EDG-5506 for Duchenne Muscular Dystrophy (LYNX Trial)
Recruiting in Palo Alto (17 mi)
+13 other locations
Age: < 18
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 tests EDG-5506, a pill taken regularly, in children aged 4 to 9 with Duchenne muscular dystrophy. It aims to see if the medication is safe and can reduce muscle damage. The study includes both children who are and are not currently on corticosteroids.
Is the drug EDG-5506 a promising treatment for Duchenne Muscular Dystrophy?The information provided does not include specific details about the drug EDG-5506 or its effects on Duchenne Muscular Dystrophy. Therefore, we cannot determine if it is a promising treatment based on the given data.1011121415
What data supports the idea that the drug EDG-5506 for Duchenne Muscular Dystrophy is an effective treatment?The available research does not provide any data on the effectiveness of EDG-5506 for Duchenne Muscular Dystrophy. The studies mentioned focus on other drugs and treatments for different conditions, such as cancer and chemotherapy-induced nausea, and do not include information on EDG-5506.46789
Do I have to stop taking my current medications for this trial?The trial protocol does not specify if you need to stop all current medications. However, if you are in Cohort 2 Non-Steroid, you should not have taken corticosteroids in the 6 months before the trial. Participants in other cohorts must be on a stable dose of corticosteroids for at least 6 months before the trial.
What safety data is available for EDG-5506 in treating Duchenne Muscular Dystrophy?The provided research does not contain any safety data specific to EDG-5506 or its alternative names like Sevasemten, EDG-5506 Dose 1, Dose 2, Dose 3, Placebo, Control, or Dummy Treatment. The studies focus on different compounds such as ethylenediamine, hexamethylenediamine, stearamidoethyl diethylamine, didecyldimethylammonium bromide, and trisodium ethylenediaminetetraacetate, none of which are related to EDG-5506. Therefore, no relevant safety data for EDG-5506 is available in the provided research.123513
Eligibility Criteria
This trial is for children with Duchenne muscular dystrophy who have a specific DMD gene mutation. They must be able to stand and climb stairs quickly, weigh between 15-35 kg, and either be aged 4-9 years on stable corticosteroids or aged 4-7 not on steroids recently.Participant Groups
The LYNX study tests different doses of EDG-5506 against a placebo in two parts: one where neither the researchers nor participants know who's getting what (double-blind), followed by an open-label part where everyone knows which treatment is given.
6Treatment groups
Experimental Treatment
Group I: Cohort 5Experimental Treatment2 Interventions
Drug: Sevasemten Drug: Placebo
Group II: Cohort 4Experimental Treatment2 Interventions
Drug: Sevasemten Drug: Placebo
Group III: Cohort 3Experimental Treatment2 Interventions
Drug: Sevasemten Drug: Placebo
Group IV: Cohort 2NSExperimental Treatment2 Interventions
Drug: Sevasemten Drug: Placebo
Group V: Cohort 2Experimental Treatment2 Interventions
Drug: Sevasemten Drug: Placebo
Group VI: Cohort 1Experimental Treatment2 Interventions
Drug: Sevasemten Drug: Placebo
EDG-5506 Dose 1 is already approved in United States for the following indications:
🇺🇸 Approved in United States as EDG-5506 for:
- No approvals yet; has received Fast Track designation for Duchenne muscular dystrophy and Becker muscular dystrophy
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Rare Disease ResearchAtlanta, GA
University of FloridaGainesville, FL
Washington University School of MedicineSaint Louis, MO
University of Massachusetts Memorial Medical CenterWorcester, MA
More Trial Locations
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Who is running the clinical trial?
Edgewise Therapeutics, Inc.Lead Sponsor
References
Subchronic inhalation toxicity of hexamethylenediamine in rats. [2019]Four groups of 15 male and 15 female Sprague-Dawley-derived (CD) rats each were exposed to aqueous hexamethylenediamine (HMD) aerosols for 6 hr/day, 5 days/week for 13 weeks at mean analytical concentrations of 0, 12.8, or 51 mg/m3. Because of exposure-related deaths in a group of male and female rats similarly exposed to 215 mg/m3 HMD, this group was terminated during the seventh week of the study. Signs of respiratory and conjunctival irritation were observed in rats at both the 51 and 215 mg/m3 HMD test levels. Body weight gain was significantly reduced in both sexes exposed to 215 mg/m3 HMD. At the 5-week study interval, slight hemopoietic stimulation of peripheral blood parameters was observed in rats of both sexes exposed to 215 mg/m3 HMD. Treatment-related microscopic lesions were seen only in rats exposed to 215 mg/m3 MD and were confined to the trachea, nasal passages, and lungs. The no-effect level in this study is considered to be 12.8 mg/m3 HMD.
Assessment of genotoxic potential of ethylenediamine: in vitro and in vivo studies. [2019]Ethylenediamine (EDA) was evaluated for potential genotoxic activity using a battery in vitro and in vivo mammalian tests. The tests employed were the Chinese hamster ovary (CHO) gene mutation assay, the sister-chromatid exchange (SCE) test with CHO cells, unscheduled DNA synthesis (UDS) assays with primary rat hepatocytes and a dominant lethal study with Fischer 344 rats. EDA did not produce a positive, dose-related, mutagenic effect in either the CHO mutation assay or in the SCE test when evaluated both with and without the addition of a rat-liver S9 activation system. With hepatocytes, no positive effects of EDA upon UDS values were noted in 2 separate studies using either a scintillation counting procedure or an autoradiographic method to determine UDS activity. In a dominant lethal study, male rats fed for 23 weeks with dietary levels of EDA X 2HCl of 0, 0.05, 0.15 or 0.50 g/kg/day, and mated with 1 virgin female/week for 3 consecutive weeks, showed no dose-related or statistically significant effects upon fertility, total number of implantations/female, or the number of living and dead implants per female; marked effects upon the incidence of dominant lethal mutations were noted in the positive control group injected intraperitoneally with one dose of 0.25 mg/kg triethylenemelamine. We conclude that EDA was not genotoxic in the in vitro and in vivo mammalian test systems employed.
Skin sensitization potential of trisodium ethylenediaminetetraacetate. [2019]A sodium salt of ethylenediaminetetraacetate (Na3EDTA) and ethylenediamine (EDA) were subjected to a repeated insult patch test on Hartley albino guinea pigs (10 per compound). All guinea pigs (10 of 10) receiving EDA were sensitized. None of the guinea pigs (0 of 10) was sensitized to Na3 EDTA. Likewise, none of the guinea pigs sensitized to EDA reacted positively when challenged with Na3 EDTA. Based on these results, it is concluded that EDTA is not likely to be a sensitizer to humans, and would not likely cross-sensitize with EDA. In addition, the presence of very small amounts of the sodium salts of EDTA in cosmetic and pharmaceutical preparations does not represent an appreciable risk of human skin sensitization.
Phase II trial of a 75-mg/m2 dose of docetaxel with prednisone premedication for patients with advanced non-small cell lung cancer. [2019]A prior Phase II study of a 100-mg/m2 dose of docetaxel conducted at the Memorial Sloan-Kettering Cancer Center (New York, NY) demonstrated a 38% response rate with grade 3 or 4 neutropenia in 76% of the patients and a grade 2 or greater rash or infusion-related reaction in 41% and 34% of the patients, respectively. The current Phase II study sought to determine the activity of a 75-mg/m2 dose of docetaxel to establish whether this lower dose, combined with prednisone, ameliorates toxicity.
[Threshold of contact allergy to stearamidoethyl diethylamine in guinea pigs]. [2016]The cationic surfactant, stearamidoethyl diethylamine (SD) is an emulsifier used in topical medications and cosmetics. It has been reported to cause allergic contact dermatitis. This report concerns a study of the sensitizing capacity of SD in guinea pigs, using the modified maximization method (8) and closed epicutaneous test (10); the induction concentration was 10% in petrolatum. By the modified maximization method, 8 of 20 (40%) of the guinea pigs were sensitized to 1% SD, mean response 1.9; and 6 (30%) to 0.5% SD, mean response 1.4. In closed epicutaneous tests, 3 of 20 (15%) guinea pigs also showed reactions to 1%, and 2 of 20 (10%) to 0.5% SD. The results from modified maximization test showed that SD is a moderate sensitizer, as the sensitizing rate is in the range of 26-50% (below 26% is classified as "mild", and above 50% is "strong"). Even with a less sensitive closed epicutaneous test, its sensitivity could also be detected. From a risk-benefit point of view, no substantial risk for cosmetic chemicals intended for extensive use on normal and diseased skin will be accepted. Drugs may be acceptable, in spite of their sensitizing potential, because of their inherent benefit. As such, this surfactant may be only suitable in prescription drugs. Allergic contact dermatitis is rarely reported from cationic surfactants. Lack of suspicion of these not-necessarily-innocent chemicals has been partially responsible. The potential widespread use of emulsifiers with sensitizing capacity warrants further surveillance, as does the possibility of cross reaction between various emulsifiers.
A double-blind crossover study comparing prophylactic intravenous granisetron alone or in combination with dexamethasone as antiemetic treatment in controlling nausea and vomiting associated with chemotherapy. [2019]The efficacies of granisetron plus dexamethasone and granisetron alone in controlling nausea and vomiting during two consecutive cycles of moderately emetogenic chemotherapy given for up to 5 days were compared in a two-centre, randomised, double-blind, placebo-controlled crossover study. In all, 110 evaluable patients received either dexamethasone, 20 mg i.v., or matching placebo, plus open-label granisetron, 3 mg i.v., given on each chemotherapy day. At cycle 2, patients crossed over to the alternative treatment; 72 patients completed the crossover. In these 72 patients, the complete response rates over 24 h for granisetron plus dexamethasone and granisetron plus placebo in cycle 1 were 87% and 70% (ns), respectively. In cycle 2 the complete response rates over 24 h were 73% and 62% (ns). Combining the two cycles, the complete response rates over 24 h were 80.6% (granisetron plus dexamethasone) and 65.3% (granisetron plus placebo; P = 0.015). Granisetron plus dexamethasone was significantly more effective in terms of times to less than complete response (P = 0.041), to first episode of moderate/severe nausea (P = 0.04), to first episode of vomiting (0.03) and to use of rescue medication (P = 0.02). Adverse events tended to be minor, with asthenia and insomnia the most common. Of those patients who expressed a preference, 67% preferred granisetron plus dexamethasone (P
[Combination effect of granisetron plus corticosteroid for prevention of cisplatin-induced emesis: a cross-over study comparing methylprednisolone and dexamethasone]. [2013]Granisetron (G) is an effective antiemetic drug that is used to prevent cisplatin-induced emesis, although it is less effective for delayed emesis. To enhance the antiemetic effects of granisetron, corticosteroid analogues such as methylprednisolone (M) and dexamethasone (D) were employed in a study of patients treated with cisplatin (CDDP). We investigated the clinical response and urinary excretion of 5-hydroxyindole acetic acid (5-HIAA), the main metabolite of serotonin, in 31 patients with ovarian cancer or uterine endometrial cancer who received CAP therapy (CDDP 75 mg/m2) in a 3-day cross-over trial comparing G + M and G + D treated patients. Both regimens were and delayed emesis than G + D. We conclude that G + D is a more efficacious combination than G + D in protecting patients from CDDP-induced acute and delayed emesis.
A double-blind randomized study comparing intramuscular (i.m.) granisetron with i.m. granisetron plus dexamethasone in the prevention of delayed emesis induced by cisplatin. The Italian Multicenter Study Group. [2013]Granisetron has been shown to exert a beneficial therapeutic effect in the prophylaxis and treatment of acute nausea and vomiting due to chemotherapy. However, limited data regarding its efficacy in the prevention and treatment of delayed emesis are available. A total of 532 patients entered this multicenter double-blind study, aimed at comparing the efficacy and safety of intramuscular (i.m.) granisetron with that of i.m. granisetron plus dexamethasone. Complete response and total control were evaluated for 3 days following the first 24 h after cisplatin administration in two groups of patients: 262 treated with granisetron 3 mg i.m. daily (plus placebo), and 265 with granisetron at the same dose plus dexamethasone 8 and 4 mg twice daily. The rate of complete response was 58.0% in the granisetron group and 78.9% in the granisetron plus dexamethasone group over days 1-3 (p
Efficacy of ondansentron treatment for acute emesis with different dosing schedules 8 vs 32 mg. A randomized study. [2013]The aim of the present randomized study was to evaluate which dose of Ondansentron (OND)(32 versus 8 mg) is appropriate for the antiemetic treatment of a uniform group of patients (pts) with Non Small Cell Lung Cancer (NSCLC) who were treated with Cisplatin (CDDP) 100 mg/m2 in combination with other less emetogenic drugs. One hundred and ten patients, with histologically confirmed NSCLC entered this randomized study. They were between 50 - 70 years old, with no previous Chemotherapy, with a PS (Karnofsky) >60%. They were randomized into two groups; Group A: OND as a 32 mg dose the first 24 hours, followed by 8 mg every 8 hrs for the following four days, combined with dexamethasone, 8 mg i.v. the first day, and 8 mg p.o., in the morning, the following three days. Group B: OND as a 8 mg dose every day for 4 days, combined with dexamethasone 8 mg i.v. and 8 mg p.o. the following three days. In this randomized study, of the 110 patients who entered, 106 were evaluable. Clinical parameters were similar between the examined groups. A higher number of patients of Group A presented complete response (P 0.0001), compared to patients of Group B who failed (P 0.004), during the first 24 hours. In the 3 days that followed, a higher number of pts of Group A presented complete response to the antiemetic therapy (P 0.001, P 0.0001), while Group B failed (P 0.007, P 0.001, P 0.019), or presented minor response (P 0.0001, P 0.004). Patients who had no antiemetic response needed additional therapy and were excluded from the evaluatio (13 pts of Group B). Retches (P 0.0001, P 0.005), and nausea (P 0.0001, P were also frequent in Group B. We concluded that reduced OND doses (8 mg) are inadequate in the prevention of emesis after high dose CDDP (100 mg/m2) and should be avoided.
The 6-minute walk test and other endpoints in Duchenne muscular dystrophy: longitudinal natural history observations over 48 weeks from a multicenter study. [2022]Duchenne muscular dystrophy (DMD) subjects ≥5 years with nonsense mutations were followed for 48 weeks in a multicenter, randomized, double-blind, placebo-controlled trial of ataluren. Placebo arm data (N = 57) provided insight into the natural history of the 6-minute walk test (6MWT) and other endpoints.
Daily prednisone treatment in Duchenne muscular dystrophy in southwest China. [2016]In this study we aimed to determine the influence of daily prednisone treatment in Duchenne muscular dystrophy (DMD) by performing a prospective, randomized, placebo-controlled trial in southwestern China.
A Novel NF-κB Inhibitor, Edasalonexent (CAT-1004), in Development as a Disease-Modifying Treatment for Patients With Duchenne Muscular Dystrophy: Phase 1 Safety, Pharmacokinetics, and Pharmacodynamics in Adult Subjects. [2018]In Duchenne muscular dystrophy (DMD), NF-κB is activated in skeletal muscle from infancy regardless of the underlying dystrophin mutation and drives inflammation and muscle degeneration while inhibiting muscle regeneration. Edasalonexent (CAT-1004) is a bifunctional orally administered small molecule that covalently links 2 compounds known to inhibit NF-κB, salicylic acid and docosahexaenoic acid (DHA). Edasalonexent is designed to inhibit activated NF-κB upon intracellular cleavage to these bioactive components. Preclinical data demonstrate disease-modifying activity in DMD animal models. Three placebo-controlled studies in adult subjects assessed the safety, pharmacokinetics, and pharmacodynamics of single or multiple edasalonexent doses up to 6000 mg. Seventy-nine adult subjects received edasalonexent, and 25 received placebo. Pharmacokinetic results were consistent with the intracellular cleavage of edasalonexent to its active components. Food increased plasma exposures of edasalonexent and salicyluric acid, an intracellularly formed metabolite of salicylic acid. The NF-κB pathway and proteosome gene expression profiles in peripheral mononuclear cells were significantly decreased (P = .02 and P = .002, respectively) after 2 weeks of edasalonexent treatment. NF-κB activity was inhibited following a single dose of edasalonexent but not by equimolar doses of salicylic acid and DHA. Edasalonexent was well tolerated, and the most common adverse events were mild diarrhea and headache. In first-in-human studies, edasalonexent was safe, well tolerated, and inhibited activated NF-κB pathways, suggesting potential therapeutic utility in DMD regardless of the causative dystrophin mutation, as well as other NF-κB-mediated diseases.
Divergent hypersensitivity responses following topical application of the quaternary ammonium compound, didecyldimethylammonium bromide. [2020]Didecyldimethylammonium bromide (DDAB) is a fourth generation dialkyl-quaternary ammonium compound (QAC) that is used in numerous products for its antimicrobial properties. While many QACs have been associated with allergic disease, the toxicity and sensitization of DDAB have not been thoroughly investigated. The purpose of these studies was to evaluate the irritancy and sensitization potential of DDAB following dermal application in a murine model. DDAB induced significant irritancy (0.0625-2%), evaluated by ear swelling in female BALB/c mice. Initial evaluation of the sensitization potential was conducted using the local lymph node assay (LLNA) at concentrations ranging from 0.0625% to 2%. A concentration-dependent increase in lymphocyte proliferation was observed with a calculated EC3 value of 0.057%. Immune cell phenotyping along with local and systemic IgE levels were evaluated following 4 and 14 days of dermal application. Phenotypic analyses revealed significant and dose-responsive increases in the absolute number of B-cells, CD4+ T-cells, CD8+ T-cells, and dendritic cells in the draining lymph nodes (DLNs) following 4 and 14 days of dermal exposure with significant increases in the number of activated B-cells and dendritic cells. However, increased activation of CD4+ T-cell and CD8+ T-cells was only observed following four days of DDAB exposure. Exposure to DDAB also induced increased production of IgE as evaluated by phenotypic analysis of DLN B-cells (IgE+ B-cells) and measurement of total serum IgE levels following 14 days but not four days of dermal application. Significant increases in gene expression were observed in the DLN (Il-4, Il-10, and ox40l) and ear (tslp) following 4 and 14 days of DDAB exposure. These results demonstrate the potential for development of irritation and hypersensitivity responses to DDAB following dermal exposure and raise concerns about the effects of exposure duration on hypersensitivity responses.
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.
A first-in-human phase I/IIa gene transfer clinical trial for Duchenne muscular dystrophy using rAAVrh74.MCK.GALGT2. [2023]In a phase 1/2, open-label dose escalation trial, we delivered rAAVrh74.MCK.GALGT2 (also B4GALNT2) bilaterally to the legs of two boys with Duchenne muscular dystrophy using intravascular limb infusion. Subject 1 (age 8.9 years at dosing) received 2.5 × 1013 vector genome (vg)/kg per leg (5 × 1013 vg/kg total) and subject 2 (age 6.9 years at dosing) received 5 × 1013 vg/kg per leg (1 × 1014 vg/kg total). No serious adverse events were observed. Muscle biopsy evaluated 3 or 4 months post treatment versus baseline showed evidence of GALGT2 gene expression and GALGT2-induced muscle cell glycosylation. Functionally, subject 1 showed a decline in 6-min walk test (6MWT) distance; an increase in time to run 100 m, and a decline in North Star Ambulatory Assessment (NSAA) score until ambulation was lost at 24 months. Subject 2, treated at a younger age and at a higher dose, demonstrated an improvement over 24 months in NSAA score (from 20 to 23 points), an increase in 6MWT distance (from 405 to 478 m), and only a minimal increase in 100 m time (45.6-48.4 s). These data suggest preliminary safety at a dose of 1 × 1014 vg/kg and functional stabilization in one patient.