ClinicalTrials.gov record NCT06948019
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
AI summaryWhat this study is about, in plain languageShow ▾Hide ▴
AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
This Phase 1/2, first-in-human, open-label study tests a single stereotactic intra‑cisterna magna dose of the gene therapy BFB-101 in children with genetically confirmed AP4B1-related SPG47. The trial is non-randomized and follows participants with safety monitoring and developmental and motor assessments for five years. It aims to collect early safety and efficacy data in this rare neurogenetic condition.
What it is studying. The study is testing whether a single dose of the AAV9-based gene therapy BFB-101 is safe and tolerable, and whether there are preliminary effects on motor function and developmental outcomes, biomarker signals, neuroimaging, and electrophysiology in children with biallelic pathogenic variants in AP4B1 (SPG47).
What the researchers hope to learn. To evaluate safety and tolerability of a single dose of BFB-101 over 60 months (including monitoring for dose-limiting toxicities, treatment-emergent adverse events, and serious adverse events). To gather preliminary efficacy data: change in major motor milestones (GMFM-88 items), developmental milestones (Bayley scales), caregiver and clinician global impressions, biomarkers of target engagement, neuroimaging and electrophysiologic changes, and time to progression or stabilization of motor milestones.
What this study is about
The study's own summary, as published on ClinicalTrials.gov. Underlined terms have a short explanation.
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
Interventions being studied
Being studied in this trial does not mean the treatment or procedure is approved or available for this condition.
- Biological
- BFB-101 (AAV9-CBh-AP4B1)
Eligibility
The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.
Inclusion criteria
- 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.
- Proband must be fully vaccinated per Centers for Disease Control recommendations for childhood vaccinations.
- Two competent custodial parents/guardians with legal capacity (legally acceptable representatives) to execute an Institutional Review Board/Independent Ethics Committee (IRB/IEC) approved consent for medical research must be able to participate in the consent process. If only one parent has sole custody to consent for medical research, then that parent must be able to actively participate in the consent process.
- Legally acceptable representatives must be able to attend all scheduled study visits and provide feedback regarding the participant's symptoms and performance as described in the protocol.
- Legally acceptable representatives agree not to post any of the participant's personal medical data or information related to the study on any website or social media site (e.g., Facebook, Instagram, Twitter, YouTube, etc.) until notified that the study is completed.
- Proband and the proband's family must demonstrate ability to travel to the study center. For the first 30 days post treatment probands will need to stay within a 100-mile radius from the treatment center.
Exclusion criteria
- 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
- ≥ 1.5 mg/dL) prior to gene replacement therapy.
- 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.
- Documented cardiomyopathy or significant congenital heart abnormalities.
- Inability to be safely sedated in the opinion of the clinical anesthesiologist.
- History of severe/life-threatening allergic reaction to sirolimus, tacrolimus, corticosteroids, or gadolinium.
- Any known history and/or family history of hemophagocytic lymphohistiocytosis (HLH) or multisystem inflammatory syndrome (MIS)
- Concomitant illness or requirement for chronic drug treatment that in the opinion of the investigator creates unnecessary risks for gene transfer.
- Concomitant chronic drug treatment that would cause clinically significant interactions with immunosuppressive agents used in the study.
- Any item which would exclude the participant from being able to undergo magnetic resonance imaging (MRI) according to local institutional policy.
- Any other situation that would exclude the participant from undergoing any other procedure required in this study.
- Visual or hearing impairment sufficient to preclude cooperation with neurodevelopmental testing.
- The presence of significant non-SPG47 related central nervous system (CNS) impairment or behavioral disturbances that would confound the scientific rigor or interpretation of results of the study.
- Recent or planned elective surgical procedures that would confound the scientific rigor or interpretation of results of the study, as determined by the Investigator/study team.
- Failure to obtain appropriate informed consent.
- Reason to believe that the participant or parents/guardians of the participant will not comply with the study procedures outlined in the study protocol.
- Receiving a live vaccine within 30 days prior to gene transfer.
- Receiving an investigational drug within 30 days prior to screening or plan to receive an investigational drug (other than gene therapy) during the study.
- Enrollment and participation in another interventional clinical trial.
Study description and what participation involves
The study's detailed description, as published on ClinicalTrials.gov.
Show the detailed description from the registry
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
AI summaryWhat participation may involve, in plain languageShow ▾Hide ▴
AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
After screening to confirm eligibility, the child will receive a single dose of the gene therapy (BFB-101) delivered into the cerebrospinal fluid by a stereotactic intra‑cisterna magna injection under sedation or anesthesia. Participants will return for many follow-up visits over a 5-year period for safety monitoring, developmental and motor assessments, neuroimaging and electrophysiology as required, and routine blood tests. The study also uses immunosuppressive medicines around the time of gene transfer. Caregivers must attend visits, provide regular feedback about the child's symptoms and performance, and follow study rules (including travel and a 100-mile stay requirement for the first 30 days and restrictions on posting personal medical data).
How the study is structured. An interventional, open-label, non-randomized, single-group Phase 1/2 trial. Participants receive one intra‑cisterna magna injection of BFB-101 and then attend scheduled safety checks and developmental/motor assessments, imaging, and other tests over a five-year follow-up period.
Questions you could ask
These questions are suggestions for a conversation with the study team or your own clinician, not advice.
- This is an early-phase study, mainly about safety and dose. What is already known about this treatment?
- The registry says recruitment has not started. When is it expected to open, and can I register interest now?
- The listed sites are in United States. Is any of them reachable for me, and does the study help with travel?
- Which of the eligibility criteria would need to be checked with tests before I could join?
More on hereditary spastic paraplegia
Important dates
- Study start
- August 2025 (estimated)
- Primary completion
- August 2030 (estimated)
- Study completion
- August 2032 (estimated)
- Target enrollment
- 5 participants (estimated)
- Last updated on registry
- Apr 28, 2025
- Data verified
- Oct 10, 2026
Sponsor and research team
The lead sponsor funds and oversees the trial. A pharmaceutical or biotech company sponsor typically means the study is testing that company's drug or device; a hospital, university, or government agency usually indicates investigator-initiated or publicly funded research.
- Lead sponsor
- BlackfinBio Ltd
- Collaborators
- Boston Children's Hospital
Central study contact
If you're interested in participating, the central contact can answer general questions about the study — including eligibility requirements and how to find a recruiting site near you. Actual eligibility is determined by the site's medical team.
- Darius Ebrahimi-Fakhari, MD, PhD 📞 617-355-0097 ✉ hsp.research@childrens.harvard.edu
- Josh Rong, BS 📞 617-355-0903 ✉ hsp.research@childrens.harvard.edu
Participating sites (1)
- Boston Children's Hospital
Boston, Massachusetts, 02115 · United States
- Darius Ebrahimi-Fakhari, MD, PhD · 617-355-0097 · hsp.research@childrens.harvard.edu
- Josh Rong, BS · 617-355-0903 · hsp.research@childrens.harvard.edu
- Darius Ebrahimi-Fakhari, MD, PhD
Terms used on this page · explanations by MedicalUpdates.ai
- Open-Label
- No masking is used, so the assigned intervention is not deliberately hidden from participants or study staff.
- screening assessments
- The checks done before enrolment to see whether a person qualifies, such as tests, scans or a review of medical history.
- follow-up
- The period after treatment or enrolment during which participants are observed or contacted, for example to record side effects or outcomes.
- concomitant medications
- Other medicines a participant takes during the study. Some must be reported; some are restricted.
- principal investigator
- The doctor or scientist responsible for running the study at a site or overall.
- upper limit of normal
- The highest value of a blood test that a laboratory considers normal. Criteria such as '≤ 3 × ULN' mean the result must be no more than three times that value.
- lumbar puncture
- A procedure in which a needle is placed between the bones of the lower back to collect spinal fluid or to give a treatment.
- contraindicated
- A reason a particular test or treatment should not be used for a person, for example a metal implant that rules out an MRI scan.
- corticosteroids
- Steroid medicines, such as prednisone, that reduce inflammation. Studies often require a stable dose at entry or measure whether the study treatment allows the dose to be reduced.
- immunosuppressive
- A medicine that reduces the activity of the immune system. Studies of autoimmune conditions often require a stable dose, a prior failure, or a washout of such medicines.
- magnetic resonance imaging
- A scan that uses magnets and radio waves, not X-rays, to make detailed pictures of the inside of the body. Some implants and metal objects mean a person cannot have one.
- informed consent
- The process of explaining a study, including its risks and what participation involves, so that a person can decide freely whether to take part. Consent is usually documented in writing, and a participant can choose to leave the study later.
- investigational drug
- A treatment that is being tested and has not been approved for this use. It may be approved for a different condition. Being studied does not mean it works or is available outside the study.
- Enrollment
- The number of participants a study plans to include, or has included. 'Estimated' means the planned number; 'actual' means the number who joined.
- Inclusion Criteria
- The conditions a person must meet to be considered for the study, for example a confirmed diagnosis, an age range or a test result.
- Exclusion Criteria
- The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy.
- first-in-human
- The first study in which a treatment is given to people. Safety is the main question and the number of participants is usually small.
- primary objective
- The main result the study is designed to measure and report on. Other results, called secondary outcomes, are also collected.
- dose-limiting toxicities
- A side effect, defined in advance, that is severe enough to limit how far the dose can be raised in a dose-escalation study. How many such events stop escalation is set by the study's rules.
- treatment-emergent adverse events
- Any unwanted medical problem that happens during a study, whether or not it was caused by the treatment. A 'serious' adverse event is one that meets specific criteria, such as causing death, being life-threatening, requiring or prolonging hospital admission, causing significant disability, or another medically important outcome.
- long-term follow-up
- Observation that continues for years after the study treatment, often required for gene and cell therapies.
- baseline
- Measurements taken at the start of the study, before any study treatment, so that later results can be compared with them.
- Biomarkers
- Something measurable in the body, such as a blood test result or an imaging finding, that indicates how a condition or treatment is behaving.
The study record on this page is reproduced from ClinicalTrials.gov, a database of the U.S. National Library of Medicine, where it was submitted by the study sponsor. MedicalUpdates.ai does not own this content, is not affiliated with or endorsed by ClinicalTrials.gov, NIH, or the U.S. Government, and does not verify the record. Plain-language notes, the glossary and the questions above are added by this site; text in the boxes marked "AI summary" was written by an AI model and may contain errors. Registry records change over time. Check the original record for the current version and discuss eligibility or participation with a qualified healthcare professional.
← Back to clinical trials