Cell-mediated skipping of exon 51 for the genetic correction of dystrophin, based upon a single injection of autologous mesoangioblasts (MABs) in individual skeletal muscles of five non-ambulant patients affected by Duchenne Muscular Dystrophy: a non randomized, open-label, phase I/IIa study

Trial details

Who runs it

Ospedale San Raffaele S.r.l.

Trial code

EU 2024-514860-14-00

Record updated

2024. december 20.

Original description

We will test safety of treatment and efficacy in restoring synthesis of dystrophin in the injected muscle. Safety 1. To assess the incidence of adverse events in DMD patients treated with intra-muscular foot injections of auto-MABS after genetic correction with a lentiviral vector expressing a small nuclear RNA engineered to skip exon 51 of the dystrophin gene. Note: In vitro/in vivo pre-clinical safety assessments will be performed on ATIMP prior to injection, as described in the IMPD. Efficacy 2. To determine dystrophin expression (>= 10% of a healthy subject) after a single intra- muscular injection into the foot medial Extensor Digitorum Brevis (EDB) of genetically corrected auto-MABS.Read full original descriptionShow less

Cell-mediated skipping of exon 51 for the genetic correction of dystrophin, based upon a single injection of autologous mesoangioblasts (MABs) in individual skeletal muscles of five non-ambulant patients affected by Duchenne Muscular Dystrophy: a non randomized, open-label, phase I/IIa study

We will test safety of treatment and efficacy in restoring synthesis of dystrophin in the injected muscle. Safety 1. To assess the incidence of adverse events in DMD patients treated with intra-muscular foot injections of auto-MABS after genetic correction with a lentiviral vector expressing a small nuclear RNA engineered to skip exon 51 of the dystrophin gene. Note: In vitro/in vivo pre-clinical safety assessments will be performed on ATIMP prior to injection, as described in the IMPD. Efficacy 2. To determine dystrophin expression (>= 10% of a healthy subject) after a single intra- muscular injection into the foot medial Extensor Digitorum Brevis (EDB) of genetically corrected auto-MABS.

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

Exclusion: Ongoing participation in any other therapeutic clinical trial or treatment with exon skipping oligonucleotides. Use of steroids is considered standard care and therefore permitted; Change of medication related to DMD within last 3 months with the exception of adjustment based on weight gain of current medications; Positive hepatitis B surface antigen, hepatitis C antibody test, or Human immunodeficiency virus (HIV) test, TPHA test; Presence of significant impairment of renal or hepatic function; Presence of immune deficiency, neoplastic or autoimmune disease (based on clinical history); Bleeding disorder; Any known allergies to products likely to be used in the study; 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; LVEF (Left Ventricle Ejection Fraction) < 45% of a healthy subject or ECG finding significant for underlying cardiac impairment; Presence of severe scoliosis (curve >50°); 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.

EU CTIS 2024-514860-14-00