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

• ClinicalTrials.gov Identifier: NCT05693142
• Recruitment Status: Recruiting
• First Posted: January 20, 2023
• Last Update Posted: March 5, 2024
• Sponsor: REGENXBIO Inc.
• Information provided by (Responsible Party): REGENXBIO Inc.

Tracking Information

• First Submitted Date: January 4, 2023
• First Posted Date: January 20, 2023
• Last Update Posted Date: March 5, 2024
• Actual Study Start Date: January 4, 2023
• Estimated Primary Completion Date: December 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 12, 2023)

Safety measured by incidence of Adverse Events and Serious Adverse Events [ Time Frame: 52 weeks ]

Evaluate incidences of AEs and SAEs

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 12, 2023)

• Efficacy measured by change in Functional Assessment [ Time Frame: Multiple timepoints through 52 weeks ]
  Longitudinal trajectory (mean and change from baseline) in North Star Ambulatory Assessment (NSAA) raw and total score
• Microdystrophin protein expression [ Time Frame: 12 weeks ]
  RGX-202 microdystrophin protein levels determined in muscle biopsy and vector genome concentrations in muscle
• Pharmacokinetics (PK) [ Time Frame: Multiple timepoints through 52 weeks ]
  Vector genome concentrations as measured by polymerase chain reaction [PCR] to RGX-202 deoxyribonucleic acid [DNA] in serum.
• Vector Shedding [ Time Frame: Multiple timepoints through 52 weeks ]
  Vector genome concentrations as measured by polymerase chain reaction [PCR] to RGX-202 deoxyribonucleic acid [DNA] in urine.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

Brief 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.

Detailed 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.

• Study Type: Interventional
• Study Phase: Phase 1; Phase 2

Study Design

Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description:

Dose Evaluation

Masking: None (Open Label)
Primary Purpose: Treatment

• Condition: Duchenne Muscular Dystrophy

Intervention

Genetic: RGX-202

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

Study Arms

• Experimental: RGX-202 Dose 1
  A single IV infusion of RGX-202 at a dose of 1×10^14 GC/kg body weight
  Intervention: Genetic: RGX-202
• Experimental: RGX-202 Dose 2
  A single IV infusion of RGX-202 at a dose of 2x10^14 GC/kg body weight
  Intervention: Genetic: RGX-202

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: January 12, 2023): 18
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2025
• Estimated Primary Completion Date: December 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: Male
• Gender Based Eligibility: Yes

• Ages: 4 Years to 11 Years (Child)
• Accepts Healthy Volunteers: No

Contacts

Contact: Patient Advocacy; (833) 711-0349; Duchenne@regenxbio.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05693142
• Other Study ID Numbers: RGX-202-1101
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: REGENXBIO Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: REGENXBIO Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: REGENXBIO Inc.
• Verification Date: March 2024