DMD06-MAB for Duchenne muscular dystrophy

Inclusion criteria

• {"criterion_text":"- Age between >= 12 and <18 years at time of study entry, provided that participants matching the eligibility criteria can be identified.\n- Non-ambulant at the time of recruitment.\n- Confirmed diagnosis of DMD with documented exon 51 skippable mutations in dystrophin gene.\n- Progression of muscle degeneration =< to 50% reduction of muscle mass as determined by quantitative MRI (grade 2: Kinali et al. 2011).\n- Written informed consent of caregivers of DMD patients and patient’s assent."}

Exclusion criteria

• {"criterion_text":"- Positive hepatitis B surface antigen, hepatitis C antibody test, or Human immunodeficiency virus (HIV) test, TPHA test.\n- Presence of severe scoliosis (curve >50°).\n- Presence of significant impairment of renal or hepatic function.\n- Presence of immune deficiency, neoplastic or autoimmune disease (based on clinical history).\n- Bleeding disorder.\n- Any known allergies to products likely to be used in the study.\n- Prior or ongoing medical condition (e.g. concomitant illness, psychiatric condition, behavioural disorder, drug abuse), medical history, physical findings, or laboratory abnormality that, in the investigator’s opinion, could adversely affect the safety of the subject, making it unlikely that the course of treatment or follow up would be completed, or could impair the assessment of study results.\n- Ongoing participation in any other therapeutic clinical trial or treatment with exon skipping oligonucleotides. Use of steroids is considered standard care and therefore permitted.\n- LVEF (Left Ventricle Ejection Fraction) < 45% of a healthy subject or ECG finding significant for underlying cardiac impairment.\n- Pulmonary function tests assessed by spirometry (if cooperative) of FEV1 and FVC <30% of the predicted values. If unable, pulse oximetry < 95 % in room air.\n- Change of medication related to DMD within last 3 months with the exception of adjustment based on weight gain of current medications."}

Primary endpoints

• {"endpoint_text":"- Safety 1. Incidence and severity of local (foot) and systemic adverse events (any grade) in DMD patients treated with intra- muscular injections of genetically corrected auto-MABS for one year from the injection.","definition_or_measurement_approach":"Incidence and severity of local and systemic adverse events will be recorded and monitored over one year from injection."}
• {"endpoint_text":"- Efficacy 2.Presence of dystrophin (≥ to 1:10 dilution of a control muscle for WB; ≥ 10% of gene expression of skipped dystrophin at ddPCR; ≥ 10% of dystrophin positive fibers for IF respect to a control muscle) on muscle biopsy of the EDB muscle transplanted with genetically corrected auto-MABS, in at least two out of the three assays (Quantitative IF , ddPCR, and Western Blot) at two months after injection.","definition_or_measurement_approach":"Dystrophin presence assessed on EDB muscle biopsy at two months post-injection by three assays: Western Blot (≥ 1:10 dilution of a control muscle), ddPCR (≥ 10% of gene expression of skipped dystrophin), and Immunofluorescence (≥ 10% dystrophin-positive fibers); endpoint met if ≥2 of 3 assays are positive."}

Italy

Earliest CTIS Part Ii Submission Date

30-05-2024

Latest Decision Or Authorization Date

20-12-2024

Processing Time Days

204

Number Of Sites

1

Number Of Participants

5

Primary sponsor

Full Name

Ospedale San Raffaele S.r.l.

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Italy

Co-sponsors

• University Of Manchester