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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

Phase 2
Conditions
Granulin Mutation
Interventions
Drug: Placebo
Registration Number
NCT02149160
Lead Sponsor
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.

Detailed Description

Not available

Recruitment & Eligibility

Status
UNKNOWN
Sex
All
Target Recruitment
30
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Placebo Comparator; Arm 3PlaceboPlacebo, Capsule, Once Daily, Day 1 through Day 28
FRM-0334; Arm 1FRM-0334low dose, Capsule, Once Daily, Day 1 through Day 28
FRM-0334; Arm 2FRM-0334high dose, Capsule, Once Daily, Day 1 through Day 28
Primary Outcome Measures
NameTimeMethod
Evaluate the safety and tolerability of FRM-0334Baseline 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

Assess the pharmacodynamic (PD) effects of FRM-0334 on the change from baseline in plasma concentrations of progranulin (PGRN) after 28 daysBaseline to Day 28 or Early Termination
Secondary Outcome Measures
NameTimeMethod
Assess the pharmacodynamic effects of FRM-0334 on the change from baseline in cerebrospinal fluid (CSF) concentrations of PGRN after 28 daysBaseline and Day 28

Change in CSF progranulin concentration from baseline

Characterize the plasma concentrations of FRM-0334 and metabolites following once daily dosing for 28 daysDay 1 to Day 28 or Early Termination

Cmax, Ctrough, tmax, t1/2, λz, AUC(0-τ), CL/F, Cav in plasma

Characterize the CSF concentrations of FRM-0334 and metabolites following once daily dosing for 28 daysDay 1 to Day 28 or Early Termination

Cmax, Ctrough, tmax, t1/2, AUC0-τ, CL/F, Cav in CSF

Trial Locations

Locations (13)

Mayo Clinic

🇺🇸

Rochester, Minnesota, United States

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

The National Hospital for Neurology and Neuroscience

🇬🇧

London, United Kingdom

Compass Research, LLC

🇺🇸

Orlando, Florida, United States

Massachusetts General Hospital

🇺🇸

Boston, Massachusetts, United States

University Hospitals Leuven

🇧🇪

Leuven, Belgium

CHU Bordeaux Hospital Pellegrin

🇫🇷

Bordeaux Cedex, France

CHU Rouen, Charles Nicolle Hospital

🇫🇷

Rouen, France

Erasmus Medical Center

🇳🇱

Rotterdam, Zuid-Holland, Netherlands

UCSF Memory and Aging Center

🇺🇸

San Francisco, California, United States

Perelman School of Medicine, University of Pennsylvania

🇺🇸

Philadelphia, Pennsylvania, United States

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