Date: 2017-12-13
Type of
information: Clinical trial authorisation
phase: 1
Announcement: clinical trial authorization
Company: Avexis (USA - IL)
Product: AVXS-101 (adeno-associated virus serotype 9 expressing the human Survival Motor Neuron gene)
Action
mechanism:
- gene therapy. ChariSMA™ is a recombinant AAV9 in which most of the AAV9’s naturally-occurring components have been removed and replaced with the SMN transgene and other elements such as the CB promoter and the Bovine Growth Hormone polyadenylation signal (BGH pA) added for hydrolytic enzymatic protection and mRNA stability. The viral vector will deliver the SMN transgene into the motor neurons. Protein synthesis from the SMN transgene will produce full-length, functional SMN protein.
Disease: spinal muscular atrophy (SMA) Type 1
Therapeutic
area: Rare diseases - Genetic diseases - Neuromuscular diseases
Country: USA
Trial
details:
- The open-label, dose-comparison, multi-center Phase 1 trial – known as STRONG – is designed to evaluate the safety, optimal dosing, and proof of concept for efficacy of AVXS-101 in two distinct age groups of patients with SMA Type 2, utilizing a one-time IT route of administration. The trial will enroll 27 infants and children with a genetic diagnosis consistent with SMA, including the bi-allelic deletion of SMN1 and three copies of SMN2 without the SMN2 genetic modifier, who are able to sit but have no historical or current ability to stand or walk.
- Two dosage strengths will be evaluated and patients will be stratified into two age groups: patients less than 24 months, and patients at least 24 months but less than 60 months. There will be at least a four-week interval between the dosing of the first three patients for each dose being studied and, based on the available safety data, a decision will be made whether to proceed.
- Cohort 1 (Dose A) will receive a dose of 6.0 x 1013 vg of AVXS-101 and enroll three patients less than 24 months of age.
If safety is established according to the Data Safety Monitoring Board (DSMB), the study will proceed to Cohort 2.
- Cohort 2 (Dose B) will receive a dose of 1.2 X 1014 vg of AVXS-101 and enroll three patients less than 60 months of age. If safety is established according to the DSMB, an additional 21 patients will be enrolled until there are a total of 12 patients less than 24 months, and 12 patients at least 24 months but less than 60 months of age, who have received Dose B. (NCT03381729)
Latest
news:
- • On December 13, 2017, AveXis announced the FDA has notified the company that, based on review of data submitted, the company may initiate its planned Phase 1 clinical trial of AVXS-101 for patients with spinal muscular atrophy (SMA) Type 2 via the intrathecal (IT) route of administration, using material produced by the company’s Good Manufacturing Practice (GMP) commercial manufacturing process at the AveXis manufacturing facility. The company plans to initiate this trial immediately.
- The trial is projected to be conducted at 11 sites in the United States, including: Ann and Robert H. Lurie Children's Hospital of Chicago, Boston Children's Hospital, Children's Hospital of Philadelphia, David Geffen School of Medicine at UCLA, Johns Hopkins Pediatric Neurology, Nationwide Children's Hospital, Stanford University Medical Center, University of Central Florida College of Medicine, University of Texas Southwestern Medical Center, University of Utah and Washington University School of Medicine.
Is
general: Yes
