Study to Assess the Safety, Tolerability, and Pharmacodynamic (PD) Effects of FRM-0334 in Subjects With Prodromal to Moderate Frontotemporal Dementia With Granulin Mutation
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
2 other identifiers
interventional
30
6 countries
13
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_2
13 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 20, 2014
CompletedFirst Posted
Study publicly available on registry
May 29, 2014
CompletedStudy Start
First participant enrolled
October 1, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 1, 2016
CompletedMarch 23, 2016
May 1, 2015
1.8 years
May 20, 2014
March 22, 2016
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
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
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
Secondary Outcomes (3)
Assess the pharmacodynamic effects of FRM-0334 on the change from baseline in cerebrospinal fluid (CSF) concentrations of PGRN after 28 days
Baseline and Day 28
Characterize the plasma concentrations of FRM-0334 and metabolites following once daily dosing for 28 days
Day 1 to Day 28 or Early Termination
Characterize the CSF concentrations of FRM-0334 and metabolites following once daily dosing for 28 days
Day 1 to Day 28 or Early Termination
Study Arms (3)
FRM-0334; Arm 1
EXPERIMENTALlow dose, Capsule, Once Daily, Day 1 through Day 28
FRM-0334; Arm 2
EXPERIMENTALhigh dose, Capsule, Once Daily, Day 1 through Day 28
Placebo Comparator; Arm 3
PLACEBO COMPARATORPlacebo, Capsule, Once Daily, Day 1 through Day 28
Interventions
Eligibility Criteria
You may qualify if:
- 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)
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (13)
UCSF Memory and Aging Center
San Francisco, California, United States
Compass Research, LLC
Orlando, Florida, United States
Massachusetts General Hospital
Boston, Massachusetts, United States
Mayo Clinic
Rochester, Minnesota, United States
Perelman School of Medicine, University of Pennsylvania
Philadelphia, Pennsylvania, United States
University Hospitals Leuven
Leuven, Belgium
CHU Bordeaux Hospital Pellegrin
Bordeaux, France
CHU Rouen, Charles Nicolle Hospital
Rouen, France
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, Italy
Erasmus Medical Center
Rotterdam, South Holland, Netherlands
The National Hospital for Neurology and Neuroscience
London, United Kingdom
Related Publications (1)
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.
PMID: 34559230DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 20, 2014
First Posted
May 29, 2014
Study Start
October 1, 2014
Primary Completion
August 1, 2016
Last Updated
March 23, 2016
Record last verified: 2015-05