Gene Transfer Clinical Trial for Krabbe Disease (RESKUE)

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

Tracking Information

• First Submitted Date: December 30, 2020
• First Posted Date: January 5, 2021
• Last Update Posted Date: January 7, 2021
• Estimated Study Start Date: January 2021
• Estimated Primary Completion Date: April 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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 (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 ]

Current Secondary Outcome Measures (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 (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: Gene Transfer Clinical Trial for Krabbe Disease
• 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)
• 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: Interventional
• Study Phase: Phase 1; Phase 2

Study Design

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: Krabbe Disease

Intervention

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

• 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

Recruitment Information

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

Eligibility Criteria

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

• Sexes Eligible for Study: All

• Ages: up to 12 Months (Child)
• Accepts Healthy Volunteers: No

Contacts

Contact: Medical Affairs; 3305549257; medicalaffairs@forgebiologics.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04693598
• Other Study ID Numbers: 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

• Plan to Share IPD: No
• Plan Description: There is no plan to share data

• Responsible Party: Forge Biologics, Inc
• Study Sponsor: Forge Biologics, Inc
• Collaborators: Not Provided

Investigators

• 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