Active clinical trials for "Muscular Dystrophy, Facioscapulohumeral"

The purpose of this study is to evaluate the pharmacodynamics, safety, tolerability, pharmacokinetics, and efficacy of RO7204239, a humanized monoclonal antibody that binds to human latent myostatin, in ambulant adult participants with facioscapulohumeral muscular dystrophy (FSHD).

A Randomized, Double-blind, Placebo-controlled, Phase 1/2 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Exploratory Efficacy of AOC 1020 Administered Intravenously to Adult Participants with Facioscapulohumeral Muscular Dystrophy (FSHD)

Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common adult muscular dystrophy with an estimated prevalence range of 2-7 per 100,000. The disease is characterized by slowly progressive, asymmetric muscle weakness that starts with the face and scapular muscles. It causes significant lifetime morbidity, with up to 20% of patients eventually requiring full-time wheelchair use. However, there is a large degree of clinical variability in both disease progression and severity. This makes predicting an individual's disease course difficult and has made clinical trial design and the development of new therapeutic strategies challenging. The disease is caused by the aberrant expression of a normally silenced gene, Double homeobox 4 (DUX4), which causes disease by a toxic gain-of-function. The emergence of the pathophysiologic model provided several possible therapeutic approaches to treat FSHD. However, as drugs move from preclinical testing into human trials, it is essential to validate clinical trial tools and methodologies to facilitate drug development from early phase studies through registration trials. Natural history studies are conducted to develop and validate new clinical outcome measures (COMs). A large international multicenter study is currently ongoing in order to validate COMs in ambulant FSHD patients (ReSolve, NCT03458832). Additionally, Nice University Hospital is conducting an ancillary study (CTRN FSHD France, NCT04038138) to evaluate muscle MRI, an additional emerging biomarker, to follow disease progression in the same patient population. Nevertheless, these studies are focused on the development of COMs collected at the hospital. In this setting, several factors that may interfere with disease progression or patient quality of life are underestimated (daily exercise, daily pain or fatigue, the psychological impact of the disease, and falls…). Consequently, and given the context of the current pandemic, the interest of pharmaceutical companies, stakeholders, clinicians, and researchers in data collected in a cohort of FSHD patients at home is rapidly increasing. Consequently, a new battery of COMs adapted for the remote evaluation needs to be developed and/or validated. There are clear benefits to remote assessments. The ability to observe an individual perform functional mobility tasks and self-care in their natural environment is meaningful and invaluable. The set-up of a reliable remote assessment will allow for ensuring drug home delivery, maintaining patients on trials, and collecting and analysing additional data to improve patient stratification in clinical trials and develop new approaches to assess the short-term and long-term efficacy of a given therapy. Remote assessment can also be the key to developing more efficient real-life studies, empowering patients and caregivers in the management of this disease, and more efficiently monitoring drug side effects or the socio-economic burden of the disease. The overall aim of the PROGRESS FSHD study is to experiment the feasibility of the remote evaluation in patients with FSHD, through the use of a patient-oriented mobile application (myFSHD app). The content of the application has been determined after extensive discussions with patients and patients' associations that have identified their unmet needs and based on preliminary results of the CTRN FSHD France project. The video-recorded exercises have been designed specifically to stress a particular body region. The myFSHD mobile application will be used by 70 FSHD1 patient during 12 months, at home and at the hospital, to administer patient-reported questionnaires on fatigue, pain, physical activity, sleep, quality of life, and socio-economic burden of the disease, as well as video of validated scores and scales. The collected data will help to: Evaluate patients' adherence to the program Evaluate the technical feasibility of remote evaluation Assess the reliability of remote evaluation Assess the robustness of new COMs compared to commonly used COMs Evaluate the quality of life and socio-economic burden of the disease Overall, this study will provide digital tools adapted to monitor disease evolution remotely in FSHD patients. The patient-generated measures collected through connected digital tools (patient full-body motion videos collected through the myFSHD app) can be used to explain, influence, and/or predict disease-related outcomes

Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common adult muscular dystrophy with an estimated prevalence range of 2-7 per 100,000. The disease is characterized by slowly progressive, asymmetric muscle weakness that starts with the face and scapular muscles. It causes significant lifetime morbidity, with up to 20% of patients eventually requiring full-time wheelchair use. However, there is a large degree of clinical variability in both disease progression and severity. This makes predicting an individual's disease course difficult and has made clinical trial design challenging. The disease is caused by the aberrant expression of a normally silenced gene, DUX4, which causes disease by a toxic gain-of-function. The establishment of a unifying model for the cause of FSHD made it possible to develop disease-specific targeted treatments. Pharmaceutical companies are actively investigating therapeutic approaches in order to knockdown or silence DUX4, including the use of antisense RNA oligonucleotides which is already investigated for spinal muscular atrophy, Duchenne muscular dystrophy, and myotonic dystrophy. The drug development pipeline for FSHD over the next 5 years looks promising but meetings with industry, advocacy groups, and FSHD scientific experts have identified several gaps that need to be addressed to accelerate efficient drug development. As drugs move from preclinical testing into human trials, it is essential to validate clinical trial tools and methodologies to facilitate drug development. There is a strong need for clinical outcome measures (COMs) including biomarkers, strength outcomes, functional measures and patient reported outcomes to follow disease progression and to evaluate treatment efficacy. A large international multicenter study is currently ongoing in order to validate COMs in ambulant FSHD patients (ReSolve, NCT03458832). Additionally, Nice University Hospital is conducting an ancillary study (CTRL FSHD France, NCT04038138) to evaluate muscle MRI, an additional emerging biomarker, to follow disease progression in the same patient population. To limit patient heterogeneity, only ambulant FSHD patients are included in these 2 ongoing studies. It is therefore important to generate data in severely affected non-ambulant FSHD patients, in order to validate COMs that are adapted to this specific subgroup of patients for future therapeutic trials.

Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common inherited myopathies in adults. It is associated with genetic and epigenetic deregulation of the D4Z4 locus on the sub-telomeric region of chromosome 4q35, resulting in abnormal expression of DUX4p. Type 1 FSHD (FSHD1) is the most common form of the disease and accounts for 95% of cases, while Type 2 FSHD (FSHD2) accounts for only 5% of all FSHD cases. FSHD1 and FSHD2 are closely related in terms of genetic and epigenetic foundations, pathophysiology and clinical manifestations. Although initially described as distinct entities based on their genetics, recent information suggests that both forms of myopathy may represent the opposite ends of a spectrum of molecular diseases in which alteration of the genetic and epigenetic factors that govern DUX4 suppression in skeletal muscle have a different impact in both forms of the disease. FSHD1 and FSHD2 are both associated with re-expression of DUX4 leading to muscle atrophy, but the genetics underlying this re-expression are different, depending on whether it is type 1 or type 2. For FSHD1, it is associated with a critical contraction of the D4Z4 region and the 4qA permissive allele, leading to the expression of DUX4. In contrast, FSHD2 is caused by the inheritance of two independent genetic variations. A heterozygous mutation, mainly located on the SMCHD1 (Structural Maintenance of Chromosome flexible Hinge Domain containing 1) gene, results in a loss of function of chromatin D4Z4 repressor. This mutation, combined with the 4qA allele bearing the DU4 polyadenylation site, makes this allele permissive for the expression of the DUX4 topical gene. Therefore, because the two forms of FSHD are genetically distinct and very few patients have FSHD2, our knowledge of the impact of chromatin D4Z4 repressors, such as SMCHD1, or the progression and severity of the disease remains very limited. It is important to note that a lack of reliable biomarkers specific to the severity and progression of the disease may prevent the development of therapies to treat patients with FSHD2. This study will allow us to better understand the natural progression of FSHD2 over time, to assess the responsiveness of clinical outcome measures (COMs) and to identify and validate inflammatory serum biomarkers predicting the severity and progression of the disease.

This clinical trial is a study to evaluate the safety, tolerability, and changes in biomarker and clinical outcome assessments of Losmapimod for patients with Facioscapulohumeral Muscular Dystrophy 1 (FSHD1) with an open-label extension.

This study is an open-label extension to evaluate the safety and tolerability of long-term dosing of Losmapimod in patients with FSHD1 who participated in the ReDux4 study.

This is a study to evaluate the safety and efficacy of losmapimod in treating participants with Facioscapulohumeral Muscular Dystrophy (FSHD). Participants diagnosed with Facioscapulohumeral muscular dystrophy type 1 (FSHD1) or Facioscapulohumeral muscular dystrophy type 2 (FSHD2) will participate in Part A (Placebo-controlled treatment period) and will be randomized in a 1:1 ratio to receive losmapimod 15 milligrams (mg) or placebo orally twice daily (BID). Upon completion of Part A, participants will have the option to rollover into Part B (open-label extension) to evaluate the long-term safety, tolerability, and efficacy of losmapimod and will receive losmapimod 15 mg orally BID.

The goal of this prospective, longitudinal, single-center study is to describe respiratory function in patients affected by FSHD at baseline and after one year using both diaphragmatic ultrasound and pulmonary function test. The primary questions this study aims to answer are: How does respiratory function assessed by diaphragmatic ultrasound and pulmonary function tests change over 12 months in FSHD patients? How accurate is diaphragmatic ultrasound in detecting respiratory abnormalities in these patients compared to pulmonary function tests? What is the relationship between ultrasound and functional indices, and how do these indices correlate with demographic, clinical, and genetic data? To achieve this, we will enroll a cohort of 34 patients affected by FSHD, and each of them will undergo a comprehensive neurological examination, body plethysmography, measurement of maximal inspiratory pressure (MIP) and maximal espiratory pressure (MEP) and nocturnal oximetry at baseline and after 12 months.

The objective of ActiLiège Next Study is to collect natural history data in Duchenne muscular dystrophy (DMD) (ambulatory and non-ambulatory patients), and in affected patients with Facio-Scapulo-Humeral dystrophy (FSHD), a disease in which results are currently lacking. It consists of obtaining longitudinal data for the patients, as well as normative data for the control subjects, with a particular emphasis on pediatric subjects using the device on both ankles (for walking) in order to qualify the ascent rate of staircase.