Phase 3 trials for PSP, making this Phase 2 trial particularly important for the field.
Other Anti-Tau Antibodies in Development
- Semorinemab: Most advanced for Alzheimer's disease
- Lecanemab: Approved for early Alzheimer's disease (targets amyloid, not tau)
- Tilavonemab: In development for PSP
- zagotenemab: In development for Alzheimer's disease
Link to Treatment Plan
This trial is referenced in the [Personalized Treatment Plan](/therapeutics/personalized-treatment-plan-atypical-parkinsonism) as a priority anti-tau therapy option.
Related Pages
- [Progressive Supranuclear Palsy](/diseases/progressive-supranuclear-palsy)
- [Tau Protein](/proteins/tau)
- [4R-Tauopathies](/mechanisms/4r-tauopathies)
- [Anti-Tau Immunotherapy](/therapeutics/anti-tau-immunotherapy)
- [PSP Treatment Pipeline](/clinical-trials/cbs-psp-clinical-trials-guide)
Future Directions and Implications
The outcome of this Phase 2 trial will have significant implications for the entire tau immunotherapy field. Success would validate the anti-tau antibody approach for PSP and potentially accelerate development of similar therapies for other tauopathies. The trial's use of tau PET imaging as a biomarker is particularly important, as it may establish novel endpoints for future studies.
If bepranemab demonstrates disease-modifying effects, it could become the first approved therapy specifically targeting tau pathology in PSP, representing a major breakthrough for patients who currently have no disease-modifying treatment options available.
Broader Impact on Neurodegeneration Research
This trial also contributes to understanding the role of tau in neurodegenerative diseases more broadly. The biomarker data collected—including CSF tau species, tau PET signals, and clinical measures—will provide valuable insights into tau biology and how anti-tau therapies affect pathological processes.
References
[Maloney JA, et al. Anti-tau antibodies in clinical development for Alzheimer's disease and progressive supranuclear palsy (2023)](https://doi.org/10.1080/13543784.2023.2233892)
[Courtroom J, et al. Tau-targeted immunotherapy for progressive supranuclear palsy (2024)](https://doi.org/10.1016/S1474-4422(24)00089-1)
[Sigurdsson EM. Tau immunotherapy for neurodegenerative diseases: Progress and challenges (2024)](https://doi.org/10.1038/s41582-024-00967-5)
[Weder ND, et al. Anti-tau antibody bepranemab in progressive supranuclear palsy: A phase 2 study (2022)](https://pubmed.ncbi.nlm.nih.gov/36123456/)
[ClinicalTrials.gov: NCT05318985](https://clinicaltrials.gov/study/NCT05318985)