Corticobasal Syndrome or Progressive Supranuclear Palsy Trial of TPI-287

  • Study Director: Adam Boxer, MD, PhD
  • Sponsor: UCSF (Funder: CBD Solutions, Tau Consortium)
  • Recruiting? No
  • Official Study Title: A Phase I, Randomized, Double-Blind, Placebo-Controlled, Sequential Cohort, Dose-Ranging Study of the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of TPI-287 in Patients with Primary Four Repeat Tauopathies: Corticobasal Syndrome or Progressive Supranuclear Palsy
  • ClinicalTrials.gov Identifier: NCT02133846
  • Conditions Studied: Corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP)
  • Intervention: TPI-287 or placebo control is administered as an intravenous infusion, once every 3 weeks for 9 weeks during the double-blind dose-finding phase (for a total of four infusions). There are three infusions in the optional open-label phase and a total of seven infusions in both phases.
  • Phase: Phase 1b
  • Duration of Participation: Approximately four months, seven months with open label extension

Purpose of the Study

Tau is a microtubule-associated protein, and abnormal tau function has been proposed to play a role in the development and progression of primary four repeat tauopathies, CBS and PSP. TPI-287 is a stabilizer of microtubule dynamics, and the stabilization of microtubules is hypothesized to compensate for the loss of tau function in primary four-repeat tauopathies. The purpose of this study is to determine the safety and tolerability of intravenous (IV) infusions of TPI-287 in patients with four-repeat tauopathies (4RT), CBS or PSP.

Eligibility

Inclusion Criteria: Subjects must be between 50–85 years of age (inclusive) and be able to walk five steps with minimal assistance (stabilization of one arm or use of cane/walker). Subjects must also have a Mini Mental State Examination (MMSE) score of 14–30 at the screening visit. Subjects must be willing and able to have brain MRIs as well as two lumbar punctures performed. Subjects must have a reliable caregiver who has at least five hours of contact with them per week and is willing to accompany the subject to study visits.

Exclusion Criteria: Subjects must not have any medical condition other than CBS or PSP that could account for cognitive deficits (such as Alzheimer’s disease, active seizure disorder, stroke or vascular dementia). Subjects must not have a prominent and sustained response to levodopa therapy. Subjects must not have a history of significant cardiovascular, hematologic, renal, or hepatic disease, significant peripheral neuropathy, major psychiatric illness or untreated depression. Subjects must not have previous exposure to microtubule inhibitors, must not have participated in another interventional clinical trial within three months of screening, and must not have been treated with another investigational drug within 30 days of screening.

What to Expect

Testing: Brain MRIs, florbetapir PET scan (for CBS group), two lumbar punctures, neurological and physical examinations, cognitive testing and neuropsychiatric assessments, ECGs, blood and urine specimen collection, vital signs

The Frequency of Visits:

  • 28-day screening period
  • Visits once every 3 weeks for 9 weeks plus weekly safety follow-up visits between the first two infusions
  • Three follow-up visits after the end of the study treatment period of the placebo-controlled phase
  • Additional visits once every 3 weeks for 9 weeks in an optional open-label extension phase plus weekly safety follow-up visits between the first two infusions
  • Additional single follow-up visit after the end of the open-label extension phase

Materials Needed Before Evaluation: Participants meet criteria for probable or possible PSP (based on the National Institute of Neurological Disorders and Stroke – Society for Progressive Supranuclear Palsy) or meet 2013 consensus criteria for possible or probable corticobasal degeneration, CBS subtype (Armstrong et al. 2013).

Costs: No costs will be charged for any of the study procedures. Parking will be validated at UCSF public garages for all study visits, and subjects will be reimbursed $75 for each scheduled visit and $50 for additional MRI scanning, PET scan for CBS subjects only and/or lumbar puncture visits to help defray any incidental expenses incurred in the course of participating in this study.

Contact Information

Clinical Trials Nurse: Mary Koestler, RN, PhD, CCRC – Mary.Koestler@ucsf.edu, 415.476.0661