Granulin MutationPhase 2NCT02149160
Study to Assess the Safety, Tolerability, and Pharmacodynamic (PD) Effects of FRM-0334 in Subjects With Prodromal to Moderate Frontotemporal Dementia With Granulin Mutation
A Phase 2 study testing FRM-0334 in people with Granulin Mutation, run by FORUM Pharmaceuticals Inc at 13 sites in 6 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 to 75 years
- Conditions the study is for
- Granulin Mutation
- What is being tested?
- FRM-0334
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 13 sitesin 6 countries
- Study dates
- Oct 2014to Aug 2016
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
Who cannot join
- 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
Trial locations and contacts
13 sites in 6 countries.
13 sites in 6 countries
United States5 sites
Massachusetts General Hospital
Boston, Massachusetts
Compass Research, LLC
Orlando, Florida
Perelman School of Medicine, University of Pennsylvania
Philadelphia, Pennsylvania
Mayo Clinic
Rochester, Minnesota
UCSF Memory and Aging Center
San Francisco, California
Italy3 sites
IRCCS - Centro S. Giovanni di Dio FateBeneFratelli
Brescia
Neurological Clinic, University of Brescia, AO Civil Hospital of Brescia
Brescia
Fondazione Universita Gabriele D'Annunzio di Chieti
Chieti Scalo
France2 sites
CHU Bordeaux Hospital Pellegrin
Bordeaux
CHU Rouen, Charles Nicolle Hospital
Rouen
United Kingdom1 site
The National Hospital for Neurology and Neuroscience
London
About this study
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
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.
- Conditions
- Granulin Mutation
- Being tested
- FRM-0334, Placebo
- Keywords
- Histone deacetylase inhibitor, Frontotemporal dementia, Granulin
- Medical subject headings
- Frontotemporal Dementia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FRM-0334Drug
PlaceboDrug
| Study group | Role | What they receive |
|---|---|---|
| FRM-0334; Arm 1 | Experimental | low dose, Capsule, Once Daily, Day 1 through Day 28 Receives: Drug: FRM-0334 |
| FRM-0334; Arm 2 | Experimental | high dose, Capsule, Once Daily, Day 1 through Day 28 Receives: Drug: FRM-0334 |
| Placebo Comparator; Arm 3 | Placebo comparator | Placebo, Capsule, Once Daily, Day 1 through Day 28 Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Measured: Baseline to Day 28 or Early Termination
Secondary outcomes (3)
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
Measured: Baseline and Day 28
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
Measured: Day 1 to Day 28 or Early Termination
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
Measured: Day 1 to Day 28 or Early Termination
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 May 2014 (estimated)
- Study startOct 2014
- Primary completionAug 2016 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Granulin MutationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- FORUM Pharmaceuticals Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02149160
- Sponsor's protocol ID
- FRM-0334-002
- Other IDs
- 2014-001489-85, 2014
- Status last verified
- May 2015
- First submitted
- 20 May 2014
- Last updated
- 23 Mar 2016
- Results posted
- No
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.
PubMed 34559230
Study at a glance
From the registry record, last updated by the sponsor on 23 Mar 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT02149160
- Acronym / sponsor ID
- FRM-0334-002
- Conditions
- Granulin Mutation
- Keywords
- Histone deacetylase inhibitor, Frontotemporal dementia, Granulin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- FORUM Pharmaceuticals IncIndustry (pharma, biotech, devices)
- Study start
- Oct 2014
- Primary completion
- Aug 2016 (estimated)
- First posted
- 29 May 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| FRM-0334; Arm 1 | Experimental | Drug: FRM-0334low dose, Capsule, Once Daily, Day 1 through Day 28 |
| FRM-0334; Arm 2 | Experimental | Drug: FRM-0334high dose, Capsule, Once Daily, Day 1 through Day 28 |
| Placebo Comparator; Arm 3 | Placebo comparator | Drug: PlaceboPlacebo, Capsule, Once Daily, Day 1 through Day 28 |
Who may qualify
- Ages
- 21 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (2 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FRM-0334 | Drug | FRM-0334; Arm 1, FRM-0334; Arm 2 |
| Placebo | Drug | Placebo Comparator; Arm 3 |
Primary outcome
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
3 secondary outcomes
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
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
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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Mar 2016.
- Derived from this study: PubMed 34559230Ljubenkov 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
13 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing FRM-0334 in people with Granulin Mutation, run by FORUM Pharmaceuticals Inc at 13 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 23 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in United States, Italy, France, Belgium, Netherlands and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Evaluate the safety and tolerability of FRM-0334 (time frame: Baseline to Day 28 or Early Termination). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02149160, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Mar 2016.