Gene Transfer Clinical Trial for Infantile and Late Infantile Krabbe Disease Treated in the Past With HSCT

This is a non-blinded, non-randomized dose escalation study of intravenous FBX-101 in which subjects who have previously received hematopoietic stem cell transplant will receive a single infusion of an adeno-associated virus gene therapy product. Data from untreated and previously transplanted patients with infantile and late infantile Krabbe disease will be used as a comparator group.

Inclusion Criteria:Group 1: Subjects transplanted for infantile onset Krabbe disease (IKD onset <12 months) with initial diagnosis based on:Galactocerebrosidase (GALC) activity levels in leukocytes compatible with the diagnosis of infantile Krabbe disease according to the lab releasing the results; AND AT LEAST ONE OF THE FOLLOWING:Elevated psychosine predictive of infantile onset disease ≥ 9 nmol/L; ORImaging or neurophysiological findings (refer to Addendum 1) consistent with Krabbe disease (CSF, MRI, NCV, ABR); ORTwo predicted pathogenic GALC mutationsGroup 2: Subjects transplanted for late infantile onset Krabbe (LIKD onset 12-47 months) with signs or symptoms of Krabbe disease, and with initial diagnosis based on:Galactocerebrosidase (GALC) activity levels in leukocytes compatible with the diagnosis of late infantile Krabbe disease according to the lab releasing the results; AND AT LEAST ONE OF THE FOLLOWING:Elevated psychosine predictive of late infantile onset disease ≥ 1.5 nmol/L; ORImaging or neurophysiological findings (refer to Addendum 1) consistent with Krabbe disease (CSF, MRI, NCV, ABR); ORTwo predicted pathogenic GALC mutations; ORNeurological/developmental exam findingsParticipants must have received HSCT at least 90 days prior to dosing dateAt least 30% engraftment of myeloid cells by month 3 post-transplant or 10% by one year and/or after post-transplant that result in GALC leukocyte levels >0.2 nmol/h/mgParticipant's parents or legal guardian consent to participate in the study and provide informed consent according to IRB/IEC guidelines prior to any study procedures being performedParent(s) and/or legal guardian able to comply with the clinical protocolExclusion Criteria:Immunoassay with total anti-AAVrh10 antibody titers of >1:100History of prior treatment with a gene therapy productInability to actively move upper extremities against gravityGrade 3 or higher abnormalities in LFTs, bilirubin, creatinine, white count, hemoglobin, platelets, PT/INR and PTT according to latest version of CTCAEPresence of any neurocognitive deficit, motor deficit, or brain damage not attributable to Krabbe diseaseSigns of active infection or disease from cytomegalovirus, adenovirus, EBV, hepatitis B or C, and HIV or other virusesActive bacterial or fungal infectionPresence of any contraindication for MRI or lumbar puncture (LP)Use of any investigational product prior to study enrollment or current enrollment in another study that involves clinical interventionsImmunizations with live viruses in the 30 days prior to immune suppressionEjection fraction of <50% by echocardiogram or other appropriate study without evidence of pulmonary hypertensionActive acute Graft Versus Host Disease (GvHD) Grade 2 or active extensive chronic GvHDAny other medical condition, serious intercurrent illness, other genetic condition or extenuating circumstance that, in the opinion of the PI, would preclude participation in the study