Safety and Efficacy of AAV9/AP4B1 For Patients With AP4B1-related Hereditary Spastic Paraplegia Type 47 (SPG47): A Phase 1/2 Single-Center, Open-Label Study of Stereotactic Intra-cisterna Magna Administration
BlackfinBio Ltd
Summary
Safety and Efficacy of AAV9/AP4B1 For Patients with AP4B1-related Hereditary Spastic Paraplegia Type 47 (SPG47): A Phase 1/2 Single-Center, Open-Label Study of Stereotactic Intra-cisterna Magna Administration. The goal of this clinical trial is to evaluate whether a gene therapy can safely treat children with SPG47, a rare genetic condition that causes progressive spasticity and developmental delays. The main questions it aims to answer are: * Is the gene therapy safe and well tolerated? * Does the gene therapy improve motor function and developmental outcomes? Participants will: * Undergo screening assessments to confirm eligibility * Receive a single dose of the gene therapy vector * Attend follow-up visits for safety monitoring and developmental assessments over the course of five years
Description
Spastic paraplegia type 47 (SPG47) is a rare, autosomal recessive, neurogenetic disorder caused by biallelic pathogenic variants in the AP4B1 gene, one of four genes that encode subunits of the adaptor protein complex 4 (AP-4). Together with SPG50, SPG51, and SPG52, SPG47 belongs to the group of AP-4-associated hereditary spastic paraplegias (AP-4-HSP). These disorders are characterized by early-onset global developmental delay, progressive lower limb spasticity, intellectual disability, microcephaly, epilepsy, and motor impairment. The clinical trajectory is typically severe and progressive,…
Eligibility
- Age range
- 1–5 years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: 1. Male and females between the ages of 12 months - 5 years at the time of treatment 2. A molecularly confirmed diagnosis of SPG47 (confirmed by a CLIA certified, CE-marked, or equivalent lab): Genomic DNA mutation analysis demonstrating bi-allelic pathogenic variants in the AP4B1 gene. 3. Proband must have features of neurologic dysfunction by clinical history and physical examination. 4. Stable doses of concomitant medications such as anti-spasticity medications, anti-epileptic medications, behavioral management medications, sleep medications, and special diets, suppleme…
Interventions
- BiologicalBFB-101 (AAV9-CBh-AP4B1)
The AAV9-CBh-AP4B1 biological drug product is an aqueous suspension of a gene transfer vector intended for CSF injection. It consists of replication deficient adeno-associated virus (AAV) vector with the AAV serotype 9 capsid enclosing a single stranded DNA with an expression cassette of AP4B1 driven by CBh promoter.
Location
- Boston Children's HospitalBoston, Massachusetts