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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

Tracking Information
First Submitted Date  ICMJE May 20, 2014
First Posted Date  ICMJE May 29, 2014
Last Update Posted Date March 23, 2016
Study Start Date  ICMJE October 2014
Estimated Primary Completion Date August 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 23, 2014)
  • 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
  • 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 ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 23, 2014)
  • 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
  • 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
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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  ICMJE 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
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 Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Granulin Mutation
Intervention  ICMJE
  • Drug: FRM-0334
  • Drug: Placebo
Study Arms  ICMJE
  • Experimental: FRM-0334; Arm 1
    low dose, Capsule, Once Daily, Day 1 through Day 28
    Intervention: Drug: FRM-0334
  • Experimental: FRM-0334; Arm 2
    high dose, Capsule, Once Daily, Day 1 through Day 28
    Intervention: Drug: FRM-0334
  • Placebo Comparator: Placebo Comparator; Arm 3
    Placebo, Capsule, Once Daily, Day 1 through Day 28
    Intervention: Drug: Placebo
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: May 23, 2014)		 30
Original Estimated Enrollment  ICMJE Same as current
Study Completion Date  ICMJE Not Provided
Estimated Primary Completion Date August 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 21 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   France,   Italy,   Netherlands,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02149160
Other Study ID Numbers  ICMJE FRM-0334-002
2014-001489-85 ( EudraCT Number )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party FORUM Pharmaceuticals Inc
Original Responsible Party Same as current
Current Study Sponsor  ICMJE FORUM Pharmaceuticals Inc
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account FORUM Pharmaceuticals Inc
Verification Date May 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP