Duchenne muscular dystrophy
Conditions
Interventions
Product Code: SRP-9001
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Delandistrogene moxeparvovec
CAS Number: 2305040-16-6
Current Sponsor code: SRP-9001
Other descriptive name: Aden
Sponsors
Sarepta Therapeutics, Inc
Eligibility
Sex/Gender
Male
Inclusion criteria
Inclusion criteria: 1. Is male at birth, ambulatory, and = 4 to = 8 years of age at the time of Screening. 2. Has a definitive diagnosis of DMD prior to Screening based on documentation of clinical findings and confirmatory genetic testing using a clinical diagnostic genetic test. Genetic report must describe a frameshift deletion, frameshift duplication, premature stop ("nonsense"), canonical splice site mutation, or other pathogenic variant in the DMD gene fully contained between exons 18 to 79 (inclusive) that is expected to lead to absence of dystrophin protein. a. Mutations between or including exons 1-17 are not eligible. b. In-frame deletions, in-frame duplications, and variants of uncertain significance (“VUS”) are not eligible. 3. Able to cooperate with motor assessment testing. 4. Is up to date with all regionally recommended immunizations for encapsulated organisms. 5. Stable dose of oral corticosteroids for at least 12 weeks before Screening and the dose is expected to remain constant (except for potential modifications to accommodate changes in weight) up to Week 52 of the study. 6. Has rAAVrh74 antibody results at Screening that are reactive by the Elecsys® anti AAVrh74 assay. 7. Subjects who are sexually active must agree to use, for the entire duration of the study, a condom and the female sexual partner must also use a medically acceptable form of birth control (eg, oral contraceptive). Refer to Section 16.1 for guidance on highly effective contraceptive methods. 8. If under the age of consent (=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Previous treatment with imlifidase. 2. High dose IVIG treatment (2 g/kg BW) within 28 days prior to imlifidase treatment. 3. Has left ventricular ejection fraction 2× upper limit of normal (ULN) • Total bilirubin > ULN. Note; elevations in total bilirubin confirmed to be due to Gilbert’s syndrome are not exclusionary. • White blood cell count > 18,500 per µl • Platelets < lower limit of normal 16. Known hypersensitivity to SRP-9001 or its excipients or to imlifidase or its excipients. 17. Family does not want to disclose subject’s study participation with general practitioner/primary care physician and other medical providers.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To evaluate micro-dystrophin expression at 12 weeks post dosing of SRP-9001 in subjects pre-treated with imlifidase • To evaluate micro-dystrophin transduction at 12 weeks post dosing of SRP-9001 in subjects pre-treated with imlifidase;Secondary Objective: • To establish the pharmacokinetic (PK) profile of imlifidase • To establish the pharmacodynamic (PD) profile of imlifidase (cleavage and recovery of IgG) • To evaluate rAAVrh74 antibody titers following imlifidase administration • To assess rAAVrh74 genome concentration in systemic circulation • To evaluate the safety of imlifidase •To evaluate the safety of imlifidase followed by SRP-9001 in combination;Primary end point(s): • Change in quantity of micro-dystrophin protein expression in biopsied muscle tissue from Baseline to Week 12 (Part 1) as measured by - Western blot - IF fiber intensity - IF PDPF • Vector genome copies using polymerase chain reaction in muscle tissue biopsy;Timepoint(s) of evaluation of this end point: The statistical analysis for micro-dystrophin protein expression and transduction will be performed after the assays for micro-dystrophin protein expression at Baseline and Week 12 and the assay for micro-dystrophin transduction at Week 12 have been completed. The observed values and change from baseline values for the primary endpoints will be summarized descriptively. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Imlifidase PK in serum up to 7 days after imlifidase administration • Imlifidase PD (total IgG) in serum up to 12 weeks after imlifidase administration • rAAVrh74 antibody titers up to 120 hours after imlifidase administration • Vector genome copies using polymerase chain reaction in serum up to 7 days after SRP-9001 administration • Incidence of treatment-emergent adverse events • Worsening of vitals or physical examination findings • Incidence of adverse events of special interest • Incidence of serious adverse events • Clinically significant abnormalities in safety laboratory assessments • Electrocardiograms (ECGs) • Echocardiograms (ECHOs);Timepoint(s) of evaluation of this end point: The PK parameter Cmax will be estimated based on actual values. The remaining PK parameters will be estimated by non-compartmental or compartmental analysis based on measurements of the serum concentration-time data of imlifidase, and the following parameters will be estimated, if possible (but not limited to): AUC, Tmax, t1/2, CL, and Vz. The PD analyses will be descriptive based on measurements of the serum concentration-time data of intact IgG, absolute concentration of IgG as well as proportion of remaining IgG. | — |
Countries
Spain
Contacts
Public ContactPatient Recruitment
Sarepta Therapeutics, Inc
Outcome results
None listed