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Gene Transfer Clinical Trial for Krabbe Disease (RESKUE)

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ClinicalTrials.gov Identifier: NCT04693598
Recruitment Status : Not yet recruiting
First Posted : January 5, 2021
Last Update Posted : January 7, 2021
Sponsor:
Information provided by (Responsible Party):
Forge Biologics, Inc

Tracking Information
First Submitted Date  ICMJE December 30, 2020
First Posted Date  ICMJE January 5, 2021
Last Update Posted Date January 7, 2021
Estimated Study Start Date  ICMJE January 2021
Estimated Primary Completion Date April 2023   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 5, 2021)
  • Safety as assessed by less than 3 incidents of organ specific AEs/SAEs at Grade 3 or higher based on CTCAE criteria attributed to the AAV administration. [ Time Frame: 12 months ]
  • Safety as assessed by lack of HSCT engraftment. [ Time Frame: 12 months ]
Original Primary Outcome Measures  ICMJE
 (submitted: December 30, 2020)
  • Safety as assessed by less than 3 incidents of organ specific AEs/SAEs at Grade 3 or higher based on CTCAE criteria attributed to the AAV administration [ Time Frame: 12 months ]
  • Safety as assessed by lack of HSCT engraftment [ Time Frame: 12 months ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 5, 2021)
  • Efficacy as assessed by improvement of the probability to achieve independent sitting compared to patients receiving HSCT. [ Time Frame: 24 months ]
  • Efficacy as assessed by improvement of gross motor function as measured by PDMS above a functional age equivalent of 12 months by 2 years post treatment. [ Time Frame: 24 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: December 30, 2020)
  • Efficacy as assessed by improvement of the probability to achieve independent sitting compared to patients receiving HSCT [ Time Frame: 24 months ]
  • Efficacy as assessed by improvement of gross motor function as measured by PDMS above a functional age equivalent of 12 months by 2 years post treatment [ Time Frame: 24 months ]
Current Other Pre-specified Outcome Measures
 (submitted: January 5, 2021)
  • Exploratory endpoint as assessed by change in motor function as measured by GMFM88 and Adaptive Behavior compared to patients receiving HSCT only. [ Time Frame: 12 months and 24 months ]
  • Exploratory endpoint as assessed by change in auditory brainstem responses compared to patients receiving HSCT only. [ Time Frame: 12 months and 24 months ]
    The brainstem auditory evoked responses are considered abnormal if either the interpeak latency of waves I to V is prolonged or if any of the obligate wave forms (I, III, or V) are missing.
  • Exploratory endpoint as assessed by change in peripheral nerve conduction velocity compared to patients receiving HSCT only. [ Time Frame: 24 months ]
  • Exploratory endpoint as assessed by change in brain MRI as measured by DTI compared to patients receiving HSCT only. [ Time Frame: 12 months and 24 months ]
  • Exploratory endpoint as assessed by reduced diseased manifestation using biomarkers measuring reduction of psychosine levels and increase in GALC enzyme activities in the blood compared to patients receiving HSCT only. [ Time Frame: 12 months and 24 months ]
Original Other Pre-specified Outcome Measures
 (submitted: December 30, 2020)
  • Exploratory endpoint as assessed by improvement in motor function as measured by GMFM88, and Adaptive Behavior compared to patients receiving HSCT only [ Time Frame: 12 months and 24 months ]
  • Exploratory endpoint as assessed by improvement in auditory brainstem responses compared to patients receiving HSCT only [ Time Frame: 12 months and 24 months ]
  • Exploratory endpoint as assessed by improvement in peripheral nerve conduction velocity compared to patients receiving HSCT only [ Time Frame: 24 months ]
  • Exploratory endpoint as assessed by improvement in brain MRI as measured by DTI compared to patients receiving HSCT only [ Time Frame: 12 months and 24 months ]
  • Exploratory endpoint as assessed by reduced diseased manifestation using biomarkers measuring reduction of psychosine levels and increase in GALC enzyme activities in the blood compared to patients receiving HSCT only [ Time Frame: 12 months and 24 months ]
 
Descriptive Information
Brief Title  ICMJE Gene Transfer Clinical Trial for Krabbe Disease
Official Title  ICMJE 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)
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 compared as a control group.
Detailed Description Not Provided
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)
    Participants will receive a single infusion at the lower dose (N=3 participants)
    Intervention: Biological: FBX-101
  • Experimental: Cohort 2 - High Dose FBX-101 (aka AAVrh.10-GALC)
    Participants will receive a single infusion at the higher dose (N=3 participants)
    Intervention: Biological: FBX-101
Publications * Not Provided

*   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 Not yet recruiting
Estimated Enrollment  ICMJE
 (submitted: December 30, 2020)
6
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 2023
Estimated Primary Completion Date April 2023   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

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

    • Galactocerebrosidase (GALC) activity < 0.20 nmol/h/mg protein in leukocytes; 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)
  4. Participant's parent 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. Participants must have a 4/6, 5/6 or 6/6 HLA matched UCB unit available with a pre-cryopreservation total nucleated cell dose of ≥ 5 x 10^7 cells/kg
  7. Participant must have adequate organ function at time of screening as measured by:

    • Creatinine ≤ 0.6 mg/dL and creatinine clearance ≥ 60 mL/min/1.73 m2 by nuclear medicine GFR
    • 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 allogeneic HCT within 4 months
  2. History of prior treatment with a gene therapy product
  3. Presence of major congenital anomaly affecting the neurological system
  4. Presence of any neurocognitive deficit not attributable to Krabbe disease
  5. Premature birth at less than 35 weeks' gestation
  6. Active aspiration
  7. Signs of infection or disease from active cytomegalovirus, adenovirus or other viruses
  8. HIV positive
  9. Uncontrolled and progressive bacterial, viral, or fungal infection.
  10. Presence of any contraindication for MRI
  11. Use of any investigational product prior to study enrollment or current enrollment in another study that involves clinical interventions
  12. Any other medical condition, serious intercurrent illness, 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 up to 12 Months   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Medical Affairs 3305549257 medicalaffairs@forgebiologics.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04693598
Other Study ID Numbers  ICMJE FBX-101
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
Plan Description: There is no plan to share data
Responsible Party Forge Biologics, Inc
Study Sponsor  ICMJE Forge Biologics, Inc
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Jessie Barnum, MD Div. of Blood & Marrow Transplantation & Cellular Therapies, UPMC Children's Hospital of Pittsburgh
PRS Account Forge Biologics, Inc
Verification Date January 2021

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