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

• ClinicalTrials.gov Identifier: NCT02149160
• Recruitment Status: Unknown
• First Posted: May 29, 2014
• Last Update Posted: March 23, 2016
• Sponsor: FORUM Pharmaceuticals Inc
• Information provided by (Responsible Party): FORUM Pharmaceuticals Inc

Tracking Information

• First Submitted Date: May 20, 2014
• First Posted Date: May 29, 2014
• Last Update Posted Date: March 23, 2016
• Study Start Date: October 2014
• Estimated Primary Completion Date: August 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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: Same as current

Current Secondary Outcome Measures (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: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Granulin Mutation

Intervention

• Drug: FRM-0334
• Drug: Placebo

Study Arms

• 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 *: Not Provided

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: May 23, 2014): 30
• Original Estimated Enrollment: Same as current
• Study Completion Date: Not Provided
• Estimated Primary Completion Date: August 2016 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 21 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, France, Italy, Netherlands, United Kingdom, United States

Administrative Information

• NCT Number: NCT02149160
• Other Study ID Numbers: FRM-0334-002; 2014-001489-85 ( EudraCT Number )
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: FORUM Pharmaceuticals Inc
• Study Sponsor: FORUM Pharmaceuticals Inc
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: FORUM Pharmaceuticals Inc
• Verification Date: May 2015