Facioscapulohumeral Muscular Dystrophy 1Phase 2REINFORCENCT06222827
Study to Evaluate the Efficacy and Safety of Satralizumab in FSHD1
A Phase 2 study testing Satralizumab Prefilled Syringe in people with Facioscapulohumeral Muscular Dystrophy 1, run by Centre Hospitalier Universitaire de Nice at 2 sites in 2 countries.
Trial summary
Facioscapulohumeral muscular dystrophy (FSHD) is characterized by clinical diversity, with FSHD1 being the most common form. It is associated with a toxic gain of function of the Double homeobox 4 (DUX4) gene, leading to muscle cell death and weakness. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Facioscapulohumeral Muscular Dystrophy 1
- What is being tested?
- Satralizumab Prefilled Syringe
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 46 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 24 Jan 2024to Mar 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Capable of understanding the written informed consent, and providing signed, dated, and witnessed written informed consent.
- Male or female subjects between the ages of 18 and 65 years, inclusive.
- Patient affiliated to a European social security system (Nice center only)
- Genetically confirmed diagnosis of typical FSHD1 with 1 to 9 D4Z4 repeats via assessment of the size of the D4Z4 array on chromosome 4. Genetic confirmation must be obtained before the subject screening assessments, including MRI, and before the baseline. Genetic confirmation can come from previous testing if verified with appropriate documentation from an accredited laboratory. 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 assessments, including MRI.
- Clinical severity score of 2 to 4 (RICCI score; range 0-5), inclusive.
- Patients with a body weight of below or equal 100 kg
Show all 11Show fewer
- On initial whole-body MRI, subjects with evidence of muscle fat replacement such that the total lean volume of muscles with an intermediate fat replacement (i.e. muscle with at least 10% of Muscle Fat Infiltration and no more than 50% of Muscle Fat Fraction) is at least 500 ml if there is only one intermediate muscle or 250 ml if there is more than one intermediate muscle.
- Subjects able to walk without support
- Willing to maintain same level of exercise (frequency and intensity) during the study.
- Willing and able to comply with scheduled visits, treatment plan, study restrictions, laboratory tests, contraceptive guidelines, and other study procedures.
- For female patients of childbearing potential: use adequate contraception during the treatment period and/or until treatment discontinuation.
Who cannot join
- 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, any major comorbidities (diabetes mellitus, cancer, severe autoimmune diseases, chronic renal failure, articular diseases that restricts exercise or participation in study assessments in the physician's opinion...), a history of relevant drug or food allergies; history of cardiovascular, respiratory, central nervous system disease; neuromuscular diseases except FSHD (e.g., myopathy, neuropathy, neuromuscular junction disorders)
- History of malignancy within the last 5 years, including solid tumors, hematologic malignancies and in situ carcinoma (except basal cell and squamous cell carcinomas of the skin, or in situ carcinoma of the cervix uteri that have been completely excised and cured)
- Subjects who are on drug(s) or supplements that may affect muscle function, as determined by the treating physician 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.
- Orthopedic conditions, such as unresolved fracture or arthrosis, interfering or precluding testing of muscle function
- Contraindication to muscle MRI as per clinic standard practice
- Articular contracture limiting movements, scapular fixation or other surgeries, preceding or planned
Show all 21Show fewer
- Any known hypersensitivity to satralizumab or any of its components and/or history of severe allergic reaction to a biologic agent (e.g., shock, anaphylactic reactions)
- Evidence of latent or active tuberculosis (TB; excluding patients receiving chemoprophylaxis for latent TB infection for at least 4 weeks prior to enrollment), active opportunistic or life-threatening infections
- History of diverticulitis or concurrent severe GI disorders (such as symptomatic diverticulosis) that, in the investigator's opinion, may lead to increased risk of complications such as GI perforation. Infection requiring hospitalization or treatment with IV anti-infective agents within 4 weeks prior to baseline visit or oral anti-infective agents within 2 weeks prior to baseline visit (Visit 1, week 0)
- Positive screen for hepatitis B surface antigen (HbsAg), antibody (anti-HbS), hepatitis C virus (HCV) antibody.
- Acute or chronic history of liver disease
- Abnormal laboratory results with: White blood cells (WBC) < 3.0x 10^9/L ; Absolute Neutrophils Counts (ANC)< 2.0x 10^9/L ; Platelet count < 10x10^4/µl ; Absolute lymphocyte count (ALC) < 0.8x 10^3/µl ; Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 1.5 times the upper limit of normal (ULN)
- Severe renal impairment (defined as a glomerular filtration rate of <30mL/min/1.73m²)
- Vaccination with live or live-attenuated vaccines within the 6 weeks prior to randomization.
- Pregnancy or lactation
- For patients of reproductive potential, a positive result from a serum pregnancy test at screening, or not willing to use reliable means of contraception (physical barrier [patient or partner] in conjunction with a spermicidal product, contraceptive pill, patch, injectable, intrauterine device or intrauterine system) during the treatment period and for at least 3 months after the last dose of study drug.
- Any current mental condition (psychiatric disorder, senility, or dementia) that, in the opinion of the investigator, may affect study compliance or prevent understanding of the aims, investigational procedures, or possible consequences of the study.
- Use of another investigational product within 6 months or 5 half-lives (whichever is longer), or currently participating in a prospective study with an investigational product, whether it concerns an experimental drug or a medical device. Note: concurrent participation in natural history studies (non-drug, non-device studies) is not allowed during the course of the study.
- Any prior treatment with any agent targeting the IL-6 inhibition pathway (e.g. tocilizumab, sarilumab), alemtuzumab treatment, total body irradiation, or bone marrow transplantation; treatment in the past 24 weeks with an anti-B-lymphocyte antigen CD20 (e.g. rituximab, ocrelizumab), eculizumab, anti-B-lymphocyte stimulator, or any other multiple sclerosis disease-modifying treatment; treatment in the past 2 years with an anti-T-cell surface glycoprotein CD4, cladribine, cyclophosphamide, or mitoxantrone; or treatment with any other investigational drug within 3 months prior to baseline. See section 4.4.4 for details on the vaccination and immunization.
- Subject, or close relative of the subject, is the investigator or a coinvestigator, research assistant, pharmacist, study coordinator, or other staff directly involved with the conduct of the study at that site.
- Patient protected by law, under guardianship or curator ship, or not able to participate in a clinical study according to the article L.1121-16 of the French Public Health Code.
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
Official title: A Bicentric, Randomized, Double Blind, Placebo-controlled Pilot Study to Evaluate the Efficacy and Safety of Satralizumab in FSHD1
Facioscapulohumeral muscular dystrophy (FSHD) is characterized by clinical diversity, with FSHD1 being the most common form. It is associated with a toxic gain of function of the Double homeobox 4 (DUX4) gene, leading to muscle cell death and weakness. Despite the lack of approved treatments, recent studies highlight inflammation's role in early FSHD progression, triggered by inappropriate DUX4 expression.
In understanding inflammation's pivotal role in FSHD, a study assessed serum cytokines in 100 adult FSHD1 patients. Out of the 20 cytokines examined, 10 showed significantly altered expression levels compared to healthy controls of similar age and sex. FSHD1 patients exhibited heightened levels of inflammatory cytokines and diminished anti-inflammatory cytokines, signaling chronic inflammation. Notably, Interleukin-6 (IL-6) emerged as a promising disease activity biomarker, displaying robust correlations with established clinical severity and functional scores.
Given the pathological significance of inflammation and the correlation of IL-6 levels with disease severity, the ReInForce study will explore the satralizumab, an IL6-receptor (IL6-R) antagonist, for its efficacy in specifically reducing muscle and systemic inflammation. By antagonizing IL-6R downstream signaling, satralizumab holds promise in mitigating inflammation and potentially curtailing fibrofatty degeneration in FSHD.
- Conditions
- Facioscapulohumeral Muscular Dystrophy 1
- Being tested
- Satralizumab Prefilled Syringe, Placebo Comparator
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Satralizumab Prefilled SyringeDrug
Satralizumab is supplied as prefilled syringe with 1 millimeter of solution for subcutaneous injection corresponding to 120mg of satralizumab. During the first period (double blind period), satralizumab will be administered at weeks 0, 2, 4 and every 4 weeks until week 48. During the second period (open label period), satralizumab will be administered at weeks 48, 50, 52 and every 4 weeks until week 96.
Placebo ComparatorDrug
Placebo prefilled syringe is identical in composition to satralizumab, but does not contain the satralizumab active agent. It is identical in appearance and packaging to satralizumab. During the first period (double blind period), placebo will be administered at weeks 0, 2, 4 and every 4 weeks until week 48. During the second period (open label period), satralizumab will be administered at weeks 48, 50, 52 and every 4 weeks until week 96.
| Study group | Role | What they receive |
|---|---|---|
| Group of patients who receive satralizumab | Experimental | Not described Receives: Drug: Satralizumab Prefilled Syringe |
| Group of patients who receive placebo | Placebo comparator | Not described Receives: Drug: Placebo Comparator |
What is being measured
The primary outcome is the main question the study is designed to answer.
The study will evaluate the efficacy of satralizumab compared to placebo, measured by the change during the Double Blind (DB) period (week 0 to week 48) on whole body muscle MRI.
Based on T1-Dixon images, muscles will be evaluated on all available sections, and a composite score describing the Muscle Fat Infiltration (MFItot, in % of total muscle), Lean Muscle Volume (LMVtot in cl) and Muscle Fat Fraction (MFFtot in % of total muscles) in intermediate muscles (muscles with at least 10% of MFI and no more than 50% of MFF) Based on T2 Short T1 Inversion Recovery (STIR), muscles will be evaluated on all available sections, and a comprehensive score describing the degree of involvement was given between 0 (absence of STIR hyperintensity) and 1 (presence of area of STIR hyperintensity).
A STIR-Magnetic Resonance Imaging (MRI) score will be calculated as the sum of the scores of involvement of the individual muscles in each patient
Measured: From baseline to week 48
The study will evaluate the efficacy of satralizumab compared to placebo, measured by the change during the Double Blind (DB) period (week 0 to week 48) on RICCI clinical severity scale score.
The RICCI score is a 10-grade scale that accounts for the extent of weakness in various muscular regions and considers the spread of symptoms to pelvic and leg muscles. Higher scores are assigned to subjects with involvement of pelvic and proximal lower limb muscles.
Measured: From baseline to week 48
The study will evaluate the efficacy of satralizumab compared to placebo, measured by the change during the Double Blind (DB) period (week 0 to week 48) on Reachable Work Space (RWS) results with and without weights.
Measured: From baseline to week 48
The study will evaluate the efficacy of satralizumab compared to placebo, measured by the change during the Double Blind (DB) period (week 0 to week 48) on muscle strength, determined by quantitative isometric dynamometry
Measured: From baseline to week 48
The study will evaluate the efficacy of satralizumab compared to placebo, measured by the change during the Double Blind (DB) period (week 0 to week 48) on FSHD-Composite Outcome Measure (FSHD-COM) total score, sub-scale scores and individual items.
The FSHD Composite Outcome Measure (FSHD-COM) is an evaluator-administered scale, specifically developed for FSHD. This instrument is comprised from several independent functional tests which, when combined, give an overall score by body region, including leg, shoulder and arm, trunk, hand and balance. The lower the score is the less affected the patient is.
Measured: From baseline to week 48
The study will evaluate the efficacy of satralizumab compared to placebo, measured by the change during the Double Blind (DB) period (week 0 to week 48) on FSHD-Rasch-built overall disability scale (FSHD-RODS) total score
The FSHD-Rasch-built overall disability scale (FSHD-RODS) is a patient-reported disease-specific interval measure suitable for detecting activity and participation restrictions in patients with FSHD. The 32-item FSHD-RODS demonstrated good discriminative validity when correlated with the MFM and an excellent test-retest reliability scores for item hierarchy and patient abilities.
Measured: From baseline to week 48
The study will evaluate the efficacy of satralizumab compared to placebo, measured by the proportion of participants with an improvement in the FSHD Patient Global Impression of Change scale (FSHD-PGIC) during the Double Blind period (week 0 to week 48)
The self-report measure FSHD-Patient Global Impression of Change (FSHD-PGIC) reflects a patient's belief about the efficacy of treatment. PGIC is a 7-point scale depicting a patient's rating of overall improvement. Patients rate their change as: Very much improved (1), Much improved (2), Minimally improved (3), No change (4), Minimally worse (5), Much worse (6), Very much worse (7).
Measured: From baseline to week 48
The study will evaluate the efficacy of satralizumab compared to placebo, measured by the proportion of participants with an improvement in FSHD Clinical Global Impressions of Change scale (FSHD-CGIC) during the Double Blind period (week 0 to week 48)
The physician-report measure FSHD-Clinical Global Impression of Change (FSHD-CGIC) asked to the clinicians to rate the degree of change observed in a patient since the beginning of the study. CGIC is a 7-point scale and physicians rate patients change as: Very much improved (1), Much improved (2), Minimally improved (3), No change (4), Minimally worse (5), Much worse (6), Very much worse (7).
Measured: From baseline to week 48
The study will evaluate the efficacy of satralizumab compared to placebo, measured by the change during the Double Blind (DB) period (week 0 to week 48) on the number of falls reported.
Measured: From baseline to week 48
The study will evaluate the efficacy of satralizumab compared to placebo, measured by the change during the Double Blind (DB) period (week 0 to week 48) on Neuromuscular Disease Independence Scale-Upper Limb Module (NMDIS-ULM) total score
The Neuromuscular Disease Independence Scale-Upper Limb Module (NMDIS-ULM) is an adaptation of the SMA Independence Scale-Upper Limb Module (SMAIS-ULM) which have been developed to measure the level of assistance required for activities related to upper limb function. Higher score are assigend to subject requiring help in daily activities.
Measured: From baseline to week 48
The study will evaluate the efficacy of satralizumab compared to placebo, measured by the change during the Double Blind (DB) period (week 0 to week 48) on Neuromuscular Disease Independence Scale-Ambulatory (NMDIS-Amb) total score.
The Neuromuscular Disease Independence Scale-Ambulatory (NMDIS-Amb) is an adaptation of the SMA Independence Scale Ambulatory module (SMAIS-Amb) which have been developed to measure the level of assistance required for activities related to motor function. Higher score are assigned to subjects unable to perform the activity present in the questionnaire
Measured: From baseline to week 48
The study will evaluate the efficacy of satralizumab compared to placebo, measured by the change during the Double Blind (DB) period (week 0 to week 48) on inflammation, and specifically on molecular biomarkers associated with inflammation.
A recent study has investigated the level of 20 inflammatory cytokines to determine severity biomarker in FSHD. Among the 20 tested cytokines, 10 of them displayed a significantly different expression level between patients and control. In the present study, the efficacy of satralizumab versus placebo to reduce the inflammatory cytokines production will be investigated by comparing the change from baseline in the molecular biomarkers associated with inflammation. Biomarkers will include, but are not limited to the following:
- Serum IL-6, sIL-6R measured by Quantikine ELISA, from R\&D System, CRP,
- Molecular biomarkers associated with inflammation such as IFN-γ, IL-1β, TNF-α, VEGF, IL1-RA, IL-6-R, sICAM-1, sVCAM-1 and SAA, measured by V-PLEX assays (MesoScale Discovery).
Measured: From baseline to week 48
The study will evaluate the safety and tolerability of satralizumab compared to placebo, measured by the type, frequency, severity, seriousness, and relationship of Adverse Events to satralizumab during the Double Blind (DB) period (week 0 to week 48).
Measured: From baseline to week 48
The study will evaluate the safety and tolerability of satralizumab compared to placebo, measured by the incidence of Adverse events of special interest (AESIs) and selected AEs during the Double Blind (DB) period (week 0 to week 48).
Measured: From baseline to week 48
The study will evaluate the safety and tolerability of satralizumab compared to placebo, measured by the number of subjects discontinuing study drug due to an AE during the Double Blind (DB) period (week 0 to week 48).
Measured: From baseline to week 48
The study will evaluate safety and tolerability of satralizumab compared to placebo, measured by frequency of clinically significant changes from baseline in laboratory test, vital signs, and physical examination results during the Double Blind period
Measured: From baseline to week 48
Secondary outcomes (16)
The study will evaluate the efficacy of satralizumab compared to placebo, measured by the change during Double Blind (DB) and Open-label (OL) periods (week 0 to week 96) on whole body muscle MRI.
Based on T1-Dixon images, muscles will be evaluated on all available sections, and a composite score describing the Muscle Fat Infiltration (MFItot, in % of total muscle), Lean Muscle Volume (LMVtot in cl) and Muscle Fat Fraction (MFFtot in % of total muscles) in intermediate muscles (muscles with at least 10% of MFI and no more than 50% of MFF) Based on T2 Short T1 Inversion Recovery (STIR), muscles will be evaluated on all available sections, and a comprehensive score describing the degree of involvement was given between 0 (absence of STIR hyperintensity) and 1 (presence of area of STIR hyperintensity).
A STIR-Magnetic Resonance Imaging (MRI) score will be calculated as the sum of the scores of involvement of the individual muscles in each patient
Measured: From baseline to week 96
The study will evaluate the efficacy of satralizumab compared to placebo, measured by the change during Double Blind (DB) and Open-label (OL) periods (week 0 to week 96) on RICCI clinical severity scale score
The RICCI score is a 10-grade scale that accounts for the extent of weakness in various muscular regions and considers the spread of symptoms to pelvic and leg muscles. Higher scores are assigned to subjects with involvement of pelvic and proximal lower limb muscles.
Measured: From baseline to week 96
The study will evaluate the efficacy of satralizumab compared to placebo, measured by the change during Double Blind (DB) and Open-label (OL) periods (week 0 to week 96) on Reachable Work Space (RWS) results with and without weights.
Measured: From baseline to week 96
The study will evaluate the efficacy of satralizumab compared to placebo, measured by the change during Double Blind (DB) and Open-label (OL) periods (week 0 to week 96) on muscle strength, determined by quantitative isometric dynamometry
Measured: From baseline to week 96
The study will evaluate the efficacy of satralizumab compared to placebo, measured by the change during Double Blind and Open-label periods on FSHD-Composite Outcome Measure (FSHD-COM) total score, sub-scale scores and individual items
The FSHD Composite Outcome Measure (FSHD-COM) is an evaluator-administered scale, specifically developed for FSHD. This instrument is comprised from several independent functional tests which, when combined, give an overall score by body region, including leg, shoulder and arm, trunk, hand and balance. The lower the score is the less affected the patient is.
Measured: From baseline to week 96
The study will evaluate the efficacy of satralizumab compared to placebo, measured by the change during Double Blind (DB) and Open-label (OL) periods (week 0 to week 96) on FSHD-Rasch-built overall disability scale (FSHD-RODS) total score
The FSHD-Rasch-built overall disability scale (FSHD-RODS) is a patient-reported disease-specific interval measure suitable for detecting activity and participation restrictions in patients with FSHD. The 32-item FSHD-RODS demonstrated good discriminative validity when correlated with the MFM and an excellent test-retest reliability scores for item hierarchy and patient abilities.
Measured: From baseline to week 96
The study will evaluate the efficacy of satralizumab compared to placebo, measured by the proportion of participants with an improvement in the FSHD Patient Global Impression of Change scale (FSHD-PGIC) during Double Blind and Open-label periods
The self-report measure FSHD-Patient Global Impression of Change (FSHD-PGIC) reflects a patient's belief about the efficacy of treatment. PGIC is a 7-point scale depicting a patient's rating of overall improvement. Patients rate their change as: Very much improved (1), Much improved (2), Minimally improved (3), No change (4), Minimally worse (5), Much worse (6), Very much worse (7).
Measured: From baseline to week 96
The study will evaluate the efficacy of satralizumab compared to placebo, measured by the proportion of participants with an improvement in the FSHD Clinical Global Impressions of Change scale (FSHD-CGIC) during Double Blind and Open-label periods
The physician-report measure FSHD-Clinical Global Impression of Change (FSHD-CGIC) asked to the clinicians to rate the degree of change observed in a patient since the beginning of the study. CGIC is a 7-point scale and physicians rate patients change as: Very much improved (1), Much improved (2), Minimally improved (3), No change (4), Minimally worse (5), Much worse (6), Very much worse (7).
Measured: From baseline to week 96
The study will evaluate the efficacy of satralizumab compared to placebo, measured by the change during Double Blind (DB) and Open-label (OL) periods (week 0 to week 96) on the number of falls reported
Measured: From baseline to week 96
The study will evaluate the efficacy of satralizumab compared to placebo, measured by the change during Double Blind (DB) and Open-label (OL) periods on Neuromuscular Disease Independence Scale-Upper Limb Module (NMDIS-ULM) total score.
The Neuromuscular Disease Independence Scale-Upper Limb Module (NMDIS-ULM) is an adaptation of the SMA Independence Scale-Upper Limb Module (SMAIS-ULM) which have been developed to measure the level of assistance required for activities related to upper limb function. Higher score are assigend to subject requiring help in daily activities.
Measured: From baseline to week 96
The study will evaluate the efficacy of satralizumab compared to placebo, measured by the change during Double Blind (DB) and Open-label (OL) periods (week 0 to week 96) on Neuromuscular Disease Independence Scale-Ambulatory (NMDIS-Amb) total score
The Neuromuscular Disease Independence Scale-Ambulatory (NMDIS-Amb) is an adaptation of the SMA Independence Scale Ambulatory module (SMAIS-Amb) which have been developed to measure the level of assistance required for activities related to motor function. Higher score are assigned to subjects unable to perform the activity present in the questionnaire
Measured: From baseline to week 96
The study will evaluate the efficacy of satralizumab compared to placebo, measured by the change during Double Blind (DB) and Open-label (OL) periods on inflammation, and specifically on molecular biomarkers associated with inflammation
A recent study has investigated the level of 20 inflammatory cytokines to determine severity biomarker in FSHD. Among the 20 tested cytokines, 10 of them displayed a significantly different expression level between patients and control. In the present study, the efficacy of satralizumab versus placebo to reduce the inflammatory cytokines production will be investigated by comparing the change from baseline in the molecular biomarkers associated with inflammation. Biomarkers will include, but are not limited to the following:
- Serum IL-6, sIL-6R measured by Quantikine ELISA, from R\&D System, CRP,
- Molecular biomarkers associated with inflammation such as IFN-γ, IL-1β, TNF-α, VEGF, IL1-RA, IL-6-R, sICAM-1, sVCAM-1 and SAA, measured by V-PLEX assays (MesoScale Discovery).
Measured: From baseline to week 96
The study will evaluate the safety and tolerability of satralizumab compared to placebo, measured by the type, frequency, severity, seriousness, and relationship of Adverse Events to satralizumab during Double Blind and Open-label periods
Measured: From baseline to week 96
The study will evaluate the safety and tolerability of satralizumab compared to placebo, measured by the incidence of Adverse events of special interest (AESIs) and selected AEs during Double Blind (DB) and Open-label (OL) periods (week 0 to week 96)
Measured: From baseline to week 96
The study will evaluate the safety and tolerability of satralizumab compared to placebo, measured by the number of subjects discontinuing study drug due to an AE during Double Blind (DB) and Open-label (OL) periods (week 0 to week 96)
Measured: From baseline to week 96
The study will evaluate safety/tolerability of satralizumab versus placebo, measured by frequency of clinically significant changes from baseline in laboratory test, vital signs, and physical examination results during Double Blind and Open-label periods
Measured: From baseline to week 96
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jan 2024
- Study start24 Jan 2024
- Primary completionMar 2027 (estimated)
- Study completionMar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Facioscapulohumeral Muscular Dystrophy 1Studies of the same condition, open and under way.
- More trials run by Centre Hospitalier Universitaire de NiceThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- First period: two groups of patients who receive either satralizumab, or placebo. Second period: all patients receive satralizumab
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 46 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre Hospitalier Universitaire de Nice
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06222827
- Sponsor's protocol ID
- 22-PP-24
- Acronym
- REINFORCE
- Status last verified
- Mar 2025
- First submitted
- 15 Dec 2023
- Last updated
- 26 Mar 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 26 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Bicentric, Randomized, Double Blind, Placebo-controlled Pilot Study to Evaluate the Efficacy and Safety of Satralizumab in FSHD1
- ClinicalTrials.gov ID
- NCT06222827
- Acronym / sponsor ID
- REINFORCE / 22-PP-24
- Conditions
- Facioscapulohumeral Muscular Dystrophy 1
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 46 participants (actual)
- Lead sponsor
- Centre Hospitalier Universitaire de NiceUniversity, hospital or other
- Study start
- 24 Jan 2024 (actual)
- Primary completion
- Mar 2027 (estimated)
- Study completion
- Mar 2027 (estimated)
- First posted
- 25 Jan 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Facioscapulohumeral muscular dystrophy (FSHD) is characterized by clinical diversity, with FSHD1 being the most common form. It is associated with a toxic gain of function of the Double homeobox 4 (DUX4) gene, leading to muscle cell death and weakness. Despite the lack of approved treatments, recent studies highlight inflammation's role in early FSHD progression, triggered by inappropriate DUX4 expression.
In understanding inflammation's pivotal role in FSHD, a study assessed serum cytokines in 100 adult FSHD1 patients. Out of the 20 cytokines examined, 10 showed significantly altered expression levels compared to healthy controls of similar age and sex. FSHD1 patients exhibited heightened levels of inflammatory cytokines and diminished anti-inflammatory cytokines, signaling chronic inflammation. Notably, Interleukin-6 (IL-6) emerged as a promising disease activity biomarker, displaying robust correlations with established clinical severity and functional scores.
Given the pathological significance of inflammation and the correlation of IL-6 levels with disease severity, the ReInForce study will explore the satralizumab, an IL6-receptor (IL6-R) antagonist, for its efficacy in specifically reducing muscle and systemic inflammation. By antagonizing IL-6R downstream signaling, satralizumab holds promise in mitigating inflammation and potentially curtailing fibrofatty degeneration in FSHD.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- First period: two groups of patients who receive either satralizumab, or placebo. Second period: all patients receive satralizumab
| Arm | Type | Receives |
|---|---|---|
| Group of patients who receive satralizumab | Experimental | Drug: Satralizumab Prefilled Syringe |
| Group of patients who receive placebo | Placebo comparator | Drug: Placebo Comparator |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Capable of understanding the written informed consent, and providing signed, dated, and witnessed written informed consent.
- Male or female subjects between the ages of 18 and 65 years, inclusive.
- Patient affiliated to a European social security system (Nice center only)
- Genetically confirmed diagnosis of typical FSHD1 with 1 to 9 D4Z4 repeats via assessment of the size of the D4Z4 array on chromosome 4. Genetic confirmation must be obtained before the subject screening assessments, including MRI, and before the baseline. Genetic confirmation can come from previous testing if verified with appropriate documentation from an accredited laboratory. 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 assessments, including MRI.
- Clinical severity score of 2 to 4 (RICCI score; range 0-5), inclusive.
Key exclusion criteria (21 listed)
- 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, any major comorbidities (diabetes mellitus, cancer, severe autoimmune diseases, chronic renal failure, articular diseases that restricts exercise or participation in study assessments in the physician's opinion...), a history of relevant drug or food allergies; history of cardiovascular, respiratory, central nervous system disease; neuromuscular diseases except FSHD (e.g., myopathy, neuropathy, neuromuscular junction disorders)
- History of malignancy within the last 5 years, including solid tumors, hematologic malignancies and in situ carcinoma (except basal cell and squamous cell carcinomas of the skin, or in situ carcinoma of the cervix uteri that have been completely excised and cured)
- Subjects who are on drug(s) or supplements that may affect muscle function, as determined by the treating physician 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.
- Orthopedic conditions, such as unresolved fracture or arthrosis, interfering or precluding testing of muscle function
- Contraindication to muscle MRI as per clinic standard practice
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Satralizumab Prefilled SyringeSatralizumab is supplied as prefilled syringe with 1 millimeter of solution for subcutaneous injection corresponding to 120mg of satralizumab. During the first period (double blind period), satralizumab will be administered at weeks 0, 2, 4 and every 4 weeks until week 48. During the second period (open label period), satralizumab will be administered at weeks 48, 50, 52 and every 4 weeks until week 96. | Drug | Group of patients who receive satralizumab |
| Placebo ComparatorPlacebo prefilled syringe is identical in composition to satralizumab, but does not contain the satralizumab active agent. It is identical in appearance and packaging to satralizumab. During the first period (double blind period), placebo will be administered at weeks 0, 2, 4 and every 4 weeks until week 48. During the second period (open label period), satralizumab will be administered at weeks 48, 50, 52 and every 4 weeks until week 96. | Drug | Group of patients who receive placebo |
Primary outcome
The study will evaluate the efficacy of satralizumab compared to placebo, measured by the change during the Double Blind (DB) period (week 0 to week 48) on whole body muscle MRI.
Time frame: From baseline to week 48
Based on T1-Dixon images, muscles will be evaluated on all available sections, and a composite score describing the Muscle Fat Infiltration (MFItot, in % of total muscle), Lean Muscle Volume (LMVtot in cl) and Muscle Fat Fraction (MFFtot in % of total muscles) in intermediate muscles (muscles with at least 10% of MFI and no more than 50% of MFF) Based on T2 Short T1 Inversion Recovery (STIR), muscles will be evaluated on all available sections, and a comprehensive score describing the degree of involvement was given between 0 (absence of STIR hyperintensity) and 1 (presence of area of STIR hyperintensity). A STIR-Magnetic Resonance Imaging (MRI) score will be calculated as the sum of the scores of involvement of the individual muscles in each patient
The study will evaluate the efficacy of satralizumab compared to placebo, measured by the change during the Double Blind (DB) period (week 0 to week 48) on RICCI clinical severity scale score.
Time frame: From baseline to week 48
The RICCI score is a 10-grade scale that accounts for the extent of weakness in various muscular regions and considers the spread of symptoms to pelvic and leg muscles. Higher scores are assigned to subjects with involvement of pelvic and proximal lower limb muscles.
The study will evaluate the efficacy of satralizumab compared to placebo, measured by the change during the Double Blind (DB) period (week 0 to week 48) on Reachable Work Space (RWS) results with and without weights.
Time frame: From baseline to week 48
The study will evaluate the efficacy of satralizumab compared to placebo, measured by the change during the Double Blind (DB) period (week 0 to week 48) on muscle strength, determined by quantitative isometric dynamometry
Time frame: From baseline to week 48
The study will evaluate the efficacy of satralizumab compared to placebo, measured by the change during the Double Blind (DB) period (week 0 to week 48) on FSHD-Composite Outcome Measure (FSHD-COM) total score, sub-scale scores and individual items.
Time frame: From baseline to week 48
The FSHD Composite Outcome Measure (FSHD-COM) is an evaluator-administered scale, specifically developed for FSHD. This instrument is comprised from several independent functional tests which, when combined, give an overall score by body region, including leg, shoulder and arm, trunk, hand and balance. The lower the score is the less affected the patient is.
The study will evaluate the efficacy of satralizumab compared to placebo, measured by the change during the Double Blind (DB) period (week 0 to week 48) on FSHD-Rasch-built overall disability scale (FSHD-RODS) total score
Time frame: From baseline to week 48
The FSHD-Rasch-built overall disability scale (FSHD-RODS) is a patient-reported disease-specific interval measure suitable for detecting activity and participation restrictions in patients with FSHD. The 32-item FSHD-RODS demonstrated good discriminative validity when correlated with the MFM and an excellent test-retest reliability scores for item hierarchy and patient abilities.
The study will evaluate the efficacy of satralizumab compared to placebo, measured by the proportion of participants with an improvement in the FSHD Patient Global Impression of Change scale (FSHD-PGIC) during the Double Blind period (week 0 to week 48)
Time frame: From baseline to week 48
The self-report measure FSHD-Patient Global Impression of Change (FSHD-PGIC) reflects a patient's belief about the efficacy of treatment. PGIC is a 7-point scale depicting a patient's rating of overall improvement. Patients rate their change as: Very much improved (1), Much improved (2), Minimally improved (3), No change (4), Minimally worse (5), Much worse (6), Very much worse (7).
The study will evaluate the efficacy of satralizumab compared to placebo, measured by the proportion of participants with an improvement in FSHD Clinical Global Impressions of Change scale (FSHD-CGIC) during the Double Blind period (week 0 to week 48)
Time frame: From baseline to week 48
The physician-report measure FSHD-Clinical Global Impression of Change (FSHD-CGIC) asked to the clinicians to rate the degree of change observed in a patient since the beginning of the study. CGIC is a 7-point scale and physicians rate patients change as: Very much improved (1), Much improved (2), Minimally improved (3), No change (4), Minimally worse (5), Much worse (6), Very much worse (7).
The study will evaluate the efficacy of satralizumab compared to placebo, measured by the change during the Double Blind (DB) period (week 0 to week 48) on the number of falls reported.
Time frame: From baseline to week 48
The study will evaluate the efficacy of satralizumab compared to placebo, measured by the change during the Double Blind (DB) period (week 0 to week 48) on Neuromuscular Disease Independence Scale-Upper Limb Module (NMDIS-ULM) total score
Time frame: From baseline to week 48
The Neuromuscular Disease Independence Scale-Upper Limb Module (NMDIS-ULM) is an adaptation of the SMA Independence Scale-Upper Limb Module (SMAIS-ULM) which have been developed to measure the level of assistance required for activities related to upper limb function. Higher score are assigend to subject requiring help in daily activities.
The study will evaluate the efficacy of satralizumab compared to placebo, measured by the change during the Double Blind (DB) period (week 0 to week 48) on Neuromuscular Disease Independence Scale-Ambulatory (NMDIS-Amb) total score.
Time frame: From baseline to week 48
The Neuromuscular Disease Independence Scale-Ambulatory (NMDIS-Amb) is an adaptation of the SMA Independence Scale Ambulatory module (SMAIS-Amb) which have been developed to measure the level of assistance required for activities related to motor function. Higher score are assigned to subjects unable to perform the activity present in the questionnaire
The study will evaluate the efficacy of satralizumab compared to placebo, measured by the change during the Double Blind (DB) period (week 0 to week 48) on inflammation, and specifically on molecular biomarkers associated with inflammation.
Time frame: From baseline to week 48
A recent study has investigated the level of 20 inflammatory cytokines to determine severity biomarker in FSHD. Among the 20 tested cytokines, 10 of them displayed a significantly different expression level between patients and control. In the present study, the efficacy of satralizumab versus placebo to reduce the inflammatory cytokines production will be investigated by comparing the change from baseline in the molecular biomarkers associated with inflammation. Biomarkers will include, but are not limited to the following: * Serum IL-6, sIL-6R measured by Quantikine ELISA, from R\&D System, CRP, * Molecular biomarkers associated with inflammation such as IFN-γ, IL-1β, TNF-α, VEGF, IL1-RA, IL-6-R, sICAM-1, sVCAM-1 and SAA, measured by V-PLEX assays (MesoScale Discovery).
The study will evaluate the safety and tolerability of satralizumab compared to placebo, measured by the type, frequency, severity, seriousness, and relationship of Adverse Events to satralizumab during the Double Blind (DB) period (week 0 to week 48).
Time frame: From baseline to week 48
The study will evaluate the safety and tolerability of satralizumab compared to placebo, measured by the incidence of Adverse events of special interest (AESIs) and selected AEs during the Double Blind (DB) period (week 0 to week 48).
Time frame: From baseline to week 48
The study will evaluate the safety and tolerability of satralizumab compared to placebo, measured by the number of subjects discontinuing study drug due to an AE during the Double Blind (DB) period (week 0 to week 48).
Time frame: From baseline to week 48
The study will evaluate safety and tolerability of satralizumab compared to placebo, measured by frequency of clinically significant changes from baseline in laboratory test, vital signs, and physical examination results during the Double Blind period
Time frame: From baseline to week 48
16 secondary outcomes
The study will evaluate the efficacy of satralizumab compared to placebo, measured by the change during Double Blind (DB) and Open-label (OL) periods (week 0 to week 96) on whole body muscle MRI.
Time frame: From baseline to week 96
The study will evaluate the efficacy of satralizumab compared to placebo, measured by the change during Double Blind (DB) and Open-label (OL) periods (week 0 to week 96) on RICCI clinical severity scale score
Time frame: From baseline to week 96
The study will evaluate the efficacy of satralizumab compared to placebo, measured by the change during Double Blind (DB) and Open-label (OL) periods (week 0 to week 96) on Reachable Work Space (RWS) results with and without weights.
Time frame: From baseline to week 96
The study will evaluate the efficacy of satralizumab compared to placebo, measured by the change during Double Blind (DB) and Open-label (OL) periods (week 0 to week 96) on muscle strength, determined by quantitative isometric dynamometry
Time frame: From baseline to week 96
The study will evaluate the efficacy of satralizumab compared to placebo, measured by the change during Double Blind and Open-label periods on FSHD-Composite Outcome Measure (FSHD-COM) total score, sub-scale scores and individual items
Time frame: From baseline to week 96
The study will evaluate the efficacy of satralizumab compared to placebo, measured by the change during Double Blind (DB) and Open-label (OL) periods (week 0 to week 96) on FSHD-Rasch-built overall disability scale (FSHD-RODS) total score
Time frame: From baseline to week 96
The study will evaluate the efficacy of satralizumab compared to placebo, measured by the proportion of participants with an improvement in the FSHD Patient Global Impression of Change scale (FSHD-PGIC) during Double Blind and Open-label periods
Time frame: From baseline to week 96
The study will evaluate the efficacy of satralizumab compared to placebo, measured by the proportion of participants with an improvement in the FSHD Clinical Global Impressions of Change scale (FSHD-CGIC) during Double Blind and Open-label periods
Time frame: From baseline to week 96
The study will evaluate the efficacy of satralizumab compared to placebo, measured by the change during Double Blind (DB) and Open-label (OL) periods (week 0 to week 96) on the number of falls reported
Time frame: From baseline to week 96
The study will evaluate the efficacy of satralizumab compared to placebo, measured by the change during Double Blind (DB) and Open-label (OL) periods on Neuromuscular Disease Independence Scale-Upper Limb Module (NMDIS-ULM) total score.
Time frame: From baseline to week 96
The study will evaluate the efficacy of satralizumab compared to placebo, measured by the change during Double Blind (DB) and Open-label (OL) periods (week 0 to week 96) on Neuromuscular Disease Independence Scale-Ambulatory (NMDIS-Amb) total score
Time frame: From baseline to week 96
The study will evaluate the efficacy of satralizumab compared to placebo, measured by the change during Double Blind (DB) and Open-label (OL) periods on inflammation, and specifically on molecular biomarkers associated with inflammation
Time frame: From baseline to week 96
The study will evaluate the safety and tolerability of satralizumab compared to placebo, measured by the type, frequency, severity, seriousness, and relationship of Adverse Events to satralizumab during Double Blind and Open-label periods
Time frame: From baseline to week 96
The study will evaluate the safety and tolerability of satralizumab compared to placebo, measured by the incidence of Adverse events of special interest (AESIs) and selected AEs during Double Blind (DB) and Open-label (OL) periods (week 0 to week 96)
Time frame: From baseline to week 96
The study will evaluate the safety and tolerability of satralizumab compared to placebo, measured by the number of subjects discontinuing study drug due to an AE during Double Blind (DB) and Open-label (OL) periods (week 0 to week 96)
Time frame: From baseline to week 96
The study will evaluate safety/tolerability of satralizumab versus placebo, measured by frequency of clinically significant changes from baseline in laboratory test, vital signs, and physical examination results during Double Blind and Open-label periods
Time frame: From baseline to week 96
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Mar 2025.
- Individual participant dataSharing planned: No
Related trials for Facioscapulohumeral Muscular Dystrophy 1
RecruitingPhase 1
Safety and Preliminary Efficacy of ULSC in Facioscapulohumeral Muscular Dystrophy (FSHD)
FSHD - Facioscapulohumeral Muscular Dystrophy
Enrolling by invitationPhase 1/2
Study of SRP-1001 in Adult and Adolescent Participants With Facioscapulohumeral Muscular Dystrophy Type 1
Muscular Dystrophy, Facioscapulohumeral
RecruitingObservational study
The United Kingdom Facioscapulohumeral Muscular Dystrophy Patient Registry
Facioscapulohumeral Muscular Dystrophy
Active, not recruitingPhase 1/2
A First-in-human Study of EPI-321 in Facioscapulohumeral Muscular Dystrophy
Facioscapulohumeral Muscular Dystrophy
RecruitingPhase 3
A Study to Evaluate Del-brax (Also Referred to as AOC 1020) in Participants With FSHD
Facioscapulohumeral Muscular Dystrophy, FSHD
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Satralizumab Prefilled Syringe in people with Facioscapulohumeral Muscular Dystrophy 1, run by Centre Hospitalier Universitaire de Nice at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 26 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Canada, France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The study will evaluate the efficacy of satralizumab compared to placebo, measured by the change during the Double Blind (DB) period (week 0 to week 48) on whole body muscle MRI. (time frame: From baseline to week 48). The study lists 16 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Mar 2025.