Gene Transfer Clinical Trial for Krabbe Disease (RESKUE)

April 10, 2024 updated by: Forge Biologics, Inc

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)

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

6

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • United States
    • California
      • Orange, California, United States, 92868
        • Children's Hospital of Orange County (CHOC)
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan Hospitals - Michigan Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year to 4 months (Child)

Accepts Healthy Volunteers

No

Description

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; AND AT LEAST ONE OF THE FOLLOWING:
    • Elevated psychosine levels predictive of infantile disease onset by DBS; OR
    • Imaging or neurophysiological findings consistent with Krabbe disease (CSF, MRI, NCV, ABR); OR
    • Two GALC mutations predictive to result in infantile onset phenotype.
  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) and a fully myeloablative reduced intensity/toxicity conditioning regimen (RIC/RTC) is/has been used
  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 > 95% 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 or any other condition that affects neurodevelopmental function
  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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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 Names:
  • 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 Names:
  • AAVrh.10-hGALC

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Safety as assessed by incidence and severity of adverse events and serious adverse events that are attributed to FBX-101.
Time Frame: 24 months
24 months
Safety as assessed by HSCT incident of engraftment.
Time Frame: 24 months
24 months

Secondary Outcome Measures

Outcome Measure
Time Frame
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
12 months and 24 months
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: 24 months
24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Forge Biologics, Inc

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 5, 2021

Primary Completion (Estimated)

July 1, 2024

Study Completion (Estimated)

July 1, 2024

Study Registration Dates

First Submitted

December 30, 2020

First Submitted That Met QC Criteria

December 30, 2020

First Posted (Actual)

January 5, 2021

Study Record Updates

Last Update Posted (Actual)

April 11, 2024

Last Update Submitted That Met QC Criteria

April 10, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FBX-101-RESKUE

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

There is no plan to share data

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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