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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05739643
Recruitment Status : Recruiting
First Posted : February 22, 2023
Last Update Posted : February 22, 2023
Sponsor:
Information provided by (Responsible Party):
Forge Biologics, Inc

Study Description
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Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Krabbe Disease Biological: FBX-101 Phase 1 Phase 2

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Dose escalation study from a low dose to a high dose following safety review
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1b Clinical Study of Intravenous AAVrh10 Vector Expressing GALC in Krabbe Subjects Who Previously Received Hematopoietic Stem Cell Transplantation (REKLAIM)
Actual Study Start Date : February 3, 2023
Estimated Primary Completion Date : December 2025
Estimated Study Completion Date : December 2025

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
Experimental: Cohort 1 - Low Dose FBX-101 (aka AAVrh.10-GALC)
Group 1: N=3 patients with Infantile Krabbe disease with previous HSCT will receive a single infusion at the low dose Group 2: N=3 patients with Late Infantile Krabbe disease with previous HSCT will receive a single infusion at the low dose
 Biological: 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.
Other Name: AAVrh.10-hGALC
Experimental: Cohort 2 - High Dose FBX-101 (aka AAVrh.10-GALC)
Group 1: N=3 patients with Infantile Krabbe disease with previous HSCT will receive a single infusion at the high dose Group 2: N=3 patients with Late Infantile Krabbe disease with previous HSCT will receive a single infusion at the high dose
 Biological: 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.
Other Name: AAVrh.10-hGALC


Outcome Measures
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Primary Outcome Measures :
  1. Safety as assessed by incidence and severity of adverse events and serious adverse events that are attributed to FBX-101 [ Time Frame: 24 months ]

Secondary Outcome Measures :
  1. Efficacy as assessed by improvement of gross motor function as measured longitudinally by Gross Motor Function Measure 88 (GMFM-88) compared to untreated patients of those receiving HSCT only [ Time Frame: 12 months and 24 months ]

Eligibility Criteria
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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Group 1: Subjects transplanted for infantile onset Krabbe disease (IKD onset <12 months) with initial diagnosis based on:

    1. 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:
    2. Elevated psychosine predictive of infantile onset disease ≥ 9 nmol/L; OR
    3. Imaging or neurophysiological findings (refer to Addendum 1) consistent with Krabbe disease (CSF, MRI, NCV, ABR); OR
    4. Two predicted pathogenic GALC mutations

  2. Group 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:

    1. 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:
    2. Elevated psychosine predictive of late infantile onset disease ≥ 1.5 nmol/L; OR
    3. Imaging or neurophysiological findings (refer to Addendum 1) consistent with Krabbe disease (CSF, MRI, NCV, ABR); OR
    4. Two predicted pathogenic GALC mutations; OR
    5. Neurological/developmental exam findings
  3. Participants must have received HSCT at least 90 days prior to dosing date
  4. At 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/mg
  5. 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
  6. 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
  2. History of prior treatment with a gene therapy product
  3. Inability to actively move upper extremities against gravity
  4. Grade 3 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 infection or disease from cytomegalovirus, adenovirus, EBV, hepatitis B or C, and HIV or other viruses
  7. Active bacterial or fungal infection
  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. Ejection fraction of <50% by echocardiogram or other appropriate study without evidence of pulmonary hypertension
  12. Active acute Graft Versus Host Disease (GvHD) Grade 2 or active extensive chronic GvHD
  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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05739643


Contacts
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Contact: Michelle Salvo 380-239-2013 advocacy@forgebiologics.com

Locations
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United States, Michigan
University of Michigan Hospitals - Michigan Medicine Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Mark Vander Lugt, MD    616-340-7643    marvande@med.umich.edu   
Contact: Bre'Anna Simpson    734-615-4630    sbreanna@med.umich.edu   
Principal Investigator: Mark Vander Lugt, MD         
Sponsors and Collaborators
Forge Biologics, Inc
More Information
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Publications:

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Responsible Party: Forge Biologics, Inc
ClinicalTrials.gov Identifier: NCT05739643    
Other Study ID Numbers: FBX-101-REKLAIM
First Posted: February 22, 2023    Key Record Dates
Last Update Posted: February 22, 2023
Last Verified: February 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Forge Biologics, Inc:
Leukodystrophy, Globoid Cell
Hereditary Central Nervous System Demyelinating Diseases
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Sphingolipidoses
Lysosomal Storage Diseases, Nervous System
 Leukoencephalopathies
Demyelinating Diseases
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lipidoses
Lipid Metabolism, Inborn Errors
Lysosomal Storage Diseases
Metabolic Diseases
Lipid Metabolism Disorders
Additional relevant MeSH terms:
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Leukodystrophy, Globoid Cell
Hereditary Central Nervous System Demyelinating Diseases
Brain Diseases, Metabolic, Inborn
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Sphingolipidoses
Lysosomal Storage Diseases, Nervous System
 Leukoencephalopathies
Demyelinating Diseases
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Lipidoses
Lipid Metabolism, Inborn Errors
Lysosomal Storage Diseases
Metabolic Diseases
Lipid Metabolism Disorders