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Gene Transfer Clinical Trial for Krabbe Disease (RESKUE)

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04693598
Recruitment Status : Active, not recruiting
First Posted : January 5, 2021
Last Update Posted : July 19, 2022
Sponsor:
Information provided by (Responsible Party):
Forge Biologics, Inc

Brief Summary:
This is a nonblinded, non-randomized dose escalation study of intravenous AAVrh10 after hematopoietic stem cell transplantation (HSCT) in which subjects will receive standard of care hematopoietic cell transplantation for Krabbe disease, followed by a single infusion of an adeno-associated virus gene therapy product. Extensive natural history subjects will be used to compare as control group.

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 6 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 1/2 Clinical Study of Intravenous Gene Transfer With an AAVrh10 Vector Expressing GALC in Krabbe Subjects Receiving Hematopoietic Stem Cell Transplantation (RESKUE)
Actual Study Start Date : November 5, 2021
Estimated Primary Completion Date : December 2024
Estimated Study Completion Date : December 2024


Arm Intervention/treatment
Experimental: Cohort 1 - Low Dose FBX-101 (aka AAVrh.10-GALC)
Participants will receive a single infusion at the lower dose (N=3 participants)
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)
Participants will receive a single infusion at the higher dose (N=3 participants)
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 ]
  2. Safety as assessed by HSCT incident of engraftment. [ Time Frame: 24 months ]

Secondary Outcome Measures :
  1. Efficacy as assessed by improvement of probability to achieve independent sitting compared to untreated patients or those receiving HSCT only. [ Time Frame: 12 months and 24 months ]
  2. Efficacy as assessed by improvement of gross motor function as measured by Peabody Developmental Motor Scale 2nd Edition (PDMS-2) above a functional age equivalent of 12 months compared to untreated patients or those receiving HSCT only [ Time Frame: 12 months and 24 months ]


Information from the National Library of Medicine

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Ages Eligible for Study:   1 Day to 12 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Diagnosis of infantile Krabbe disease, characterized by the following criteria outlined below:

    • Galactocerebrosidase (GALC) activity levels in leukocytes compatible with the diagnosis of Krabbe disease according to the lab releasing the results; AND AT LEAST ONE OF THE FOLLOWING:
    • Elevated psychosine predictive of infantile disease ≥ 9.0 nmol/L; OR
    • Imaging or neurophysiological findings consistent with Krabbe disease (CSF, MRI, NCV, ABR); OR
    • Two predicted pathogenic GALC mutations.
  2. Age at the time of screening: 1 day to 12 months
  3. Participant has been deemed eligible for treatment with HSCT (standard of care) or is within two weeks of HSC infusion
  4. Participant's parents or legal guardian consents to participate in the study and provides informed consent according to IRB guidelines prior to any study procedures being performed
  5. Parent(s) and/or legal guardian able to comply with the clinical protocol
  6. Participant must have adequate organ function at time of screening as measured by:

    • Creatinine ≤ 1.5x upper limit of age appropriate normal and creatinine clearance ≥ 60 mL/min/1.73 m2
    • Hepatic transaminases (ALT/AST) ≤ 2x age related upper limit of normal
    • Ejection fraction of > 50% by echocardiogram or other appropriate study without evidence of pulmonary hypertension.
    • Pulmonary evaluation testing demonstrating resting pulse oximeter > 92% on room air
    • Coagulation tests within 110% of normal ranges for age. (PT/INR and PTT)

Exclusion Criteria:

  1. History of prior treatment with a gene therapy product
  2. Presence of major congenital anomaly affecting the neurological system
  3. Presence of any neurocognitive deficit or brain damage not attributable to Krabbe disease
  4. Active aspiration
  5. Signs of active infection or disease from cytomegalovirus, adenovirus or other viruses
  6. HIV positive
  7. Uncontrolled and progressive bacterial or fungal infection.
  8. Presence of any contraindication for MRI
  9. Use of any investigational product prior to study enrollment or current enrollment in another study that involves clinical interventions
  10. Any other medical condition, serious intercurrent illness, or extenuating circumstance that, in the opinion of the PI, would preclude participation in the study
  11. Ongoing veno-occlusive disease (VOD) as determined by liver ultrasound (moderate ascites and static or retrograde portal vein flow) the day before FBX-101 infusion.

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): NCT04693598


Locations
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United States, Michigan
University of Michigan Hospitals - Michigan Medicine
Ann Arbor, Michigan, United States, 48109
United States, Pennsylvania
UPMC Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15224
Sponsors and Collaborators
Forge Biologics, Inc
Additional Information:
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Responsible Party: Forge Biologics, Inc
ClinicalTrials.gov Identifier: NCT04693598    
Other Study ID Numbers: FBX-101-RESKUE
First Posted: January 5, 2021    Key Record Dates
Last Update Posted: July 19, 2022
Last Verified: July 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: There is no plan to share data

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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:
Lysosomal Storage Disorder
Globoid Cell Leukodystrophy
Leukodystrophy
GALC
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