EDG-5506 for Becker Muscular Dystrophy
Recruiting in Palo Alto (17 mi)
+54 other locations
Age: < 65
Sex: Male
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Waitlist Available
Sponsor: Edgewise Therapeutics, Inc.
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?
This trial is testing a new drug called sevasemten to see if it can help people with Becker muscular dystrophy, a condition that weakens muscles. The study aims to find out if the drug is safe and effective in improving muscle function and reducing symptoms.
Do I have to stop taking my current medications for this trial?
The trial protocol does not specify if you must stop taking your current medications. However, you cannot have taken oral corticosteroids for Becker muscular dystrophy in the past 6 months or any investigational drug within 30 days or 5 half-lives before the screening.
What data supports the idea that EDG-5506 for Becker Muscular Dystrophy is an effective treatment?
The available research does not provide specific data on the effectiveness of EDG-5506 for Becker Muscular Dystrophy. However, it mentions that there are no drugs and few clinical trials for this condition, indicating a lack of direct evidence for EDG-5506. In contrast, another treatment, prednisone, showed dramatic and sustained improvement in strength for some patients with Becker Muscular Dystrophy, suggesting it might be a more effective option based on current data.12345
What safety data is available for EDG-5506 in Becker Muscular Dystrophy?
The provided research does not contain specific safety data for EDG-5506 in Becker Muscular Dystrophy. The studies mentioned focus on other treatments and conditions, such as Drisapersen, DT-DEC01, Edasalonexent, and Vamorolone, primarily in Duchenne Muscular Dystrophy or animal models. Therefore, no relevant safety data for EDG-5506 is available in the given research.678910
Is the drug EDG-5506, Placebo a promising treatment for Becker Muscular Dystrophy?
The information provided does not mention EDG-5506 or Placebo as promising treatments for Becker Muscular Dystrophy. The articles focus on other aspects of the disease and different treatments, like vamorolone, which shows potential in increasing dystrophin protein and improving muscle function in a mouse model. Therefore, there is no evidence here to suggest that EDG-5506, Placebo is promising for Becker Muscular Dystrophy.2591112
Eligibility Criteria
This trial is for adolescents (12-17) and adults (18-50) with Becker muscular dystrophy confirmed by genetic testing. Participants must be able to complete a 100-meter walk within certain times, perform specific physical assessments, and have been ambulatory beyond certain ages with or without steroids.Inclusion Criteria
I can complete a mobility test with a score between 10 and 32.
I can walk 100 meters in less than 200 seconds, with or without help from a device.
I can do a specific physical test and score between 5 and 32.
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Exclusion Criteria
Medical history or clinically significant physical examination/laboratory result that, in the opinion of the investigator, would render the participant unsuitable for the study. This includes contraindications to magnetic resonance imaging such as non-compatible implanted medical devices or severe claustrophobia
Receipt of an investigational drug within 30 days or 5 half-lives (whichever is longer) of the screening visit in the present study
My lung function is severely reduced or I need help breathing during the day.
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Treatment Details
Interventions
- EDG-5506 (Small Molecule)
- Placebo (Drug)
Trial OverviewThe GRAND CANYON study tests the safety and effectiveness of EDG-5506 at different doses (5 mg, 10 mg, 12.5 mg) compared to a placebo in treating Becker muscular dystrophy. It's randomized and double-blind, meaning neither participants nor researchers know who gets the drug or placebo.
Participant Groups
5Treatment groups
Experimental Treatment
Group I: Adult Cohort 6Experimental Treatment2 Interventions
Drug: Sevasemten Drug: Placebo
Group II: Adult Cohort 2Experimental Treatment2 Interventions
Drug: Sevasemten Drug: Placebo
Group III: Adult Cohort 1Experimental Treatment2 Interventions
Drug: Sevasemten Drug: Placebo
Group IV: Adolescent Cohort 5Experimental Treatment2 Interventions
Drug: Sevasemten Drug: Placebo
Group V: Adolescent Cohort 4Experimental Treatment2 Interventions
Drug: Sevasemten Drug: Placebo
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
UC San DiegoLa Jolla, CA
UC Irvine Medical CenterOrange, CA
Washington University School of MedicineSaint Louis, MO
University of Cincinnati Gardner Neuroscience InstituteCincinnati, OH
More Trial Locations
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Who Is Running the Clinical Trial?
Edgewise Therapeutics, Inc.Lead Sponsor
SysnavIndustry Sponsor
Medpace, Inc.Industry Sponsor
ImagingNMDCollaborator
SYSNAVIndustry Sponsor
References
Neurodevelopmental, behavioral, and emotional symptoms in Becker muscular dystrophy. [2020]Becker muscular dystrophy (BMD) results in decreased dystrophin with implications for mental health.
An update on Becker muscular dystrophy. [2023]The purpose of this review is to summarise the recent developments in trial readiness, natural history studies, and interventional clinical trials for Becker muscular dystrophy (BMD).
The X-linked Becker muscular dystrophy (bmx) mouse models Becker muscular dystrophy via deletion of murine dystrophin exons 45-47. [2023]Becker muscular dystrophy (BMD) is a genetic neuromuscular disease of growing importance caused by in-frame, partial loss-of-function mutations in the dystrophin (DMD) gene. BMD presents with reduced severity compared with Duchenne muscular dystrophy (DMD), the allelic disorder of complete dystrophin deficiency. Significant therapeutic advancements have been made in DMD, including four FDA-approved drugs. BMD, however, is understudied and underserved-there are no drugs and few clinical trials. Discordance in therapeutic efforts is due in part to lack of a BMD mouse model which would enable greater understanding of disease and de-risk potential therapeutics before first-in-human trials. Importantly, a BMD mouse model is becoming increasingly critical as emerging DMD dystrophin restoration therapies aim to convert a DMD genotype into a BMD phenotype.
Prednisone therapy in Becker's muscular dystrophy. [2017]Two boys with Becker's muscular dystrophy had a dramatic and sustained improvement in strength with therapeutic use of pred nisone. Both had documented Xp-21 defects on DNA testing. Concurrently with improvement, there was a decrease in their serum creatine kinase levels. One patient had two muscle biopsies, the first before prednisone treatment and the second during treatment. Both biopsies demonstrated an immunoblot decrease in the quantity of muscle dystrophin. Routine histology on the first biopsy was consistent with muscle dystrophy, and the second biopsy was normal. These two patients suggest that a small percentage of patients with Becker's muscular dystrophy have a dramatic and sus tained improvement in strength with the use of therapeutic corticosteroids. All patients with Becker's muscular dystrophy should be given a careful trial of prednisone to define those who benefit.
Dystrophin levels and clinical severity in Becker muscular dystrophy patients. [2017]Becker muscular dystrophy (BMD) is characterised by broad clinical variability. Ongoing studies exploring dystrophin restoration in Duchenne muscular dystrophy ask for better understanding of the relation between dystrophin levels and disease severity. We studied this relation in BMD patients with varying mutations, including a large subset with an exon 45-47 deletion.
Placebo-controlled Phase 2 Trial of Drisapersen for Duchenne Muscular Dystrophy. [2022]This double-blind, randomized, placebo-controlled Phase 2 study (NCT01462292) assessed the 24-week efficacy, safety, tolerability, and pharmacokinetics of two different subcutaneous drisapersen doses, and the 24-week off-dose persistent effect, in ambulant Duchenne muscular dystrophy (DMD) patients.
Assessment of Motor Unit Potentials Duration as the Biomarker of DT-DEC01 Cell Therapy Efficacy in Duchenne Muscular Dystrophy Patients up to 12 Months After Systemic-Intraosseous Administration. [2023]Duchenne muscular dystrophy (DMD) is a lethal X-linked disease caused by mutations in the dystrophin gene, leading to muscle degeneration and wasting. Electromyography (EMG) is an objective electrophysiological biomarker of muscle fiber function in muscular dystrophies. A novel, DT-DEC01 therapy, consisting of Dystrophin Expressing Chimeric (DEC) cells created by fusing allogeneic myoblasts from normal donors with autologous myoblasts from DMD-affected patients, was assessed for safety and preliminary efficacy in boys of age 6-15 years old (n = 3). Assessments included EMG testing of selected muscles of upper (deltoideus, biceps brachii) and lower (rectus femoris and gastrocnemius) extremities at the screening visit and at 3, 6, and 12 months following systemic-intraosseous administration of a single low dose of DT-DEC01 therapy (Bioethics Committee approval no. 46/2019). No immunosuppression was administered. Safety of DT-DEC01 was confirmed by the lack of therapy-related Adverse Events or Serious Adverse Events up to 22 months following DT-DEC01 administration. EMG of selected muscles of both, ambulatory and non-ambulatory patients confirmed preliminary efficacy of DT-DEC01 therapy by an increase in motor unit potentials (MUP) duration, amplitudes, and polyphasic MUPs at 12 months. This study confirmed EMG as a reliable and objective biomarker of functional assessment in DMD patients after intraosseous administration of the novel DT-DEC01 therapy.
Disease-modifying effects of edasalonexent, an NF-κB inhibitor, in young boys with Duchenne muscular dystrophy: Results of the MoveDMD phase 2 and open label extension trial. [2021]Chronic activation of NF-κB is a key driver of muscle degeneration and suppression of muscle regeneration in Duchenne muscular dystrophy. Edasalonexent (CAT-1004) is an orally-administered novel small molecule that covalently links two bioactive compounds (salicylic acid and docosahexaenoic acid) that inhibit NF-κB. This placebo-controlled, proof-of-concept phase 2 study with open-label extension in boys ≥4-<8 years old with any dystrophin mutation examined the effect of edasalonexent (67 or 100 mg/kg/day) compared to placebo or off-treatment control. Endpoints were safety/tolerability, change from baseline in MRI T2 relaxation time of lower leg muscles and functional assessment, as well as pharmacodynamics and biomarkers. Treatment was well-tolerated and the majority of adverse events were mild, and most commonly of the gastrointestinal system (primarily diarrhea). There were no serious adverse events in the edasalonexent groups. Edasalonexent 100 mg/kg was associated with slowing of disease progression and preservation of muscle function compared to an off-treatment control period, with decrease in levels of NF-κB-regulated genes and improvements in biomarkers of muscle health and inflammation. These results support investigating edasalonexent in future trials and have informed the design of the edasalonexent phase 3 clinical trial in boys with Duchenne.
Vamorolone improves Becker muscular dystrophy and increases dystrophin protein in bmx model mice. [2023]There is no approved therapy for Becker muscular dystrophy (BMD), a genetic muscle disease caused by in-frame dystrophin deletions. We previously developed the dissociative corticosteroid vamorolone for treatment of the allelic, dystrophin-null disease Duchenne muscular dystrophy. We hypothesize vamorolone can treat BMD by safely reducing inflammatory signaling in muscle and through a novel mechanism of increasing dystrophin protein via suppression of dystrophin-targeting miRNAs. Here, we test this in the bmx mouse model of BMD. Daily oral treatment with vamorolone or prednisolone improves bmx grip strength and hang time phenotypes. Both drugs reduce myofiber size and decrease the percentage of centrally nucleated fibers. Vamorolone shows improved safety versus prednisolone by avoiding or reducing key side effects to behavior and growth. Intriguingly, vamorolone increases dystrophin protein in both heart and skeletal muscle. These data indicate that vamorolone, nearing approval for Duchenne, shows efficacy in bmx mice and therefore warrants clinical investigation in BMD.
A Randomized, Double-Blind, Placebo-Controlled, Global Phase 3 Study of Edasalonexent in Pediatric Patients with Duchenne Muscular Dystrophy: Results of the PolarisDMD Trial. [2021]Edasalonexent (CAT-1004) is an orally-administered novel small molecule drug designed to inhibit NF-κB and potentially reduce inflammation and fibrosis to improve muscle function and thereby slow disease progression and muscle decline in Duchenne muscular dystrophy (DMD).
Outcome reliability in non-ambulatory boys/men with Duchenne muscular dystrophy. [2021]Therapeutic trials in Duchenne muscular dystrophy (DMD) often exclude non-ambulatory individuals. Here we establish optimal and reliable assessments in a multicenter trial.
Generation of a human induced pluripotent stem cell line (INNDSUi003-A) derived from patient with Becker muscular dystrophy (BMD). [2022]Becker muscular dystrophy (BMD), an X-linked recessive disorder caused of mutation in the dystrophin gene, is characterized by progressive muscle degeneration and proximal muscle weakness. We generated a human induced pluripotent stem cell (hiPSC) line from the fibroblasts isolated from patient with BMD by non-integrating reprogramming methods. The iPSC line highly expresses pluripotency markers, displays the normal karyotype and is able to differentiate into the three germ layers in vitro. The iPSC line will be a useful tool to study the pathogenesis of BMD and for drug screening.