The primary objective of this study is the further evaluation and optimization of skeletal muscle tissue and MRI biomarkers for a planned POC study of FTX-1821 in FSHD. Therefore, this study is not a drug trial but rather a preparatory biomarker…
ID
Source
Brief title
Condition
- Musculoskeletal and connective tissue disorders congenital
- Musculoskeletal and connective tissue disorders congenital
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is the measurement of DUX4-activation under natural
history conditions using a panel of DUX4-regulated gene transcripts in skeletal
muscle needle biopsies from FSHD patients obtained 4-8 weeks apart (DUX4
activation Endpoint).
Secondary outcome
The secondary endpoint is the measurement of skeletal muscle tissue replacement
by fat in FSHD patients under natural history conditions using whole body MRI
obtained 4-12 weeks apart (MRI fat fraction Endpoint).
Background summary
Fulcrum, in collaboration with leading academic investigators, will perform a
biomarker preparatory study to further optimize the methodology and procedures
for key molecular (Evidence of DUX4 activation) and imaging (skeletal muscle
tissue replacement by fat) efficacy biomarker endpoints in anticipation of a
planned proof of concept study of FTX-1821 in FSHD.
The proposed key efficacy biomarkers for this preparatory study are the
following:
(1) Evidence of DUX4 activation: A molecular panel of DUX4-regulated gene
transcripts to measure DUX4 activation in skeletal muscle needle biopsies from
patients with FSHD.
(2) Skeletal Muscle Tissue Replacement by Fat: A whole-body MRI imaging
protocol and analysis algorithms to measure replacement of skeletal muscle
tissue by fat in FSHD.
Study objective
The primary objective of this study is the further evaluation and optimization
of skeletal muscle tissue and MRI biomarkers for a planned POC study of
FTX-1821 in FSHD. Therefore, this study is not a drug trial but rather a
preparatory biomarker study to enable a planned therapeutic trial.
Study design
This will be a prospective, longitudinal, observational, multicenter study
Study burden and risks
Participants will be asked for 4 visits to the outpatient clinic at the
department of neurology. Their medical history will be taken, they will undergo
clinical examination and they will fill out questionnaires. Blood samples will
be collected at each visit.
MRI scanning and muscle biopsies will be performed at two of the visits. Risks
to subjects may be physical (e.g., bruising during muscle strength testing).
There is a small risk of bruising from blood draws. Muscle biopsy is an
invasive procedure that can be painful, and can lead to complications such as
hematoma or infections. All procedures will be performed according to standard
accepted techniques to minimize risk exposure for subjects. We classify the
risk of this study as negligible.
Landsdowne Street 26
Cambridge MA 02139
US
Landsdowne Street 26
Cambridge MA 02139
US
Listed location countries
Age
Inclusion criteria
(1) Age 18-60 years old.
(2) Ability to provide informed consent.
(3) Confirmed diagnosis of FSHD1 with 1-7 repeats via assessment of the size of the D4Z4 array on chromosome 4. Enrollment may be controlled to ensure that patients with both lower (1-3) and higher (4-7) repeat numbers are included.
(4) Clinical Severity Score between 2 and 4 on Ricci*s scale (scale range is from 0 to 5).
(5) Commitment to complete the two visits for skeletal muscle needle biopsy and whole-body MRI.
(6) Able to complete the RWS, TUG and FSHD PRO at the screening visit.
(7) Presence of STIR positive signal in at least one leg skeletal muscle eligible for needle biopsy, at screening MRI.
Exclusion criteria
(1) Any condition that in the opinion of the principal investigator or the sponsor makes the subject unlikely to complete the study schedule of assessments.
(2) Any contraindication for MRI (including severe claustrophobia and any shrapnel or metal implants in the body that are not MRI compatible).
(3) Any contraindication for skeletal muscle needle biopsy (including current or recent use of anticoagulants or aspirin).
(4) Any ongoing medical problems in need of urgent medical care or hospitalization or scheduled procedures that will interfere with the schedule of assessments.
(5) Pregnancy.
(6) Any anticoagulants for at least one month and anti-platelet agents for at least 1 week before each biopsy are prohibited as they increase the risk of hematomas following skeletal muscle needle biopsy.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL67007.091.18 |