Facioscapulohumeral Muscular Dystrophy (FSHD)Phase 2FSHDNCT04003974
Efficacy and Safety of Losmapimod in Subjects With Facioscapulohumeral Muscular Dystrophy (FSHD)
A Phase 2 study testing Losmapimod oral tablet in people with Facioscapulohumeral Muscular Dystrophy (FSHD), run by Fulcrum Therapeutics at 17 sites in 4 countries.
Trial summary
This is a study to evaluate the safety and efficacy of Losmapimod in treating patients with Facioscapulohumeral Muscular Dystrophy (FSHD) over 48 weeks. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Facioscapulohumeral Muscular Dystrophy (FSHD)
- What is being tested?
- Losmapimod oral tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 17 sitesin 4 countries
- Study dates
- 9 Aug 2019to 28 Jan 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- The patient must have consented to participate and must have provided signed, dated and witnessed IRB-approved informed consent form that conforms to federal and institutional guidelines.
- Male or female subjects
- Confirmed diagnosis of FSHD1 with 1 to 9 repeats via assessment of the size of the D4Z4 array on chromosome 4. Genetic confirmation must be obtained prior to the screening MRI and baseline muscle biopsy.
- Clinical severity score of 2 to 4 (RICCI Score; Range 0-5), inclusive at screening
- Must have a MRI-eligible muscle for biopsy
- Must be willing and able to comply with scheduled visits, treatment plan, study restrictions, laboratory tests, contraceptive guidelines and other study procedures.
- Will practice an approved method of birth control
Who cannot join
- Has a history of any illness or any clinical condition that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the subject. This may include, but is not limited to, a history of relevant drug or food allergies; history of cardiovascular or central nervous system disease; neuromuscular diseases except FSHD (eg, myopathy, neuropathy, neuromuscular junction disorders); or clinically significant history of mental disease.
- For subjects who are on drug(s) or supplements that may affect muscle function, as determined by the treating physician, or that are included in the list of drugs presented in the protocol, subjects must be on a stable dose of that drug(s) or supplement for at least 3 months prior to the first dose of study drug and remain on that stable dose for the duration of the study. Changes to the dose or treatment discontinuation during the study can only be done for strict medical reasons by the treating physician with clear documentation and notification to the sponsor.
- Acute or chronic history of liver disease or known to have current alanine aminotransferase ≥2 × upper limit of normal (ULN) or total bilirubin >1.5 × ULN, or known history of hepatitis B or C.
- Known severe renal impairment (defined as a glomerular filtration rate of <30 mL/min/1.73m2).
- Positive screen for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, or antibodies against human immunodeficiency virus (HIV)-1 and -2.
- Male subjects with a female partner who is planning to become pregnant during the study or within 90 days after the last dose of study drug.
- Use of another investigational product within 30 days or 5 half-lives (whichever is longer), or according to local regulations, or currently participating in a study with an investigational product. Note: concurrent participation in other non-drug studies may be acceptable if confirmed in writing by the sponsor.
Trial locations and contacts
17 sites in 4 countries.
17 sites in 4 countries
United States12 sites
Kennedy Krieger Institute
Baltimore, Maryland, 21205
Ohio State University
Columbus, Ohio, 43221
University of Florida
Gainesville, Florida, 32610
University of California Irvine
Irvine, California, 92868
University of Kansas Medical Center
Kansas City, Kansas, 66160
University of California Los Angeles (UCLA)
Los Angeles, California, 90095
Virginia Commonwealth University
Richmond, Virginia, 23298
University of Rochester Medical Center
Rochester, New York, 14642
University of Utah
Salt Lake City, Utah, 84132
University of Washinton Medical Center
Seattle, Washington, 98195
Washington University School of Medicine
St Louis, Missouri, 63110
University of Massachusetts Memorial Medical Center
Worcester, Massachusetts, 01655
Canada2 sites
Montreal Neurological Institute and Hospital
Montreal, Quebec, H3A 2B4
Ottawa Hospital Research Institute
Ottawa, Ontario, K1Y 4E9
Spain2 sites
Hospital de la Sta Creu i St Pau
Barcelona, 08041
Hospital UiP La Fe
Valencia, 46026
About this study
Official title: A Phase 2, Randomized, Double-Blind, Placebo-Controlled, 48-Week, Parallel-Group Study of the Efficacy and Safety of Losmapimod in Treating Subjects With Facioscapulohumeral Muscular Dystrophy (FSHD)
This is a study to evaluate the safety and efficacy of Losmapimod in treating patients with Facioscapulohumeral Muscular Dystrophy (FSHD) over 48 weeks.
Read the detailed description
This study is a Phase 2, randomized, double-blind, placebo-controlled, parallel-group, multicenter study designed to evaluate the efficacy and safety of losmapimod in treating patients with Facioscapulohumeral Muscular Dystrophy (FSHD) over 48 weeks. Patients will participate in this study for approximately 53 weeks. This will include a 4-week screening period, a 48-week, placebo-controlled treatment period and a 7 day safety follow-up period. Patients must have a confirmed diagnosis of FSHD1 and genetic confirmation must be obtained prior to the screening MRI and baseline muscle biopsy. Patients will be randomized to receive 15 mg of losmapimod or placebo twice daily given as two 7.5 mg tablets per dose by mouth; for a total of 4 pills or 30 mg daily for 48 weeks. All patients will be asked to attend the study clinic for each scheduled visit.
The primary endpoint of the study is to evaluate the efficacy of losmapimod in inhibiting or reducing expression of DUX4, as measured by a subset of DUX4-regulated gene transcripts in skeletal muscle biopsies of FSHD patients. Secondary endpoints include evaluation of the safety and tolerability of losmapimod, the plasma concentrations of losmapimod, levels of losmapimod in skeletal muscle and losmapimod target engagement in blood and skeletal muscle in FSHD patients.
This study was conducted during the Coronavirus Disease-2019 (COVID-19) Pandemic. The pandemic restrictions limited some assessments in the FSHD1 population in the clinic, including collection of some data for Week 24.
- Being tested
- Losmapimod oral tablet, Placebo oral tablet
- Keywords
- FSHD, FSHD1, Muscular Dystrophies, Muscular Dystrophy, Facioscapulohumeral Muscular Disorders, Musculoskeletal Diseases, Neuromuscular Diseases
- Medical subject headings
- Muscular Dystrophy, Facioscapulohumeral, Muscular Dystrophies, Musculoskeletal Diseases, Neuromuscular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Losmapimod oral tabletDrug
Losmapimod will be administered with food when possible.
Placebo oral tabletDrug
Also called Placebo
Placebo will be administered with food when possible
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | FSHD1 patients with genetic confirmation will receive Losmapimod 15 mg twice daily given as two 7.5 mg tablets per dose by mouth; for a total of 4 pills or 30 mg daily for 48 weeks. Receives: Drug: Losmapimod oral tablet |
| Placebo | Placebo comparator | FSHD1 patients with genetic confirmation will receive a Placebo twice daily given as two 7.5 mg tablets per dose by mouth; for a total of 4 pills or 30 mg daily for 48 weeks. Receives: Drug: Placebo oral tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change From Baseline in Double Homeobox 4 (DUX4) Activity in Affected Skeletal Muscle
Skeletal muscle biopsies were collected at Baseline and post-Baseline. DUX4 activity in skeletal muscle biopsies was assessed by measuring expression levels of a panel of 6 genes known to be regulated by DUX4. Expression levels of genes were measured using a validated quantitative RT-PCR assay and expressed as Ct (PCR cycles). Raw Ct for each of the 6 genes was normalized to the specified reference genes to generate a normalized Ct. The DUX4 activity is the average of the normalized Cts of each of the identified 6 genes, where the Ct for each of the 6 genes is first normalized to reference genes before the average is generated. Change in Baseline is calculated as [average delta Ct across the 6 genes post-baseline] minus [average delta Ct across the 6 genes at baseline].
Measured: Baseline and Week 16 to Week 36
Secondary outcomes (11)
Number of Participants With Type of Adverse Events (AEs) to Losmapimod
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. A Serious adverse event (SAE) is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgment. A treatment emergent adverse events (TEAE) is defined as any event that was not present before exposure to study drug or any event that was already present but worsens in either intensity or frequency after exposure to study drug. Number of participants with type of AEs to losmapimod has been presented which included: TEAEs and SAEs.
Measured: Up to Week 48
Number of Participants With Severity of AEs to Losmapimod
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE is any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgment. Number of participants with severity grading of AEs to losmapimod has been presented: Mild (An event that is usually transient in nature and generally does not interfere with normal activities), Moderate (An AE that is sufficiently discomforting to interfere with normal activities) and Severe (An AE that is incapacitating and prevents normal activities). The higher the grade, the more severe the symptoms.
Measured: Up to Week 48
Number of Participants With Relationship of AEs to Losmapimod
An AE is any untoward medical occurrence in a clinical study participant,temporally associated with use of a study intervention, whether or not considered related to study intervention. An SAE is any untoward medical occurrence that, at any dose results in death,is life-threatening,requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgment. Number of participants with relationship of AEs to losmapimod has been presented:Unlikely related(most likely produced by other factors and temporal relationship of AE to drug makes a causal relationship unlikely),not related (no association between drug and AE), possibly related (treatment with drug caused/contributed to AE),probably related (reasonable temporal sequence of event with drug exists) and definitely related (definite causal relationship exists between drug and AE)
Measured: Up to Week 48
Number of Participants With Adverse Events of Special Interest (AESIs)
An AESI (serious or non-serious) is one of scientific and medical concern for which ongoing monitoring and rapid communication by the investigator to the sponsor can be appropriate. Adverse events of special interest for this study included liver tests that met the criteria for potential drug-induced liver injury (DILI), in accordance with the Unites States (US) Food and Drug Administration (FDA) Guidance for Industry-Drug-Induced Liver Injury: Premarketing Clinical Evaluation. Number of participants with AESIs has been presented.
Measured: Up to Week 48
Number of Participants Who Prematurely Discontinued Study Drug Due to a Treatment Emergent Adverse Event (TEAE)
TEAE was an AE that began on or after the first dose of study drug and before the stop of study drug + 7 days or begins before the first dose of study drug and worsened in severity on or after the first dose of study drug and before the stop of study drug + 7 days. An AE with completely missing onset and end dates were considered as treatment-emergent AE. Number of participants who prematurely discontinued study drug due to a TEAE has been presented.
Measured: Up to Week 48
Change From Baseline in Muscle Fat Fraction (MFF) at Week 12, Week 24 and Week 48
Measurement of the extent of skeletal muscle tissue replacement by fat in FSHD participants were done through automatic skeletal muscle segmentation for the 3D muscle volumes and fat fraction analysis via robust algorithms using Dixon imaging. Composite variables, incorporating pre-selected muscles, were derived for longitudinal analysis of MFF. Baseline was defined as the last non-missing evaluation on or before the day of first dose of study drug. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Measured: Baseline and at Week 12, Week 24 and Week 48
Change From Baseline in Lean Muscle Volume (LMV) at Week 12, Week 24 and Week 48
Measurement of the extent of skeletal muscle tissue replacement by fat in FSHD participants were done through automatic skeletal muscle segmentation for the 3D muscle volumes and fat fraction analysis via robust algorithms using Dixon imaging. Composite variables, incorporating pre-selected muscles, were derived for longitudinal analysis of LMV. Baseline was defined as the last non-missing evaluation on or before the day of first dose of study drug. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Measured: Baseline and at Week 12, Week 24 and Week 48
Change From Baseline in Muscle Fat Infiltration (MFI) at Week 12, Week 24 and Week 48
Measurement of the extent of skeletal muscle tissue replacement by fat in FSHD participants were done through automatic skeletal muscle segmentation for the 3D muscle volumes and fat fraction analysis via robust algorithms using Dixon imaging. Composite variables, incorporating pre-selected muscles, were derived for longitudinal analysis of MFI. Baseline was defined as the last non-missing evaluation on or before the day of first dose of study drug. Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Measured: Baseline and at Week 12, Week 24 and Week 48
Plasma Concentration After Administration of Losmapimod
Blood samples were collected at indicated time points for pharmacokinetic (PK) analysis of losmapimod.
Measured: Pre dose, 4 hours post dose, Week 4 pre dose, Week 4: 4 hours post dose, Week 12, Week 16 pre dose, Week 16: 4 hours post dose, Week 24, Week 36 pre dose, Week 36: 4 hours post dose, Week 48
Concentration of Losmapimod in Skeletal Muscle Biopsy
Skeletal muscle biopsy samples were collected at indicated time points for the assessment of concentration of losmapimod.
Measured: Baseline, Week 16 and Week 36
Percent Change From Baseline in Phosphorylated Heat Shock Protein 27 (pHSP27)/Total Heat Shock Protein 27 (tHSP27)
Blood samples were collected for Pharmacodynamic (PD) analysis of pHSP27/tHSP27. Baseline was defined as the last non-missing evaluation on or before the day of first dose of study drug. Percent change from Baseline was defined as value of post Baseline minus Baseline value divided by Baseline value and multiplied by 100.
Measured: Baseline and at Day 1: 4 hours post dose, Week 16: pre dose, Week 16: 4 hours post dose, Week 36 pre dose, Week 36: 4 hours post dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jul 2019
- Study start9 Aug 2019
- Primary completion28 Jan 2021
- Study completion28 Jan 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Facioscapulohumeral Muscular Dystrophy (FSHD)Studies 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
- Model description
- This study is a randomized, double-blind, placebo-controlled, 48-week parallel-group study.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- Fulcrum Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Michelle Mellion, MD, Study director, Fulcrum Therapeutics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04003974
- Sponsor's protocol ID
- FIS-002-2019
- Acronym
- FSHD
- Status last verified
- Jun 2024
- First submitted
- 25 Jun 2019
- Last updated
- 10 Jul 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Barbour AM, Sarov-Blat L, Cai G, Fossler MJ, Sprecher DL, Graggaber J, McGeoch AT, Maison J, Cheriyan J. Safety, tolerability, pharmacokinetics and pharmacodynamics of losmapimod following a single intravenous or oral dose in healthy volunteers. Br J Clin Pharmacol. 2013 Jul;76(1):99-106. doi: 10.1111/bcp.12063.
PubMed 23215699Cheriyan J, Webb AJ, Sarov-Blat L, Elkhawad M, Wallace SM, Maki-Petaja KM, Collier DJ, Morgan J, Fang Z, Willette RN, Lepore JJ, Cockcroft JR, Sprecher DL, Wilkinson IB. Inhibition of p38 mitogen-activated protein kinase improves nitric oxide-mediated vasodilatation and reduces inflammation in hypercholesterolemia. Circulation. 2011 Feb 8;123(5):515-23. doi: 10.1161/CIRCULATIONAHA.110.971986. Epub 2011 Jan 24.
PubMed 21262998de Greef JC, Lemmers RJ, van Engelen BG, Sacconi S, Venance SL, Frants RR, Tawil R, van der Maarel SM. Common epigenetic changes of D4Z4 in contraction-dependent and contraction-independent FSHD. Hum Mutat. 2009 Oct;30(10):1449-59. doi: 10.1002/humu.21091.
PubMed 19728363Han JJ, Kurillo G, Abresch RT, de Bie E, Nicorici A, Bajcsy R. Reachable workspace in facioscapulohumeral muscular dystrophy (FSHD) by Kinect. Muscle Nerve. 2015 Feb;51(2):168-75. doi: 10.1002/mus.24287. Epub 2014 Nov 19.
PubMed 24828906Jagannathan S, Shadle SC, Resnick R, Snider L, Tawil RN, van der Maarel SM, Bradley RK, Tapscott SJ. Model systems of DUX4 expression recapitulate the transcriptional profile of FSHD cells. Hum Mol Genet. 2016 Oct 15;25(20):4419-4431. doi: 10.1093/hmg/ddw271.
PubMed 28171552Statland JM, Tawil R. Risk of functional impairment in Facioscapulohumeral muscular dystrophy. Muscle Nerve. 2014 Apr;49(4):520-7. doi: 10.1002/mus.23949. Epub 2014 Feb 10.
PubMed 23873337Wang LH, Friedman SD, Shaw D, Snider L, Wong CJ, Budech CB, Poliachik SL, Gove NE, Lewis LM, Campbell AE, Lemmers RJFL, Maarel SM, Tapscott SJ, Tawil RN. MRI-informed muscle biopsies correlate MRI with pathology and DUX4 target gene expression in FSHD. Hum Mol Genet. 2019 Feb 1;28(3):476-486. doi: 10.1093/hmg/ddy364.
PubMed 30312408Tawil R, Wagner KR, Hamel JI, Leung DG, Statland JM, Wang LH, Genge A, Sacconi S, Lochmuller H, Reyes-Leiva D, Diaz-Manera J, Alonso-Perez J, Muelas N, Vilchez JJ, Pestronk A, Gibson S, Goyal NA, Hayward LJ, Johnson N, LoRusso S, Freimer M, Shieh PB, Subramony SH, van Engelen B, Kools J, Leinhard OD, Widholm P, Morabito C, Moxham CM, Cadavid D, Mellion ML, Odueyungbo A, Tracewell WG, Accorsi A, Ronco L, Gould RJ, Shoskes J, Rojas LA, Jiang JG. Safety and efficacy of losmapimod in facioscapulohumeral muscular dystrophy (ReDUX4): a randomised, double-blind, placebo-controlled phase 2b trial. Lancet Neurol. 2024 May;23(5):477-486. doi: 10.1016/S1474-4422(24)00073-5.
PubMed 38631764Jagannathan S, de Greef JC, Hayward LJ, Yokomori K, Gabellini D, Mul K, Sacconi S, Arjomand J, Kinoshita J, Harper SQ. Meeting report: the 2021 FSHD International Research Congress. Skelet Muscle. 2022 Jan 17;12(1):1. doi: 10.1186/s13395-022-00287-8.
PubMed 35039091
Study at a glance
From the registry record, last updated by the sponsor on 10 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Randomized, Double-Blind, Placebo-Controlled, 48-Week, Parallel-Group Study of the Efficacy and Safety of Losmapimod in Treating Subjects With Facioscapulohumeral Muscular Dystrophy (FSHD)
- ClinicalTrials.gov ID
- NCT04003974
- Acronym / sponsor ID
- FSHD / FIS-002-2019
- Keywords
- FSHD, FSHD1, Muscular Dystrophies, Muscular Dystrophy, Facioscapulohumeral Muscular Disorders, Musculoskeletal Diseases, Neuromuscular Diseases
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- Fulcrum TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- 9 Aug 2019 (actual)
- Primary completion
- 28 Jan 2021 (actual)
- Study completion
- 28 Jan 2021 (actual)
- First posted
- 1 Jul 2019 (actual)
- Results
- Posted 10 Jul 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a study to evaluate the safety and efficacy of Losmapimod in treating patients with Facioscapulohumeral Muscular Dystrophy (FSHD) over 48 weeks.
Detailed description
This study is a Phase 2, randomized, double-blind, placebo-controlled, parallel-group, multicenter study designed to evaluate the efficacy and safety of losmapimod in treating patients with Facioscapulohumeral Muscular Dystrophy (FSHD) over 48 weeks. Patients will participate in this study for approximately 53 weeks. This will include a 4-week screening period, a 48-week, placebo-controlled treatment period and a 7 day safety follow-up period. Patients must have a confirmed diagnosis of FSHD1 and genetic confirmation must be obtained prior to the screening MRI and baseline muscle biopsy. Patients will be randomized to receive 15 mg of losmapimod or placebo twice daily given as two 7.5 mg tablets per dose by mouth; for a total of 4 pills or 30 mg daily for 48 weeks. All patients will be asked to attend the study clinic for each scheduled visit.
The primary endpoint of the study is to evaluate the efficacy of losmapimod in inhibiting or reducing expression of DUX4, as measured by a subset of DUX4-regulated gene transcripts in skeletal muscle biopsies of FSHD patients. Secondary endpoints include evaluation of the safety and tolerability of losmapimod, the plasma concentrations of losmapimod, levels of losmapimod in skeletal muscle and losmapimod target engagement in blood and skeletal muscle in FSHD patients.
This study was conducted during the Coronavirus Disease-2019 (COVID-19) Pandemic. The pandemic restrictions limited some assessments in the FSHD1 population in the clinic, including collection of some data for Week 24.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- This study is a randomized, double-blind, placebo-controlled, 48-week parallel-group study.
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Drug: Losmapimod oral tabletFSHD1 patients with genetic confirmation will receive Losmapimod 15 mg twice daily given as two 7.5 mg tablets per dose by mouth; for a total of 4 pills or 30 mg daily for 48 weeks. |
| Placebo | Placebo comparator | Drug: Placebo oral tabletFSHD1 patients with genetic confirmation will receive a Placebo twice daily given as two 7.5 mg tablets per dose by mouth; for a total of 4 pills or 30 mg daily for 48 weeks. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- The patient must have consented to participate and must have provided signed, dated and witnessed IRB-approved informed consent form that conforms to federal and institutional guidelines.
- Male or female subjects
- Confirmed diagnosis of FSHD1 with 1 to 9 repeats via assessment of the size of the D4Z4 array on chromosome 4. Genetic confirmation must be obtained prior to the screening MRI and baseline muscle biopsy.
- Clinical severity score of 2 to 4 (RICCI Score; Range 0-5), inclusive at screening
- Must have a MRI-eligible muscle for biopsy
Key exclusion criteria (7 listed)
- Has a history of any illness or any clinical condition that, in the opinion of the investigator, might confound the results of the study or pose an additional risk in administering study drug to the subject. This may include, but is not limited to, a history of relevant drug or food allergies; history of cardiovascular or central nervous system disease; neuromuscular diseases except FSHD (eg, myopathy, neuropathy, neuromuscular junction disorders); or clinically significant history of mental disease.
- For subjects who are on drug(s) or supplements that may affect muscle function, as determined by the treating physician, or that are included in the list of drugs presented in the protocol, subjects must be on a stable dose of that drug(s) or supplement for at least 3 months prior to the first dose of study drug and remain on that stable dose for the duration of the study. Changes to the dose or treatment discontinuation during the study can only be done for strict medical reasons by the treating physician with clear documentation and notification to the sponsor.
- Acute or chronic history of liver disease or known to have current alanine aminotransferase ≥2 × upper limit of normal (ULN) or total bilirubin >1.5 × ULN, or known history of hepatitis B or C.
- Known severe renal impairment (defined as a glomerular filtration rate of <30 mL/min/1.73m2).
- Positive screen for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody, or antibodies against human immunodeficiency virus (HIV)-1 and -2.
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 |
|---|---|---|
| Losmapimod oral tabletLosmapimod will be administered with food when possible. | Drug | Treatment |
| Placebo oral tabletAlso: PlaceboPlacebo will be administered with food when possible | Drug | Placebo |
Primary outcome
Change From Baseline in Double Homeobox 4 (DUX4) Activity in Affected Skeletal Muscle
Time frame: Baseline and Week 16 to Week 36
Skeletal muscle biopsies were collected at Baseline and post-Baseline. DUX4 activity in skeletal muscle biopsies was assessed by measuring expression levels of a panel of 6 genes known to be regulated by DUX4. Expression levels of genes were measured using a validated quantitative RT-PCR assay and expressed as Ct (PCR cycles). Raw Ct for each of the 6 genes was normalized to the specified reference genes to generate a normalized Ct. The DUX4 activity is the average of the normalized Cts of each of the identified 6 genes, where the Ct for each of the 6 genes is first normalized to reference genes before the average is generated. Change in Baseline is calculated as [average delta Ct across the 6 genes post-baseline] minus [average delta Ct across the 6 genes at baseline].
11 secondary outcomes
Number of Participants With Type of Adverse Events (AEs) to Losmapimod
Time frame: Up to Week 48
Number of Participants With Severity of AEs to Losmapimod
Time frame: Up to Week 48
Number of Participants With Relationship of AEs to Losmapimod
Time frame: Up to Week 48
Number of Participants With Adverse Events of Special Interest (AESIs)
Time frame: Up to Week 48
Number of Participants Who Prematurely Discontinued Study Drug Due to a Treatment Emergent Adverse Event (TEAE)
Time frame: Up to Week 48
Change From Baseline in Muscle Fat Fraction (MFF) at Week 12, Week 24 and Week 48
Time frame: Baseline and at Week 12, Week 24 and Week 48
Change From Baseline in Lean Muscle Volume (LMV) at Week 12, Week 24 and Week 48
Time frame: Baseline and at Week 12, Week 24 and Week 48
Change From Baseline in Muscle Fat Infiltration (MFI) at Week 12, Week 24 and Week 48
Time frame: Baseline and at Week 12, Week 24 and Week 48
Plasma Concentration After Administration of Losmapimod
Time frame: Pre dose, 4 hours post dose, Week 4 pre dose, Week 4: 4 hours post dose, Week 12, Week 16 pre dose, Week 16: 4 hours post dose, Week 24, Week 36 pre dose, Week 36: 4 hours post dose, Week 48
Concentration of Losmapimod in Skeletal Muscle Biopsy
Time frame: Baseline, Week 16 and Week 36
Percent Change From Baseline in Phosphorylated Heat Shock Protein 27 (pHSP27)/Total Heat Shock Protein 27 (tHSP27)
Time frame: Baseline and at Day 1: 4 hours post dose, Week 16: pre dose, Week 16: 4 hours post dose, Week 36 pre dose, Week 36: 4 hours post dose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jul 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 23215699Barbour AM, Sarov-Blat L, Cai G, Fossler MJ, Sprecher DL, Graggaber J, McGeoch AT, Maison J, Cheriyan J. Safety, tolerability, pharmacokinetics and pharmacodynamics of losmapimod following a single intravenous or oral dose in healthy volunteers. Br J Clin Pharmacol. 2013 Jul;76(1):99-106. doi: 10.1111/bcp.12063.
- Background: PubMed 21262998Cheriyan J, Webb AJ, Sarov-Blat L, Elkhawad M, Wallace SM, Maki-Petaja KM, Collier DJ, Morgan J, Fang Z, Willette RN, Lepore JJ, Cockcroft JR, Sprecher DL, Wilkinson IB. Inhibition of p38 mitogen-activated protein kinase improves nitric oxide-mediated vasodilatation and reduces inflammation in hypercholesterolemia. Circulation. 2011 Feb 8;123(5):515-23. doi: 10.1161/CIRCULATIONAHA.110.971986. Epub 2011 Jan 24.
- Background: PubMed 19728363de Greef JC, Lemmers RJ, van Engelen BG, Sacconi S, Venance SL, Frants RR, Tawil R, van der Maarel SM. Common epigenetic changes of D4Z4 in contraction-dependent and contraction-independent FSHD. Hum Mutat. 2009 Oct;30(10):1449-59. doi: 10.1002/humu.21091.
- Background: PubMed 24828906Han JJ, Kurillo G, Abresch RT, de Bie E, Nicorici A, Bajcsy R. Reachable workspace in facioscapulohumeral muscular dystrophy (FSHD) by Kinect. Muscle Nerve. 2015 Feb;51(2):168-75. doi: 10.1002/mus.24287. Epub 2014 Nov 19.
- Background: PubMed 28171552Jagannathan S, Shadle SC, Resnick R, Snider L, Tawil RN, van der Maarel SM, Bradley RK, Tapscott SJ. Model systems of DUX4 expression recapitulate the transcriptional profile of FSHD cells. Hum Mol Genet. 2016 Oct 15;25(20):4419-4431. doi: 10.1093/hmg/ddw271.
- Background: PubMed 23873337Statland JM, Tawil R. Risk of functional impairment in Facioscapulohumeral muscular dystrophy. Muscle Nerve. 2014 Apr;49(4):520-7. doi: 10.1002/mus.23949. Epub 2014 Feb 10.
- Background: PubMed 30312408Wang LH, Friedman SD, Shaw D, Snider L, Wong CJ, Budech CB, Poliachik SL, Gove NE, Lewis LM, Campbell AE, Lemmers RJFL, Maarel SM, Tapscott SJ, Tawil RN. MRI-informed muscle biopsies correlate MRI with pathology and DUX4 target gene expression in FSHD. Hum Mol Genet. 2019 Feb 1;28(3):476-486. doi: 10.1093/hmg/ddy364.
- Derived from this study: PubMed 38631764Tawil R, Wagner KR, Hamel JI, Leung DG, Statland JM, Wang LH, Genge A, Sacconi S, Lochmuller H, Reyes-Leiva D, Diaz-Manera J, Alonso-Perez J, Muelas N, Vilchez JJ, Pestronk A, Gibson S, Goyal NA, Hayward LJ, Johnson N, LoRusso S, Freimer M, Shieh PB, Subramony SH, van Engelen B, Kools J, Leinhard OD, Widholm P, Morabito C, Moxham CM, Cadavid D, Mellion ML, Odueyungbo A, Tracewell WG, Accorsi A, Ronco L, Gould RJ, Shoskes J, Rojas LA, Jiang JG. Safety and efficacy of losmapimod in facioscapulohumeral muscular dystrophy (ReDUX4): a randomised, double-blind, placebo-controlled phase 2b trial. Lancet Neurol. 2024 May;23(5):477-486. doi: 10.1016/S1474-4422(24)00073-5.
- Derived from this study: PubMed 35039091Jagannathan S, de Greef JC, Hayward LJ, Yokomori K, Gabellini D, Mul K, Sacconi S, Arjomand J, Kinoshita J, Harper SQ. Meeting report: the 2021 FSHD International Research Congress. Skelet Muscle. 2022 Jan 17;12(1):1. doi: 10.1186/s13395-022-00287-8.
- Individual participant dataSharing planned: No
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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.
Michelle Mellion, MD study director
Fulcrum Therapeutics
17 sites in 4 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Losmapimod oral tablet in people with Facioscapulohumeral Muscular Dystrophy (FSHD), run by Fulcrum Therapeutics at 17 sites in 4 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 7 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: finished, as of the sponsor's last update on 10 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in United States, Canada, Spain, France. 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?
Yes. Results are posted in the registry (first posted 10 Jul 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Change From Baseline in Double Homeobox 4 (DUX4) Activity in Affected Skeletal Muscle (time frame: Baseline and Week 16 to Week 36). 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 NCT04003974, which also lists 9 linked publications.
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 10 Jul 2024.