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Muscular Dystrophy, DuchennePhase 2NORTH POLE DMDNCT01918384

Phase II Study of NPC-14 (Arbekacin Sulfate) to Explore Safety, Tolerability, and Efficacy in Duchenne Muscular Dystrophy

A Phase 2 study testing NPC-14 in people with Muscular Dystrophy, Duchenne, run by Kobe University at 4 sites in Japan.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

Duchenne Muscular Dystrophy (DMD) is inherited neuromuscular disorders due to mutation in the gene that encodes critical muscle protein called dystrophin. Currently, there is no effective treatment option for the disease. Read more about this study

Who is it for?
Ages 4 years and older, men only
Conditions the study is for
Muscular Dystrophy, Duchenne
What is being tested?
NPC-14
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
21 participants
Where
4 sitesJapan
Study dates
Aug 2013to Oct 2015
Phase
Phase 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 years and older
  • Men only
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • Diagnosis of DMD resulting from a nonsense mutation by whole genome sequencing of the dystrophin gene
  • To have intact right or left biceps muscles, or an alternative muscle group that is able to be underwent for appropriate evaluation of efficacy
  • To meet the following criteria at screening (baseline visit), within 30 days prior to the first dose of study drug
  • Ambulant and able to walk at least 75 meters during the 6MWT
  • Able to comply with and complete all protocol requirements, and judged by the investigator to be appropriate to participate in the study from the screening results
  • Aged at least 4 years at the time of giving informed consent
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  • Male
  • Able to be hospitalized for the study requirement
  • Signed Informed consent by parents/legal guardian and/or signed assent by the subject (age of assent to be determined by IRB)

Who cannot join

  • Prior exposure to investigational medicines that have a potential of restoring dystrophin or other functional protein (readthrough, exon skipping, utrophin upregulation therapy etc.)
  • Known mutation at nucleotide 1555 in 12S rRNA gene of mitochondrial DNA, and/or personally or families have been treated or have a history of eight cranial nerve disorder (hearing loss、vertigo、tinnitus etc.)as a result of aminoglycoside use
  • Inability to hear within the range of 0 to 25 dB by pure tone audiometry, abnormalities on auditory brainstem response audiometry, and/or loss of frequency by distortion product oto acoustic emissions at screening
  • Poor oral intake or enable to oral intake, and/or bad general status
  • Known allergies to NPC-14, other aminoglycosides, and/or bacitracin
  • Presence of anti-dystrophin antibody at the baseline assessments
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  • Cys-C ≥1.2 mg/L and/or creatinine concentration >1.5 times the upper limit of age corrected normal range
  • Left ventricular ejection fraction (EF) <40% or left ventricular fractional shortening (FS) <25%, and/or ≥480 msec QTc (corrected QT interval by Fridericia's method)
  • Need of mechanical ventilation
  • Forced vital capacity (FVC) <50% predicted
  • Clinically significant concomitant diseases (hematology, psychoneurotic, hepatic, pulmonary, endocrine, immune, renal, and gastroenterological diseases), and/or cancer
  • Impairment of intellectual functions, and/or expressive language ability which might interfere with study assessments
  • Treatment with other systemic aminoglycoside within 6 months prior to the first administration of study drug
  • Initiation of systemic glucocorticosteroids treatment, and/or start exercise cure, physical therapy, or occupational therapy which might interfere with study assessments. Changing of dose and schedule of systemic glucocorticosteroids within 6 months prior to the first administration of study drug
  • History of any surgical procedure within months prior to the first administration of study drug or have a plan during study
  • History of sever allergy from food and medicine like an anaphylaxis shock or generalized rash
  • Participation in any other clinical trial and intake of any investigational drug within 6month of study entry

Trial locations and contacts

4 sites in 1 country.

Japan4 sites
  • Kobe university hospital, department of pediatrics

    Kobe, Hyōgo, 650-0017

  • National center of neurology and psychiatry

    Kodaira, Tokyo, 187-8551

  • Hyogo College of Medicine

    Nishinomiya, Hyōgo, 663-8501

  • Tokyo Women's Medical University

    Shinjuku-ku, Tokyo, 162-8666

Other trials in Japan

About this study

Official title: Phase II Study of Nonsense Readthrough Compound NPC-14 (Arbekacin Sulfate) to Explore Safety, Tolerability, and Efficacy in Duchenne Muscular Dystrophy Patients (NORTH POLE DMD Study)

Duchenne Muscular Dystrophy (DMD) is inherited neuromuscular disorders due to mutation in the gene that encodes critical muscle protein called dystrophin. Currently, there is no effective treatment option for the disease. A pharmacological approach by promoting mRNA translation regardless of the presence of premature stop codons by nonsense mutation, called the readthrough strategy, has been developing recently for DMD with nonsense mutation. NPC-14 is a candidate compound for the readthrough strategy, since effective readthrough activities were demonstrated in nonclinical studies. This study is a phase II study designed to assess safety, tolerability, and efficacy of NPC-14 in ambulant DMD patients with nonsense mutation that were confirmed by whole genome analysis. These goals will be accomplished by monitoring adverse events by physical examination, cardiac, pulmonary, auditory, balance, and laboratory tests as safety endpoints, and dystrophin expression in muscle biopsy as primary efficacy endpoint, muscle function (NSAA, timed test, muscle strength (QMT, MMT) , dairy activities by lifecorder), and biomarkers as secondary efficacy endpoints. The study is a randomized, double blind, placebo-controlled study in 21 DMD patients. After screening, eligible patients are allocated dynamically to weekly NPC-14 or a placebo (saline) in a 2:1 ratio and will receive study drugs for 36 weeks.

Being tested
NPC-14, Placebo
Keywords
Duchenne muscular dystrophy, NPC-14, Arbekacin, nonsense, readthrough
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.

  • NPC-14Drug

    Also called Arbekacin

    NPC-14 will be administrated as following steps. The dose of NPC-14 will be calculated and adjusted by a non-blinded medical doctor and/or a non-blinded pharmacist.

    • An initial dose of NPC-14 will be half of that calculated by distribution volume:Vd based on patient age for safety reason.
    • After the initial administration, the dose of NPC-14 will be adjusted and maintained by actual Vd, therapeutic drug monitoring of peak serum levels of NPC-14
  • PlaceboDrug

    Dose will be adjusted by volume of distribution (Vd) of patients in accordance with the NPC-14 dose regimen

Study groups in NCT01918384
Study groupRoleWhat they receive
NPC-14ExperimentalIntravenous drip, QW, 36 weeks, Dose will be adjusted and maintained by therapeutic drug monitoring of peak serum levels of NPC-14
Receives: Drug: NPC-14
PlaceboPlacebo comparatorDose will be adjusted by volume of distribution (Vd) of patients in accordance with the NPC-14 dose regimen
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety and tolerability (Adverse events)

    Measured: Up to 38 weeks (36 weeks treatment period and 2 weeks follow up period)

  2. Change of dystrophin expression rate in muscle tissues from the baseline assessment

    Measured: At 37 weeks (1 week after from 36 weeks treatment period)

Secondary outcomes (5)
  1. North Star Ambulatory Assessment

    Measured: At 36 weeks

  2. Timed test (6MWT, time to walk/run 10 meters, time to climb/descent four steps, time to rise from the floor)

    Measured: At 36 weeks

  3. Muscle strength (MMT, QMT)

    Measured: At 36 weeks

  4. Dairy activities

    Measured: At 36 weeks

  5. Biomarkers (CK, ALD)

    Measured: At 36 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Aug 2013 (estimated)
  2. Study startAug 2013
  3. Primary completionOct 2015 (estimated)
  4. Study completionOct 2015 (estimated)

Resources

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 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
21 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01918384
Sponsor's protocol ID
NPC-14-1
Other IDs
JMA-IIA00134
Acronym
NORTH POLE DMD
Status last verified
Sep 2015
First submitted
1 Aug 2013
Last updated
3 Sep 2015
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing NPC-14 in people with Muscular Dystrophy, Duchenne, run by Kobe University at 4 sites 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 17 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: status not confirmed, as of the sponsor's last update on 3 Sep 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 4 sites 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

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?

Results are not available in the source record.

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?

Safety and tolerability (Adverse events) (time frame: Up to 38 weeks (36 weeks treatment period and 2 weeks follow up period)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
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 3 Sep 2015.

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