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

26 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called WVE-N531, an experimental therapy for Duchenne muscular dystrophy (DMD), a genetic disorder that causes muscle weakness. The goal is to assess the safety and effectiveness of this treatment for patients with a specific type of DMD gene mutation that can benefit from skipping exon 53, a part of the gene. Participants should be males diagnosed with DMD, possess the specific gene mutation, and be able to walk. They must also have stable heart and lung function and have been on a steady dose of corticosteroids for at least six months.

As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group. It offers participants the chance to contribute to groundbreaking advancements in DMD treatment.

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.

Is there any evidence suggesting that WVE-N531 is likely to be safe for humans?

Previous studies have shown that WVE-N531 is generally safe and well tolerated in boys with Duchenne muscular dystrophy. Research indicates there were no serious side effects or concerning patterns in lab results. Importantly, no safety issues were related to the type of genetic treatment WVE-N531 represents, known as exon skipping. These findings suggest that WVE-N531 is safe enough for continued testing in human trials. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for Duchenne Muscular Dystrophy, which often involve corticosteroids or exon-skipping therapies targeting different exons, WVE-N531 is designed to target exon 53 specifically. This precision allows for a more tailored approach in treating patients with mutations amenable to exon 53 skipping. Researchers are excited about WVE-N531 because it uses advanced oligonucleotide chemistry to potentially increase the efficiency and specificity of exon skipping, which could lead to improved muscle function and slower disease progression. This novel mechanism of action differentiates it from existing treatments and fuels hope for more effective management of the condition.

What evidence suggests that WVE-N531 might be an effective treatment for Duchenne muscular dystrophy?

Research has shown that WVE-N531, the investigational treatment in this trial, may help treat Duchenne muscular dystrophy (DMD). In an earlier study, patients stood up 3.8 seconds faster, demonstrating improved muscle function. The study also reported a 7.8% increase in dystrophin, a protein crucial for muscle strength. Additionally, there was a 50% reduction in creatine kinase, an enzyme linked to muscle damage, indicating less muscle breakdown. WVE-N531 also successfully skipped exon 53, a key step in restoring some muscle function. These results suggest that WVE-N531 could improve muscle health in people with DMD. ^{1 2 6 7 8}

Who Is on the Research Team?

Medical Director, MD

Principal Investigator

Wave Life Sciences

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: WVE-N531 Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Wave Life Sciences Ltd.

Lead Sponsor

Trials

14

Recruited

630+

Published Research Related to This Trial

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]

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]

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]

Citations

1.

ir.wavelifesciences.com

ir.wavelifesciences.com/news-releases/news-release-details/wave-life-sciences-announces-positive-data-forward-53-clinical

Reimagining RNA medicine

The trial showed a 3.8-second improvement in Time-to-Rise, reduced fibrosis, 7.8% dystrophin expression, and a 50% decline in creatine kinase.

2.

vivli.org

vivli.org/analysis-of-pro-dmd-01-functional-data-to-inform-endpoints-in-waves-forward-53-study-of-wve-n531-for-duchenne-muscular-dystrophy-dmd-exon-53-skipping-therapy/

Analysis of PRO-DMD-01 Functional Data to Inform ...

The research analyzes PRO-DMD-01 data to compare with FORWARD-53, assessing WVE-N531's activity, using functional outcomes like muscle strength and mobility.

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT07209332

Open-Label Extension Study of WVE-N531 in Patients With ...

Open-Label Extension Study of WVE-N531 in Patients With Duchenne Muscular Dystrophy. ClinicalTrials.gov ID NCT07209332. Sponsor Wave ...

4.

neurologylive.com

neurologylive.com/view/wve-n531-improves-muscle-health-latest-phase-2-trial-duchenne-muscular-dystrophy

WVE-N531 Improves Muscle Health in Latest Phase 2 Trial ...

WVE-N531, an investigational exon-skipping therapy, showed promising 48-week results in the FORWARD-53 study, marking the first-ever improvement in muscle ...

5.

mdaconference.org

mdaconference.org/abstract-library/wve-n531-supports-53-mean-exon-53-skipping-in-skeletal-muscle-of-boys-with-duchenne-muscular-dystrophy-dmd-after-six-weeks-of-treatment/

WVE-N531 supports 53% mean exon 53 skipping in ...

WVE-N531 achieved 53% mean exon 53 skipping in DMD boys after six weeks, with a mean concentration of 42 ug/g in muscle tissue.

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT04906460

Open-label Study of WVE-N531 in Patients With Duchenne ...

This is a Phase 1b/2 open-label study to evaluate the safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD), and clinical effects of intravenous ...

7.

parentprojectmd.org

parentprojectmd.org/wave-life-sciences-announces-positive-interim-data-from-forward-53-clinical-trial-evaluating-wve-n531-in-individuals-with-duchenne-amenable-to-exon-53-skipping/

Wave Life Sciences Announces Positive Interim Data from ...

Wave Life Sciences has announced positive interim data from the ongoing Phase 2 FORWARD-53 study of WVE-N531, an exon skipping oligonucleotide being ...

8.

wavelifesciences.com

wavelifesciences.com/wp-content/uploads/2024/03/WVE-N531-Fact-Sheet.pdf

What is an exon skipping treatment?

WVE-N531 was generally safe and well tolerated and the safety profile supports further clinical development. Data so far supports dosing by intravenous ...