bidridistrogene xeboparvovec for Limb-girdle muscular dystrophy (LGMD2E/R4) | β-sarcoglycanopathy

Inclusion criteria

• {"criterion_text":"- Cohort 1, only ambulatory subjects - ≥ 4 years of age - Able to walk without assistive aid - 10MWR < 30 seconds - NSAD total score ≥ 25"}
• {"criterion_text":"- Cohort 2, only non-ambulatory subjects − ≥ 4 years of age − 10MWR ≥ 30 seconds or unable to perform − PUL 2.0 entry scale score ≥ 3"}
• {"criterion_text":"- Has AAVrh74 antibody titers < 1:400 (ie, not elevated) as determined by AAVrh74 Antibody ELISA."}
• {"criterion_text":"- Is willing to provide informed consent. Alternatively, is willing to provide assent (if applicable) and has (a) parent(s) or legal guardian(s) who is (are) willing to provide informed consent for the subject to participate in the study."}
• {"criterion_text":"- Willing and able to comply with the study protocol required assessments"}
• {"criterion_text":"- Possesses 1 homozygous or 2 heterozygous pathogenic and/or likely pathogenic β-SG DNA gene mutations as documented prior to Screening. Results to be confirmed by Sponsor at a CLIA/CAP/ISO15189 certified laboratory prior to dosing."}
• {"criterion_text":"- Able to cooperate with muscle testing"}
• {"criterion_text":"- Male or female who are of childbearing potential must agree to use, through Month 24, a highly-effective method of contraception (Appendix 1)., Section 11.4.1.1). A woman is considered of childbearing potential (i.e., fertile) following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy."}
• {"criterion_text":"- Stable dose equivalent of oral glucocorticoids for at least 12 weeks before Screening/Baseline and the dose is expected to remain constant (except for modifications to accommodate changes in weight) throughout the first year of the study"}

Exclusion criteria

• {"criterion_text":"- Has a symptomatic infection (eg, upper respiratory tract infection, pneumonia, pyelonephritis, meningitis) within 4 weeks before study treatment infusion (in such case, enrollment may be postponed). If symptomatic infection occurs between Day -7 (±3d) baseline testing and infusion baseline Day 1, the baseline Day -7 (±3d) testing will need to be repeated."}
• {"criterion_text":"- Any contraindication to the use of glucocorticoids."}
• {"criterion_text":"- Has hypersensitivity to any component of the study drug"}
• {"criterion_text":"- Major surgery within 3 months prior to Day 1 or planned surgery or procedure that would interfere with the conduct of the study for any time during this study"}
• {"criterion_text":"- Treatment with any of the following therapies according to the time frames specified • Any time: − Gene therapy − Cell based therapy (eg, stem cell transplantation) − Clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9), or any other form of gene editing • Within 3 months of Day 1: − Use of human growth factor • Within 6 months of the Screening/Baseline visit: Any investigational medication (other than glucocorticoids)"}
• {"criterion_text":"- Has received a live virus vaccine within 4 weeks or an inactive vaccine (including a coronavirus disease vaccine) within 2 weeks of the Day 1 visit or expects to receive a vaccine during the first 3 months after Day 1."}
• {"criterion_text":"- Has LVEF < 40% on the Screening/Baseline ECHO or clinical signs and/or symptoms of cardiomyopathy"}
• {"criterion_text":"- Has FVC ≤ 40% of predicted value at Screening/Baseline and/or requirement for nocturnal ventilation."}
• {"criterion_text":"- Serological evidence of current, chronic, or active human immunodeficiency virus infection, or hepatitis B or C infection or active viral or bacterial infection based on clinical observations."}
• {"criterion_text":"- Diagnosis of (or ongoing treatment for) an autoimmune disease and on active immunosuppressant treatment."}
• {"criterion_text":"- Has abnormal laboratory values considered clinically significant by the Investigator upon medical review including but not limited to: − Gamma-glutamyl transferase upper limit normal (ULN) − Total bilirubin ULN. Note that elevations on total bilirubin due to Gilbert’s syndrome are not exclusionary. − White blood cell count − Platelets"}
• {"criterion_text":"- Presence of any other clinically significant illness or medical condition, including cardiac, hepatic, renal, hematologic, immunologic, neuromuscular (other than LGMD2E/R4), or behavioral disease, or infection or malignancy or concomitant illness or requirement for chronic drug treatment that in the opinion of the Investigator creates unnecessary risks for gene transfer or a medical condition or extenuating circumstance that, in the opinion of the Investigator, might compromise the subject’s ability to comply with the protocol required testing or procedures or compromise the subject’s wellbeing, safety, or clinical interpretability."}
• {"criterion_text":"- Orthopedic comorbidity, such as scoliosis or joint contractures in the upper or lower extremity that would significantly inhibit accurate motor function testing, in the opinion of the Investigator."}

Primary endpoints

• {"endpoint_text":"- Change from Baseline in β-SG expression at Day 60 post-dose as measured by IF PβSGPF for subjects in Cohort 1 (ambulatory subjects)","definition_or_measurement_approach":"Measured by immunofluorescence (IF) percent β-SG positive fibers (PβSGPF) at Day 60 post-dose for Cohort 1 (ambulatory subjects)."}

Secondary endpoints

• {"endpoint_text":"- Change from Baseline in β-SG expression at Day 60 post-dose as measured by IF PβSGPF for subjects in Cohort 1 (ambulatory subjects)","definition_or_measurement_approach":"Measured by immunofluorescence (IF) percent β-SG positive fibers (PβSGPF) at Day 60 post-dose."}
• {"endpoint_text":"- Change from Baseline in β-SG expression at Day 60 post-dose for subjects in Cohorts 1 (ambulatory subjects) and 2 (non-ambulatory subjects) as measured by IF PFI","definition_or_measurement_approach":"Measured by immunofluorescence (IF) percent fluorescent intensity (PFI) at Day 60 post-dose."}
• {"endpoint_text":"- Change from Baseline in β-SG expression at Day 60 post-dose as measured by Western","definition_or_measurement_approach":"Measured by Western assay of biopsied muscle tissue at Day 60 post-dose."}
• {"endpoint_text":"- Change from Baseline in β-SG expression at Day 60 post-dose as measured by IF PβSGPF for subjects in Cohort 2 (non-ambulatory subjects)","definition_or_measurement_approach":"Measured by immunofluorescence (IF) percent β-SG positive fibers (PβSGPF) at Day 60 post-dose for Cohort 2 (non-ambulatory subjects)."}
• {"endpoint_text":"- Change from Baseline through Month 60 in the following physical function for subjects in Cohorts 1(ambulatory subject) and 2 (non-ambulatory subject) − NSAD total score − PUL 2.0 total score","definition_or_measurement_approach":"Physical function assessed through Month 60 using NSAD total score and PUL 2.0 total score."}
• {"endpoint_text":"- Change from Baseline through Month 60 in the following timed function tests for subjects in Cohort 1 (ambulatory subject): − Time to rise from the floor − Time to complete the 10MWR − Time to ascend 4 steps − Time to complete the 100MWR − Timed up and go","definition_or_measurement_approach":"Timed function tests recorded through Month 60 for specified tasks (time measurements)."}
• {"endpoint_text":"- Incidence of TEAEs","definition_or_measurement_approach":"Recording incidence of treatment-emergent adverse events."}
• {"endpoint_text":"- Incidence of adverse events of special interest","definition_or_measurement_approach":"Recording incidence of predefined adverse events of special interest."}
• {"endpoint_text":"- Incidence of treatment-emergent SAEs","definition_or_measurement_approach":"Recording incidence of treatment-emergent serious adverse events."}
• {"endpoint_text":"- Incidence of clinically significant laboratory abnormalities","definition_or_measurement_approach":"Monitoring and recording clinically significant laboratory abnormalities."}
• {"endpoint_text":"- Clinically significant changes in ECGs, ECHOs","definition_or_measurement_approach":"Monitoring and recording clinically significant changes in ECGs and ECHOs."}
• {"endpoint_text":"- Change from Baseline through Month 60 in CK level","definition_or_measurement_approach":"Change in creatine kinase (CK) level assessed through Month 60."}
• {"endpoint_text":"- Time to change of disease milestones","definition_or_measurement_approach":"Time-to-event measurement for disease milestones (e.g., loss of ambulation)."}

Methods

• Site-based recruitment via participating hospitals/centres (site contacts and neuromuscular reference centres are listed for each country).
• Printed materials and outreach: brochures, flyers, gene-therapy information sheets and GP letters (country-specific versions available: DE, BE, IT, etc.).
• Recruitment arrangements documents and informed-consent flowcharts provided (K1/K2 documents) for country-specific recruitment.
• Central patient recruitment contact (SareptAlly@sarepta.com, telephone +18887273782) listed for potential participants.

Spain

Earliest CTIS Part Ii Submission Date

26-03-2024

Latest Decision Or Authorization Date

23-04-2025

Processing Time Days

393

Number Of Sites

1

Number Of Participants

2

Germany

Earliest CTIS Part Ii Submission Date

25-03-2024

Latest Decision Or Authorization Date

29-04-2025

Processing Time Days

400

Number Of Sites

2

Number Of Participants

2

Belgium

Earliest CTIS Part Ii Submission Date

29-03-2024

Latest Decision Or Authorization Date

16-10-2025

Processing Time Days

535

Number Of Sites

2

Number Of Participants

2

Italy

Earliest CTIS Part Ii Submission Date

10-04-2024

Latest Decision Or Authorization Date

21-10-2025

Processing Time Days

559

Number Of Sites

1

Number Of Participants

2

Primary sponsor

Full Name

Sarepta Therapeutics Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

PPD Development LP

Responsibilities

Sponsor duties codes: 1, 12, 13, 14, 4, 5, 6, 7 (as listed in record)

Name

Biotel Research LLC

Responsibilities

Central ECG / Echo / MRI

Third parties

• {"country":"United States","full_name":"Biotel Research LLC","duties_or_roles":"Central ECG / Echo / MRI","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"Sponsor duties codes: 1, 12, 13, 14, 4, 5, 6, 7 (as listed in record)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"United Biosource LLC","duties_or_roles":"Pharmacovigilance","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Greenphire LLC","duties_or_roles":"Patient Reimbursement","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Chillibean Limited","duties_or_roles":"filming of the clincial assessments and evaluation","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Sarepta GTCOE","duties_or_roles":"Code 4 (sponsor duty listed)","organisation_type":"Health care"}
• {"country":"United States","full_name":"4g Clinical LLC","duties_or_roles":"Code 3 (sponsor duty listed)","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Athena Diagnostics Inc.","duties_or_roles":"Code 4 (sponsor duty listed)","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"France","full_name":"Sysnav","duties_or_roles":"Wearable activity tracker","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Cellular Technology Ltd.","duties_or_roles":"T-cell immune response (ELISPOT); Code 4","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Signant Health Global Solutions Limited","duties_or_roles":"Code 7 (sponsor duty listed)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"Code 6 (sponsor duty listed)","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Germany","full_name":"Catalent Germany Schorndorf GmbH","duties_or_roles":"Code 14 (sponsor duty listed)","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Longboat Clinical Limited","duties_or_roles":"Site portal","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Bioagilytix Labs LLC","duties_or_roles":"specialized lab - biomarkers; Code 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Biopier Inc.","duties_or_roles":"Code 10 (sponsor duty listed)","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Atom International Limited","duties_or_roles":"Clinical Evaluator Training","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Vitalograph Limited","duties_or_roles":"Code 13 (sponsor duty listed)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Perkinelmer Genetics Inc.","duties_or_roles":"Code 4 (sponsor duty listed)","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Matthews Media Group Inc.","duties_or_roles":"Patient recruitment","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Professional Case Management Clinical Trials LLC","duties_or_roles":"Home Health Care","organisation_type":"Laboratory/Research/Testing facility"}