A Phase 3 Global, Randomized, Double-Blind, Placebo-Controlled, 48-Week, ParallelGroup Study of the Efficacy and Safety of Losmapimod in Treating Patients with Facioscapulohumeral Muscular Dystrophy (REACH)

Part A:
* Patients will have a diagnosis of FSHD1 or FSHD2 verified by genetic testing
* Patients will have a Clinical Severity Score of 2 to 4 (Ricci score; range 0
to 5) at screening. Patients who are wheelchair-dependent or dependent on
walker or wheelchair for activities are not permitted to enroll in the study.
* Patients with screening total RSA (Q1-Q4) without weight in the dominant UE
assessed by RWS >= 0.2 and <= 0.7.
* No contraindications to MRI.
* Patients (male and female) will be between the ages of 18 and 65 years at the
time of consent, inclusive
* A female patient is eligible to participate if she is of non-child bearing
potential, defined as pre-menopausal females with a documented hysterectomy,
bilateral salpingectomy, or bilateral oophorectomy; if she is postmenopausal,
defined as no menses for 12 months without an alternative medical cause; OR if
of child-bearing potential, she is using a highly effective method for
avoidance of pregnancy for the duration of dosing and until 90 days after the
last dose of study drug.
* Male patients must agree to use one of the contraception methods listed in
Section 5.5.1 of the protocol from the time of the first dose of study
medication and until 90 days after the last dose of study drug.

Part B:
* Patient completed 48 weeks of treatment during Part A.
* Female patients of childbearing potential agree to continue using a highly
effective method for avoidance of pregnancy for the duration of dosing and
until 90 days after the last dose.
* Male patients must agree to use one of the contraception methods listed in
Section 5.5.1 of the protocol from the time of the first dose of study
medication and until 90 days after the last dose of study drug.

Part A:
* Hx of any illness or any clinical condition that might confound the results
of the study or pose an additional risk in administering study drug to the
patient.
* Previously diagnosed cancer that has not been in complete remission for at
least 5 years. Localized carcinomas of the skin and carcinoma in situ of the
cervix that have been resected or ablated for cure are not exclusionary.
* For patients who are on drug(s) or supplements that may affect muscle
function or that are included in the list of drugs presented in Appendix 3 of
the Protocol: pt 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.
* History of febrile illness within 5 days before the first study drug dose
* Known active opportunistic or life-threatening infections including HIV and
hepatitis B or C
* Known active or inactive tuberculosis infection.
* Current acute liver disease or chronic liver disease as defined by any of the
following: current ALT >=2 × upper limit of normal (ULN) or total bilirubin >1.5
× ULN (unless participant has Gilbert's syndrome characterized by the
combination of total bilirubin < 3 × ULN, direct bilirubin within the normal
range and normal ALT and AST, or the presence of mutations in the UDP
glucuronosyltransferase 1 gene, indicative of Gilbert's syndrome); or Positive
for hepatitis B or surface antigen; or Positive for hepatitis C antibody unless
additional testing for hepatitis C viral RNA is negative, ALT is < 2 × ULN and
total bilirubin is <= 1.5 × ULN, indicating inactive/resolved hepatitis C
infection
* Known severe renal impairment (defined as a glomerular filtration rate of <
30 mL/min/1.73 m2).
* Standard 12-lead ECG demonstrating QTcF >450 msec for male patients and QTcF
>470 msec for female patients at screening. If QTcF exceeds 450 msec for males
or 470 msec for females, the ECG will be repeated 2 more times, and the average
of the 3 QTcF values will be used to determine the patient's eligibility.
* History of cardiac dysrhythmias requiring anti-arrhythmia treatment(s); or
history or evidence of abnormal ECGs
* Male patients with a female partner who is planning to become pregnant during
the study or within 90 days after the last study drug dose
* Concomitant use of cytotoxic chemotherapy for cancer or known ongoing or
anticipated use of chronic severe immunosuppressive agents.
* Positive pregnancy test or known to be pregnant or lactating or planning to
become pregnant during study drug administration and until 90 days after last
dose
* Any current mental condition (psychiatric disorder, senility or dementia)
* Patient has any condition possibly affecting drug absorption
* History of alcohol, analgesic/opioid, and/or illicit drug abuse, as defined
by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition
(American Psychiatric Association, 2013), in the last 6 months before screening
or a positive test for drugs of abuse at screening. Use of CBD/THC is permitted
* Use of another IP within 30 days or 5 half-lives
* Current or anticipated participation in a natural hx study.
* Known hypersensitivity or intolerance to losmapimod or any of its excipients
* Previous participation in a Fulcrum-sponsored FSHD losmapimod study
* Abnormal laboratory results indicative of any significant medical disease

Part B:
* 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 patient.
* Male patients with a female partner who is planning to become pregnant during
the study or within 90 days after the last study drug dose.
- Anticipated inability to comply with any study procedures, including
participation in study visits.