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

March 22, 2016 updated by: FORUM Pharmaceuticals Inc

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Anticipated)

30

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
      • Leuven, Belgium
        • University Hospitals Leuven
  • France
      • Bordeaux Cedex, France
        • CHU Bordeaux Hospital Pellegrin
      • Rouen, France
        • CHU Rouen, Charles Nicolle Hospital
  • Italy
      • Brescia, Italy
        • IRCCS - Centro S. Giovanni di Dio Fatebenefratelli
      • Brescia, Italy
        • Neurological Clinic, University of Brescia, AO Civil Hospital of Brescia
      • Chieti Scalo, Italy
        • Fondazione Universita Gabriele D'Annunzio di Chieti
  • Netherlands
    • Zuid-Holland
      • Rotterdam, Zuid-Holland, Netherlands
        • Erasmus Medical Center
  • United Kingdom
      • London, United Kingdom
        • The National Hospital for Neurology and Neuroscience
  • United States
    • California
      • San Francisco, California, United States
        • UCSF Memory and Aging Center
    • Florida
      • Orlando, Florida, United States
        • Compass Research, LLC
    • Massachusetts
      • Boston, Massachusetts, United States
        • Massachusetts General Hospital
    • Minnesota
      • Rochester, Minnesota, United States
        • Mayo Clinic
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States
        • Perelman School of Medicine, University of Pennsylvania

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

19 years to 73 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
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
Time Frame: Baseline to Day 28 or Early Termination
Baseline to Day 28 or Early Termination

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Baseline and Day 28
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
Day 1 to Day 28 or Early Termination
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
Day 1 to Day 28 or Early Termination

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

FORUM Pharmaceuticals Inc

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2014

Primary Completion (Anticipated)

August 1, 2016

Study Registration Dates

First Submitted

May 20, 2014

First Submitted That Met QC Criteria

May 23, 2014

First Posted (Estimate)

May 29, 2014

Study Record Updates

Last Update Posted (Estimate)

March 23, 2016

Last Update Submitted That Met QC Criteria

March 22, 2016

Last Verified

May 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FRM-0334-002
  • 2014-001489-85 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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