Gene Therapy for Spastic Paraplegia

Overseen By Josh Rong, BS

Age: < 18

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: BlackfinBio Ltd

Must be taking: Anti-spasticity, Anti-epileptic

Must not be taking: Immunosuppressive interactions

Disqualifiers: Cardiomyopathy, CNS impairment, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 7

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates a new gene therapy, BFB-101 (AAV9-CBh-AP4B1), to determine its safety in treating children with SPG47, a rare condition causing muscle stiffness and developmental delays. Researchers aim to assess the treatment's safety and its potential to improve movement and development over time. Eligible children have a confirmed SPG47 diagnosis and experience neurological issues, such as difficulty walking or developmental delays. Participants will receive one dose of the therapy and attend regular check-ins for five years to monitor progress and safety. As a Phase 1/Phase 2 trial, this study focuses on understanding the treatment's effects in people and measuring its effectiveness in an initial, smaller group, offering participants a chance to be among the first to potentially benefit from this innovative therapy.

Do I have to stop taking my current medications for the trial?

The trial does not require you to stop taking your current medications, but your doses must be stable for at least 3 months before screening. If there have been recent changes in your medications, the investigator will decide if you can still participate.

Is there any evidence suggesting that this gene therapy is likely to be safe for humans?

In a previous study, researchers developed BFB-101, a gene therapy, to address the genetic cause of SPG47 by providing a functional copy of the AP4B1 gene. This therapy targets hereditary spastic paraplegia, a condition that leads to muscle stiffness and movement difficulties. The gene therapy is administered once into the fluid surrounding the brain.

Research has shown that the FDA approved the start of this trial, indicating that earlier studies did not reveal serious safety issues. However, as this is an early-stage trial, its primary goal is to confirm safety. More detailed safety information will become available as the trial progresses. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for spastic paraplegia, which often involve physical therapy and medications to manage symptoms, BFB-101 offers a new approach by directly addressing the genetic cause of the condition. BFB-101 is an innovative gene therapy that uses the AAV9-CBh-AP4B1 vector to deliver a healthy copy of the AP4B1 gene, potentially correcting the underlying genetic defect. This targeted approach could slow or even halt disease progression rather than just managing symptoms, which is why researchers are so excited about its potential.

What evidence suggests that this gene therapy is effective for SPG47?

Research shows that BFB-101, a gene therapy under study in this trial, aims to address the main cause of Hereditary Spastic Paraplegia Type 47 (SPG47) by providing a healthy version of the faulty gene. Studies on similar gene therapies have shown promising results, suggesting possible improvements in movement and development. Although researchers are still gathering direct human data for BFB-101, these early signs offer hope for its effectiveness in treating SPG47. Overall, this approach is promising because it targets the genetic problem causing the condition. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

This trial is for children with a rare genetic disorder called SPG47, which leads to progressive muscle stiffness and developmental delays. Participants must pass screening assessments confirming their condition.

Inclusion Criteria

Proband must be fully vaccinated per CDC recommendations

Legally acceptable representatives must attend all scheduled study visits and provide feedback

Legally acceptable representatives agree not to post participant's data on social media until study completion

Exclusion Criteria

Failure to obtain appropriate informed consent

Clinically significant abnormal laboratory values prior to gene replacement therapy

Inability to be safely sedated according to clinical anesthesiologist

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive a single dose of the gene therapy vector via intra-cisterna magna injection

1 day

1 visit (in-person)

Follow-up

Participants attend follow-up visits for safety monitoring and developmental assessments

60 months

Regular visits over 5 years

What Are the Treatments Tested in This Trial?

Interventions

• BFB-101 (AAV9-CBh-AP4B1)

Trial Overview The study tests the safety and effectiveness of BFB-101 (AAV9-CBh-AP4B1), a gene therapy administered once into the fluid surrounding the brain and spinal cord, in improving motor function and development over five years.

How Is the Trial Designed?

Group I: Treatment Arm Experimental Treatment 1 Intervention

BFB-101, a gene therapy product

Who Is Running the Clinical Trial?

BlackfinBio Ltd

Lead Sponsor

Boston Children's Hospital

Collaborator

Trials

801

Recruited

5,584,000+

Published Research Related to This Trial

AAV-mediated AP4M1 gene replacement therapy shows promise in preclinical studies for treating spastic paraplegia 50 (SPG50), demonstrating the ability to partially rescue functional defects in cellular and mouse models.

The therapy exhibited acceptable safety profiles in both rodent and monkey models, paving the way for potential clinical trials and representing a significant advancement in the search for effective treatments for SPG50.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Paving a way to treat spastic paraplegia 50. Brent, JR., Deng, HX.[2023]

AAV9/AP4M1 gene therapy shows promise for treating spastic paraplegia 50 (SPG50) in preclinical studies, with effective phenotypic rescue observed in patient-derived fibroblasts and significant therapeutic benefits in Ap4m1-KO mice when treated early and with higher doses.

The therapy demonstrated an acceptable safety profile in toxicology studies across various species, including nonhuman primates, indicating that it is safe for potential use in human clinical trials for SPG50.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intrathecal AAV9/AP4M1 gene therapy for hereditary spastic paraplegia 50 shows safety and efficacy in preclinical studies. Chen, X., Dong, T., Hu, Y., et al.[2023]

AAVrh10, a specific adeno-associated virus serotype, was found to be the most effective for gene delivery in a chronic spinal cord injury mouse model, showing the highest photon count in bioluminescence imaging and greater expression of the reporter protein Venus.

This serotype demonstrated favorable targeting of key cell types in the spinal cord, including neurons, astrocytes, and oligodendrocytes, suggesting its potential as a safe and effective tool for gene therapy in chronic spinal cord injuries.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The adeno-associated virus rh10 vector is an effective gene transfer system for chronic spinal cord injury. Hoshino, Y., Nishide, K., Nagoshi, N., et al.[2021]

The study successfully constructed both wild-type and mutant SPAST vectors to investigate hereditary spastic paraplegia, using COS7 cells for transfection and analysis.

Results showed that while wild-type spastin localized in the plasma membrane, the mutant spastin maintained the same localization and neither form co-localized with microtubules or mitochondria, suggesting a specific role for spastin that does not involve these cellular structures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Construction of wild-type and mutant SPAST vectors for the study of molecular mechanism of hereditary spastic paraplegia]. Yan, YP., Pu, JL., Zhang, BR., et al.[2019]

Citations

1. centerwatch.com centerwatch.com/clinical-trials/listings/NCT06948019/safety-and-efficacy-of-aav9-ap4b1-bfb-101-for-patients-with-ap4b1-related-hereditary-spastic-paraplegia-type-47-spg47?activelyRecruiting=false&page=24&id=423&slug=chemotherapy

Safety and Efficacy of AAV9/AP4B1 (BFB-101) For Patients ... 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 ...

2. clinicaltrialsarena.com clinicaltrialsarena.com/news/fda-blackfinbio-trial/

FDA approves BlackfinBio's trial for hereditary spastic ... The US FDA has cleared BlackfinBio's application for a Phase I/II trial of BFB-101, an AAV gene therapy designed to treat hereditary SPG47.

3. blackfin.bio blackfin.bio/blackfinbio-announces-fda-clearance-to-initiate-phase-1-2-clinical-trial-for-novel-aav-gene-therapy-bfb-101-to-treat-the-rare-neurological-disease-hereditary-spastic-paraplegia-type-47-spg47/

BlackfinBio Announces FDA Clearance to Initiate Phase 1/ ... BFB-101 aims to address the underlying genetic cause of Hereditary Spastic Paraplegia, Type 47 (SPG47) by delivering a functional copy of the ...

4. withpower.com withpower.com/trial/gene-therapy-for-spastic-paraplegia-77f8c

Gene Therapy for Spastic Paraplegia · Info for Participants What data supports the effectiveness of the treatment BFB-101 (AAV9-CBh-AP4B1) for spastic paraplegia? Preclinical studies show that a similar gene therapy ...

5. synapse.patsnap.com synapse.patsnap.com/article/blackfinbio-gets-fda-nod-for-phase-12-trial-of-gene-therapy-bfb-101-for-spg47

BlackfinBio Gets FDA Nod for Phase 1/2 Trial of Gene ... Preliminary studies have shown promising safety and efficacy results for BFB-101. The planned clinical trial will adopt an open-label, single- ...

6. clinconnect.io clinconnect.io/trials/NCT06948019

Safety and Efficacy of AAV9/AP4B1 (BFB-101) For Patients This clinical trial is investigating a new gene therapy called AAV9/AP4B1 (BFB-101) to see if it can safely help children with a rare genetic condition known ...