Clinical Trials Register

Summary
EudraCT Number:	2022-000389-16
Sponsor's Protocol Code Number:	1821-FSH-301
National Competent Authority:	Denmark - DHMA
Clinical Trial Type:	EEA CTA
Trial Status:	Trial now transitioned
Date on which this record was first entered in the EudraCT database:	2022-07-13
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Denmark - DHMA

A.2

EudraCT number

2022-000389-16

A.3

Full title of the trial

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

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A Phase 3 study to determine the Efficacy and Safety of Losmapimod in Treating Patients with Facioscapulohumeral Muscular Dystrophy

A.4.1

Sponsor's protocol code number

1821-FSH-301

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT05397470

A.5.4

Other Identifiers

Name:

IND

Number:

138739

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Fulcrum Therapeutics
B.1.3.4	Country	United States
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Fulcrum Therapeutics, Inc.
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Fulcrum Therapeutics, Inc.
B.5.2	Functional name of contact point	Marie-Helene Jouvin
B.5.3	Address:
B.5.3.1	Street Address	26 Landsdowne Street, 5th floor
B.5.3.2	Town/ city	Cambridge
B.5.3.3	Post code	02139
B.5.3.4	Country	United States
B.5.4	Telephone number	+1617678 4980
B.5.6	E-mail	mjouvin@fulcrumtx.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	Yes
D.2.5.1	Orphan drug designation number	EU/3/20/2263
D.3 Description of the IMP
D.3.1	Product name	Losmapimod
D.3.2	Product code	FTX-1821
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Losmapimod
D.3.9.1	CAS number	585543-15-3
D.3.9.2	Current sponsor code	FTX-1821
D.3.9.4	EV Substance Code	SUB189237
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	15
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Tablet
D.8.4	Route of administration of the placebo	Oral use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Facioscapulohumeral Muscular Dystrophy

E.1.1.1

Medical condition in easily understood language

Muscular Disease

E.1.1.2

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	PT
E.1.2	Classification code	10064087
E.1.2	Term	Facioscapulohumeral muscular dystrophy
E.1.2	System Organ Class	10010331 - Congenital, familial and genetic disorders

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

Part A:
To evaluate the efficacy of losmapimod for the treatment of FSHD on
disease progression assessed by RWS quantification of total RSA Q1-Q5with 500 g wrist weight averaged over both arms.

Part B:
To assess the long-term safety and tolerability of losmapimod in patients with FSHD

E.2.2

Secondary objectives of the trial

Part A:
1. To evaluate PGIC relative to placebo
2. To evaluate efficacy of losmapimod to slow accumulation of fat in
muscle by MFI with WB MSK MRI relative to placebo
3. To evaluate relative change from baseline in shoulder strength by
hand-held quantitative dynamometry relative to placebo
4. To evaluate the change in Neuro-QoL UE relative to placebo
5. To assess safety and tolerability of losmapimod in patients with FSHD

Part B: No Secondary objectives

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Part A:
1. Patient will sign and date an informed consent form (ICF).
2. Patients will have a diagnosis of FSHD1 or FSHD2 verified by genetic testing
− Randomization will be stratified for FSHD1 to ensure that treatment allocation is balanced across FSHD repeat number categories (ie, 1 to 3 repeats versus 4 to 9 repeats).
− Randomization will be stratified for FSHD2 to ensure that an equal number of patients will be allocated to treatment and placebo.
3. 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.
4. Patients with screening total RSA (Q1-Q4) without weight in the dominant UE assessed by RWS ≥ 0.2 and ≤ 0.7.
5. Willing and able to comply with scheduled visits, treatment plan, study restrictions, laboratory tests, contraceptive guidelines, and other study procedures.
6. No contraindications to MRI.
7. 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 tubal ligation or 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. 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.
− Male patients must agree to use one of the contraception methods. This criterion must be followed from the time of the first dose of study medication and until 90 days after the last dose of study drug.

Part B:
1. Patient completed 48 weeks of treatment during Part A.
2. Patient will sign and date an ICF.
3. Patient is willing and able to comply with scheduled visits, treatment plan, study restrictions, laboratory tests, contraceptive guidelines, and
other study procedures.
4. Patients agree to the following methods of contraception:
- 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. For details regarding contraception requirements. 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.
- Male patients must agree to use one of the contraception methods listed in Section 5.5.1 of the protocol. This criterion must be followed
from the time of the first dose of study medication and until 90 days after the last dose of study drug.

E.4

Principal exclusion criteria

Part A:
1. 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.
2. 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.
3. 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.
4. History of febrile illness within 5 days before the first study drug dose
5. Known active opportunistic or life-threatening infections including
HIV and hepatitis B or C
6. Known active or inactive tuberculosis infection.
7. 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 forhepatitis C viral RNA is negative, ALT is < 2 × ULN and total bilirubin is ≤ 1.5 × ULN, indicating inactive/resolved hepatitis C infection
8. Known severe renal impairment (defined as a glomerular filtration
rate of < 30 mL/min/1.73 m2).
9. 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.
10. History of cardiac dysrhythmias requiring anti-arrhythmia
treatment(s); or history or evidence of abnormal ECGs
11. 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
12. Concomitant use of cytotoxic chemotherapy for cancer or known
ongoing or anticipated use of chronic severe immunosuppressive agents.
13. 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
14. Any current mental condition (psychiatric disorder, senility or
dementia)
15. Patient has any condition possibly affecting drug absorption
16. 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
17. Use of another IP within 30 days or 5 half-lives
18. Current or anticipated participation in a natural hx study.
19. Known hypersensitivity or intolerance to losmapimod or any of its excipients
20. Previous participation in a Fulcrum-sponsored FSHD losmapimod
study
21. Anticipated inability to comply with any study procedures, study
visits according to the visit schedule through 48 weeks.
22. Abnormal laboratory results indicative of any significant medical
disease
23. Pt, or close relative of the patient to staff directly involved with the conduct of the study
24. Pt is vulnerable (i.e., deprived of freedom), including inmates of
psychiatric wards and prison or state institutions, patients with
commitments to an institution, or a patient who is detained or
committed to an institution by a law court or by legal authorities.
25. For Italy only: Vaccination with a live attenuated vaccine within 6
weeks prior to randomization until the safety follow-up visit

Part B:
1. 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.
2. 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.
3. Anticipated inability to comply with any study procedures, including participation in study visits.

E.5 End points

E.5.1

Primary end point(s)

Part A:
Change from baseline in average total RSA Q1-Q5 with 500 g wrist
weight at Week 48, where average is applied over both arms

Part B:
Safety and tolerability of long-term treatment with losmapimod, based on the assessment of AEs, clinical laboratory tests, ECGs, vital signs, and physical examinations

E.5.1.1

Timepoint(s) of evaluation of this end point

RSA Q1-Q5 with 500 g wrist weight at Week 48, where average is
applied over both arms

E.5.2

Secondary end point(s)

Part A:
1. PGIC at Week 48
2. Change from baseline in WB longitudinal composite MFI of B muscles
at Week 48
3. Relative change from baseline in average shoulder abductor strength
by hand-held quantitative dynamometry at Week 48
4. Change from baseline in Neuro-QoL UE at Week 48
5. Safety and tolerability, based on the assessment of AEs, clinical
laboratory tests , ECGs, vital signs and physical examinations.

Part B: No secondary endpoints

E.5.2.1

Timepoint(s) of evaluation of this end point

At Week 48 and throughout the study

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

Yes

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Canada

United Kingdom

United States

Denmark

France

Germany

Italy

Netherlands

Spain

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

The end of the study is defined as the date on which the last patient completes the last visit (includes the safety follow-up visit).

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

260

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

144

F.4.2.2

In the whole clinical trial

260

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

All patients who discontinue from treatment early or who choose not to rollover into Part B will return for a complete safety follow-up visit 7±3 days after the last dose of study drug and will complete a safety follow-up phone screen 30±5 days after the last dose of study drug. Patients may continue to receive study drug in Part B for the duration of the study as specified in the visit schedule on the Protocol (Table 8) or until the study is discontinued by the sponsor.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2022-08-25

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-08-26

P. End of Trial
P.	End of Trial Status	Trial now transitioned

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