Safety Study of TPI-287 to Treat CBS and PSP
Condition: Primary Four Repeat Tauopathies (4RT); Corticobasal Syndrome (CBS); Progressive Supranuclear Palsy (PSP); Corticobasal Degeneration (CBD)
MeSH terms: Supranuclear Palsy, Progressive; Tauopathies; Corticobasal Degeneration; Syndrome
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to determine the safety and tolerability [maximum tolerated dose
      (MTD) within planned dosing range] of intravenous (IV) infusions of TPI 287 administered once
      every 3 weeks for 9 weeks (for a total of 4 infusions) in patients with primary four repeat
      tauopathies (4RT), corticobasal syndrome (CBS; also called corticobasal degeneration, CBD) or
      progressive supranuclear palsy (PSP).
    

Detailed description: 
      The maximum tolerated dose of TPI-287 will be determined through a planned dose escalation
      over 3 sequential cohorts, each comprising of 11 participants randomized to either TPI-287 or
      placebo. TPI-287 or placebo will be administered as an intravenous infusion once every 3
      weeks for 9 weeks, for a total of 4 infusions. Participants who successfully complete this
      phase will have the option of entering into the open label extension phase during which
      TPI-287 will be administered once every 3 weeks for an additional 6 weeks, for a total of 3
      extra infusions.

      The dose of TPI 287 will be escalated in sequential cohorts. In the low dose cohort 11
      subjects each diagnosis (i.e., separate dose escalations will be performed for CBS and PSP)
      will be enrolled. The medium and high dose cohorts will be comprised of 11 subjects; combined
      CBS and PSPdiagnoses. Subjects will be assigned to cohorts in the order of study entry.

      Pre-medications of diphenhyramine 25 mg (Benadryl), dexamethasone 10 mg, and famotidine 20 mg
      (or the H2 blocker ranitidine 50 mg) will be given IV within 60 minutes prior to each study
      infusion.

      Safety and tolerability will be assessed through reporting of adverse events, physical and
      neurological testing, ECGs, as well as blood and urine analyses. Baseline and end-point
      measures of cognition and function, MRI brain scans, and cerebrospinal fluid (CSF) biomarker
      analyses will be used to determine preliminary efficacy of TPI-287 in mild-moderate AD.
      Pharmacokinetic and pharmacodynamic properties of TPI-287 will be calculated from blood
      plasma collected after the first infusion, and from CSF collected on the last visit of the
      placebo-controlled phase.
    

Intervention name(s): TPI 287 2 mg/m2; TPI-287 20 mg/m2; Placebo; TPI-287 6.3 mg/m2
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): 2 mg/m2 of TPI-287 diluted with 500mL 0.9% sodium chloride. TPI-287 is a microtubule inhibitor belonging to the taxane diterpenoid (taxoid) family, and specifically to the abeotaxane class.Drug: Placebo Drug: Placebo 500mL 0.9% sodium chloride.; 20 mg/m2 of TPI-287 diluted with 500mL 0.9% sodium chloride. TPI-287 is a microtubule inhibitor belonging to the taxane diterpenoid (taxoid) family, and specifically to the abeotaxane class; 500mL 0.9% sodium chloride; 6.3 mg/m2 of TPI-287 diluted with 500mL 0.9% sodium chloride. TPI-287 is a microtubule inhibitor belonging to the taxane diterpenoid (taxoid) family, and specifically to the abeotaxane class
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: 4RT, CBS, PSP, CBD, TPI-287