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Brief Title

Rho Kinase (ROCK) Inhibitor in Tauopathies - 1

Official Title

A Phase 2a Open-Label Preliminary Safety, Tolerability, and Biomarker Study of Oral Fasudil in Patients With the 4-Repeat Tauopathies of Progressive Supranuclear Palsy-Richardson Syndrome or Corticobasal Syndrome.

Brief Summary

      A Phase 2a Open-Label Preliminary Safety, Tolerability, and Biomarker Study of Oral Fasudil
      in Patients with the 4-Repeat Tauopathies of Progressive Supranuclear Palsy-Richardson
      Syndrome or Corticobasal Syndrome
    

Detailed Description

      After consent, participants will undergo screening evaluations, which may occur over the
      course of up to 6 weeks. Subjects who meet inclusion/exclusion criteria will be enrolled into
      the study and complete baseline evaluations. Dosing with study drug will begin on Day 1 and
      continue for 48 weeks. Participants will return to the clinic at Week 1 (7 ± 2 days after the
      first study drug administration) and at Weeks 12, 24, 36, and 48 for study evaluations, and
      at Week 52 for post-treatment follow-up evaluations. Plasma biomarker collection will occur
      at baseline, and Weeks 12, 24, 36, and 48. Cerebrospinal fluid (CSF) Biomarker collection
      will occur at screening, Week 24 and Week 48. Brain magnetic resonance imaging (MRI) will
      occur at screening, and Weeks 24 and 48. Safety labs will be collected at each study visit as
      well as during Week 4.

      Adverse events (AEs) will be assessed at all visits and subjects will be contacted one day
      after the start of treatment (that is, one day after Visit 1), and monthly thereafter
      including at each visit. Subject will also be contacted one day after Visit 6/last day of
      dosing with study drug for subjects who discontinue early.

      Subjects/caregivers will be queried for study drug compliance one day after the start of
      treatment (that is, one day after Visit 1), and monthly thereafter.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Adverse events

Secondary Outcome

 Phosphorylated tau

Condition

Progressive Supranuclear Palsy

Intervention

Fasudil

Study Arms / Comparison Groups

 Treatment
Description:  Oral fasudil 180 mg/day

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

15

Start Date

January 22, 2021

Completion Date

July 30, 2022

Primary Completion Date

July 30, 2022

Eligibility Criteria

        Inclusion Criteria:

          1. Between 35 and 80 years of age (inclusive).

          2. Able to walk at least 10 steps with minimal assistance (stabilization of one arm or
             use of cane/walker).

          3. MRI at Screening is consistent with the underlying neurodegenerative disease of the
             respective diagnostic cohort (i.e. PSP-RS or CBS), with no large strokes or severe
             white matter disease.

          4. Mini-Mental State Exam (MMSE) at Screening is between 20 and 30 (inclusive).

          5. For CBS: Amyloid beta (Aβ) positron emission tomography (PET) scan (florbetapir or
             equivalent) at Screening is not consistent with underlying Alzheimer's disease (AD).
             Previous Aβ PET scan negativity (assessed by a certified neuroradiologist) or previous
             AD CSF biomarker (Aβ/tau level, P-tau181 or Aβ1-40 / Aβ1-42) or plasma AD biomarker
             (P-tau181 or P-tau217) negativity may be used instead of performing an Aβ PET scan at
             Screening at the Principal Investigator's (PI's) discretion.

          6. The following medications are allowed, but must be stable for 2 months prior to
             Baseline:

               1. FDA-approved AD medications

               2. FDA-approved Parkinson's Disease (PD) medications

          7. Other prescription medications are allowed as long as the dose is stable for 30 days
             prior to Baseline. (Note Exclusion Criteria 17 and 18.)

          8. Has a reliable study partner who agrees to accompany the participant to visits, and
             spends at least 5 hours per week with the participant.

          9. Signed and dated written informed consent obtained from the participant/legally
             authorized representative (LAR) and the participant's study partner in accordance with
             local Institutional Review Board (IRB) regulations.

         10. Women of childbearing potential (WCBP) must agree to abstain from sex or use an
             adequate method of contraception for the duration of the screening period, the study
             drug treatment period, and for 28 days after the last dose of study drug.

         11. Males must agree to abstain from sex with WCBP or use an adequate method of
             contraception for the duration of the study drug treatment period and for 75 days
             after.

             For PSP-RS Only

         12. Meets 2017 consensus criteria for possible or probable progressive supranuclear
             palsy-Richardson syndrome (PSP-RS).

             For CBS Only

         13. Meets 2013 consensus criteria for possible or probable corticobasal degeneration
             (CBD), CBS subtype.

        Exclusion Criteria:

          1. Meets criteria for probable AD established by the National Institute on Aging and the
             Alzheimer's Association (NIA-AA).

          2. Any other medical condition other than PSP-RS or CBS that could account for cognitive
             or motor deficits (e.g., active seizure disorder, stroke, vascular dementia, substance
             abuse or alcoholism).

          3. History of a prominent and sustained response to levodopa therapy in the opinion of
             the PI.

          4. Presence of significant cardiovascular, hematologic, renal, or hepatic disease.

          5. Suicidal ideation per the Columbia-Suicide Severity Rating Scale (C-SSRS) that in the
             opinion of the PI would pose a safety risk or interfere with the appropriate
             interpretation of study data

          6. History of major psychiatric illness or untreated depression that in the opinion of
             the PI would pose a safety risk or interfere with the appropriate interpretation of
             study data.

          7. Neutrophil count <1,500/mm3, platelets <100,000/mm3, total bilirubin ≥1.5 x Upper
             Limit of Normal (ULN), alanine aminotransferase (ALT) ≥3 x ULN, aspartate
             aminotransferase (AST) ≥3 x ULN, or International Normalized Ratio (INR) >1.2.

          8. Serum creatinine >1.3 mg/dL.

          9. Evidence of any clinically significant findings on screening or baseline evaluations
             which, in the opinion of the PI would pose a safety risk or interfere with appropriate
             interpretation of study data.

         10. Current or recent history (within four weeks prior to Screening) of a clinically
             significant bacterial, fungal, or mycobacterial infection.

         11. Current clinically significant viral infection.

         12. Major surgery within four weeks prior to Screening.

         13. Any contraindication for MRI or unable to tolerate MRI scan at Screening.

         14. Any contraindication to or unable to tolerate lumbar puncture at Screening, including
             use of anticoagulant medications such as warfarin. Daily administration of aspirin up
             to 81mg is not a contraindication, as long as the dose is stable for 30 days prior to
             Screening.

         15. Participants who, in the opinion of the PI, are unable or unlikely to comply with the
             dosing schedule or study evaluations.

         16. Treatment with another investigational drug within 30 days or 5 half-lives of drug
             before Baseline, whichever is longer. Treatment with investigational drugs other than
             fasudil while on study will not be allowed.

         17. Treatment with systemic corticosteroids within 30 days or 5 half-lives of drug before
             Baseline, whichever is longer.

         18. On more than one of the following drug classes: long-acting nitrates, beta-blockers,
             or calcium channel blockers.

         19. Known hypersensitivity to the inactive ingredients in the study drug (fasudil).

         20. Known to be pregnant or lactating; or positive pregnancy test at Screening or Baseline
             (Day 1) for WCBP.

         21. Cancer within 5 years of Screening, except for basal cell carcinoma.

         22. History of serum or plasma progranulin level less than one standard deviation below
             the normal participant mean for the laboratory performing the assay.

         23. History or evidence at Screening of known disease-associated mutations in GRN, TBK1,
             C9ORF72, TARBP, CHMPB2, or VCP genes (FTLD causative gene mutations not associated
             with underlying tau pathology).

         24. Blood pressure < 90/60.

         25. Evidence of orthostatic hypotension.
      

Gender

All

Ages

35 Years - 80 Years

Accepts Healthy Volunteers

No

Contacts

Peter Ljubenkov, MD, 415-476-2941, [email protected]

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT04734379

Organization ID

WP-0512-002


Responsible Party

Sponsor

Study Sponsor

Woolsey Pharmaceuticals


Study Sponsor

Peter Ljubenkov, MD, Principal Investigator, UCSF Weill Institute for Neurosciences


Verification Date

July 2021