Granulin Mutation Clinical Trial
Official 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
The purposes of this study are to investigate the safety, tolerability, and pharmacodynamics of FRM-0334 in subjects with prodromal to moderate frontotemporal dementia with granulin mutation.
| Status | Active, not recruiting |
| Enrollment | 30 |
| Est. completion date | |
| Est. primary completion date | August 2016 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 21 Years to 75 Years |
| Eligibility |
Inclusion Criteria: - Male or female ages aged =21 and =75 years - Genotyped positive for a FTD-GRN mutation, and aware of it - Prodromal to moderate FTD-GRN - Resides in a stable living situation, living at home, senior residential setting, or an institutional setting without the need for continuous (ie, 24-hour) nursing care - Proficiency (oral and written) in the language in which study-related documents, including the ICF and standardized tests, will be administered - Able to swallow capsules - Be in good general health, willing and able to comply with the protocol requirements, and expected to complete the study as designed (in the judgment of the investigator) Exclusion Criteria: - Clinically significant abnormalities on physical examination, medical history, ECG, vital signs, laboratory values, or unstable medical or psychiatric illness - Females who are pregnant, breastfeeding, or planning to become pregnant during the study |
Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| Belgium | University Hospitals Leuven | Leuven | |
| France | CHU Bordeaux Hospital Pellegrin | Bordeaux Cedex | |
| France | CHU Rouen, Charles Nicolle Hospital | Rouen | |
| Italy | IRCCS - Centro S. Giovanni di Dio FateBeneFratelli | Brescia | |
| Italy | Neurological Clinic, University of Brescia, AO Civil Hospital of Brescia | Brescia | |
| Italy | Fondazione Universita Gabriele D'Annunzio di Chieti | Chieti Scalo | |
| Netherlands | Erasmus Medical Center | Rotterdam | Zuid-Holland |
| United Kingdom | The National Hospital for Neurology and Neuroscience | London | |
| United States | Massachusetts General Hospital | Boston | Massachusetts |
| United States | Compass Research, LLC | Orlando | Florida |
| United States | Perelman School of Medicine, University of Pennsylvania | Philadelphia | Pennsylvania |
| United States | Mayo Clinic | Rochester | Minnesota |
| United States | UCSF Memory and Aging Center | San Francisco | California |
| Lead Sponsor | Collaborator |
|---|---|
| FORUM Pharmaceuticals Inc |
United States, Belgium, France, Italy, Netherlands, United Kingdom,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Evaluate the safety and tolerability of FRM-0334 | Number and percentage of subjects with AEs Number and percentage of subjects with SAEs Number and percentage of subjects who discontinue due to AEs Number and percentage of subject deaths |
Baseline to Day 28 or Early Termination | Yes |
| Primary | Assess the pharmacodynamic (PD) effects of FRM-0334 on the change from baseline in plasma concentrations of progranulin (PGRN) after 28 days | Baseline to Day 28 or Early Termination | No | |
| Secondary | Assess the pharmacodynamic effects of FRM-0334 on the change from baseline in cerebrospinal fluid (CSF) concentrations of PGRN after 28 days | Change in CSF progranulin concentration from baseline | Baseline and Day 28 | No |
| Secondary | Characterize the plasma concentrations of FRM-0334 and metabolites following once daily dosing for 28 days | Cmax, Ctrough, tmax, t1/2, ?z, AUC(0-t), CL/F, Cav in plasma | Day 1 to Day 28 or Early Termination | No |
| Secondary | Characterize the CSF concentrations of FRM-0334 and metabolites following once daily dosing for 28 days | Cmax, Ctrough, tmax, t1/2, AUC0-t, CL/F, Cav in CSF | Day 1 to Day 28 or Early Termination | No |