EDG-5506 for Duchenne Muscular Dystrophy

(LYNX Trial)

Recruiting at 13 trial locations

Overseen By Edgewise Therapeutics

Age: < 18

Sex: Male

Trial Phase: Phase 2

Sponsor: Edgewise Therapeutics, Inc.

Must be taking: Corticosteroids

Must not be taking: Investigational drugs

Disqualifiers: Cardiac issues, Respiratory issues, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

76 Participants Needed

What You Need to Know Before You Apply

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.

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.

Will I have to stop taking my current medications?

If you are in Cohort 2 Non-Steroid, you should not have taken corticosteroids in the past 6 months. For other cohorts, you need to be on a stable dose of corticosteroids for at least 6 months before starting 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. ^{1 2 3 4 5}

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. ^{6 7 8 9 10}

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. ^{11 12 13 14 15}

Who Is on the Research Team?

Sam Collins, MBBS, PhD

Principal Investigator

Edgewise Therapeutics, Inc.

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

I can stand up from lying down in less than 10 seconds and climb four stairs in less than 10 seconds.

I am 4-7 years old and haven't taken corticosteroids in the last 6 months.

My weight is between 15 kg and 35 kg.

Exclusion Criteria

A cardiac echocardiography showing left ventricular ejection < 45% at the Screening visit

Receipt of an investigational drug within 30 days or 5 half-lives (whichever is longer) of the Screening visit in the present study

I have not taken oral steroids for Duchenne muscular dystrophy in the last 6 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment Part A

Randomized, double-blind, placebo-controlled treatment period

12 weeks

Regular visits for monitoring and assessments

Open-label Extension Part B

Participants receive open-label sevasemten treatment

92 weeks

Regular visits for monitoring and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• EDG-5506 Dose 1
• EDG-5506 Dose 2
• EDG-5506 Dose 3
• Placebo

Trial Overview 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.

How Is the Trial Designed?

Group I: Cohort 5 Experimental Treatment 2 Interventions

Drug: Sevasemten Drug: Placebo

Group II: Cohort 4 Experimental Treatment 2 Interventions

Drug: Sevasemten Drug: Placebo

Group III: Cohort 3 Experimental Treatment 2 Interventions

Drug: Sevasemten Drug: Placebo

Group IV: Cohort 2NS Experimental Treatment 2 Interventions

Drug: Sevasemten Drug: Placebo

Group V: Cohort 2 Experimental Treatment 2 Interventions

Drug: Sevasemten Drug: Placebo

Group VI: Cohort 1 Experimental Treatment 2 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

Who Is Running the Clinical Trial?

Edgewise Therapeutics, Inc.

Lead Sponsor

Trials

13

Recruited

1,000+

Published Research Related to This Trial

In a study involving 31 patients with ovarian or uterine endometrial cancer, the combination of granisetron and dexamethasone (G + D) was found to be more effective than granisetron and methylprednisolone (G + M) in preventing both acute and delayed nausea and vomiting caused by cisplatin treatment.

The study measured clinical responses and urinary excretion of 5-hydroxyindole acetic acid (5-HIAA), indicating that G + D provides better protection against cisplatin-induced emesis, enhancing the overall antiemetic effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Combination effect of granisetron plus corticosteroid for prevention of cisplatin-induced emesis: a cross-over study comparing methylprednisolone and dexamethasone]. Tanaka, K., Sekine, M., Serikawa, T., et al.[2013]

In a Phase II study involving 20 untreated patients with advanced non-small cell lung cancer, a lower dose of docetaxel (75 mg/m2) combined with prednisone showed significant antitumor activity, with a 25% response rate and a median duration of response of 9.1 months.

The lower dose resulted in a comparable rate of severe neutropenia (70%) to the higher 100 mg/m2 dose, but reduced the incidence of rash and infusion-related reactions to 25% each, suggesting improved tolerability with the lower dose regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II trial of a 75-mg/m2 dose of docetaxel with prednisone premedication for patients with advanced non-small cell lung cancer. Miller, VA., Rigas, JR., Francis, PA., et al.[2019]

In a study of 110 patients undergoing moderately emetogenic chemotherapy, the combination of granisetron and dexamethasone significantly improved the control of nausea and vomiting compared to granisetron alone, with a complete response rate of 80.6% versus 65.3%.

The addition of dexamethasone not only enhanced overall efficacy but also delayed the onset of nausea and vomiting, with 67% of patients preferring the combination treatment, indicating a favorable safety profile with mostly minor side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Kirchner, V., Aapro, M., Terrey, JP., et al.[2019]

In a study of 110 patients with Non Small Cell Lung Cancer receiving high-dose Cisplatin, a higher dose of Ondansetron (32 mg) resulted in significantly better antiemetic responses compared to a lower dose (8 mg), particularly in the first 24 hours and over the following three days.

Patients receiving the lower dose of Ondansetron experienced more frequent nausea and retching, indicating that the reduced dose is inadequate for preventing vomiting after high-dose chemotherapy and should be avoided.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of ondansentron treatment for acute emesis with different dosing schedules 8 vs 32 mg. A randomized study. Tsavaris, N., Kosmas, CH., Vadiaka, M., et al.[2013]

In a study of 532 patients, the combination of intramuscular granisetron and dexamethasone significantly improved the prevention of delayed nausea and vomiting after chemotherapy, achieving a complete response rate of 78.9% compared to 58.0% with granisetron alone.

The combination therapy also provided better overall control of symptoms, with total control rates of 65.3% versus 44.7% for granisetron alone, indicating that adding dexamethasone enhances the efficacy of granisetron in managing chemotherapy-induced emesis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

Ethylenediamine (EDA) was tested for genotoxicity using various in vitro and in vivo methods, including assays with Chinese hamster ovary cells and primary rat hepatocytes, and showed no evidence of mutagenic effects.

In a dominant lethal study with male rats over 23 weeks, EDA did not affect fertility or lead to significant genetic mutations, indicating that EDA is not genotoxic in the tested systems.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of genotoxic potential of ethylenediamine: in vitro and in vivo studies. Slesinski, RS., Guzzie, PJ., Hengler, WC., et al.[2019]

Exposure to high concentrations of hexamethylenediamine (HMD) aerosols (51 mg/m3 and 215 mg/m3) caused respiratory and eye irritation, as well as reduced body weight gain in male and female rats, indicating potential health risks at these levels.

The study identified a no-effect level for HMD exposure at 12.8 mg/m3, suggesting that lower concentrations may not cause significant adverse effects, while higher concentrations led to serious health issues and microscopic lesions in the respiratory system.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subchronic inhalation toxicity of hexamethylenediamine in rats. Johannsen, FR., Levinskas, GJ., Ben-Dyke, R., et al.[2019]

The study found that stearamidoethyl diethylamine (SD) is a moderate sensitizer, with 40% of guinea pigs showing sensitization to 1% SD, indicating a potential risk for allergic contact dermatitis in topical applications.

Despite its sensitizing potential, SD may still be acceptable for use in prescription drugs due to their therapeutic benefits, but caution is advised for its use in cosmetics, highlighting the need for further monitoring of emulsifiers with sensitizing properties.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Threshold of contact allergy to stearamidoethyl diethylamine in guinea pigs]. Sun, CC., Chen, LY.[2016]

Didecyldimethylammonium bromide (DDAB) caused significant skin irritancy in a murine model, with ear swelling observed at concentrations as low as 0.0625%, indicating potential safety concerns for dermal applications.

The study found that DDAB exposure led to a dose-dependent sensitization response, increasing immune cell activation and IgE production, which suggests a risk of allergic reactions with prolonged exposure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Divergent hypersensitivity responses following topical application of the quaternary ammonium compound, didecyldimethylammonium bromide. Shane, HL., Lukomska, E., Stefaniak, AB., et al.[2020]

In a study involving 20 Hartley albino guinea pigs, all subjects sensitized to ethylenediamine (EDA) showed no sensitization to sodium salt of ethylenediaminetetraacetate (Na3EDTA), indicating that Na3EDTA is unlikely to cause skin sensitization in humans.

The results suggest that very small amounts of Na3EDTA in cosmetics and pharmaceuticals pose a minimal risk for human skin sensitization, making it a safe ingredient for use in these products.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Skin sensitization potential of trisodium ethylenediaminetetraacetate. Henck, JW., Lockwood, DD., Olson, KJ.[2019]

In a Phase 2 study involving 51 ambulant Duchenne muscular dystrophy (DMD) patients, drisapersen at a dose of 6 mg/kg/week showed a potential benefit in improving the 6-minute walking distance (6MWD) compared to placebo, with a mean difference of 27.1 meters at week 24.

Drisapersen was generally well-tolerated, with the most common side effects being injection site reactions and subclinical proteinuria, indicating a manageable safety profile for this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Placebo-controlled Phase 2 Trial of Drisapersen for Duchenne Muscular Dystrophy. McDonald, CM., Wong, B., Flanigan, KM., et al.[2022]

Edasalonexent (CAT-1004) is a promising treatment for Duchenne muscular dystrophy (DMD) that works by inhibiting the NF-κB pathway, which is linked to inflammation and muscle degeneration, showing significant effects in reducing NF-κB activity in a study with 79 adult participants.

The treatment was found to be safe and well tolerated, with mild side effects like diarrhea and headache, indicating its potential for therapeutic use in DMD and other diseases related to NF-κB activation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Donovan, JM., Zimmer, M., Offman, E., et al.[2018]

In a study involving 66 children with Duchenne muscular dystrophy (DMD), daily treatment with prednisone at 0.75 mg/kg/day for 12 months led to significant improvements in muscle strength, function, quality of life, and muscle ultrasound measurements compared to a placebo group.

The treatment was found to be safe, with moderate side effects that were generally well tolerated, and it did not significantly affect body weight, height, or blood pressure, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daily prednisone treatment in Duchenne muscular dystrophy in southwest China. Hu, J., Ye, Y., Kong, M., et al.[2016]

In a 48-week study involving 57 DMD patients, the 6-minute walk distance (6MWD) was confirmed as a strong predictor of ambulation decline, with a baseline distance of less than 350 meters indicating a higher risk of functional decline.

The study found that only 2.3% of subjects who could stand from a supine position lost their ability to walk, highlighting the importance of baseline functional assessments in predicting outcomes in DMD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The 6-minute walk test and other endpoints in Duchenne muscular dystrophy: longitudinal natural history observations over 48 weeks from a multicenter study. McDonald, CM., Henricson, EK., Abresch, RT., et al.[2022]

In a phase 1/2 trial involving two boys with Duchenne muscular dystrophy, the treatment with rAAVrh74.MCK.GALGT2 showed preliminary safety, as no serious adverse events were reported after administering doses up to 1 × 10^14 vector genomes per kg.

Functional outcomes varied between the two subjects: while one experienced a decline in mobility, the younger subject at a higher dose showed improvements in muscle function over 24 months, indicating potential efficacy of the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A first-in-human phase I/IIa gene transfer clinical trial for Duchenne muscular dystrophy using rAAVrh74.MCK.GALGT2. Flanigan, KM., Vetter, TA., Simmons, TR., et al.[2023]

Citations

1. Japan pubmed.ncbi.nlm.nih.gov

[Combination effect of granisetron plus corticosteroid for prevention of cisplatin-induced emesis: a cross-over study comparing methylprednisolone and dexamethasone]. [2013]

2. United States pubmed.ncbi.nlm.nih.gov

Phase II trial of a 75-mg/m2 dose of docetaxel with prednisone premedication for patients with advanced non-small cell lung cancer. [2019]

3. England pubmed.ncbi.nlm.nih.gov

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]

4. England pubmed.ncbi.nlm.nih.gov

Efficacy of ondansentron treatment for acute emesis with different dosing schedules 8 vs 32 mg. A randomized study. [2013]

5. England pubmed.ncbi.nlm.nih.gov

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]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Assessment of genotoxic potential of ethylenediamine: in vitro and in vivo studies. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Subchronic inhalation toxicity of hexamethylenediamine in rats. [2019]

8. Singapore pubmed.ncbi.nlm.nih.gov

[Threshold of contact allergy to stearamidoethyl diethylamine in guinea pigs]. [2016]

9. England pubmed.ncbi.nlm.nih.gov

Divergent hypersensitivity responses following topical application of the quaternary ammonium compound, didecyldimethylammonium bromide. [2020]

10. United States pubmed.ncbi.nlm.nih.gov

Skin sensitization potential of trisodium ethylenediaminetetraacetate. [2019]

11. United States pubmed.ncbi.nlm.nih.gov

Placebo-controlled Phase 2 Trial of Drisapersen for Duchenne Muscular Dystrophy. [2022]

12. England pubmed.ncbi.nlm.nih.gov

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]

13. United States pubmed.ncbi.nlm.nih.gov

Daily prednisone treatment in Duchenne muscular dystrophy in southwest China. [2016]

14. United States pubmed.ncbi.nlm.nih.gov

The 6-minute walk test and other endpoints in Duchenne muscular dystrophy: longitudinal natural history observations over 48 weeks from a multicenter study. [2022]

15. United States pubmed.ncbi.nlm.nih.gov

A first-in-human phase I/IIa gene transfer clinical trial for Duchenne muscular dystrophy using rAAVrh74.MCK.GALGT2. [2023]