Study of Safety, Tolerability and Efficacy of PBKR03 in Pediatric Subj
Research type
Research Study
Full title
A Phase 1/2 Open-Label, Multicenter, Dose Ranging and Confirmatory Study to Assess the Safety, Tolerability and Efficacy of PBKR03 Administered to Pediatric Subjects with Early Infantile Krabbe Disease (Globoid Cell Leukodystrophy)
IRAS ID
293224
Contact name
Simon Allan Jones
Contact email
Sponsor organisation
Passage Bio, Inc.
Eudract number
2020-005229-95
Clinicaltrials.gov Identifier
27113, IND Number
Duration of Study in the UK
8 years, 6 months, days
Research summary
Krabbe disease (globoid cell leukodystrophy)an inherited disease, is one of a family of diseases referred to as lysosomal storage diseases, the child affected has mutations in the gene which codes for a specific enzyme called galactosylceramidase (galactocerebrosidase; GALC). GALC assists in breaking down chemicals. Because GALC does not work properly, specific chemicals cannot be broken down, leading to a build-up in the body. PBKR03 brings GALC into the cells using a viral vector (ie, a virus that has been changed so that it no longer causes diseases) called adeno-associated virus (AAV). Krabbe disease has a variable presentation that is classified, based on age of onset, into early/late infantile, juvenile and adult forms. The early infantile is the most common, most aggressive, and best-characterized form of the disease and if untreated, is associated with numerous clinical sequelae and poor survival. The only disease modifying treatment available is hematopoietic stem cell transplant (HSCT). Due to limited efficacy of HSCT in patients that are candidates for HSCT, many centers do not offer HSCT to any Krabbe disease patients, including early infantile patients that have been identified prior to onset of symptoms, e.g. in siblings of Krabbe disease patients. Outside the US, HSCT is generally not considered to be a viable option and is not offered for asymptomatic or symptomatic patients. Therefore, there is an ongoing need for alternatives to HSCT.
Passage Bio has manufactured a gene therapy called PBKR03, which carries a normal copy of the GALC gene. It is thought that if a copy of the normal gene is given to patients with Krabbe disease, then the disease may be treated.
The study will test the theory that administered of PBKR03 by intra-cisterna magna (ICM) injection to participants with early infantile Krabbe disease aged >/=1 to <9 months will be safe and well tolerated, and will increase brain and peripheral GALC enzyme activity (to slow or stabilize disease progression and potentially improve developmental progression and quality of life). This single study includes 2 components, 1) a first-in-human dose ranging phase and 2) an expanded, confirmatory phase.
One UK Site will be participating in the Study. Safety will be monitored through the entire study period including independent group of experts will determine if the first dose shows no safety concerns.REC name
London - West London & GTAC Research Ethics Committee
REC reference
21/LO/0129
Date of REC Opinion
20 Apr 2021
REC opinion
Further Information Favourable Opinion