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)
- Conditions
- Krabbe DiseaseMedDRA version: 20.0Level: PTClassification code: 10023492Term: Krabbe's disease Class: 100000004850Therapeutic area: Diseases [C] - Nervous System Diseases [C10]
- Registration Number
- CTIS2023-504900-28-00
- Lead Sponsor
- Forge Biologics Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 6
Diagnosis of infantile Krabbe disease, characterized by the following criteria: a. Galactocerebrosidase (GALC) activity levels in leukocytes compatible with the diagnosis of Krabbe disease; AND AT LEAST ONE OF THE FOLLOWING: b. Elevated psychosine levels predictive of infantile onset by DBS; OR c. Imaging or neurophysiological findings consistent with Krabbe disease (CSF, MRI, NCV, ABR, refer to Addendum 1); OR, d. Two GALC mutations predictive to result in infantile onset phenotype, Age at the time of screening: 1 day to 12 months, 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, 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, Parent(s) and/or legal guardian able to comply with the clinical protocol, Participant must have adequate organ function at time of screening or evaluation as measured by: a. Creatinine =1.5× of upper limit of age appropriate normal and creatinine clearance = 60 mL/min/1.73 m2; b. Hepatic transaminases (ALT/AST) = 2 x age related upper limit of normal; c. Ejection fraction of > 50% by echocardiogram or other appropriate study without evidence of pulmonary hypertension; d. Pulmonary evaluation testing demonstrating resting pulse oximeter > 95% on room air; e. Coagulation tests within 110% of normal ranges for age. (PT/INR and PTT)
History of prior treatment with a gene therapy product, Any other medical condition, serious intercurrent illness, or extenuating circumstance that, in the opinion of the PI, would preclude participation in the study, 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, Presence of major congenital anomaly or any other condition that affects neurodevelopmental function, Presence of any neurocognitive deficit or brain damage not attributable to Krabbe disease, Active aspiration, Signs of active infection or disease from cytomegalovirus, adenovirus or other viruses, HIV positive, Uncontrolled and progressive bacterial or fungal infection, Presence of any contraindication for MRI, Use of any investigational product prior to study enrollment or current enrollment in another study that involves clinical interventions
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: The primary objective of this clinical trial is to show that the investigational product, AAVrh.10-hGALC, is safe for administration to infantile Krabbe subjects when delivered intravenously 21 to 60 days following stem cell transplant.;Secondary Objective: The secondary objective is to collect evidence of possible therapeutic benefit of this treatment regimen.;Primary end point(s): Incidence and severity of adverse events and serious adverse events that are attributed to FBX-101, HSCT incident of engraftment
- Secondary Outcome Measures
Name Time Method Secondary end point(s):Improvement of probability to achieve independent sitting compared to untreated patients or those receiving HSCT only at one year and two years post gene therapy;Secondary end point(s):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, at 2 years post gene therapy