NS-089/NCNP-02 for Duchenne Muscular Dystrophy

Recruiting at 10 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

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 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.

What safety data exists for NS-089/NCNP-02 in humans?

NS-089/NCNP-02 has been tested in a phase 1/2 clinical trial for Duchenne muscular dystrophy, focusing on safety and how the body processes the drug. While specific safety results for NS-089/NCNP-02 are not detailed, a similar drug, NS-065/NCNP-01, showed no severe adverse reactions in a trial, suggesting a potentially favorable safety profile. ^{1 2 3 4 5}

What is the purpose of this trial?

This trial tests an IV medication called NS-089/NCNP-02 in boys aged 4 to 14 with a specific type of Duchenne Muscular Dystrophy. The treatment aims to help their bodies make better muscle proteins by skipping over a broken part of their gene. NS-089/NCNP-02 is a new drug utilizing exon-skipping therapy, similar to NS-065/NCNP-01, which targets specific deletions in the dystrophin gene.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

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]

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]

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]

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]

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

Exon 44 skipping in Duchenne muscular dystrophy: NS-089/NCNP-02, a dual-targeting antisense oligonucleotide. [2023]

3. 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]

4. United States 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. [2022]

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

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