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

Phase 2RecruitingNCT05996003

NS Pharma, Inc.20 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Duchenne Muscular Dystrophy Exon 44 DMD

Interventions

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

Eligibility

Sex: MALEMin age: 4 YearsMax age: 14 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 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. Exclusion Criteria: * 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 taken any gene therapy. * Having received exon skipping oligonucleotide within 1 year prior to the first dose of IP or is expected to receive exon skipping oligonucleotide prior to completion of study. * Other exclusion criteria may apply.

Locations (22)

Children's Hospital Colorado

Aurora, Colorado, United States

RECRUITING

Rare Disease Research, LLC - FL

Kissimmee, Florida, United States

RECRUITING

Rare Disease Research

Atlanta, Georgia, United States

RECRUITING

Ann and Robert H. Lurie Children's Hospital of Chicago

Chicago, Illinois, United States

RECRUITING

University of Kansas Medical Center (KUMC)

Kansas City, Kansas, United States

RECRUITING

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

RECRUITING

The Children's Hospital of Philadelphia (CHOP)

Philadelphia, Pennsylvania, United States

RECRUITING

University of Pittsburgh School of Medicine

Pittsburgh, Pennsylvania, United States

RECRUITING

UT Southwestern/Children's Health

Dallas, Texas, United States

RECRUITING

Virginia Commonwealth University Health System

Richmond, Virginia, United States

RECRUITING

...and 12 more locations

Outcomes

Primary Outcomes

Adverse Event and Adverse Drug Reaction

Time frame: through study completion, up to follow-up phone call for Part 2

Plasma pharmacokinetic (PK) parameters

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: [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

Time frame: 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

Time frame: 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).

Time frame: Baseline, Week25

Secondary Outcomes

Change from baseline in skeletal muscle dystrophin protein by mass spectrometry.

Time frame: Baseline, Week25

Change from baseline in skeletal muscle dystrophin protein levels by immunofluorescence staining.

Time frame: Baseline, Week25

Change from baseline in percentage of exon 44-skipped mRNA of skeletal muscle dystrophin

Time frame: Baseline, Week25

North Star Ambulatory Assessment (NSAA) score

The NSAA is a functional scale devised for use in ambulant children with Duchenne muscular dystrophy (DMD). It consists of 17 activities graded 0 (unable to perform), 1 (performs with modifications), 2 (normal movement). It assesses abilities necessary to remain ambulant that have been found to progressively deteriorate in untreated DMD patients, as well as in other muscular dystrophies such as Becker Muscular Dystrophy. NSAA Total Score ranges from 0 to 34, with a score of 34 implying normal function.