NS-089/NCNP-02 for Duchenne Muscular Dystrophy

Recruiting at 19 trial locations

Overseen By Trial info

Age: < 18

Sex: Male

Trial Phase: Phase 2

Sponsor: NS Pharma, Inc.

Must be taking: Glucocorticoids

Must not be taking: Anabolic steroids, Resveratrol

Disqualifiers: Symptomatic cardiomyopathy, Gene therapy, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 25

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called NS-089/NCNP-02 for boys with Duchenne Muscular Dystrophy (DMD), a condition that weakens muscles over time. The focus is on boys who can walk independently and have a specific genetic mutation treatable by skipping exon 44, a part of their DNA. The treatment is administered through weekly IV infusions to evaluate its effectiveness and safety. Boys living with DMD who can complete a standing test in under 20 seconds might be suitable candidates for this trial. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of participants.

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 at least 3 months before and during the study. If you are taking anabolic steroids, resveratrol, adenosine triphosphate, or any investigational drugs, you must stop these at least 3 months before starting the trial.

Is there any evidence suggesting that NS-089/NCNP-02 is likely to be safe for humans?

Research has shown that NS-089/NCNP-02 is generally safe and well-tolerated in people. In an earlier study, participants did not experience any major safety issues. Importantly, there were no signs of harmful immune reactions, such as the body producing antibodies that attack itself. This indicates that the treatment is stable and does not cause negative immune responses. Overall, participants in that study improved without significant side effects, making NS-089/NCNP-02 a promising treatment option for Duchenne Muscular Dystrophy. ^{1 2 3 4 5}

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

Unlike the standard treatments for Duchenne Muscular Dystrophy, which often focus on managing symptoms and slowing the disease progression through corticosteroids and physical therapy, NS-089/NCNP-02 offers a novel approach. This treatment is unique because it is designed as a solution for infusion, potentially allowing for more precise delivery of the therapeutic agent directly into the bloodstream. Researchers are particularly excited about its potential to target and repair the underlying genetic defect in Duchenne Muscular Dystrophy, which could lead to more effective and lasting improvements in muscle function.

What evidence suggests that NS-089/NCNP-02 might be an effective treatment for Duchenne Muscular Dystrophy?

Research has shown that NS-089/NCNP-02, the investigational treatment in this trial, could help treat Duchenne Muscular Dystrophy (DMD) through a method called exon 44 skipping. This technique enables the body to produce shorter but functional versions of dystrophin, a protein lacking in DMD patients. Early study results suggest that NS-089/NCNP-02 can successfully induce exon 44 skipping, potentially improving muscle function. Specifically, previous patients demonstrated promising safety outcomes and possible improvements in muscle strength and function. This offers hope that NS-089/NCNP-02 could be effective for those with certain genetic mutations related to DMD. ^{1 4 5 6 7}

Are You a Good Fit for This Trial?

This trial is for boys aged 4 to under 15 with Duchenne Muscular Dystrophy (DMD) who can stand up quickly without help and walk on their own. They must have a specific mutation in the dystrophin gene and be on a stable dose of glucocorticoids for at least three months.

Inclusion Criteria

My DMD is due to a specific mutation that can be treated by skipping exon 44.

I can stand up from sitting without help in less than 7 seconds.

I have been on a stable dose of glucocorticoid for at least 3 months.

Exclusion Criteria

Previously treated in an interventional study of NS-089/NCNP-02

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

I haven't taken steroids, resveratrol, or ATP products in the last 3 months.

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-089/NCNP-02 via weekly IV infusion

13 weeks

13 visits (in-person)

Treatment Part 2

Continuation of NS-089/NCNP-02 treatment with additional participants

12 weeks

12 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• NS-089/NCNP-02

Trial Overview The study tests NS-089/NCNP-02, given weekly through an IV, aiming to skip exon 44 in the dystrophin gene. It's divided into two parts: an initial phase with six participants followed by a second part including another fourteen boys.

How Is the Trial Designed?

Group I: NS-089/NCNP-02 Experimental Treatment 1 Intervention

Experimental: NS-089/NCNP-02 NS-089/NCNP-02 solution for infusion (Cohort 1) NS-089/NCNP-02 solution for infusion (Cohort 2)

NS-089/NCNP-02 is already approved in United States, Japan for the following indications:

Approved in United States as NS-089/NCNP-02 for:

• Duchenne muscular dystrophy (DMD) amenable to exon 44 skipping

Approved in Japan as NS-089/NCNP-02 for:

• Duchenne muscular dystrophy (DMD) amenable to exon 44 skipping

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

Antisense oligonucleotide (AON)-mediated exon skipping is a promising therapy for Duchenne muscular dystrophy (DMD), potentially benefiting 47% of patients by producing functional protein through targeted skipping of specific exons.

Analysis of data from 765 DMD patients revealed that certain exon deletions, particularly exon 44 and exon 8, are associated with prolonged ambulation, suggesting that specific genetic mutations can influence disease progression and severity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

DMD genotype correlations from the Duchenne Registry: Endogenous exon skipping is a factor in prolonged ambulation for individuals with a defined mutation subtype. Wang, RT., Barthelemy, F., Martin, AS., et al.[2022]

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]

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 study developed a novel antisense oligonucleotide, NS-089/NCNP-02, designed for exon 44 skipping in Duchenne muscular dystrophy, which showed significantly improved activity by targeting two splicing regulators simultaneously.

In both cell cultures from patients and in vivo tests on cynomolgus monkeys, NS-089/NCNP-02 effectively induced exon 44 skipping and increased dystrophin protein expression, demonstrating its potential as a therapeutic option for approximately 6% of Duchenne muscular dystrophy patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exon 44 skipping in Duchenne muscular dystrophy: NS-089/NCNP-02, a dual-targeting antisense oligonucleotide. Watanabe, N., Tone, Y., Nagata, T., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05996003

Study Details | NCT05996003 | NS-089/NCNP-02-201 in ... This is a Phase 2, open-label, multi-center, 2-part study of NS-089/NCNP-02 administered by weekly IV infusion to ambulant boys aged ≥4 to <15 years with ...

2. prnewswire.com prnewswire.com/news-releases/brogidirsen-ns-089ncnp-02-3-5-year-clinical-trial-data-for-the-treatment-of-duchenne-muscular-dystrophy-presented-at-2025-world-muscle-society-congress-302580951.html

Brogidirsen (NS-089/NCNP-02) 3.5 Year Clinical Trial Data ... Brogidirsen (NS-089/NCNP-02) 3.5 Year Clinical Trial Data for the Treatment of Duchenne Muscular Dystrophy Presented at 2025 World Muscle ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37326950/

Study protocol for a phase I/II clinical trial The purpose of this study is to evaluate the safety and pharmacokinetics of the novel morpholino oligomer NS-089/NCNP-02 which can induce exon 44 skipping, in ...

4. mdaconference.org mdaconference.org/abstract-library/a-phase-i-ii-study-of-ns-089-ncnp-02-exon-44-skipping-drug-in-patients-with-duchenne-muscular-dystrophy/

A Phase I/II study of NS-089/NCNP-02, Exon 44 skipping ... Herein, we report data of safety, efficacy, and pharmacokinetics of NS-089/NCNP-02 from this study. BBB Accredited Charity. Home. Muscular Dystrophy Association ...

5. nmd-journal.com nmd-journal.com/article/S0960-8966(22)00441-2/abstract

P.123 A Phase I/II study of NS-089/NCNP-02, Exon 44 ... Our first-in-human studies shall provide critical data of safety, potential efficacy and pharmacokinetics of NS-089/NCNP-02 for subsequent ...

6. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0960896622004412

P.123 A Phase I/II study of NS-089/NCNP-02, Exon 44 ... NS-089/NCNP-02 were well tolerated, showed no sign of safety signals, and production of anti-dystrophin antibody. All participants showed significant increases ...

7. mytomorrows.com mytomorrows.com/trials/discover-ns-089/en-us/

Enrollment now open for NS-089/NCNP-02 clinical trial ... The purpose of the DISCOVER study is to find out if the investigational drug NS-089/NCNP-02 works, if it is safe, and if it is tolerable in boys with Duchenne.