Early Infantile Krabbe Disease Globoid Cell Leukodystrophy
Conditions
Interventions
In order to more effectively deliver GALC to cells throughout the CNS while
minimizing procedure-related morbidity, AAV vector delivery into the CSF has
been evaluated.
PBKR03 to be administered b
Sponsors
Passage Bio, Inc.
Eligibility
Age
No minimum to 1 Years
Inclusion criteria
Inclusion criteria: 1. >= 1 month and 10 nM 4. Biallelic pathogenic GALC gene variants associated with early infantile Krabbe disease or variants classified as likely pathogenic (testing must be done at a Clinical Laboratory Improvement Amendments [CLIA] or CLIA-equivalent laboratory certified per local standard. If the GALC gene analysis is performed in the UK or the European Union (EU) a Conformité Européenne (CE) marked test will be used). See also Appendix 2 of Protocol, Classification of GALC Gene Variants. Note: Subjects without documentation of two pathogenic or likely pathogenic GALC variants but who meet all other inclusion criteria, including low GALC activity and high psychosine level, may be considered eligible for the study. In this case the totality of available data, including relevant family history, must be consistent with a diagnosis of early infantile Krabbe disease. For the full list of inclusion criteria see chapter 6.1 of the protocol
Exclusion criteria
Exclusion criteria: 1. Any clinically significant neurocognitive deficit not attributable to Krabbe disease 2. An acute illness requiring hospitalization within 30 days of enrollment that in the opinion of the investigator would interfere with the evaluation of the investigational product or interpretation of subject safety or study results. 3. History of chronic ventilation assisted respiratory support (defined as use of more than 12 hours/day of bilevel positive airway pressure, continuous positive airway pressure, or ventilator) or a need for tracheostomy as a result of their disease. Note: This does not exclude subjects who use respiratory vests. 4. Intractable seizure or uncontrolled epilepsy defined as having had an episode of status epilepticus, or seizures requiring hospitalization. a. This does not exclude subjects who have a history of staring spells that have not been associated with EEG findings 5. Family history of seizure disorders or epilepsy of infantile or childhood onset, other than febrile seizures a. This does not exclude subjects with a family history of Krabbe disease 6. Any contraindication to ICM administration procedure, including contraindications to fluoroscopic imaging, IT contrast and anesthesia, or any condition that would increase the risk of adverse outcomes from the ICM procedure, including but not limited to the presence of space occupying lesion causing mass effect or signs of increased intracranial pressure, non-communicating hydrocephalus, space-occupying lesion in the posterior fossa or foramen magnum, aberrant vascular anatomy such as a large midline posterior inferior cerebellar artery, venous anomaly such as a large midline cerebellar vein or occipital sinus, congenital anatomical abnormalities such as Chiari malformation.For the full list of exclusion criteria see chapter 6.2 of the protocol
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| To assess the safety and tolerability of PBKR03 | — |
Secondary
| Measure | Time frame |
|---|---|
| To assess the efficacy of PBKR03 To assess the pharmacokinetics of PBKR03 To assess the effects of PBKR03 on pharmacodynamic and disease biomarkers To assess the effects of PBKR03 on disease progression To assess the effects of PBKR03 on quality of life and healthcare resource utilization | — |
Countries
Netherlands
Outcome results
None listed