Clinical Trials Register

Summary
EudraCT Number:	2022-000389-16
Sponsor's Protocol Code Number:	1821-FSH-301
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Trial now transitioned
Date on which this record was first entered in the EudraCT database:	2022-05-17
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

France - ANSM

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 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.4.1

Sponsor's protocol code number

1821-FSH-301

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	Christopher Morabito
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	+1617651-8851
B.5.6	E-mail	cmorabito@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

To evaluate the efficacy of losmapimod for the treatment of FSHD by demonstrating slowing of disease progression assessed by RWS quantification of RSA Q1-Q5 with 500 g wrist weight in the dominant arm.

E.2.2

Secondary objectives of the trial

1. To evaluate the change in Neuro-QoL UE relative to placebo
2. To evaluate Patient Global Impression of Change (PGIC) relative to placebo
3. To evaluate efficacy of losmapimod to slow accumulation of fat in muscle by MFI with WB MSK MRI relative to placebo
4. To assess safety and tolerability of losmapimod in patients with FSHD

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

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 baseline total RSA (Q1-Q4) without weight in the dominant UE assessed by RWS ≥ 0.2 and ≤ 0.7.
5. At least one short tau inversion recovery (STIR)-positive muscle in the lower extremities.
6. Willing and able to comply with scheduled visits, treatment plan, study restrictions, laboratory tests, contraceptive guidelines, and other study procedures.
7. No contraindications to MRI.
8. Patients (male and female) will be between the ages of 18 and 65 years, 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; if she is postmenopausal, defined as 12 months of spontaneous amenorrhea; OR
− if of child-bearing potential, she is using a highly effective method for avoidance of pregnancy for the duration of dosing and until 2 weeks 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.

E.4

Principal exclusion criteria

1. 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 patient. 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.
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, as determined by the Investigator, or that are included in the list of drugs presented in
Appendix 2 of the Protocol: patients 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.
4. History of febrile illness within 5 days before the first study drug dose. Patients who were healthy during screening but develop febrile illness in the 5 days before randomization need to have the baseline visit postponed until the febrile illness is fully resolved (fever-free without the use of antipyretic agents for 24 hours). Once the febrile illness is fully resolved, the patient’s baseline visit can be scheduled. The duration of the screening period in such cases can be extended to up to 35 days.
5. Known active opportunistic or life-threatening infections including HIV and hepatitis B or C.
6. Acute or chronic history of liver disease or known to have current ALT ≥2 × upper limit of normal (ULN) or total bilirubin >1.5 × ULN or known history of hepatitis B or C.
7. Known severe renal impairment (defined as a glomerular filtration rate of < 30 mL/min/1.73 m2).
8. 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.
9. 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 patient’s participation in the study.
10. 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.
11. Concomitant use of cytotoxic chemotherapy for cancer or known ongoing or anticipated use of chronic severe immunosuppressive agents.
12. Positive pregnancy test or known to be pregnant or lactating.
13. Any current mental condition (psychiatric disorder, senility or dementia) that may affect study compliance or prevent understanding of the aims, investigational procedures, or possible consequences of the study.
14. Patient has any condition possibly affecting drug absorption (eg, gastrectomy, cholecystectomy, or other gastrointestinal tract surgery, except appendectomy).
15. 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.
16. 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 of an investigational device.
17. Anticipated inability to comply with any study procedures, including participation in study visits according to the visit schedule through 48 weeks.
18. Abnormal laboratory results indicative of any significant medical disease that, in the opinion of the Investigator, would preclude the patient's participation in the study.
19. Patient, or close relative of the patient, 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.

E.5 End points

E.5.1

Primary end point(s)

Change from baseline compared to placebo in total RSA Q1-Q5 with 500 g wrist weight in dominant arm at Week 48

E.5.1.1

Timepoint(s) of evaluation of this end point

RSA Q1-Q5 with 500 g wrist weight in dominant arm at Week 48

E.5.2

Secondary end point(s)

1. Change from baseline compared to placebo in Neuro-QoL UE at Week 48
2. Change from baseline compared to placebo in PGIC at Week 48
3. Change from baseline compared to placebo in WB longitudinal composite MFI at Week 48
4. Safety and tolerability, based on the assessment of AEs, SAEs, clinically significant laboratory test abnormalities, ECGs, and vital signs

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 States

France

Netherlands

Spain

Germany

Italy

Denmark

United Kingdom

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

E.8.9.2

In all countries concerned by the trial days

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:

230

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

F.4.2.2

In the whole clinical trial

230

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)

None

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

2022-07-12

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2022-08-08

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

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