Duchenne Muscular DystrophyPhase 1/2NCT04129294
Exploratory Study of NS-089/NCNP-02 in DMD
A Phase 1/2 study testing NS-089/NCNP-02 in people with Duchenne Muscular Dystrophy, run by National Center of Neurology and Psychiatry, Japan at 1 site in Japan.
Trial summary
This study is designed to assess the safety, tolerability, efficacy and pharmacokinetics (PK) of NS-089/NCNP-02 in subjects diagnosed with Duchenne muscular dystrophy (DMD), and to determine the dosage for subsequent studies. Read more about this study
- Who is it for?
- Ages 4 to 17 years, men only
- Conditions the study is for
- Duchenne Muscular Dystrophy
- What is being tested?
- NS-089/NCNP-02
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteJapan
- Study dates
- 2 Dec 2019to 31 May 2022
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 4 to 17 years
- Men only
- No healthy volunteers
- Child
Who may be able to join
- Has an out of frame deletion(s) that could be corrected by skipping exon 44 as confirmed by any of methodology at the time of visit 1. If not confirmed by any of methodology that evaluates the relative copy number of all exons (i.e. MLPA etc), must be confirmed through these techniques by the time of visit 3.
- DNA sequencing of exon 44 confirms that no DNA polymorphisms occur that could compromise duplex formation between NS-089/NCNP-02 and pre-mRNA.
- Male and >= 8 years and < 17 years of age at the time of obtaining informed consent and/or assent. Subjects aged >= 4 years and < 8 years can be enrolled according to the circumstances.
- Able to give informed consent in writing signed by parent(s) or legal guardian who is able to understand all of the study procedure requirements. If applicable, able to give informed assent in writing signed by the subject.
- Life expectancy of at least 1 year
- Able to ambulate. Non-ambulant subject can be enrolled according to the circumstances.
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- Have intact muscles, which have adequate quality for biopsy. (No lacks or severe atrophy of biceps brachii or tibialis anterior muscle)
- QTc <450 msec (based on 12-lead ECGs), or <480 msec for subject with Bundle Branch Block.
- Glucocorticoid-naive patients, or patients who have used systemic glucocorticoids for at least 6 months prior to enrollment in this study with no dose changes for at least 3 months prior to enrollment.
Who cannot join
- Has participated in other pharmacological clinical trial that might recover dystrophin protein by the readthrough or the exon-skipping therapy, and/or upregulate the dystrophin-associated proteins such as utrophin.
- A forced vital capacity (FVC) < 50% of predicted.
- Continuous use of artificial respirator (except for use of NPPV while sleeping)
- A left ventricular ejection fraction (EF) < 40% or fractional shortening (FS) < 25% based on echocardiogram (ECHO).
- Surgery within the last 3 months prior to the first anticipated administration of study medication or planned for anytime between visit 1 of Part 1 and the last visit of Part 2.
- Positive hepatitis B surface antigen (HbsAg), hepatitis C antibody test (HCV), or human immunodeficiency virus (HIV) test at screening.
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- Current diagnosis of any immune deficiency or autoimmune disease.
- Current diagnosis of any active or uncontrolled infection, cardiomyopathy, or liver or renal disease.
- Use of any other investigational agents and/or experimental agents within 3 months prior to the first anticipated administration of study medication.
- History of any severe drug allergy.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Exploratory Study of NS-089/NCNP-02 in Duchenne Muscular Dystrophy
This study is designed to assess the safety, tolerability, efficacy and pharmacokinetics (PK) of NS-089/NCNP-02 in subjects diagnosed with Duchenne muscular dystrophy (DMD), and to determine the dosage for subsequent studies.
- Conditions
- Duchenne Muscular Dystrophy
- Being tested
- NS-089/NCNP-02
- Keywords
- Duchenne Muscular Dystrophy
- Medical subject headings
- Muscular Dystrophy, Duchenne
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NS-089/NCNP-02Drug
NS-089/NCNP-02 for Infusion is packaged as 50 mg/mL with 3 mL per vial. Study dosages will be infused over a 1 hour period at the following dose levels.
"[Part 1] NS-089/NCNP-02 is administered at dose levels 1 and 3 in Cohort 1 and at dose levels 2 and 4 in Cohort 2.
Dose level 1: 1.62 mg/kg once weekly for 2 weeks; Dose level 2: 10 mg/kg once weekly for 2 weeks; Dose level 3: 40 mg/kg once weekly for 2 weeks; Dose level 4: 80 mg/kg once weekly for 2 weeks [Part 2] Based on the results from Part 1, two dosages are selected as study dosages in Part 2. Each selected dose are administered once a week for 24 weeks."
| Study group | Role | What they receive |
|---|---|---|
| NS-089/NCNP-02 | Experimental | NS-089/NCNP-02 Receives: Drug: NS-089/NCNP-02 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse event and adverse drug reaction [Safety and Tolerability]
adverse event and adverse drug reaction
Measured: At the end of Part 2 (24 weeks treatment period and 12 weeks follow up period)
Secondary outcomes (10)
Expression of dystrophin protein
Expression of dystrophin protein
Measured: At the end of the treatment period (24 weeks) of Part 2
NSAA
North Star Ambulatory Assessment
Measured: At the end of the treatment period (24 weeks) of Part 2
TTSTAND
Time to Stand Test
Measured: At the end of the treatment period (24 weeks) of Part 2
TTRW
Time to Run/Walk 10 Meters test
Measured: At the end of the treatment period (24 weeks) of Part 2
6MWT and 2MWT
Six-Minute Walk Test (6MWT) and Two-Minute Walk Test (2MWT)
Measured: At the end of the treatment period (24 weeks) of Part 2
TUG
Timed Up \& Go (TUG) test
Measured: At the end of the treatment period (24 weeks) of Part 2
PUL
Performance of Upper Limb test
Measured: At the end of the treatment period (24 weeks) of Part 2
Detection of exon 44-skipped mRNA of dystrophin in muscle tissue
Detection of exon 44-skipped mRNA of dystrophin in muscle tissue
Measured: At the end of the treatment period (24 weeks) of Part 2
NS-089/NCNP-02 concentration of the blood plasma
NS-089/NCNP-02 concentration of the blood plasma
Measured: At the end of Part 2 (24 weeks treatment period and 12 weeks follow up period)
Serum Creatine kinase concentration
Serum Creatine kinase concentration
Measured: At the end of Part 2 (24 weeks treatment period and 12 weeks follow up period)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Oct 2019
- Study start2 Dec 2019
- Primary completion31 May 2022
- Study completion31 May 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Duchenne Muscular DystrophyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Center of Neurology and Psychiatry, Japan
- Sponsor type
- University, hospital or other
- Collaborators
- Nippon Shinyaku Co., Ltd.
- Responsible party
- Principal investigator, Hirofumi Komaki, National Center of Neurology and Psychiatry, Japan
- Investigators
- Hirofumi Komaki, MD, PhD, Principal investigator, National Center of Neurology and Psychiatry, Japan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04129294
- Sponsor's protocol ID
- NCNP/DMT02
- Other IDs
- UMIN000038505
- Status last verified
- Sep 2022
- First submitted
- 15 Oct 2019
- Last updated
- 29 Sep 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Komaki H, Takeshita E, Kunitake K, Ishizuka T, Shimizu-Motohashi Y, Ishiyama A, Sasaki M, Yonee C, Maruyama S, Hida E, Aoki Y. Phase 1/2 trial of brogidirsen: Dual-targeting antisense oligonucleotides for exon 44 skipping in Duchenne muscular dystrophy. Cell Rep Med. 2025 Jan 21;6(1):101901. doi: 10.1016/j.xcrm.2024.101901. Epub 2025 Jan 9.
PubMed 39793573Ishizuka T, Komaki H, Asahina Y, Nakamura H, Motohashi N, Takeshita E, Shimizu-Motohashi Y, Ishiyama A, Yonee C, Maruyama S, Hida E, Aoki Y. 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. Neuropsychopharmacol Rep. 2023 Jun;43(2):277-286. doi: 10.1002/npr2.12335. Epub 2023 Apr 3.
PubMed 37326950
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Exploratory Study of NS-089/NCNP-02 in Duchenne Muscular Dystrophy
- ClinicalTrials.gov ID
- NCT04129294
- Acronym / sponsor ID
- NCNP/DMT02
- Conditions
- Duchenne Muscular Dystrophy
- Keywords
- Duchenne Muscular Dystrophy
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- National Center of Neurology and Psychiatry, JapanUniversity, hospital or other
- Collaborators
- Nippon Shinyaku Co., Ltd.
- Study start
- 2 Dec 2019 (actual)
- Primary completion
- 31 May 2022 (actual)
- Study completion
- 31 May 2022 (actual)
- First posted
- 16 Oct 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is designed to assess the safety, tolerability, efficacy and pharmacokinetics (PK) of NS-089/NCNP-02 in subjects diagnosed with Duchenne muscular dystrophy (DMD), and to determine the dosage for subsequent studies.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| NS-089/NCNP-02 | Experimental | Drug: NS-089/NCNP-02NS-089/NCNP-02 |
Who may qualify
- Ages
- 4 to 17 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (9 listed)
- Has an out of frame deletion(s) that could be corrected by skipping exon 44 as confirmed by any of methodology at the time of visit 1. If not confirmed by any of methodology that evaluates the relative copy number of all exons (i.e. MLPA etc), must be confirmed through these techniques by the time of visit 3.
- DNA sequencing of exon 44 confirms that no DNA polymorphisms occur that could compromise duplex formation between NS-089/NCNP-02 and pre-mRNA.
- Male and >= 8 years and < 17 years of age at the time of obtaining informed consent and/or assent. Subjects aged >= 4 years and < 8 years can be enrolled according to the circumstances.
- Able to give informed consent in writing signed by parent(s) or legal guardian who is able to understand all of the study procedure requirements. If applicable, able to give informed assent in writing signed by the subject.
- Life expectancy of at least 1 year
Key exclusion criteria (10 listed)
- Has participated in other pharmacological clinical trial that might recover dystrophin protein by the readthrough or the exon-skipping therapy, and/or upregulate the dystrophin-associated proteins such as utrophin.
- A forced vital capacity (FVC) < 50% of predicted.
- Continuous use of artificial respirator (except for use of NPPV while sleeping)
- A left ventricular ejection fraction (EF) < 40% or fractional shortening (FS) < 25% based on echocardiogram (ECHO).
- Surgery within the last 3 months prior to the first anticipated administration of study medication or planned for anytime between visit 1 of Part 1 and the last visit of Part 2.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NS-089/NCNP-02NS-089/NCNP-02 for Infusion is packaged as 50 mg/mL with 3 mL per vial. Study dosages will be infused over a 1 hour period at the following dose levels. "[Part 1] NS-089/NCNP-02 is administered at dose levels 1 and 3 in Cohort 1 and at dose levels 2 and 4 in Cohort 2. Dose level 1: 1.62 mg/kg once weekly for 2 weeks; Dose level 2: 10 mg/kg once weekly for 2 weeks; Dose level 3: 40 mg/kg once weekly for 2 weeks; Dose level 4: 80 mg/kg once weekly for 2 weeks [Part 2] Based on the results from Part 1, two dosages are selected as study dosages in Part 2. Each selected dose are administered once a week for 24 weeks." | Drug | NS-089/NCNP-02 |
Primary outcome
Adverse event and adverse drug reaction [Safety and Tolerability]
Time frame: At the end of Part 2 (24 weeks treatment period and 12 weeks follow up period)
adverse event and adverse drug reaction
10 secondary outcomes
Expression of dystrophin protein
Time frame: At the end of the treatment period (24 weeks) of Part 2
NSAA
Time frame: At the end of the treatment period (24 weeks) of Part 2
TTSTAND
Time frame: At the end of the treatment period (24 weeks) of Part 2
TTRW
Time frame: At the end of the treatment period (24 weeks) of Part 2
6MWT and 2MWT
Time frame: At the end of the treatment period (24 weeks) of Part 2
TUG
Time frame: At the end of the treatment period (24 weeks) of Part 2
PUL
Time frame: At the end of the treatment period (24 weeks) of Part 2
Detection of exon 44-skipped mRNA of dystrophin in muscle tissue
Time frame: At the end of the treatment period (24 weeks) of Part 2
NS-089/NCNP-02 concentration of the blood plasma
Time frame: At the end of Part 2 (24 weeks treatment period and 12 weeks follow up period)
Serum Creatine kinase concentration
Time frame: At the end of Part 2 (24 weeks treatment period and 12 weeks follow up period)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2022.
- Derived from this study: PubMed 39793573Komaki H, Takeshita E, Kunitake K, Ishizuka T, Shimizu-Motohashi Y, Ishiyama A, Sasaki M, Yonee C, Maruyama S, Hida E, Aoki Y. Phase 1/2 trial of brogidirsen: Dual-targeting antisense oligonucleotides for exon 44 skipping in Duchenne muscular dystrophy. Cell Rep Med. 2025 Jan 21;6(1):101901. doi: 10.1016/j.xcrm.2024.101901. Epub 2025 Jan 9.
- Derived from this study: PubMed 37326950Ishizuka T, Komaki H, Asahina Y, Nakamura H, Motohashi N, Takeshita E, Shimizu-Motohashi Y, Ishiyama A, Yonee C, Maruyama S, Hida E, Aoki Y. 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. Neuropsychopharmacol Rep. 2023 Jun;43(2):277-286. doi: 10.1002/npr2.12335. Epub 2023 Apr 3.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Hirofumi Komaki, MD, PhD principal investigator
National Center of Neurology and Psychiatry, Japan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing NS-089/NCNP-02 in people with Duchenne Muscular Dystrophy, run by National Center of Neurology and Psychiatry, Japan at 1 site in Japan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adverse event and adverse drug reaction [Safety and Tolerability] (time frame: At the end of Part 2 (24 weeks treatment period and 12 weeks follow up period)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04129294, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Sep 2022.