A Phase 1b Clinical Study of Intravenous AAVrh10 Vector Expressing GALC in Krabbe Subjects Who Previously Received Hematopoietic Stem Cell Transplantation (REKLAIM)

FBX-101-REKLAIM

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

2023-02-03

2026-07-01

2026-07-01

Recruiting

Early phase I

9

Inclusion Criteria: 1. Group Infantile Krabbe: Subjects who are going to be transplanted or have already been transplanted for asymptomatic infantile onset Krabbe disease with initial diagnosis based on: 1. Galactocerebrosidase (GALC) activity levels in leukocytes compatible with the diagnosis of infantile Krabbe disease; AND AT LEAST ONE OF THE FOLLOWING: 2. Psychosine levels predictive of infantile onset by Dried Blood Spot (DBS); OR 3. Imaging or neurophysiological findings consistent with Krabbe disease (CSF, MRI, NCV, ABR); OR 4. Two GALC mutations predictive to result in infantile onset phenotype. 2. Group Late Infantile Krabbe: Subjects who are going to be transplanted or have already been transplanted for symptomatic late infantile onset Krabbe with initial diagnosis based on: 1. Galactocerebrosidase (GALC) activity levels in leukocytes compatible with the diagnosis of late infantile Krabbe disease; AND AT LEAST ONE OF THE FOLLOWING: 2. Psychosine levels predictive of late infantile onset by DBS; OR 3. Imaging or neurophysiological findings consistent with Krabbe disease (CSF, MRI, NCV, ABR); OR 4. Two GALC mutations predictive to result in late infantile onset phenotype; OR 5. Neurological/developmental exam findings consistent with late infantile Krabbe disease 3. Participants must be considered candidates for HSCT or have received HSCT at least 21 days prior to dosing date 4. For patients already transplanted and followed for more than 3 months chimerism should reflect at least 30% of myeloid cells from the donor by month 3 post-transplant, from 30 to 10% between 3 months and one year post-transplant or 10% by one year post-transplant. 5. Participant must have adequate organ function at time of screening or evaluation as measured by: 1. Ejection fraction of \> 50% by echocardiogram or other appropriate study without evidence of pulmonary hypertension. 2. Pulmonary evaluation testing demonstrating resting pulse oximeter \> 95% on room air. 6. Absence of active aspiration 7. Participant'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 performed 8. Parent(s) and/or legal guardian able to comply with the clinical protocol Exclusion Criteria: 1. Immunoassay with total anti-AAVrh10 antibody titers of \>1:100. This criteria will not apply to children screened before they have received HSCT or for children who sign the inform consent within 60 days from HSCT. 2. History of prior treatment with a gene therapy product 3. Inability to actively move upper extremities against gravity 4. Grade 2 or higher abnormalities in LFTs, bilirubin, creatinine, white count, hemoglobin, platelets, PT/INR and PTT according to latest version of CTCAE 5. Presence of any neurocognitive deficit, motor deficit, or brain damage not attributable to Krabbe disease 6. Signs of active infections or disease from cytomegalovirus, adenovirus, EBV, hepatitis B or C, and HIV or other viruses excluding rhinovirus from RVP and asymptomatic norovirus presence in stool. Patients showing HIV positive results will be excluded from the study. 7. Active bacterial or fungal infection documented the preceding 7 days. 8. Presence of any contraindication for MRI or lumbar puncture (LP) 9. Use of any investigational product prior to study enrollment or current enrollment in another study that involves clinical interventions 10. Immunizations with live viruses in the 30 days prior to immune suppression 11. Active acute Graft Versus Host Disease (GvHD) Grade II or higher according to modified Glucksberg criteria (Przepiorka et al., 1995) or active, moderate or severe, chronic GvHD according to revised NIH criteria (Jagasia et al., 2015) 12. Any 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

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1', 'PHASE2'], 'designInfo': {'allocation': 'NON_RANDOMIZED', 'interventionModel': 'SEQUENTIAL', 'interventionModelDescription': 'Dose escalation study from a low dose to a high dose following safety review', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 9, 'type': 'ESTIMATED'}}

2024-04-26