A Gene Transfer Therapy Study to Evaluate the Safety of SRP-9004 (Patidistrogene Bexoparvovec) in Participants With Limb-Girdle Muscular Dystrophy, Type 2D (LGMD2D)

NCT01976091 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: 9004-1015U01AR060911
• Study Type: interventional
• Target: 6
• Locations: 0 countries
• Sites: N/A

Brief Summary

This is an open-label, dose escalation gene transfer therapy study evaluating the safety of SRP-9004 (patidistrogene bexoparvovec) via isolated limb infusion (ILI) administration in approximately 6 participants with LGMD2D.

Conditions

Limb-Girdle Muscular Dystrophy, Type 2D

Keywords

limb girdle muscular dystrophy; LGMD2D; alpha-sarcoglycan; gene transfer; adeno-associated virus

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Adverse Events (AEs).

  An AE is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered study drug related. An AE was considered serious if, in the view of the investigator or sponsor, it resulted in any of the following outcomes: death, a life-threatening AE, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect. Treatment-related Treatment Emergent Adverse Event (TEAE) is defined as an TEAE that was classified by the investigator as related to treatment.

  Up to 2 Years

Secondary Outcomes (1)

• Change From Baseline of the Distance Walked in 6 Minutes (6MWT)

  Baseline, Up to 2 Years

Study Arms (3)

Cohort 1A: SRP-9004 Low Dose (Single Limb Perfusion)

EXPERIMENTAL

Non-ambulant participants with LGMD2D will receive 1 low dose of SRP-9004 via ILI to a single limb on Day 0.

Genetic: SRP-9004

Cohort 1B Low Dose (Bilateral Limb Perfusion)

EXPERIMENTAL

Participants with LGMD2D will receive 1 low dose of SRP-9004 via ILI to both limbs on Day 0.

Genetic: SRP-9004

Cohort 2 High Dose (Bilateral Limb Perfusion)

EXPERIMENTAL

Participants with LGMD2D will receive 1 high dose of SRP-9004 via ILI to both limbs on Day 0.

Genetic: SRP-9004

Interventions

SRP-9004 GENETIC

Isolated Limb Infusion (ILI)

Also known as: patidistrogene bexoparvovec

Cohort 1A: SRP-9004 Low Dose (Single Limb Perfusion); Cohort 1B Low Dose (Bilateral Limb Perfusion); Cohort 2 High Dose (Bilateral Limb Perfusion)

Eligibility Criteria

• Age: 7 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Cohort 1A must be adult and wheelchair-dependent; Cohorts 1B and 2 will be participants of age 7 or older.
• Confirmed alpha-sarcoglycan deficiency or identified sarcoglycan alpha (SGCA) deoxyribonucleic acid (DNA) mutation.
• Participants enrolled in Cohorts 1B or 2 must be able to walk independently, but must exhibit signs of lower extremity weakness (that is, a Gowers' sign, use a handrail for climbing stairs) and walk ≤80% of predicted distance on the 6 minute walk test (6MWT) based on normative data.

You may not qualify if:

• Active viral infection based on clinical observations.
• The presence of SGCA mutations without weakness or loss of function.
• Symptoms or signs of cardiomyopathy.
• Serological evidence of human immunodeficiency virus (HIV), Hepatitis B, or C infection.
• Diagnosis of (or ongoing treatment for) an autoimmune disease.
• Participants with AAVrh74 or AAV8 binding antibody titers ≥ 1:50 as determined by enzyme-linked immunosorbent assay (ELISA) immunoassay.

Sponsors & Collaborators

• Sarepta Therapeutics, Inc.: lead
• Nationwide Children's Hospital: collaborator

Related Publications (3)

• Mendell JR, Chicoine LG, Al-Zaidy SA, Sahenk Z, Lehman K, Lowes L, Miller N, Alfano L, Galliers B, Lewis S, Murrey D, Peterson E, Griffin DA, Church K, Cheatham S, Cheatham J, Hogan MJ, Rodino-Klapac LR. Gene Delivery for Limb-Girdle Muscular Dystrophy Type 2D by Isolated Limb Infusion. Hum Gene Ther. 2019 Jul;30(7):794-801. doi: 10.1089/hum.2019.006. Epub 2019 Apr 19.

  PMID: 30838895 BACKGROUND

• Mendell JR, Rodino-Klapac LR, Rosales XQ, Coley BD, Galloway G, Lewis S, Malik V, Shilling C, Byrne BJ, Conlon T, Campbell KJ, Bremer WG, Taylor LE, Flanigan KM, Gastier-Foster JM, Astbury C, Kota J, Sahenk Z, Walker CM, Clark KR. Sustained alpha-sarcoglycan gene expression after gene transfer in limb-girdle muscular dystrophy, type 2D. Ann Neurol. 2010 Nov;68(5):629-38. doi: 10.1002/ana.22251.

  PMID: 21031578 BACKGROUND

• Mendell JR, Rodino-Klapac LR, Rosales-Quintero X, Kota J, Coley BD, Galloway G, Craenen JM, Lewis S, Malik V, Shilling C, Byrne BJ, Conlon T, Campbell KJ, Bremer WG, Viollet L, Walker CM, Sahenk Z, Clark KR. Limb-girdle muscular dystrophy type 2D gene therapy restores alpha-sarcoglycan and associated proteins. Ann Neurol. 2009 Sep;66(3):290-7. doi: 10.1002/ana.21732.

  PMID: 19798725 BACKGROUND

MeSH Terms

Conditions

Sarcoglycanopathies; Muscular Dystrophies, Limb-Girdle

Condition Hierarchy (Ancestors)

Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Respiration Disorders; Respiratory Tract Diseases; Neuromuscular Diseases; Nervous System Diseases; Cardiomyopathies; Heart Diseases; Cardiovascular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Medical Information
• Organization: Sarepta Therapeutics, Inc

SareptAlly@sarepta.com

1-800-690-2003

Study Officials

• Medical Director

  Sarepta Therapeutics, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 24, 2013
• First Posted: November 5, 2013
• Study Start: February 1, 2015
• Primary Completion: March 14, 2019
• Study Completion: March 14, 2019
• Last Updated: June 15, 2023
• Results First Posted: April 1, 2022

Record last verified: 2023-04