AFFINITY DUCHENNE: RGX-202 Gene Therapy in Participants With Duchenne Muscular Dystrophy (DMD)

Duchenne Muscular Dystrophy Clinical Trial

Official title:

A Phase 1/2 Open-label, Dose Escalation and Dose Expansion Study to Evaluate the Safety, Tolerability, Pharmacodynamics, and Pharmacokinetics of Intravenous RGX-202 Gene Therapy in Males With Duchenne Muscular Dystrophy (DMD)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05693142
• Other study ID #: RGX-202-1101
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: January 4, 2023
• Est. completion date: December 2025

Study information

• Verified date: May 2024
• Source: REGENXBIO Inc.
• Contact: Patient Advocacy
• Phone: (833) 711-0349
• Email: Duchenne[@]regenxbio.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

RGX-202 is a gene therapy designed to deliver a transgene for a novel microdystrophin that includes functional elements of naturally-occurring dystrophin including the C-Terminal (CT) domain. This is a multicenter, open-label dose evaluation clinical study to assess the safety, tolerability and clinical efficacy of a one-time intravenous (IV) dose of RGX-202 in participants with Duchenne.

Description:

Duchenne muscular dystrophy (Duchenne) is a rare genetic disorder, caused by mutations in the gene responsible for making dystrophin, a protein of central importance for muscle cell structure and function. The absence of functional dystrophin protein in individuals with Duchenne results in cell damage during muscle contraction leading to cell death, inflammation, and fibrosis in muscle tissues, and ultimately progressive muscle weakness. RGX-202 is designed to use the AAV8 vector to deliver a transgene to muscle cells that encodes a novel microdystrophin that includes the functional elements of naturally occurring dystrophin including the C-Terminal (CT) domain. This is a Phase 1/2, multicenter, open-label, dose evaluation clinical study to assess the safety, tolerability, pharmacodynamics (microdystrophin protein levels), pharmacokinetics, and preliminary clinical efficacy of RGX-202 in 2 dose groups over 52 weeks when administered by one-time intravenous infusion (IV) in ambulatory male pediatric participants with Duchenne. Four ambulatory, pediatric participants (ages 4-11 years old) with Duchenne are expected to enroll in two dose groups, with doses of 1x10^14 genome copies (GC)/kg body weight (n=2) and 2x10^14 GC/kg body weight (n=2). The first 2 participants in each dose group will be dosed in staggered fashion, at least 4 weeks apart, following increasing body weight: ≤25kg and ≤35kg. After an independent safety data review for each dose group, an expansion phase of the trial may allow for up to seven additional participants to be enrolled at each dose (for a total of up to nine participants in each dose group). A total of up to 18 participants may be enrolled in the study. A comprehensive, short-term, prophylactic immunosuppression regimen will be administered during treatment to mitigate a potential immune response.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 18
• Est. completion date: December 2025
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 4 Years to 11 Years

Eligibility

Inclusion Criteria:

• DMD gene mutation in exons 18 and above, and a clinical picture consistent with typical DMD.
• Participant is able to walk 100 meters independently without assistive devices, as assessed at screening.
• Participant is able to complete the TTSTAND per protocol-specific criteria.
• Participant has been on a stable dose of systemic glucocorticoids according to the standard of care for at least 12 weeks prior to obtaining the pharmacodynamic assessments, imaging assessments, patient-reported outcomes, and functional clinical outcome assessments within the Day -60 to Day -3 screening period.
• Clinical laboratory test results, including hepatic and renal function, are within the normal range during screening, or if abnormal, are not clinically significant, in the opinion of the investigator.

Exclusion Criteria:

• Participant has any condition that would contraindicate treatment with immunosuppression.
• Participant has received ataluren (a protein restoration therapy) or an exon-skipping therapy for the treatment of DMD within 6 months of study entry or is unable to refrain from taking ataluren or exon-skipping therapy for a duration of 5 years from the time of RGX-202 administration.
• Participant has received any investigational or commercial gene therapy product over his lifetime.
• Participant is currently taking any other investigational intervention or has taken any other investigational intervention within 3 months prior to the scheduled Day 1 intervention.
• Participant has detectable AAV8 total binding antibodies in serum.
• Participant has impaired cardiac function defined as a left ventricular ejection fraction of < 55% on screening cardiac assessments (echocardiogram or MRI).
• Participant is not a good candidate for the study, in the opinion of the investigator.

Related Conditions & MeSH terms

• Duchenne Muscular Dystrophy
• Muscular Dystrophies
• Muscular Dystrophy, Duchenne

Intervention

Genetic:
• RGX-202
RGX-202 is a recombinant AAV8 containing a transgene encoding a novel microdystrophin

Locations

Country	Name	City	State
United States	Ann & Robert H. Lurie Children's Hospital of Chicago	Chicago	Illinois
United States	The University of Texas Southwestern Medical Center	Dallas	Texas
United States	Arkansas Children's Hospital	Little Rock	Arkansas
United States	Stanford School of Medicine /Division of Neuromuscular Medicine	Palo Alto	California
United States	Children's Hospital of Richmond at Virginia Commonwealth University	Richmond	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
REGENXBIO Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety measured by incidence of Adverse Events and Serious Adverse Events	Evaluate incidences of AEs and SAEs	52 weeks
Secondary	Efficacy measured by change in Functional Assessment	Longitudinal trajectory (mean and change from baseline) in North Star Ambulatory Assessment (NSAA) raw and total score	Multiple timepoints through 52 weeks
Secondary	Microdystrophin protein expression	RGX-202 microdystrophin protein levels determined in muscle biopsy and vector genome concentrations in muscle	12 weeks
Secondary	Pharmacokinetics (PK)	Vector genome concentrations as measured by polymerase chain reaction [PCR] to RGX-202 deoxyribonucleic acid [DNA] in serum.	Multiple timepoints through 52 weeks
Secondary	Vector Shedding	Vector genome concentrations as measured by polymerase chain reaction [PCR] to RGX-202 deoxyribonucleic acid [DNA] in urine.	Multiple timepoints through 52 weeks