Efficacy and Safety of BIIB092 in Patients with Progressive Supranuclear Palsy: PASSPORT Phase 2 Study Design (P6.073)

Objective: To describe the design of the PASSPORT study (NCT03068468) in progressive supranuclear palsy (PSP), a neurodegenerative disease characterized by atypical Parkinsonism and tau pathology. Background: BIIB092 is a humanized monoclonal antibody that binds to tau at the N-terminal domain (eTau); eTau is believed to cause neuronal dysfunction directly and may be partially responsible for the spreading of tau pathology. A murine version of BIIB092 has been shown to slow progression of locomotor impairment and limit tau pathology spread in murine models of tauopathy. In patients with PSP, BIIB092 reduced cerebrospinal fluid free eTau in a dose-dependent manner in a multiple ascending dose study. Design/Methods: PASSPORT is a phase 2, randomized, double-blind, placebo-controlled, parallel-group study. Qualified participants aged 41–86 years with protocol-defined probable or possible PSP for ≥1 year and body weight ≥43 kg and ≤120 kg will be randomized to BIIB092 or placebo administered intravenously every 4 weeks for 52 weeks. After Week 52, all participants will be eligible for an open-label extension phase. The primary efficacy endpoint will compare the change from baseline to Week 52 in Progressive Supranuclear Palsy Rating Scale score in BIIB092- vs. placebo-treated patients. The primary safety endpoint will assess proportion of participants with deaths, serious adverse events, adverse events leading to discontinuation, and Grade 3 and 4 laboratory abnormalities. Key secondary endpoints include the change from baseline to Week 52 in BIIB092- vs. placebo-treated participants: Movement Disorder Society - modified-Unified Parkinson’s Disease Rating Scale Part II score; Clinical Global Impression of Change scale; Repeatable Battery for the Assessment of Neuropsychological Disease Severity scale; and Progressive Supranuclear Palsy Quality of Life scale. Results: Globally, 94 sites are expected to enroll approximately 396 participants. Conclusions: PASSPORT will investigate the safety and efficacy of BIIB092 for patients with PSP. Study Supported by: The study was funded by Biogen (Cambridge, MA, USA). Writing and editorial support for the preparation of this poster was provided by Excel Scientific Solutions (Southport, CT, USA): funding was provided by Biogen. Disclosure: Dr. Dam has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Merck. Dr. Dam holds stock and/or stock options in Merck, which sponsored research in which Dr. Dam was involved as an investigator. Dr. Boxer has nothing to disclose. Dr. Golbe has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with BMS, AbbVie, USB. Dr. Golbe has received research support from research funds went to university. Dr. Hoglinger has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with AbbVie, Alzprotect, Asceneuron, Bristol-Myers Squibb, Novartis, Roche, Sellas Life Sciences Group, UCB. Dr. Morris has nothing to disclose. Dr. Litvan has received personal compensation for serving onthe scientific steering committee of the Biotie/Parkinson Study Group clinical trial Dr. Corvol has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with BMS, Theranexus, BrainEver. Dr. Corvol holds stock and/or stock options in Hold stock from B&A therapeutics, sold out in April 2017. Dr. Corvol has received research support from Actelion. Dr. Lang has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Abbvie, Acorda, Avanir Pharmaceuticals, Biogen, Bristol Myers Squibb, Sun Pharma, Cipla, Intekrin, Merck, Medichem, Medtronic, Teva, UCB, and Sunovion, . Dr. Yuasa has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, consultant. Dr. Bechtold has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with BMS. Dr. Grundman holds stock and/or stock options in Prothena Biosciences Inc., which sponsored research in which Dr. Grundman was involved as an investigator. Dr. Grundman has received research support from Prothena Biosciences Inc. Dr. Qureshi has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with BMS, Biohaven. Dr. Qureshi holds stock and/or stock options in former BMS employee: Biohaven Pharmaceutical employee.