Frontotemporal Dementia Trial of a Histone Deacetylase Inhibitor

  • Study Director: Adam Boxer, MD, PhD
  • Sponsor: FORUM Pharmaceuticals
  • Recruiting? No
  • Official Study Title: A Randomized, Double-Blind, Placebo-Controlled, Dose-Escalating, Phase 2a Safety, Tolerability, and Pharmacodynamic Study of Two Doses of an Histone Deacetylase Inhibitor (FRM-0334) in Subjects with Prodromal to Moderate Frontotemporal Dementia with Granulin Mutation
  • ClinicalTrials.gov Identifier: NCT02149160
  • Conditions Studied: Symptomatic and asymptomatic progranulin mutation carriers
  • Intervention: FRM-0334-002 or placebo will be administered orally with food and water in the morning at approximately the same time each day for 28 days
  • Phase: Phase 2a

Purpose of the Study

The purpose of this study is to evaluate the safety and tolerability of two fixed doses of FRM-0334 (300 or 500mg) over 28 days in subjects with prodromal to moderate frontotemporal dementia with granulin gene mutation (FTD-GRN). Additionally, we will assess the pharmacodynamic effects of FRM-0334 on the change from baseline in plasma concentrations of progranulin after 28 days.

Eligibility

Inclusion Criteria: Age 21 to 75 years of age (inclusive) who are genotyped positive for an FTD-GRN mutation (gene carrier status known). Subjects can be symptomatic or asymptomatic. Subjects must reside in a stable living situation, be able to swallow capsules, and in good general health. Subjects must be willing to complete two lumbar punctures, a brain MRI, and a brain PET scan.

Exclusion Criteria:

  • Medical: Clinically significant abnormalities on physical examination, medical history, ECG, vital signs, laboratory values or unstable medical or psychiatric illness. Subjects must not have a history of malignant tumor within three years before screening, with the exception of squamous and basal cell carcinoma or cervical carcinoma in situ. Subjects must not be pregnant, breastfeeding or planning to become pregnant during the study.
  • Prohibited Medications: Subjects must not have previous exposure to investigational drug, biologic or medical device within 30 days before screening. Subjects must not have hypersensitivity to histone deacetylase inhibitor (HDACi) medication or currently be taking HDACis, including valproic acid and amisulpride. Subjects must not be taking warfarin-derived anticoagulants or immunosuppressants including systemic corticosteroids or daily intake of nonsteroidal anti-inflammatory drugs.

What to Expect

Testing: One brain MRI, one brain PET scan, two lumbar punctures, neurological and physical examinations, cognitive testing and neuropsychiatric assessments, ECGs, blood and urine specimen collection, vital signs

The Frequency of Visits:

  • Expected duration of 88 days, including up to 30 days of screening, 28 days of double-blinded treatment, and safety follow up 10 and 30 days after last dose
  • Eight visits to UCSF: two screening visits, baseline visit (Day 1), Day 7, Day 8, Day 28, Day 29, Day 38

Materials Needed Before Evaluation: GRN mutation carrier (gene carrier status must be known)

Costs: No costs will be charged for any of the study procedures. Parking will be validated at UCSF public garages for all study visits.

Contact Information

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