Gene Transfer Clinical Trial for Infantile and Late Infantile Krabbe Disease Treated Previously With HSCT

NCT ID: NCT05739643

Last Updated: 2025-11-20

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

9 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-02-03

Study Completion Date

2026-11-30

Brief Summary

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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 more than 21 days of the HSCT (UCBT preferred HSCT source). Data from previously transplanted patients with infantile and late infantile Krabbe disease will be used as a comparator group.

Detailed Description

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The FBX-101-REKLAIM study has been modified on Q4 2023 to allow a broader patient recruitment of infantile and late infantile Krabbe patients. The updated REKLAIM study merges the recruitment populations of the previous FBX-101-RESKUE clinical trial (NCT04693598) and the FBX-101-REKLAIM clinical trial (NCT05739643).

Conditions

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Krabbe Disease

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Dose escalation study from a low dose to a high dose following safety review
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Cohort 1 - Low Dose FBX-101 (aka AAVrh.10-GALC)

N=3 patients with Infantile or Late Infantile Krabbe disease will receive a single infusion at the low dose

Group Type EXPERIMENTAL

FBX-101

Intervention Type BIOLOGICAL

A replication-deficient adeno-associated virus gene transfer vector expressing the human galactocerebrosidase (GALC) cDNA will be delivered one-time through a venous catheter inserted into a peripheral limb vein.

Cohort 2 - High Dose FBX-101 (aka AAVrh.10-GALC)

N=3-6 patients with Infantile or Late Infantile Krabbe disease will receive a single infusion at the high dose

Group Type EXPERIMENTAL

FBX-101

Intervention Type BIOLOGICAL

A replication-deficient adeno-associated virus gene transfer vector expressing the human galactocerebrosidase (GALC) cDNA will be delivered one-time through a venous catheter inserted into a peripheral limb vein.

Interventions

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FBX-101

A replication-deficient adeno-associated virus gene transfer vector expressing the human galactocerebrosidase (GALC) cDNA will be delivered one-time through a venous catheter inserted into a peripheral limb vein.

Intervention Type BIOLOGICAL

Other Intervention Names

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AAVrh.10-hGALC

Eligibility Criteria

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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-AAV10 antibody titers of \>1:100. This criterion will not apply to children screened before they have received HSCT or for children who sign the inform consent within 6 months from HSCT. In children who test positive to anti-AAV10 antibody with titers of \>1:100 under this exception, the ISR regime proposed by the PI and approved/modified by the ISR committee may include immunosuppressive drugs that prevent the potential development of a secondary immune response to AAVrh10 after FBX-101 administration.
2. History of prior treatment with a gene therapy product
3. Motor function evaluated by age with PDMS-II by a study physical therapist:

a. Inability to hold head for patients older than 5 months; b. Inability to sit independently for patients older than 12 months; c. Inability to walk with assistance for patients older than 24 months.
5. Grade 2 or higher abnormalities in LFTs, bilirubin, creatinine, white count, hemoglobin, platelets, PT/INR and PTT according to latest version of CTCAE
6. Presence of any neurocognitive deficit, motor deficit, or brain damage not attributable to Krabbe disease
7. 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.
8. Active bacterial or fungal infection documented the preceding 7 days.
9. Presence of any contraindication for MRI or lumbar puncture (LP)
10. Use of any investigational product prior to study enrollment or current enrollment in another study that involves clinical interventions
11. Immunizations with live viruses in the 30 days prior to immune suppression
12. 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)
13. 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
Maximum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Forge Biologics, Inc

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Children's Hospital of Orange County (CHOC)

Orange, California, United States

Site Status

University of Michigan Hospitals - Michigan Medicine

Ann Arbor, Michigan, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

Countries

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United States

References

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Wright MD, Poe MD, DeRenzo A, Haldal S, Escolar ML. Developmental outcomes of cord blood transplantation for Krabbe disease: A 15-year study. Neurology. 2017 Sep 26;89(13):1365-1372. doi: 10.1212/WNL.0000000000004418. Epub 2017 Aug 30.

Reference Type BACKGROUND
PMID: 28855403 (View on PubMed)

Gupta A, Poe MD, Styner MA, Panigrahy A, Escolar ML. Regional differences in fiber tractography predict neurodevelopmental outcomes in neonates with infantile Krabbe disease. Neuroimage Clin. 2014 Sep 26;7:792-8. doi: 10.1016/j.nicl.2014.09.014. eCollection 2015.

Reference Type BACKGROUND
PMID: 25844309 (View on PubMed)

Bascou N, DeRenzo A, Poe MD, Escolar ML. A prospective natural history study of Krabbe disease in a patient cohort with onset between 6 months and 3 years of life. Orphanet J Rare Dis. 2018 Aug 9;13(1):126. doi: 10.1186/s13023-018-0872-9.

Reference Type BACKGROUND
PMID: 30089515 (View on PubMed)

Beltran-Quintero ML, Bascou NA, Poe MD, Wenger DA, Saavedra-Matiz CA, Nichols MJ, Escolar ML. Early progression of Krabbe disease in patients with symptom onset between 0 and 5 months. Orphanet J Rare Dis. 2019 Feb 18;14(1):46. doi: 10.1186/s13023-019-1018-4.

Reference Type BACKGROUND
PMID: 30777126 (View on PubMed)

Escolar ML, Poe MD, Provenzale JM, Richards KC, Allison J, Wood S, Wenger DA, Pietryga D, Wall D, Champagne M, Morse R, Krivit W, Kurtzberg J. Transplantation of umbilical-cord blood in babies with infantile Krabbe's disease. N Engl J Med. 2005 May 19;352(20):2069-81. doi: 10.1056/NEJMoa042604.

Reference Type BACKGROUND
PMID: 15901860 (View on PubMed)

Escolar ML, West T, Dallavecchia A, Poe MD, LaPoint K. Clinical management of Krabbe disease. J Neurosci Res. 2016 Nov;94(11):1118-25. doi: 10.1002/jnr.23891.

Reference Type BACKGROUND
PMID: 27638597 (View on PubMed)

Rafi MA, Luzi P, Wenger DA. Conditions for combining gene therapy with bone marrow transplantation in murine Krabbe disease. Bioimpacts. 2020;10(2):105-115. doi: 10.34172/bi.2020.13. Epub 2020 Mar 24.

Reference Type BACKGROUND
PMID: 32363154 (View on PubMed)

Yoon IC, Bascou NA, Poe MD, Szabolcs P, Escolar ML. Long-term neurodevelopmental outcomes of hematopoietic stem cell transplantation for late-infantile Krabbe disease. Blood. 2021 Apr 1;137(13):1719-1730. doi: 10.1182/blood.2020005477.

Reference Type BACKGROUND
PMID: 33150395 (View on PubMed)

Escolar ML, Poe MD, Smith JK, Gilmore JH, Kurtzberg J, Lin W, Styner M. Diffusion tensor imaging detects abnormalities in the corticospinal tracts of neonates with infantile Krabbe disease. AJNR Am J Neuroradiol. 2009 May;30(5):1017-21. doi: 10.3174/ajnr.A1476. Epub 2009 Apr 22.

Reference Type BACKGROUND
PMID: 19386732 (View on PubMed)

Bradbury AM, Bagel J, Swain G, Miyadera K, Pesayco JP, Assenmacher CA, Brisson B, Hendricks I, Wang XH, Herbst Z, Pyne N, Odonnell P, Shelton GD, Gelb M, Hackett N, Szabolcs P, Vite CH, Escolar M. Combination HSCT and intravenous AAV-mediated gene therapy in a canine model proves pivotal for translation of Krabbe disease therapy. Mol Ther. 2024 Jan 3;32(1):44-58. doi: 10.1016/j.ymthe.2023.11.014. Epub 2023 Nov 11.

Reference Type BACKGROUND
PMID: 37952085 (View on PubMed)

Greco MR, Lopez MA, Beltran-Quintero ML, Tuc Bengur E, Poe MD, Escolar ML. Infantile Krabbe disease (0-12 months), progression, and recommended endpoints for clinical trials. Ann Clin Transl Neurol. 2024 Dec;11(12):3064-3080. doi: 10.1002/acn3.52114. Epub 2024 Nov 5.

Reference Type RESULT
PMID: 39499628 (View on PubMed)

Other Identifiers

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FBX-101-REKLAIM

Identifier Type: -

Identifier Source: org_study_id

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