Page last updated: February 19, 2024
Page reviewed by: Dr. Cara O’Neill, FAAP
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Study: “Open-label, Single-arm, Multi-center Study of Intracerebral Administration of Adeno-associated Viral (AAV) Serotype rh.10 Carrying Human N-sulfoglucosamine Sulfohydrolase (SGSH) cDNA for Treatment of Mucopolysaccharidosis Type IIIA”
Status: Listed as unknown on ClinicalTrials.gov. In June 2020, FDA placed a clinical hold on the study. This two-year study has now ended.
Trial Listing: Read this clinical trial’s information on ClinicalTrials.gov, for more details about the study.
This phase II-III study aimed to assess the efficacy of LYS-SAF302 gene therapy in improving or stabilizing the neurodevelopmental state of patients with Sanfilippo syndrome type A (MPS IIIA). LYS-SAF302 is a gene therapy which utilized the AAVrh.10 viral vector to deliver a functional copy of the SGSH (Sanfilippo A) gene into cells of the brain. In a previous phase I-II study, an earlier version (LYS-SAF301) of the gene therapy was trialed in 4 children (scroll down for more info). Each of version of this gene therapy was intended for only one time administration.
LYS-SAF302 Study Design: Interventional, single arm and multi-center. Evolution under treatment will be compared to expected natural evolution based on natural history studies.
Route of Delivery: Treatment involved direct injections of the investigational product into both sides of the brain through image-guided tracks, in a single neurosurgical session. Direct injections into the brain are also referred to as intraparenchymal injections.
Dose: A single dose level was given to all patients. 7.2e12 viral genomes/ per patient were injected into 3 sites per hemisphere of the brain; into the white matter and basal ganglia.
A total of 19 children were treated with LYS-SAF302. White matter changes and cystic lesions at the site of previous injections were noted on MRIs after treatment in a number of patients and are described in the publication below by Bugiani et. al. In this publication, the pathology was hypothesized to be from overexpression of SGSH enzyme locally at the injection sites.
LYS-SAF302 gene therapy was designed to have higher SGSH enzyme expression and a higher viral vector dose (10 times higher) compared to the SAF-301 product that was trialed in the earlier Phase I/II study. White matter lesions of this nature were not found after treatment with the first generation vector SAF-301.
In 2020, a 5-year-old girl, who was treasured by her loving family and our community, passed away during her time in the study. The cause of her death was not concluded.
Press releases and web articles associated with LYS-SAF302 clinical trial
- Lysogene Announces the Conversion of the Reorganization Proceedings into Judicial Liquidation and its Delisting, May 2023
- Lysogene Provides Updates and Topline Results from Phase 2/3 AAVance Gene Therapy Clinical Study
- Cure Sanfilippo Foundation Commentary, November 2022
For children who were treated at under 30 months of age (under 2.5 years), the overall data is showing a better outcome on selected endpoints than what would be expected for the natural course of the disease. Over time and as children continue to grow, more information will be learned about how the treatment may be impacting them. This is encouraging data which holds hope that this specific treatment will provide significant benefit across multiple disease symptoms when administered very early in life.
However, Cure Sanfilippo Foundation is saddened to hear that the endpoints were not able to demonstrate a positive effect of the treatment based on what was measured in children who were treated at an age of 30 months (2.5 years) or older. It is even more difficult for the families who were part of the trial and our thoughts are with them.“
We believe it is also important to remember that the way treatment impact in a clinical trial is measured may not always reflect more subtle changes that parents may notice in their individual children, said Dr. Cara O’Neill, Foundation Chief Science Officer. “Again, it is our belief that there is more to learn from the children over time. We continue to work in the field to find and develop trial outcome measures (endpoints) that can detect subtle but meaningful changes for our children of all ages, as well as support new treatment strategies through research and additional clinical trials to benefit all.”
Lysogene is hosting a live webcast update on Nov. 23, 2022, at 7:30 a.m. EST for those interested to learn more. Please also feel free to reach out directly at Cure Sanfilippo Foundation. If your child participated in this trial and you have specific questions about your child, you are encouraged to reach out to your trial doctor directly.
- Cure Sanfilippo Foundation Commentary, November 2022
- Gene Therapy LYS-SAF302 Continuing to Help Sanfilippo Type A Children in Trial, March 2021
- Lysogene Reports LYS-SAF302 Biomarker Data Presented at the WORLDSymposium 2021, February 2021
- FDA Puts Hold on LYS-SAF302 Gene Therapy Trial for Sanfilippo Type A, June 2020
Publications associated with LYS-SAF302 study
- Bugiani M, Abbink TEM, Edridge AWD, van der Hoek L, Hillen AEJ, van Til NP, Hu-A-Ng GV, Breur M, Aiach K, Drevot P, Hocquemiller M, Laufer R, Wijburg FA, van der Knaap MS. Focal lesions following intracerebral gene therapy for mucopolysaccharidosis IIIA. Ann Clin Transl Neurol. 2023 Jun;10(6):904-917. doi: 10.1002/acn3.51772. Epub 2023 May 11. PMID: 37165777; PMCID: PMC10270249.
- Philippidis A. “Profoundly Saddened” Lysogene Discloses Child’s Death in Phase II/III Trial. Hum Gene Ther. 2020 Nov;31(21-22):1141-1143. doi: 10.1089/hum.2020.29139.bfs. PMID: 33200963.