NS-050/NCNP-03 for Duchenne Muscular Dystrophy

Recruiting at 11 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

Trial Summary

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.

What safety data exists for NS-050/NCNP-03 in humans?

In a clinical trial for a similar treatment, NS-065/NCNP-01, no severe adverse reactions were observed in patients with Duchenne muscular dystrophy, indicating a favorable safety profile. ^{1 2 3 4 5}

What is the purpose of this trial?

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 dose of NS-050/NCNP-03 administered once weekly to ambulant boys with DMD, who have a DMD exon deletion amenable to exon 50 skipping.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

References

1. 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]

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

Development of Exon Skipping Therapies for Duchenne Muscular Dystrophy: A Critical Review and a Perspective on the Outstanding Issues. [2022]

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

Exon-skipping advances for Duchenne muscular dystrophy. [2019]

4. United States 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. [2023]

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

Safety pharmacology and genotoxicity evaluation of AVI-4658. [2016]