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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

Primary Purpose

Granulin Mutation

Status
Unknown status
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
FRM-0334
Placebo
Sponsored by
FORUM Pharmaceuticals Inc
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Granulin Mutation focused on measuring Histone deacetylase inhibitor, Frontotemporal dementia, Granulin

Eligibility Criteria

21 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • UCSF Memory and Aging Center
  • Compass Research, LLC
  • Massachusetts General Hospital
  • Mayo Clinic
  • Perelman School of Medicine, University of Pennsylvania
  • University Hospitals Leuven
  • CHU Bordeaux Hospital Pellegrin
  • CHU Rouen, Charles Nicolle Hospital
  • IRCCS - Centro S. Giovanni di Dio FateBeneFratelli
  • Neurological Clinic, University of Brescia, AO Civil Hospital of Brescia
  • Fondazione Universita Gabriele D'Annunzio di Chieti
  • Erasmus Medical Center
  • The National Hospital for Neurology and Neuroscience

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Placebo Comparator

Arm Label

FRM-0334; Arm 1

FRM-0334; Arm 2

Placebo Comparator; Arm 3

Arm Description

low dose, Capsule, Once Daily, Day 1 through Day 28

high dose, Capsule, Once Daily, Day 1 through Day 28

Placebo, Capsule, Once Daily, Day 1 through Day 28

Outcomes

Primary Outcome Measures

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
Assess the pharmacodynamic (PD) effects of FRM-0334 on the change from baseline in plasma concentrations of progranulin (PGRN) after 28 days

Secondary Outcome Measures

Assess the pharmacodynamic effects of FRM-0334 on the change from baseline in cerebrospinal fluid (CSF) concentrations of PGRN after 28 days
Change in CSF progranulin concentration from baseline
Characterize the plasma concentrations of FRM-0334 and metabolites following once daily dosing for 28 days
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 days
Cmax, Ctrough, tmax, t1/2, AUC0-τ, CL/F, Cav in CSF

Full Information

First Posted
May 20, 2014
Last Updated
March 22, 2016
Sponsor
FORUM Pharmaceuticals Inc
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1. Study Identification

Unique Protocol Identification Number
NCT02149160
Brief Title
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

2. Study Status

Record Verification Date
May 2015
Overall Recruitment Status
Unknown status
Study Start Date
October 2014 (undefined)
Primary Completion Date
August 2016 (Anticipated)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
FORUM Pharmaceuticals Inc

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Granulin Mutation
Keywords
Histone deacetylase inhibitor, Frontotemporal dementia, Granulin

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
FRM-0334; Arm 1
Arm Type
Experimental
Arm Description
low dose, Capsule, Once Daily, Day 1 through Day 28
Arm Title
FRM-0334; Arm 2
Arm Type
Experimental
Arm Description
high dose, Capsule, Once Daily, Day 1 through Day 28
Arm Title
Placebo Comparator; Arm 3
Arm Type
Placebo Comparator
Arm Description
Placebo, Capsule, Once Daily, Day 1 through Day 28
Intervention Type
Drug
Intervention Name(s)
FRM-0334
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Evaluate the safety and tolerability of FRM-0334
Description
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
Time Frame
Baseline to Day 28 or Early Termination
Title
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 Measure Information:
Title
Assess the pharmacodynamic effects of FRM-0334 on the change from baseline in cerebrospinal fluid (CSF) concentrations of PGRN after 28 days
Description
Change in CSF progranulin concentration from baseline
Time Frame
Baseline and Day 28
Title
Characterize the plasma concentrations of FRM-0334 and metabolites following once daily dosing for 28 days
Description
Cmax, Ctrough, tmax, t1/2, λz, AUC(0-τ), CL/F, Cav in plasma
Time Frame
Day 1 to Day 28 or Early Termination
Title
Characterize the CSF concentrations of FRM-0334 and metabolites following once daily dosing for 28 days
Description
Cmax, Ctrough, tmax, t1/2, AUC0-τ, CL/F, Cav in CSF
Time Frame
Day 1 to Day 28 or Early Termination

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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
Facility Information:
Facility Name
UCSF Memory and Aging Center
City
San Francisco
State/Province
California
Country
United States
Facility Name
Compass Research, LLC
City
Orlando
State/Province
Florida
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
Country
United States
Facility Name
Perelman School of Medicine, University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
Country
United States
Facility Name
University Hospitals Leuven
City
Leuven
Country
Belgium
Facility Name
CHU Bordeaux Hospital Pellegrin
City
Bordeaux Cedex
Country
France
Facility Name
CHU Rouen, Charles Nicolle Hospital
City
Rouen
Country
France
Facility Name
IRCCS - Centro S. Giovanni di Dio FateBeneFratelli
City
Brescia
Country
Italy
Facility Name
Neurological Clinic, University of Brescia, AO Civil Hospital of Brescia
City
Brescia
Country
Italy
Facility Name
Fondazione Universita Gabriele D'Annunzio di Chieti
City
Chieti Scalo
Country
Italy
Facility Name
Erasmus Medical Center
City
Rotterdam
State/Province
Zuid-Holland
Country
Netherlands
Facility Name
The National Hospital for Neurology and Neuroscience
City
London
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
34559230
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.
Results Reference
derived

Learn more about this trial

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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