What side effects are associated with this type of intervention?

Gene therapy for Krabbe Disease, such as PBKR03 which delivers a functional GALC gene, is still under investigation. Known side effects from similar gene therapies can include immune reactions to the viral vector used for gene delivery, which may manifest as fever, inflammation, or more severe immune responses. Other potential side effects include insertional mutagenesis, where the integration of the new gene disrupts other genes, potentially leading to malignancies. Additionally, there may be risks of off-target effects where the therapy affects cells other than the intended target cells.

What prior FDA approvals exist?

As of now, there are no FDA-approved gene therapies specifically for Krabbe Disease that deliver a functional GALC gene, similar to PBKR03. Current treatments for Krabbe Disease primarily focus on supportive care and hematopoietic stem cell transplantation (HSCT), which can help slow disease progression if administered early. Research and clinical trials, such as the one involving PBKR03, are ongoing to explore the efficacy and safety of gene therapy for this condition.

What other types of research exist?

As of 2024, promising novel alternatives to PBKR03 for Krabbe Disease patients include other gene therapies targeting the GALC gene, enzyme replacement therapies that provide functional GALC enzyme, and small molecule therapies aimed at reducing the accumulation of psychosine, a toxic substrate in Krabbe Disease. Specific examples include investigational gene therapies like AVROBIO's AVR-RD-01 and Lysogene's LYS-GM101, which are in various stages of clinical development.

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Gene Therapy

Gene Therapy for Krabbe Disease (GALax-C Trial)

Q: What is the mechanism of action of this treatment?

Gene therapy for Krabbe Disease, such as PBKR03, works by delivering a functional copy of the GALC gene to the brain and peripheral tissues. The GALC gene is responsible for producing the enzyme galactocerebrosidase, which is crucial for the breakdown of certain lipids in the nervous system. In Krabbe Disease, mutations in the GALC gene lead to a deficiency of this enzyme, causing toxic accumulation of lipids and subsequent damage to the nervous system. By introducing a functional GALC gene, gene therapy aims to restore enzyme activity, reduce lipid accumulation, and prevent or mitigate neurological damage. This approach is significant for Krabbe Disease patients as it targets the root cause of the disease, offering the potential for more effective and long-lasting treatment outcomes compared to symptomatic therapies.

Phase 1 & 2

Waitlist Available

Research Sponsored by Passage Bio, Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be younger than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years (multiple visits)

Awards & highlights

No Placebo-Only Group

Summary

This trial tests PBKR03, a gene therapy for infants with early infantile Krabbe Disease. The treatment uses a virus to deliver a healthy gene to help produce a necessary enzyme. Previous studies have shown that this type of gene therapy can extend lifespan and reduce symptoms in mouse models of Krabbe disease. The study will determine the best dose and check if the treatment is safe and effective.

Who is the study for?

This trial is for infants aged 1-9 months with early infantile Krabbe Disease, showing certain neurological functions and having specific genetic markers. They must have blood psychosine levels above a threshold and low leukocyte GALC activity. Those with significant neurocognitive deficits not due to Krabbe, prior gene therapy or stem cell transplants, recent participation in other trials, chronic ventilation support, recent vaccines, MRI or lumbar puncture contraindications, kidney issues, abnormal blood counts or liver enzymes cannot participate.

What is being tested?

The study tests PBKR03 gene therapy intended to deliver a functional GALC gene to combat Krabbe Disease. It will first assess safety and tolerability of two doses across different age groups before confirming the best dose for further evaluation of its effectiveness in slowing down or stabilizing the disease progression.

What are the potential side effects?

While specific side effects are not listed here as it's an investigational treatment, potential risks may include reactions at the injection site, immune responses to the new genes introduced into the body (like inflammation), complications from procedures like lumbar punctures or anesthesia used during administration.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years (multiple visits)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years (multiple visits)

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 years (multiple visits) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Assess Humoral Response Against the Vector and Transgene in CSF

Assess Humoral Response Against the Vector and Transgene in Serum

Change from baseline in nerve conduction and velocity in motor nerve conduction studies

+3 more

Secondary study objectives

Change from Baseline in Developmental Milestones as Assessed by the Bayley Scale of Infant and Toddler Development, Third Edition

Change from Baseline in Developmental Milestones as Assessed by the Vineland Adaptive Behavior Scale-II

Change in Biomarkers of GALC Activity in Blood

+10 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: Part 2: Expansion Cohort designed to confirm the safety and efficacy of PBKR03Experimental Treatment1 Intervention

Cohort 5: Subjects aged \>1 to \<9 months Drug: PBKR03 Single dose of PBKR03, via intra cisterna magna Dose to be used for the confirmatory cohorts in Part 2 will be defined after a review of data from Part 1. \*GC/g: genome copiesy per gram of estimated brain weight

Group II: Part 1: Dose Escalation Cohorts designed to identify the optimal dose of PBKR03Experimental Treatment1 Intervention

Cohort 1: Subjects aged \>4 to \<9 months Drug: PBKR03 1.5 x 10\^11 GC/g\* Single dose of PBKR03, via intra cisterna magna Cohort 2: Subjects aged \>4 to \<9 months Drug: PBKR03 5.0 x 10\^11 GC/g\* Single dose of PBKR03, via intra cisterna magna Cohort 3: Subjects aged \>1 to \<4 months Drug: PBKR03 1.5 x 10\^11 GC/g\* Single dose of PBKR03, via intra cisterna magna Cohort 4: Subjects aged \>1 to \<4 months Drug: PBKR03 5.0 x 10\^11 GC/g\* Single dose of PBKR03, via intra cisterna magna \*GC/g: genome copiesy per gram of estimated brain weight

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Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Gene therapy for Krabbe Disease, such as PBKR03, works by delivering a functional copy of the GALC gene to the brain and peripheral tissues. The GALC gene is responsible for producing the enzyme galactocerebrosidase, which is crucial for the breakdown of certain lipids in the nervous system. In Krabbe Disease, mutations in the GALC gene lead to a deficiency of this enzyme, causing toxic accumulation of lipids and subsequent damage to the nervous system. By introducing a functional GALC gene, gene therapy aims to restore enzyme activity, reduce lipid accumulation, and prevent or mitigate neurological damage. This approach is significant for Krabbe Disease patients as it targets the root cause of the disease, offering the potential for more effective and long-lasting treatment outcomes compared to symptomatic therapies.