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

ConditionsHSPHereditary Spastic ParaplegiaHereditary Spastic ParaparesisHereditary Spastic Paraplegia Type 50Hereditary Spastic Paraplegia Type 47Hereditary Spastic Paraplegia Type 51Hereditary Spastic Paraplegia Type 52SPG47AP4B1Neurogenetic DisordersNeurodevelopmental ConditionsMovement DisordersGene Therapy
Trial statusNot yet recruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age12-60
SponsorBlackfinBio Ltd

About this trial

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

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Male and females between the ages of 12 months - 5 years at the time of treatment

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.

Proband must have features of neurologic dysfunction by clinical history and physical examination.

Stable doses of concomitant medications such as anti-spasticity medications, anti-epileptic medications, behavioral management medications, sleep medications, and special diets, supplements or nutritional support for at least 3 months prior to Screening. If recent changes (< 3 months) in medications, the participant may be allowed per Investigator judgement.

Disqualifiers

Inability to participate in the clinical evaluation as determined by the principal investigator.

Clinically significant abnormal laboratory values (hemoglobin < 8 or > 20 g/dL; white blood cell > 20,000 per cmm, platelets count < 100,000 per cmm; international normalized ratio [INR] > upper limit of normal [ULN]; gamma-glutamyl transferase [GGT], alanine aminotransferase [ALT], and aspartate aminotransferase [AST] or total bilirubin > 1.5 × ULN, creatinine

Presence of a concomitant medical condition that precludes a cisterna magna or lumbar puncture or use of anesthetics for sedated procedures.

Bleeding disorder or any other medical condition or circumstance in which a cisterna magna or lumbar puncture is contraindicated according to local institutional policy.

Trial design

Design model

Single group

Treatments tested in this trial

  • BFB-101 (AAV9-CBh-AP4B1)

    Biological/Vaccine

    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.

Treatment groups

5 Participants
are divided into 1 treatment group
Group A: Treatment ArmExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

Incidence of unanticipated treatment-related toxicities, Grade 3 or higher in participants with SPG47

Incidence of unanticipated treatment-related toxicities, Grade 3 or higher, in participants with SPG47 will be determined from the collection of occurrence and severity of serious adverse events (SAEs). Adverse events will be determined according to Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.

Time frame
60 months

Secondary outcomes

1

Score of predefined Major Motor Milestones derived from the Gross Motor Function Measure (GMFM-88)

Change in score of the 8 Major Motor Milestones derived from the GMFM-88 from Baseline to Month 60. The Major Motor Milestone Score is the sum of 8 items derived from the full-scale GMFM- 88, scored using the conventional scoring key (0 = does not initiate; 1 = initiates or partially completes; 2 = completes) with the minimal possible score being 0 and the maximal possible score being 16.

Time frame
60 months
2

Developmental Milestones

Bayley Scale of Infant and Toddler Development Fourth Edition

Time frame
60 months

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

BlackfinBio Ltd

Lead sponsor

Boston Children's Hospital

Collaborator

Source ClinicalTrials.gov

This trial is not recruiting at the moment. You can still explore other options: