NS-089/NCNP-02-201 in Boys With Duchenne Muscular Dystrophy (DMD)

Официальное название

A Phase 2 Study to Assess the Efficacy, Safety, Tolerability, and Pharmacokinetics of NS-089/NCNP-02 in Boys With Duchenne Muscular Dystrophy (DMD)

Обзор

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 DMD due to mutations amenable to exon 44 skipping. Participants will receive a selected dose of NS-089/NCNP-02 administered once weekly. The study consists of 2 parts: Part 1 and Part 2. Six participants (Cohort 1) will participate in both Part 1 and Part 2, and 14 participants (Cohort 2) will be added for Part 2.

Вмешательства

• Препарат NS-089/NCNP-02
  Cohort 1: Part 1 Dose Level 1-3: a 4-week Treatment Phase at each treatment dose level Part 2 Single Dose Level: a 24-week Treatment Phase at the MTD of Part 1 Cohort 2: Part 2 Single Dose Level: a 24-week Treatment Phase at the MTD of Part 1

Первичные конечные точки

• Adverse Event and Adverse Drug Reaction [Срок оценки: through study completion, up to follow-up phone call for Part 2]
• Plasma pharmacokinetic (PK) parameters [Срок оценки: Day1, Week4 for each dose for Part 1, Day1 and Week24 for Part 2] Maximum plasma concentration (Cmax) of NS-089/NCNP-02]
• Plasma pharmacokinetic (PK) parameters [Срок оценки: Day1, Week4 for each dose for Part 1, Day1 and Week24 for Part 2] Time of the maximum plasma concentration (Tmax) of NS-089/NCNP-02]
• Plasma pharmacokinetic (PK) parameters [Срок оценки: Day1, Week4 for each dose for Part 1, Day1 and Week24 for Part 2] Terminal half-life (T1/2) of NS-089/NCNP-02]
• Plasma pharmacokinetic (PK) parameters [Срок оценки: Day1, Week4 for each dose for Part 1, Day1 and Week24 for Part 2] Area under the concentration-time curve from time 0 to the last time point (AUC0-t) of NS-089/NCNP-02]
• Plasma pharmacokinetic (PK) parameters [Срок оценки: Day1, Week4 for each dose for Part 1, Day1 and Week24 for Part 2] Area under the concentration-time curve from time 0 to infinity (AUC0-∞) of NS-089/NCNP-02]
• Plasma pharmacokinetic (PK) parameters [Срок оценки: [Time Frame: Day1, Week4 for each dose for Part 1, Day1 and Week24 for Part 2] Total body clearance (CLtot) of NS-089/NCNP-02]
• Plasma pharmacokinetic (PK) parameters [Срок оценки: Day1, Week4 for each dose for Part 1, Day1 and Week24 for Part 2] The volume in the terminal state (Vz) of NS-089/NCNP-02]
• Urine pharmacokinetic parameters [Срок оценки: Day1, Week4 for each dose for Part 1, Day1 and Week24 for Part 2] Urinary excretion of NS-089/NCNP-02]
• Change from baseline in skeletal muscle dystrophin protein by immunoblot (Western blot). [Срок оценки: Baseline, Week25]

Вторичные конечные точки (11)

• Change from baseline in skeletal muscle dystrophin protein by mass spectrometry. [Срок оценки: Baseline, Week25]
• Change from baseline in skeletal muscle dystrophin protein levels by immunofluorescence staining. [Срок оценки: Baseline, Week25]
• Change from baseline in percentage of exon 44-skipped mRNA of skeletal muscle dystrophin [Срок оценки: Baseline, Week25]
• North Star Ambulatory Assessment (NSAA) score [Срок оценки: Baseline, Week13, Week25]
• Time to Run/Walk 10 Meters (TTRW) [Срок оценки: Baseline, Week13, Week25]
• Time to Stand (TTSTAND) [Срок оценки: Baseline, Week13, Week25]
• Total distance of 6 Minute Walk Test (6MWT) [Срок оценки: Baseline, Week13, Week25]
• Time to Climb 4 Stairs (TTCLIMB) [Срок оценки: Baseline, Week13, Week25]
• Muscle strength measured by Quantitative Muscle Testing (QMT) [Срок оценки: Baseline, Week13, Week25]
• Grip and pinch strength [Срок оценки: Baseline, Week13, Week25]
• Performance of Upper Limb (PUL) 2.0. score [Срок оценки: Baseline, Week13, Week25]

Критерии участия

Критерии включения

• Male ≥ 4 years and <15 years of age
• Confirmed DMD mutation(s) in the dystrophin gene that is amenable to skipping of exon 44 to restore the dystrophin mRNA reading frame
• Able to walk independently without assistive devices
• Ability to complete the TTSTAND without assistance in <20 seconds
• Stable dose of glucocorticoid for at least 3 months and the dose is expected to remain on a stable dose for the duration of the study.
• Other inclusion criteria may apply.

Критерии исключения

• Has a body weight of <20 kg at the time of informed consent (applies to participants screening for Part 1 only)
• Evidence of symptomatic cardiomyopathy
• Current or previous treatment with anabolic steroids (e.g., oxandrolone) or products containing resveratrol or adenosine triphosphate within 3 months prior to first dose of study drug
• Current or previous treatment with any other investigational drug within 3 months prior to the first dose of study drug or within 5 times the half-life of a medication, whichever is longer
• Surgery within the 3 months prior to the first dose of study drug or planned during the study duration
• Previously treated in an interventional study of NS-089/NCNP-02
• Having received exon skipping oligonucleotide within 1 year prior to the first dose of IP
• Other exclusion criteria may apply.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 10 центров

• Children's Hospital Colorado — Aurora
• Rare Disease Research, LLC - FL — Kissimmee
• Rare Disease Research — Atlanta
• Ann and Robert H. Lurie Children's Hospital of Chicago — Chicago
• University of Kansas Medical Center (KUMC) — Kansas City
• Cincinnati Children's Hospital Medical Center — Cincinnati
• The Children's Hospital of Philadelphia (CHOP) — Philadelphia
• University of Pittsburgh School of Medicine — Pittsburgh
• … и ещё 2 центра

Япония · 5 центров

• Fukui Prefectural Hospital — Fukui-shi
• National Hospital Organization Nagara Medical Center — Nagara
• NHO Osaka Toneyama Medical Center — Toyonaka
• Shiga General Hospital — Moriyama-shi
• National Center of Neurology and Psychiatry — Kodaira

Канада · 3 центра

• Alberta Children's Hospital — Calgary
• British Columbia Children's Hospital — Vancouver
• London Health Sciences Centre — London

Turkey (Türkiye) · 3 центра

• Ankara Bilkent City Hospital — Ankara
• Yeditepe University Kosuyolu Hospital — Istanbul
• S.B.U. Dr. Behcet uz Pediatric Diseases and Surgery Training and Research Hospital — Izmir

South Korea · 2 центра

• Pusan National University Yangsan Hospital — Yangsan
• Seoul National University Hospital — Seoul

Австралия · 1 центр

• Perth Children's Hospital — Nedlands

Новая Зеландия · 1 центр

• Starship Children's Hospital — Auckland

Идентификаторы

NCT: NCT05996003 · NS-089/NCNP-02-201

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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