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Study to Assess the Safety, Tolerability, and Pharmacodynamic (PD) Effects of FRM-0334 in Subjects With Prodromal to Moderate Frontotemporal Dementia With Granulin Mutation

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ClinicalTrials.gov Identifier: NCT02149160
Recruitment Status : Unknown
Verified May 2015 by FORUM Pharmaceuticals Inc.
Recruitment status was:  Active, not recruiting
First Posted : May 29, 2014
Last Update Posted : March 23, 2016
Sponsor:
Information provided by (Responsible Party):
FORUM Pharmaceuticals Inc

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.

Condition or disease Intervention/treatment Phase
Granulin Mutation Drug: FRM-0334 Drug: Placebo Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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 Start Date : October 2014
Estimated Primary Completion Date : August 2016


Arm Intervention/treatment
Experimental: FRM-0334; Arm 1
low dose, Capsule, Once Daily, Day 1 through Day 28
Drug: FRM-0334
Experimental: FRM-0334; Arm 2
high dose, Capsule, Once Daily, Day 1 through Day 28
Drug: FRM-0334
Placebo Comparator: Placebo Comparator; Arm 3
Placebo, Capsule, Once Daily, Day 1 through Day 28
Drug: Placebo



Primary Outcome Measures :
  1. Evaluate the safety and tolerability of FRM-0334 [ Time Frame: Baseline to Day 28 or Early Termination ]
    • 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

  2. Assess the pharmacodynamic (PD) effects of FRM-0334 on the change from baseline in plasma concentrations of progranulin (PGRN) after 28 days [ Time Frame: Baseline to Day 28 or Early Termination ]

Secondary Outcome Measures :
  1. Assess the pharmacodynamic effects of FRM-0334 on the change from baseline in cerebrospinal fluid (CSF) concentrations of PGRN after 28 days [ Time Frame: Baseline and Day 28 ]
    Change in CSF progranulin concentration from baseline

  2. Characterize the plasma concentrations of FRM-0334 and metabolites following once daily dosing for 28 days [ Time Frame: Day 1 to Day 28 or Early Termination ]
    Cmax, Ctrough, tmax, t1/2, λz, AUC(0-τ), CL/F, Cav in plasma

  3. Characterize the CSF concentrations of FRM-0334 and metabolites following once daily dosing for 28 days [ Time Frame: Day 1 to Day 28 or Early Termination ]
    Cmax, Ctrough, tmax, t1/2, AUC0-τ, CL/F, Cav in CSF



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Ages Eligible for Study:   21 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02149160


Locations
United States, California
UCSF Memory and Aging Center
San Francisco, California, United States
United States, Florida
Compass Research, LLC
Orlando, Florida, United States
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States
United States, Pennsylvania
Perelman School of Medicine, University of Pennsylvania
Philadelphia, Pennsylvania, United States
Belgium
University Hospitals Leuven
Leuven, Belgium
France
CHU Bordeaux Hospital Pellegrin
Bordeaux Cedex, France
CHU Rouen, Charles Nicolle Hospital
Rouen, France
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, Italy
Netherlands
Erasmus Medical Center
Rotterdam, Zuid-Holland, Netherlands
United Kingdom
The National Hospital for Neurology and Neuroscience
London, United Kingdom
Sponsors and Collaborators
FORUM Pharmaceuticals Inc

Responsible Party: FORUM Pharmaceuticals Inc
ClinicalTrials.gov Identifier: NCT02149160     History of Changes
Other Study ID Numbers: FRM-0334-002
2014-001489-85 ( EudraCT Number )
First Posted: May 29, 2014    Key Record Dates
Last Update Posted: March 23, 2016
Last Verified: May 2015

Keywords provided by FORUM Pharmaceuticals Inc:
Histone deacetylase inhibitor
Frontotemporal dementia
Granulin

Additional relevant MeSH terms:
Frontotemporal Dementia
Pick Disease of the Brain
Dementia
Aphasia, Primary Progressive
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurocognitive Disorders
Mental Disorders
Frontotemporal Lobar Degeneration
TDP-43 Proteinopathies
Neurodegenerative Diseases
Proteostasis Deficiencies
Metabolic Diseases
Aphasia
Speech Disorders
Language Disorders
Communication Disorders
Neurobehavioral Manifestations
Neurologic Manifestations
Signs and Symptoms
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action