WVE-N531 for Duchenne Muscular Dystrophy

Recruiting at 3 trial locations

Overseen By Clinical Operations

Age: < 65

Sex: Male

Trial Phase: Phase 1 & 2

Sponsor: Wave Life Sciences Ltd.

Must be taking: Corticosteroids

Disqualifiers: Major surgery, Substance use disorder, others

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

Compensation: Varies

Number of Visits: Unknown

11 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must be on a stable corticosteroid therapy regimen for at least 6 months before joining the study.

What data supports the effectiveness of the drug WVE-N531 for Duchenne Muscular Dystrophy?

Research on similar treatments, like eteplirsen, which also uses exon skipping to help produce dystrophin protein, shows increased dystrophin production and improved muscle function in patients. This suggests that WVE-N531, which likely uses a similar mechanism, could also be effective in treating Duchenne Muscular Dystrophy. ^{1 2 3 4 5}

What safety data exists for WVE-N531 or similar treatments for Duchenne Muscular Dystrophy?

The safety of similar treatments, like NS-065/NCNP-01, has been evaluated in clinical trials, showing no severe adverse reactions and no treatment discontinuations. Additionally, studies on other related therapies, such as DT-DEC01, reported no adverse events up to 21 months after administration, indicating a favorable safety profile. ^{4 5 6 7 8}

What is the purpose of this trial?

This is a Phase 1b/2 open-label study to evaluate the safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD), and clinical effects of intravenous (IV) WVE-N531 in patients with Duchenne muscular dystrophy (DMD). To participate in the study, patients must have a documented mutation of the DMD gene that is amenable to exon 53 skipping intervention. This study has 2 parts, Part A and Part B. Part A is completed. Part B is completed. Following completion of Part B, all patients have elected to continue to receive study drug in an optional open-label extension arm.

Research Team

Medical Director, MD

Principal Investigator

Wave Life Sciences

Eligibility Criteria

This trial is for patients with Duchenne muscular dystrophy (DMD) who have a specific mutation in the DMD gene that can be targeted by exon 53 skipping. Participants should show certain levels of muscle function, have stable breathing capacity, and heart function within set ranges. They must also be on a consistent corticosteroid treatment for at least six months.

Inclusion Criteria

New patients may also be screened for Part B

I am a man, able to walk or not.

My DMD gene mutation can be treated with exon 53 targeting.

Exclusion Criteria

Clinically significant medical finding on the physical examination other than DMD that, in the judgment of the Investigator, will make the patient unsuitable for participation in, and/or completion of the study procedures

I haven't had major surgery in the last 3 months and don't plan any during the study.

Diagnosis of active alcohol, cannabinoid, or other substance use disorder (except nicotine) within 6 months prior to the Screening visit

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part A

Participants received WVE-N531 at 10 mg/kg every other week (Q2W)

24 weeks

Treatment Part B

New patients enrolled and continued treatment with WVE-N531, initially at Q2W, then switched to Q4W dosing

48 weeks

Open-label Extension

Participants elected to continue receiving WVE-N531 at Q4W for up to 1 year

1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

10 months

Treatment Details

Interventions

• WVE-N531

Trial Overview The study is testing WVE-N531, administered intravenously to see if it's safe and how it affects the body (pharmacokinetics) and disease symptoms (pharmacodynamics). The trial has two parts; Part A is finished. It aims to understand how this drug could help manage Duchenne muscular dystrophy.

Participant Groups

Group I: WVE-N531 Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Wave Life Sciences Ltd.

Lead Sponsor

Trials

14

Recruited

630+

Findings from Research

A study involving 91 non-ambulatory boys and men with Duchenne muscular dystrophy (DMD) demonstrated that reliable assessments of their physical abilities can be achieved, with high reliability scores (ICCs) for various tests, including forced vital capacity (FVC) and upper extremity function.

The research indicated that different forms of corticosteroids had beneficial effects on upper extremity function, lung capacity, and hand strength, suggesting that corticosteroid use should be considered in clinical trials for DMD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcome reliability in non-ambulatory boys/men with Duchenne muscular dystrophy. Connolly, AM., Malkus, EC., Mendell, JR., et al.[2021]

In a phase 3 study involving 79 patients aged 7-16 with Duchenne muscular dystrophy, eteplirsen treatment for 96 weeks resulted in a significant increase in dystrophin production (7-fold) and exon skipping (18.7-fold), indicating its efficacy in addressing the underlying cause of the disease.

The study also demonstrated a favorable safety profile, with most adverse events being mild to moderate and unrelated to the treatment, while showing a notable slowing of disease progression compared to untreated controls.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open-Label Evaluation of Eteplirsen in Patients with Duchenne Muscular Dystrophy Amenable to Exon 51 Skipping: PROMOVI Trial. McDonald, CM., Shieh, PB., Abdel-Hamid, HZ., et al.[2022]

In a phase 1 clinical trial involving 10 patients with Duchenne muscular dystrophy (DMD), the morpholino antisense oligonucleotide NS-065/NCNP-01 was found to have a favorable safety profile, with no severe adverse reactions reported during the 12-week treatment period.

NS-065/NCNP-01 successfully induced exon 53 skipping in dystrophin mRNA in a dose-dependent manner, leading to increased dystrophin expression in 7 out of 10 patients, suggesting its potential efficacy and warranting further investigation in phase 2 trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic administration of the antisense oligonucleotide NS-065/NCNP-01 for skipping of exon 53 in patients with Duchenne muscular dystrophy. Komaki, H., Nagata, T., Saito, T., et al.[2019]

The DT-DEC01 cell therapy demonstrated a strong safety profile with no adverse events reported up to 21 months after administration, indicating it is a safe treatment option for patients with Duchenne Muscular Dystrophy (DMD).

Functional improvements were observed in patients, including better performance in the 6-Minute Walk Test and other assessments, suggesting that DT-DEC01 may effectively enhance muscle function and overall health in DMD patients over a 12-month period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of DT-DEC01 Therapy in Duchenne Muscular Dystrophy Patients: A 12 - Month Follow-Up Study After Systemic Intraosseous Administration. Siemionow, M., Biegański, G., Niezgoda, A., et al.[2023]

References

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

Outcome reliability in non-ambulatory boys/men with Duchenne muscular dystrophy. [2021]

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

Dystrophinopathy Phenotypes and Modifying Factors in DMD Exon 45-55 Deletion. [2023]

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

Long-term natural history data in Duchenne muscular dystrophy ambulant patients with mutations amenable to skip exons 44, 45, 51 and 53. [2020]

4. Switzerland pubmed.ncbi.nlm.nih.gov

2'-O-Methyl RNA/Ethylene-Bridged Nucleic Acid Chimera Antisense Oligonucleotides to Induce Dystrophin Exon 45 Skipping. [2019]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Open-Label Evaluation of Eteplirsen in Patients with Duchenne Muscular Dystrophy Amenable to Exon 51 Skipping: PROMOVI Trial. [2022]

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

Systemic administration of the antisense oligonucleotide NS-065/NCNP-01 for skipping of exon 53 in patients with Duchenne muscular dystrophy. [2019]

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

Long-term efficacy of systemic multiexon skipping targeting dystrophin exons 45-55 with a cocktail of vivo-morpholinos in mdx52 mice. [2022]

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

Safety and Efficacy of DT-DEC01 Therapy in Duchenne Muscular Dystrophy Patients: A 12 - Month Follow-Up Study After Systemic Intraosseous Administration. [2023]