An Open-Label Pilot Study of Losmapimod to Evaluate the Safety, Tolerability, and Changes in Biomarker and Clinical Outcome Assessments in Subjects With Facioscapulohumeral Muscular Dystrophy 1 (FSHD1) with Extension

1.FSHD1 subjects age 18-65 years., 2.Subject will sign and date an informed
consent form (ICF)., 3.3. Subjects will have a confirmed diagnosis of FSHD1
with 1 to 9 repeats via assessment of the size of the D4Z4 array on chromosome
4 using the calculator provided by the sponsor. Genetic confirmation must be
obtained prior to the screening MRI and baseline muscle biopsy; genetic
confirmation can come from previous testing if verified with appropriate
documentation. Due to stable transmission of repeat sizes within families,
subjects with a clinical diagnosis of FSHD who have a first degree relative
with a genetically confirmed diagnosis of FSHD1 may be entered into the study
for screening and MRI. During screening, a confirmatory genetic diagnosis is
conducted. If genetic testing during screening is necessary, the 4-week
screening window will not start until the results are obtained and verified by
the principal investigator. , 4.Subject will be willing and able to comply with
scheduled visits, treatment plan, study restrictions, laboratory tests,
contraceptive guidelines, scheduled needle muscle biopsies, and other study
procedures., 5.Male or female subjects:, a.A female subject is eligible to
participate if she is of non-childbearing potential defined as pre-menopausal
females with a documented tubal ligation or hysterectomy; or postmenopausal
defined as 12 months of spontaneous amenorrhoea or if of childbearing potential
is using a highly effective method for avoidance of pregnancy (refer to Section
5.5) for the duration of the clinical trial and until 90 days following the
last dose. The decision to include or exclude women of childbearing potential
may be made at the discretion of the investigator and in accordance with local
practice in relation to adequate contraception., b.Male subjects must agree to
use one of the contraception methods listed in Section 5.5. This criterion must
be followed from the time of the first dose of study medication until 90 days
after the last study drug dose., 6. Subject has a Clinical Severity Score
between 2 and 4 on Ricci*s scale (scale range is from 0 to 5). Patients that
use a wheelchair or walker for any activity are not permitted to enroll in the
study., 7. Subject commitment to complete the 2 visits for skeletal muscle
needle biopsy and all visits for whole body MRI., 8. Subject is able to
complete the RWS, TUG, and FSHD PROs (FSHD-RODS and FSHD HI) at the screening
visit., 9. Subject has an MRI-eligible muscle for biopsy as determined by the
central reader.

1. Subject 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, history of relevant drug or food allergies; history of
cardiovascular or central nervous system disease; history or presence of
clinically significant pathology; clinically significant history of mental
disease; and history of cancer, except for squamous cell skin cancer, basal
cell skin cancer, and Stage 0 cervical carcinoma in situ (all 3 with no
recurrence for the last 5 years)., 2. Subject has a known or clinically
suspected infection with human immunodeficiency virus or hepatitis B or C
viruses., 3. Subject has current clinically significant liver or kidney
dysfunction., 4. Subject screens positive for hepatitis B surface antigen,
hepatitis C virus (HCV) antibody, or antibodies against human immunodeficiency
viruses 1 and 2 (HIV 1/HIV 2 antibodies)., 5. Subject has any condition
possibly affecting drug absorption (eg, gastrectomy, cholecystectomy, or other
gastrointestinal tract surgery, except appendectomy)., 6. Subject has a
standard 12-lead ECG demonstrating QT interval by Fredericia (QTcF) >450 msec
for male subjects and QTcF >470 msec for female subjects 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
subject*s eligibility., 7. Subject has a history of cardiac dysrhythmias
requiring anti-arrhythmia treatment(s); or history or evidence of abnormal ECGs
that, in the opinion of the investigator or Medical Monitor, would preclude the
subject*s participation in the study., 8. Male subject has a female partner who
is planning to become pregnant during the study or within 90 days after the
last study drug dose., 9. Subject has donated blood (of approximately 1 pint
[500 mL] or more) or has had any significant loss of blood within 90 days
before the first study drug dose, as determined by the investigator., 10.
Vaccination with a live attenuated vaccine within 6 weeks of randomization.,
11. Subject has a history of alcohol, analgesic/opioid, and/or illicit drug
abuse as defined by the American Psychiatric Association Diagnostic and
Statistical Manual of Mental Disorders, Fifth Edition, in the last 6 months
before screening, or a positive test for drugs of abuse at screening.
12. Subject has participated in a clinical trial in which they have received an
investigational product within the following time period prior to enrolment in
the current study: 30 days, 5 half-lives or twice the duration of the
biological effect of the investigational product (whichever was longer)., 13.
For subjects that are on drug(s) or supplements that may affect muscle function
as determined by the treating physician or included in the list of drugs
presented in Appendix 15.1: subjects must be on a stable dose of that drug(s)
or supplement for at least 3 months prior to enrolment in the study and remain
on that stable dose for the duration of the study (list of drugs presented in
Appendix 15.1). 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., 14. Subject has a
history of sensitivity to any of the study medications or components thereof,
or a history of drug or other allergy that, in the opinion of the investigator
or Medical Monitor, contraindicated their participation., 15. Female subject is
pregnant as determined by positive urine human Chorionic Gonadotropin test at
Screening or prior to dosing., 16. Female subject is lactating., 17. Subject is
unwilling or unable to follow the procedures outlined in the protocol., 18.
Subject has any contraindication for MRI (including severe claustrophobia and
any shrapnel or metal implants in the body that are not MRI compatible)., 19.
Subject was mentally or legally incapacitated up to 2 years prior to
enrolment., 20. Subject has abnormal laboratory results indicative of any
significant medical disease that, in the opinion of the investigator or the
medical monitor, would preclude the subject*s participation in the study., 21.
Subject, or close relative of the subject, is the investigator or a
subinvestigator, research assistant, pharmacist, study coordinator, or other
staff directly involved with the conduct of the study at that site., 22.
Subject has taken any anticoagulants for at least 1 month and anti-platelet
agents for at least 1 week before each muscle biopsy. Such agents are
prohibited, as they increase the risk of hematomas following skeletal muscle
needle biopsy.