Evaluation of Safety, Tolerability, and Changes in Biomarker and Clinical Outcome Assessments of Losmapimod for FSHD1 With Extension (FSHD)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fulcrum Therapeutics Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Musculoskeletal Diseases [C05], Diseases [C] - Nervous System Diseases [C10]

Trial duration

23 Aug 2019 → 1 Nov 2024

Decision date (initial)

2024-06-11

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Fulcrum Therapeutics

External identifiers

EU CT number

2024-512736-29-00

EudraCT number

2019-001006-20

ClinicalTrials.gov

NCT04004000

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Pharmacokinetic, Others, Safety

To evaluate the safety and tolerability of long-term dosing of losmapimod tablets in subjects with FSHD1

Conditions and MedDRA coding

Facioscapulohumeral Muscular Dystrophy 1 (FSHD1)

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. 1. FSHD1 subjects age 18-65 years.
2. 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. 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. 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. 6. Subject has a Clinical Severity Score between 2 and 4 on Ricci’s scale (scale range is from 0 to 5). Subjects that use a wheelchair or walker for any activity are not permitted to enroll in the study.
7. 7. Subject commitment to complete the 2 visits for skeletal muscle needle biopsy and all visits for whole-body MRI.
8. 8. Subject is able to complete the RWS, Timed Up and Go (TUG), and FSHD patientreported outcomes (PROs) (FSHD-RODS and FSHD-HI) at the screening visit.
9. 9. Subject has an MRI-eligible muscle for biopsy as determined by the central reader.
10. 10. Subject must complete the main study through the Week 60 visit in order to participate in the extension.

Exclusion criteria 22

1. 1. Subject has a history 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 subject.
2. 2. Subject has a known or clinically suspected infection with human immunodeficiency virus or hepatitis B or C viruses.
3. 3. Subject has current clinically significant liver or kidney dysfunction.
4. 4. Subject screens positive for hepatitis B surface antigen, HCV antibody, or antibodies against HIV 1/HIV 2 antibodies.
5. 5. Subject has any condition possibly affecting drug absorption,
6. 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.
7. 7. Subject has a history of cardiac dysrhythmias requiring anti-arrhythmia treatment(s); or history or evidence of abnormal ECGs that would preclude the subject’s participation in the study.
8. 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. 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
10. 10. Vaccination with a live attenuated vaccine within 6 weeks of randomisation.
11. 11. Subject has a history of alcohol, analgesic/opioid, and/or illicit drug abuse.
12. 12. Subject has participated in a clinical trial in which they have received an investigational product 30 days prior to enrolment in the current study.
13. 13. For subjects that are on drug(s) or supplements that may affect muscle function 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.
14. 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 contraindicated their participation.
15. 15. Female subject is pregnant.
16. 16. Female subject is lactating.
17. 17. Subject is unwilling or unable to follow the procedures outlined in the protocol.
18. 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. 19. Subject was mentally or legally incapacitated up to 2 years prior to enrolment.
20. 20. Subject has abnormal laboratory results indicative of any significant medical disease That would preclude the subject’s participation in the study.
21. 21. Subject, or close relative of the subject, is not a staff member directly involved with the conduct of the study at that site.
22. 22. Subject has taken any anticoagulants for at least 1 month and anti-platelet agents for at least 1 week before each muscle biopsy.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Safety and tolerability based on AEs, clinical laboratory test results, ECGs, and vital signs.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fulcrum Therapeutics Inc.

Sponsor organisation

Fulcrum Therapeutics Inc.

Address

26 Landsdowne Street

City

Cambridge

Postcode

02139-4216

Country

United States

Scientific contact point

Organisation

Fulcrum Therapeutics Inc.

Contact name

Marie-Helene Jouvin

Public contact point

Organisation

Fulcrum Therapeutics Inc.

Contact name

Marie-Helene Jouvin

Third parties 3

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 5 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications