Trials / Not Yet Recruiting

Not Yet RecruitingNCT06948019

Safety and Efficacy of AAV9/AP4B1 (BFB-101) For Patients With AP4B1-related Hereditary Spastic Paraplegia Type 47 (SPG47)

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

Status: Not Yet Recruiting
Phase: Phase 1 / Phase 2
Study type: Interventional
Enrollment: 5 (estimated)

Sponsor: BlackfinBio Ltd · Industry
Sex: All
Age: 12 Months – 60 Months
Healthy volunteers: Not accepted

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

Detailed 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, with most children ultimately requiring full support for mobility, communication, and daily living activities. There are currently no approved disease-modifying therapies for SPG47. Adaptor protein complexes such as AP-4 are key regulators of vesicle-mediated protein trafficking. While the precise role of AP-4 is not fully understood, research suggests it is involved in the sorting and transport of cargo proteins through the Golgi and plays a critical role in autophagy and neuronal maintenance. Loss of function in any AP-4 subunit results in shared disruption of intracellular trafficking pathways and a common neurological phenotype. This first-in-human, Phase 1/2 open-label clinical trial is designed to evaluate the safety, tolerability, and preliminary efficacy of BFB-101, a gene therapy candidate consisting of an adeno-associated virus serotype 9 (AAV9) vector encoding a codon-optimized full-length human AP4B1 cDNA under control of a ubiquitous promoter. The therapy is delivered as a single dose by intra-cisterna magna injection to target cells in the central nervous system. The primary objective of this trial is to assess the safety and tolerability of a single dose of BFB-101. This will be evaluated by monitoring for dose-limiting toxicities, treatment-emergent adverse events (TEAEs), and serious adverse events (SAEs) over a long-term follow-up period of 5 years. Secondary objectives include assessing preliminary efficacy across several domains: * Change from baseline in functional motor and developmental assessments (e.g., GMFM-88, Bayley Scales) * Evaluation of global clinical impression and caregiver-reported outcomes * Biomarkers of disease activity and target engagement (as available) * Time to progression or stabilization of motor milestones * Neuroimaging and electrophysiologic changes over time

Conditions

Interventions

Type	Name	Description
BIOLOGICAL	BFB-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.

Timeline

Start date: 2025-08-01
Primary completion: 2030-08-01
Completion: 2032-08-01
First posted: 2025-04-28
Last updated: 2025-04-28

Locations

1 site across 1 country: United States

Regulatory

FDA-regulated drug study

Source: ClinicalTrials.gov record NCT06948019. Inclusion in this directory is not an endorsement.