Study to Assess the Safety, Tolerability, and Efficacy of Viltolarsen in Ambulant and Non-Ambulant Boys With DMD (Galactic53)

Study Overview
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Brief Summary
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This is a phase II, open-label study where weekly doses of 80 mg/kg viltolarsen is administered intravenously over a 48-week treatment period to ambulant and non-ambulant DMD patients over the age of 8 years.

Official Title
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A Phase 2 Open-label Study to Assess the Safety, Tolerability, and Efficacy of Viltolarsen in Ambulant and Non-Ambulant Boys With Duchenne Muscular Dystrophy (DMD) Compared to Natural History Controls

Conditions
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Duchenne Muscular Dystrophy

Intervention / Treatment
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* Drug: Viltolarsen


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient (if age 18 years or older) or patient's parent(s) or legal guardian(s) has (have) provided written informed consent and Health Insurance Portability and Accountability Act authorization, where applicable, prior to any study-related procedures; patients younger than age 18 years will be asked to give written or verbal assent according to local requirements; Patient has a confirmed diagnosis of DMD defined as: Patient is male with clinical signs compatible with DMD; and Patient has a confirmed DMD mutation(s) in the dystrophin gene that is amenable to skipping of exon 53 to restore the dystrophin messenger ribonucleic acid reading frame including determination of unambiguously defined exon boundaries (using techniques such as multiplex ligation-dependent probe amplification, comparative genomic hybridization array, or other techniques with similar capability); Patient is more than 8 years of age at time of first infusion in the study; Patient has a Brooke scale rating of 3 or better OR an upright FVC 30% or greater at Screening; Patient, if sexually active, is willing to abstain from sexual intercourse or employ a barrier or medical method of contraception during and for 3 months following completion of IP administration; Patient and patient's parent(s)/guardian(s) (if patient is <18 years of age) and/or caregiver(s) are willing and able to comply with scheduled visits, IP administration plan, and study procedures; Patient must be on a stable dose of glucocorticoid (GC) or not treated with GC for at least 3 months prior to the first dose of IP and is expected to remain on stable dose of GC treatment or off GC for the duration of the study. Other inclusion criteria may apply Exclusion Criteria: Patient has had an acute illness within 4 weeks prior to the first dose of IP; Patient has evidence of symptomatic cardiomyopathy (New York Heart Association Class III or higher); Patient requires ventilation support while awake during the day; Patient has an allergy or hypersensitivity to IP or any of its constituents; Patient has severe behavioral or cognitive problems that preclude participation in the study, in the opinion of the investigator; Patient has a previous or ongoing medical condition, medical history, physical findings, or laboratory abnormalities that could affect patient safety, make it unlikely that treatment and follow-up will be correctly completed, or impair the assessment of study results, in the opinion of the investigator; Patient has had surgery within 3 months prior to the first anticipated administration of IP or has known plans to have surgery during the Treatment Period; Patient has positive test results for hepatitis B antigen, hepatitis C antibody, or human immunodeficiency virus antibody at Screening; Patient has been diagnosed with asthma that requires chronic treatment with a long-acting beta agonist; Patient has relevant history of or current drug or alcohol abuse or use of any tobacco/marijuana products by smoking or vaping within 3 months prior to treatment with IP; Patient is currently taking any other investigational drug or has taken any other investigational drug within 3 months prior to the first dose of IP or within 5 times the half-life of a medication, whichever is longer; Patient has taken any gene therapy; Patient is currently taking any other exon skipping agent or has taken any other exon skipping agent within 3 months prior to the first dose of IP; Patient has hydronephrosis, hydroureter, renal or urinary tract calculi, or ureteral stenosis by renal ultrasound; Patient was previously enrolled in an interventional study of viltolarsen. Other exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 8 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Viltolarsen<br>Patients amenable to exon 53 skipping will receive viltolarsen intravenous (IV) infusions, weekly, at 80 mg/kg for up to 48 weeks. | Drug: Viltolarsen<br>* Received during weekly intravenous infusions<br>* Other names: NS-065/NCNP-01;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with treatment related Adverse Events as assessed by CTCAE v4.03 |  | baseline to up to 48 weeks of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Peak Expiratory Flow (PEF) |  | baseline to 48 weeks of treatment | 
| Forced Vital Capacity (FVC) |  | baseline to 48 weeks of treatment | 
| Forced expiratory volume in 1 second (FEV1) |  | baseline to 48 weeks of treatment | 
| Performance of Upper Limb (PUL) | The PUL 2.0 provides both a total score and sub-scores for the 3 domains (shoulder, middle, and distal) that in DMD are progressively involved with a proximal to distal gradient. The PUL includes 22 items with an entry item to define the starting functional level. The 22 items are subdivided into the high level shoulder dimension (6 items), middle level elbow dimension (9 items), and distal wrist and hand dimension (7 items). For weaker patients, a low score on the entry item (0 2) means high level items do not need to be performed. Scoring options vary across the scale between 0-1 and 0-2 according to performance. Each dimension can be scored separately with a maximum score of 12 for the high level shoulder dimension, 17 for the middle level elbow dimension, and 13 for the distal wrist and hand dimension. A total score can be achieved by adding the 3 level scores (maximum total score of 42). | baseline to 48 weeks of treatment | 
| Brooke scale | The Brooke scale for upper limb has grades ranging from 1 to 6. Grade 1 is given to the patient who can keep both his arms by his sides in the starting position and is then able to abduct the arms fully so that both the arms are touching over the head. Grade 6 is given when the patient is unable to raise his hands to his mouth, and the hands show no functional usefulness. | baseline to 48 weeks of treatment | 
| Vignos scale | The Vignos scale for lower limb has grades ranging from 1 to 10; 1 means that the patient is able to walk and climb stairs without assistance, while 10 means that the patient is bed bound. Ambulant patients score 1 to 6 and non-ambulant patients score 7 to 10 on the Vignos scale. | baseline to 48 weeks of treatment | 
| Muscle Strength Measured by Hand-Held Dynamometer |  | baseline to 48 weeks of treatment | 
| North Star Ambulatory Assessment (NSAA) | 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. | baseline to 48 weeks of treatment |