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Gene Transfer Clinical Trial for Infantile and Late Infantile Krabbe Disease Treated Previously 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 : April 11, 2024
Sponsor:
Information provided by (Responsible Party):
Forge Biologics, Inc

Brief Summary:
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. Data from 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

Detailed Description:
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).

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 9 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 : July 2026
Estimated Study Completion Date : July 2026


Arm Intervention/treatment
Experimental: 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
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)
N=3-6 patients with Infantile or Late Infantile Krabbe disease 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




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 PDMS-2, BOTMP2, or by GMFM-88, depending on the age, compared to patients receiving HSCT only [ Time Frame: 12 months and 24 months ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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 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

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: Kelly Bossola advocacy@forgebiologics.com

Locations
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United States, California
Children's Hospital of Orange County (CHOC) Recruiting
Orange, California, United States, 92868
Contact: Nina Movsesyan, PhD    714-509-3008    nmovsesyan@choc.org   
Contact: Raymond Wang, MD       rawang@choc.org   
Principal Investigator: Raymond Wang, MD         
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
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: April 11, 2024
Last Verified: April 2024
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