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

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ClinicalTrials.gov Identifier: NCT05739643
Recruitment Status : Recruiting
First Posted : February 22, 2023
Last Update Posted : December 28, 2023
Sponsor:
Information provided by (Responsible Party):
Forge Biologics, Inc

Tracking Information
First Submitted Date  ICMJE February 13, 2023
First Posted Date  ICMJE February 22, 2023
Last Update Posted Date December 28, 2023
Actual Study Start Date  ICMJE February 3, 2023
Estimated Primary Completion Date July 2026   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 13, 2023)
Safety as assessed by incidence and severity of adverse events and serious adverse events that are attributed to FBX-101 [ Time Frame: 24 months ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 21, 2023)
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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: February 13, 2023)
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 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Gene Transfer Clinical Trial for Infantile and Late Infantile Krabbe Disease Treated Previously With HSCT
Official Title  ICMJE A Phase 1b Clinical Study of Intravenous AAVrh10 Vector Expressing GALC in Krabbe Subjects Who Previously Received Hematopoietic Stem Cell Transplantation (REKLAIM)
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.
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).
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE 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
Condition  ICMJE Krabbe Disease
Intervention  ICMJE 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
Study Arms  ICMJE
  • 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
    Intervention: Biological: FBX-101
  • 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
    Intervention: Biological: FBX-101
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: December 21, 2023)
9
Original Estimated Enrollment  ICMJE
 (submitted: February 13, 2023)
12
Estimated Study Completion Date  ICMJE July 2026
Estimated Primary Completion Date July 2026   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Michelle Salvo 380-239-2013 advocacy@forgebiologics.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05739643
Other Study ID Numbers  ICMJE FBX-101-REKLAIM
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party Forge Biologics, Inc
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Forge Biologics, Inc
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Forge Biologics, Inc
Verification Date December 2023

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP