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

Conditions

Duchenne Muscular Dystrophy

Brief summary

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.

Harper AD, Topaloglu H, Mercuri E, Suslov V, Wu L, Ayanoglu CY, Tansey M, Previtera ML, Crozier RA, Magnus L, Clemens PR.

2024-10-083 citations

10.1038/s41598-024-70783-y

Interventions

DRUGViltolarsen

Received during weekly intravenous infusions

Study design

Allocation

NA

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

MALE

Age

8 Years to No maximum

Healthy volunteers

No

Inclusion criteria

1. 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; 2. Patient has a confirmed diagnosis of DMD defined as: 1. Patient is male with clinical signs compatible with DMD; and 2. 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); 3. Patient is more than 8 years of age at time of first infusion in the study; 4. Patient has a Brooke scale rating of 3 or better OR an upright FVC 30% or greater at Screening; 5. 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; 6. 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; 7. 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

1. Patient has had an acute illness within 4 weeks prior to the first dose of IP; 2. Patient has evidence of symptomatic cardiomyopathy (New York Heart Association Class III or higher); 3. Patient requires ventilation support while awake during the day; 4. Patient has an allergy or hypersensitivity to IP or any of its constituents; 5. Patient has severe behavioral or cognitive problems that preclude participation in the study, in the opinion of the investigator; 6. 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; 7. 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; 8. Patient has positive test results for hepatitis B antigen, hepatitis C antibody, or human immunodeficiency virus antibody at Screening; 9. Patient has been diagnosed with asthma that requires chronic treatment with a long-acting beta agonist; 10. 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; 11. 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; 12. Patient has taken any gene therapy; 13. 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; 14. Patient has hydronephrosis, hydroureter, renal or urinary tract calculi, or ureteral stenosis by renal ultrasound; 15. Patient was previously enrolled in an interventional study of viltolarsen. Other

Design outcomes

Primary

Measure	Time frame	Description
Number of Participants With Treatment Emergent Adverse Events	baseline to up to 48 weeks of treatment	No statistical analysis was performed for this endpoint. The information has been introduced in the section Adverse Events.
Number of Participants With Treatment Emergent Adverse Events by Maximum Severity	baseline to up to 48 weeks of treatment	No statistical analysis was performed for this endpoint. The information has been introduced in the section Adverse Events.
Number of Participants With Treatment Emergent Adverse Events by Highest Intervention Level Regarding Investigational Product	baseline to up to 48 weeks of treatment	No statistical analysis was performed for this endpoint. The information has been introduced in the section Adverse Events.
Number of Participants With Treatment Emergent Adverse Events by Worst Outcome	baseline to up to 48 weeks of treatment	No statistical analysis was performed for this endpoint. The information has been introduced in the section Adverse Events.
Number of Participants With Investigational Product-related Treatment Emergent Adverse Events	baseline to up to 48 weeks of treatment	No statistical analysis was performed for this endpoint. The information has been introduced in the section Adverse Events.
Number of Participants With Investigational Product-related Treatment Emergent Adverse Events by Maximum Severity	baseline to up to 48 weeks of treatment	No statistical analysis was performed for this endpoint. The information has been introduced in the section Adverse Events.
Number of Participants With Investigational Product-related Treatment Emergent Adverse Events by Highest Intervention Level Regarding Investigational Product	baseline to up to 48 weeks of treatment	No statistical analysis was performed for this endpoint. The information has been introduced in the section Adverse Events.
Number of Participants With Investigational Product-related Treatment Emergent Adverse Events by Worst Outcome	baseline to up to 48 weeks of treatment	No statistical analysis was performed for this endpoint. The information has been introduced in the section Adverse Events.
Number of Participants With Adverse Event of Special Interest	baseline to up to 48 weeks of treatment	No statistical analysis was performed for this endpoint. The information has been introduced in the section Adverse Events.

Countries

China, Italy, Russia, Spain, Turkey (Türkiye), United States

Participant flow

Recruitment details

Participants were enrolled in the study from July 1, 2021 to July 22, 2022 at 8 sites in the United States, Italy, Russia, Spain, and China.

Pre-assignment details

A total of 27 participants were screened, but 3 participants did not meet inclusion or exclusion criteria and 4 participants failed to screen for other reasons.

Participants by arm

Arm	Count
Viltolarsen 80mg/kg Participants who confirmed DMD with genetic deletions amenable to exon 53 skipping were administered an intravenous infusion of Viltolarsen 80 mg/kg once a week for up to 48 weeks.	20
Total	20

Baseline characteristics

Characteristic	Viltolarsen 80mg/kg
Age, Continuous	12.8 years STANDARD_DEVIATION 5.47
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	20 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants
Race (NIH/OMB) Asian	5 Participants
Race (NIH/OMB) Black or African American	0 Participants
Race (NIH/OMB) More than one race	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants
Race (NIH/OMB) White	15 Participants
Sex: Female, Male Female	0 Participants
Sex: Female, Male Male	20 Participants

Adverse events

Event type	EG000 affected / at risk
deaths Total, all-cause mortality	0 / 20
other Total, other adverse events	19 / 20
serious Total, serious adverse events	0 / 20

Outcome results

Primary

Number of Participants With Adverse Event of Special Interest

No statistical analysis was performed for this endpoint. The information has been introduced in the section Adverse Events.