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) (GALax-C)
- Conditions
- Early Infantile Krabbe DiseaseGloboid Cell Leukodystrophy1002742410012303
- Registration Number
- NL-OMON51988
- Lead Sponsor
- Passage Bio, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Pending
- Sex
- Not specified
- Target Recruitment
- 3
1. >= 1 month and <9 months of age at enrollment, and are presymptomatic or
symptomatic with first symptoms of Krabbe disease at <=6 months of age
2. Leukocyte GALC activity <=lower limit of normal (LLN)
3. Whole blood (dried blood spot) psychosine > 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
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
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>To assess the safety and tolerability of PBKR03 </p><br>
- Secondary Outcome Measures
Name Time Method <p>To assess the efficacy of PBKR03<br /><br>To assess the pharmacokinetics of PBKR03<br /><br>To assess the effects of PBKR03 on pharmacodynamic and disease biomarkers<br /><br>To assess the effects of PBKR03 on disease progression<br /><br>To assess the effects of PBKR03 on quality of life and healthcare resource<br /><br>utilization</p><br>