First Phase 3 Gene Therapy trial in spinal muscular atrophy at The John Walton Muscular Dystrophy Centre
The John Walton Muscular Dystrophy Research Centre opened their first Phase 3 Gene Therapy trial in spinal muscular atrophy (SMA) Type 1 (STRIVE-EU) at the Great North Children's Hospital on 4 December 2018, this study is an NIHR portfolio study and sponsored by AveXis, Inc.
This is the first Gene Therapy study in SMA in Newcastle-upon-Tyne and the first Gene Therapy study for Principal Investigator (PI) Professor Volker Straub.
SMA is a severe neuromuscular disease characterised by the loss of motor neurons leading to progressive muscle weakness and paralysis. SMA is caused by a genetic defect in the SMN1 gene that codes SMN, a protein necessary for survival of motor neurons. The incidence of SMA is approximately one in 10,000 live births and is the leading genetic cause of infant mortality. The most severe form of SMA is Type 1, which results in mortality or the need for permanent ventilation support by 24 months of age for more than 90 percent of patients.
Professor Straub explained: “The prospect of a new treatment for SMA that may alter the disease course and improve the outcome for SMA patients is extremely exciting for both families and healthcare professionals.”
STRIVE-EU is a Phase 3, open-label, single-arm, single-dose, trial of AVXS-101 (gene replacement therapy) in patients with SMA Type 1 who meet enrolment criteria and are genetically defined by a biallelic pathogenic mutation of the survival motor neuron 1 gene (SMN1) with one or two copies of survival motor neuron 2 gene (SMN2). Up to 30 patients < 6 months (< 180 days) of age at the time of gene replacement therapy (Day 1) will be enrolled.
The trial includes a screening period, a gene replacement therapy period, and a follow-up period. During the screening period (Days -30 to -2), patients whose parent(s)/legal guardian(s) provide informed consent will complete screening procedures to determine eligibility for trial enrolment. Patients who meet the entry criteria will enter the in-patient gene replacement therapy period (Day -1 to Day 3). On Day -1, patients will be admitted to the hospital for pre-treatment baseline procedures. On Day 1, patients will receive a one-time intravenous (IV) infusion of AVXS-101, and will undergo in-patient safety monitoring over the next 48 hours. Patients may be discharged 48 hours after the infusion, based on Investigator judgment. During the outpatient follow-up period (Days 4 to End of Trial at 18 months of age), patients will return at regularly scheduled intervals for efficacy and safety assessments until the End of Trial when the patient reaches 18 months of age. After the End of Trial visit, eligible patients will be asked to rollover into the long-term follow up trial.
STRIVE-EU is testing the safety and efficacy of AVXS-101, a single-dose gene-replacement therapy that uses a non-replicating AAV-9 viral vector, crossing the blood-brain barrier, to deliver a healthy copy of the SMN1 gene to a patient.
AveXis is delighted to be working with Professor Straub and the clinical research team at The John Walton Muscular Dystorphy Clinical Research Centre.
Professor Stephen Robson, Clinical Director, NIHR Clinical Research Network North East and North Cumbria said: “I would like to congratulate Professor Straub and the team at the Great North Children’s Hospital for screening their first patient within a week of opening and against their recruitment target of one. This is a fantastic achievement for the team and demonstrates just what our region can offer to life sciences research.”
STRIVE-EU (EudraCT: 2017-000266-29; CT.gov: NCT03461289)
