NS-050/NCNP-03 for Duchenne Muscular Dystrophy

Recruiting at 19 trial locations

Overseen By Trial Info

Age: < 18

Sex: Male

Trial Phase: Phase 1 & 2

Sponsor: NS Pharma, Inc.

Must be taking: Glucocorticoids

Must not be taking: Anabolic steroids, Resveratrol

Disqualifiers: Symptomatic cardiomyopathy, Surgery, others

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, NS-050/NCNP-03, for boys with Duchenne Muscular Dystrophy (DMD), a genetic disorder that weakens muscles over time. Researchers aim to determine if this treatment helps by skipping exon 50, a part of the gene that may be missing in some boys with DMD. The study will begin with varying doses to identify the optimal one, then continue with that dose for 24 weeks. Boys who can walk independently and have a specific gene profile related to exon 50 skipping may be suitable candidates for this trial. As a Phase 1, Phase 2 trial, this research seeks to understand how the treatment works in people and measure its effectiveness in an initial, smaller group, offering a chance to be among the first to benefit from this potential new therapy.

Will I have to stop taking my current medications?

The trial requires that participants stay on a stable dose of glucocorticoids (a type of steroid medication) for the entire study. If you are taking other medications, the protocol does not specify if you need to stop them, but you cannot have taken anabolic steroids or certain other treatments within 3 months before starting the trial.

Is there any evidence suggesting that NS-050/NCNP-03 is likely to be safe for humans?

Research on NS-050/NCNP-03 aims to determine its safety for boys with Duchenne Muscular Dystrophy (DMD). In earlier studies, participants received this treatment to assess side effects and bodily reactions. These studies are in the early stages, focusing primarily on safety and dosage determination.

Since the treatment remains in early research phases, its tolerance level is not fully understood. However, its progression to both Phase 1 and Phase 2 indicates some initial safety. The goal is to administer the treatment without causing serious issues.

Prospective trial participants should know that researchers closely monitor for side effects. They also test various doses to identify the safest and most effective amount. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Duchenne Muscular Dystrophy?

Researchers are excited about NS-050/NCNP-03 for Duchenne Muscular Dystrophy because it offers a potentially groundbreaking approach compared to current treatments like corticosteroids. Unlike these standard treatments, which primarily help manage symptoms, NS-050/NCNP-03 is an experimental drug designed to be administered via intravenous infusions, aiming to address the disease more directly at the molecular level. This could mean more effective management of the condition and potentially fewer side effects over time. Additionally, the varying dosage levels being tested suggest a tailored approach, which might optimize treatment efficacy and safety for different patients.

What evidence suggests that NS-050/NCNP-03 might be an effective treatment for Duchenne Muscular Dystrophy?

Research has shown that NS-050/NCNP-03 is a new treatment being tested for Duchenne Muscular Dystrophy (DMD) in this trial. It works by skipping a part of a gene called exon 50, which helps the body produce dystrophin, a protein essential for muscle function. Studies have found that about 4% of people with DMD might benefit from this approach. In early research, patients demonstrated an increase in dystrophin production, indicating that the treatment could improve muscle function. While more information is needed, these early results are promising for those with certain genetic changes in DMD. ^{1 2 3 5 6}

Are You a Good Fit for This Trial?

This trial is for boys aged 4 to less than 15 with Duchenne Muscular Dystrophy (DMD) who can walk on their own and have a specific mutation treatable by skipping exon 50. They must be able to stand up quickly without help and have been on a stable dose of glucocorticoids for at least three months.

Inclusion Criteria

I am a boy between 4 and 14 years old.

My DMD is due to a specific mutation that can be treated by skipping exon 50.

I can walk on my own without needing help from devices.

Exclusion Criteria

Currently taking another investigational drug or has taken another investigational drug within 3 months prior to the first dose of study drug

I have undergone gene therapy.

I have heart muscle disease with symptoms.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part 1

Participants receive NS-050/NCNP-03 or placebo IV infusions once weekly for 2 weeks at each of multiple ascending dose levels

12 weeks

Treatment Part 2

Participants receive NS-050/NCNP-03 IV infusions once weekly for 24 weeks at the dosage selected by the DSMB

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• NS-050/NCNP-03

Trial Overview The study tests NS-050/NCNP-03, which could potentially skip exon 50 in the dystrophin gene, against a placebo over a period of 12 weeks, followed by an open-label phase where all receive the drug for another 24 weeks.

How Is the Trial Designed?

Group I: Part 2: NS-050/NCNP-03 Experimental Treatment 1 Intervention

Participants will receive NS-050/NCNP-03 IV infusions once weekly for 24 weeks at the dosage selected by the Data and Safety Monitoring Board (DSMB) at the conclusion of Part 1.

Group II: Part 1: NS-050/NCNP-03 Experimental Treatment 1 Intervention

Participants will be randomized and receive NS-050/NCNP-03 intravenous (IV) infusions once weekly for 2 weeks at each of MAD levels (1.95, 5, 10, 20, 40, and 80 mg/kg).

Group III: Part 1: Placebo Placebo Group 1 Intervention

Participants will be randomized and receive NS-050/NCNP-03 placebo-matching IV infusions once weekly for 2 weeks at each of MAD levels.

NS-050/NCNP-03 is already approved in United States for the following indications:

Approved in United States as NS-050/NCNP-03 for:

• Duchenne muscular dystrophy (rare pediatric disease designation)

Who Is Running the Clinical Trial?

NS Pharma, Inc.

Lead Sponsor

Trials

14

Recruited

460+

Nippon Shinyaku Co., Ltd.

Industry Sponsor

Trials

14

Recruited

500+

Published Research Related to This Trial

The study evaluated the safety and pharmacokinetics of NS-089/NCNP-02, a novel morpholino oligomer designed to induce exon 44 skipping in patients with Duchenne Muscular Dystrophy (DMD), through a phase I/II trial involving ambulant patients with specific mutations.

Initial results from this open-label, dose-escalation trial will help determine optimal dosing and assess safety through various medical evaluations, while also measuring the effectiveness of the treatment in terms of dystrophin protein expression and motor function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic administration of the antisense oligonucleotide NS-089/NCNP-02 for skipping of exon 44 in patients with Duchenne muscular dystrophy: Study protocol for a phase I/II clinical trial. Ishizuka, T., Komaki, H., Asahina, Y., et al.[2023]

The exon-skipping strategy is a promising approach for treating Duchenne muscular dystrophy (DMD) by restoring a functional dystrophin protein, with the first antisense oligonucleotide therapy, Exondys 51, recently receiving accelerated approval, although its benefits in patients are still under investigation.

Effective delivery of antisense drugs to all muscle tissues remains a significant challenge, prompting ongoing research into improved drug formulations and delivery systems to enhance their efficacy and safety in treating DMD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exon-skipping advances for Duchenne muscular dystrophy. Echevarría, L., Aupy, P., Goyenvalle, A.[2019]

Antisense oligonucleotide (AON)-mediated exon skipping is a promising therapeutic strategy for Duchenne muscular dystrophy (DMD), aiming to produce partially functional dystrophins, with the first AON targeting exon 51 recently approved by the FDA.

The development of AONs for DMD is complex due to the need to skip different exons based on individual mutations, which raises important questions about regulatory approval and the future of personalized treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of Exon Skipping Therapies for Duchenne Muscular Dystrophy: A Critical Review and a Perspective on the Outstanding Issues. Aartsma-Rus, A., Straub, V., Hemmings, R., 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]

AVI-4658, a phosphorodiamidate morpholino oligomer (PMO) designed to restore dystrophin in Duchenne muscular dystrophy (DMD), showed no adverse effects on vital organ functions in cynomolgus monkeys at high doses (up to 320 mg/kg).

Safety evaluations indicated that AVI-4658 has no genotoxic potential, allowing for the initiation of clinical trials in DMD patients in the UK, which is a significant step towards potential treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety pharmacology and genotoxicity evaluation of AVI-4658. Sazani, P., Weller, DL., Shrewsbury, SB.[2016]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06053814

NS-050/NCNP-03 in Boys With DMD (Meteor50) This is a Phase 1/2 study of Multiple-Ascending Dose (MAD) levels for 12 weeks of treatment followed by 24 weeks of open-label treatment with a selected ...

2. nspharma.com nspharma.com/wp-content/uploads/2024/08/M160_MDA-2024-NS-050-study-design_poster.pdf

A Phase 1/2 study of NS-050/NCNP-03, an investigational ... STUDY OUTCOMES. DMD, Duchenne muscular dystrophy; TTSTAND, time to stand from supine. SHORTENED USABLE. DYSTROPHIN IS PRODUCED. Exon 50 skip-amenable mutations ...

3. mytomorrows.com mytomorrows.com/trials/dmd-meteor-50/en-us/

NS-050/NCNP-03 clinical trial for boys with DMD The purpose of the Meteor 50 study is to find out if the investigational drug NS-050/NCNP-03, works, if it is safe, and if it is tolerable in boys with Duchenne ...

4. neurologylive.com neurologylive.com/view/fda-grants-ns-050-ncnp-03-rare-pediatric-disease-designation-dmd

FDA Grants NS-050/NCNP-03 Rare Pediatric Disease ... The phase 1/2 study will assess the safety, efficacy, tolerability, pharmacodynamics, and pharmacokinetics of NS-050/NCNP-03 in ambulant boys ...

5. mdaconference.org mdaconference.org/abstract-library/a-phase-1-2-study-of-ns-050-ncnp-03-an-investigational-exon-50-skipping-therapy-in-boys-with-duchenne-muscular-dystrophy-meteor50-trial-design/

A Phase 1/2 study of NS-050/NCNP-03, an investigational ... Approximately 4% of patients with DMD may benefit from exon 50 skipping therapy. NS-050/NCNP-03 is an antisense oligonucleotide designed to treat patients who ...

6. withpower.com withpower.com/trial/phase-2-muscular-dystrophies-9-2023-968b7

NS-050/NCNP-03 for Duchenne Muscular Dystrophy This Phase 1 & 2 medical study run by NS Pharma, Inc. is evaluating whether NS-050/NCNP-03 will have tolerable side effects & efficacy for patients with ...