Gene Transfer Clinical Trial for Krabbe Disease

Inclusion criteria

• Diagnosis of infantile Krabbe disease, characterized by the following criteria outlined below:

• Galactocerebrosidase (GALC) activity levels in leukocytes compatible with the diagnosis of Krabbe disease; AND AT LEAST ONE OF THE FOLLOWING:
• Elevated psychosine levels predictive of infantile disease onset by DBS; OR
• Imaging or neurophysiological findings consistent with Krabbe disease (CSF, MRI, NCV, ABR); OR
• Two GALC mutations predictive to result in infantile onset phenotype.
• Age at the time of screening: 1 day to 12 months
• Participant has been deemed eligible for treatment with HSCT (standard of care) and a fully myeloablative reduced intensity/toxicity conditioning regimen (RIC/RTC) is/has been used
• Participant's parents or legal guardian consents to participate in the study and provides informed consent according to IRB guidelines prior to any study procedures being performed
• Parent(s) and/or legal guardian able to comply with the clinical protocol
• Participant must have adequate organ function at time of screening as measured by:

• Creatinine ≤ 1.5x upper limit of age appropriate normal and creatinine clearance ≥ 60 mL/min/1.73 m2
• Hepatic transaminases (ALT/AST) ≤ 2x age related upper limit of normal
• Ejection fraction of > 50% by echocardiogram or other appropriate study without evidence of pulmonary hypertension
• Pulmonary evaluation testing demonstrating resting pulse oximeter > 95% on room air
• Coagulation tests within 110% of normal ranges for age. (PT/INR and PTT)

Exclusion criteria

• History of prior treatment with a gene therapy product
• Presence of major congenital anomaly or any other condition that affects neurodevelopmental function
• Presence of any neurocognitive deficit or brain damage not attributable to Krabbe disease
• Active aspiration
• Signs of active infection or disease from cytomegalovirus, adenovirus or other viruses
• HIV positive
• Uncontrolled and progressive bacterial or fungal infection
• Presence of any contraindication for MRI
• Use of any investigational product prior to study enrollment or current enrollment in another study that involves clinical interventions
• Any other medical condition, serious intercurrent illness, or extenuating circumstance that, in the opinion of the PI, would preclude participation in the study
• Ongoing veno-occlusive disease (VOD) as determined by liver ultrasound (moderate ascites and static or retrograde portal vein flow) the day before FBX-101 infusion.