Clinical trial NCT02149160: Study to Assess the Safety, Tolerability, and Pharmacodynamic (PD) Effects of FRM-0334 in Subjects With Prodromal to Moderate Frontotemporal Dementia With Granulin Mutation
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Granulin Mutation
Keywords: Histone deacetylase inhibitor
Frontotemporal dementia
Granulin
Lead sponsor: FORUM Pharmaceuticals Inc
Sponsor class: INDUSTRY
First posted: 2014-05-29
Enrollment: 30
Sex: ALL
Minimum age (years): 21
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Evaluate the safety and tolerability of FRM-0334
timeFrame: Baseline to Day 28 or Early Termination
measure: Assess the pharmacodynamic (PD) effects of FRM-0334 on the change from baseline in plasma concentrations of progranulin (PGRN) after 28 days
timeFrame: Baseline to Day 28 or Early Termination
Secondary outcomes:
measure: Assess the pharmacodynamic effects of FRM-0334 on the change from baseline in cerebrospinal fluid (CSF) concentrations of PGRN after 28 days
timeFrame: Baseline and Day 28
measure: Characterize the plasma concentrations of FRM-0334 and metabolites following once daily dosing for 28 days
timeFrame: Day 1 to Day 28 or Early Termination
measure: Characterize the CSF concentrations of FRM-0334 and metabolites following once daily dosing for 28 days
timeFrame: Day 1 to Day 28 or Early Termination
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: UCSF Memory and Aging Center
state: California
city: Orlando
country: United States
facility: Compass Research, LLC
state: Florida
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Philadelphia
country: United States
facility: Perelman School of Medicine, University of Pennsylvania
state: Pennsylvania
city: Leuven
country: Belgium
facility: University Hospitals Leuven
city: Bordeaux Cedex
country: France
facility: CHU Bordeaux Hospital Pellegrin
city: Rouen
country: France
facility: CHU Rouen, Charles Nicolle Hospital
city: Brescia
country: Italy
facility: IRCCS - Centro S. Giovanni di Dio FateBeneFratelli
city: Brescia
country: Italy
facility: Neurological Clinic, University of Brescia, AO Civil Hospital of Brescia
city: Chieti Scalo
country: Italy
facility: Fondazione Universita Gabriele D'Annunzio di Chieti
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
state: Zuid-Holland
city: London
country: United Kingdom
facility: The National Hospital for Neurology and Neuroscience
Study officials:
References:
citation: Ljubenkov PA, Edwards L, Iaccarino L, La Joie R, Rojas JC, Koestler M, Harris B, Boeve BF, Borroni B, van Swieten JC, Grossman M, Pasquier F, Frisoni GB, Mummery CJ, Vandenberghe R, Le Ber I, Hannequin D, McGinnis SM, Auriacombe S, Onofrj M, Goodman IJ, Riordan HJ, Wisniewski G, Hesterman J, Marek K, Haynes BA, Patzke H, Koenig G, Hilt D, Moebius H, Boxer AL. Effect of the Histone Deacetylase Inhibitor FRM-0334 on Progranulin Levels in Patients With Progranulin Gene Haploinsufficiency: A Randomized Clinical Trial. JAMA Netw Open. 2021 Sep 1;4(9):e2125584. doi: 10.1001/jamanetworkopen.2021.25584.