Study to assess safety, tolerability and efficacy of PBKR03 in pediatric subjects with Krabbe disease (GALax-C)
- Conditions
- Krabbe disease (globoid cell leukodystrophy) is an autosomal recessive lysosomal storage disease (LSD) caused by mutations in the gene encoding the hydrolytic enzyme galactosylceramidase (galactocerebrosidaseGALC)MedDRA version: 20.0Level: PTClassification code 10023492Term: Krabbe's diseaseSystem Organ Class: 10010331 - Congenital, familial and genetic disordersTherapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
- Registration Number
- EUCTR2020-005229-95-NL
- Lead Sponsor
- Passage Bio, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 28
1. =1 month and <9 months of age at enrollment, either presymptomatic or symptomatic with first symptoms of Krabbe disease at =6 months of age
2. Leukocyte GALC activity below the lower limit of normal (LLN) of the testing central laboratory (e.g., <0.30 nmol/hour/mg protein )
3. Whole blood 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, 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 the available data, including relevant family history, must be consistent with a diagnosis of early infantile Krabbe disease.
5. Parents or the subject’s legally authorized representative (LAR) provide(s) written informed consent prior to any study-related procedures, including screening evaluations
6. Symptomatic subjects must exhibit a minimum level of neurological and developmental function that indicates they have the potential to benefit from treatment, at least with slowing or stabilization of their disease. In particular, the subject must demonstrate the following clinical features (when age-appropriate):
a. Thrusting of legs in play (Bayley motor scale, gross motor subset, item 1)
b. Lifting of head (Bayley motor scale, gross motor subset, item 3)
c. Eyes follow moving person (Bayley motor scale, fine motor subset, item 2)
d. Smiles in response to speaker’s attention (Bayley language scale, expressive, item 2)
Are the trial subjects under 18? yes
Number of subjects for this age range: 28
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
1. Any clinically significant neurocognitive deficit not attributable to KD
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 (= use of more than 12 h/day of BiPap, Cpap 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/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/epilepsy of infantile or childhood onset, other than febrile seizures
a. This does not exclude subjects with a family history of KD
6. Any contraindication to ICM admin procedure, including contraindications to fluoroscopic imaging, intrathecal 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.
7. Any contraindication to MRI or LP
8. Prior gene therapy.
9. Enrollment in any other clinical study with an investigational product within 4 weeks prior to Screening or within 5 half-lives of the investigational product used in that clinical study, whichever is longer
10. Prior HSCT
11. Receipt of a vaccine within 14 days prior to and up to 30 days after dosing
12. eGFR <60 mL/min/1.73 m2 based on creatinine, determined using the Bedside Schwartz equation
13. Hematological abnormalities:
a. Coagulopathy (INR > 1.5 or aPTT > 40 seconds)
b. Thrombocytopenia (platelet count < 100,000 per µL)
c. WBC <5.5 x 10^3 cells/µL
d. Hemoglobin <10 g/dL.
14. AST or ALT >3 x ULN or total bilirubin >1.5 x ULN.
15. Abnormal respiratory function:
a. Required suctioning in the absence of upper respiratory tract infection
b. Hypoxemia (oxygen [O2] saturation awake < 96% or O2 saturation asleep < 96%, without ventilation support) as assessed during screening. Ventilatory support defined as dependence on supplemental O2 or use of a ventilator or BiPap or Cpap machine.
16. Poor peripheral perfusion or temperature instability in the absence of intercurrent illness
17. Medical conditions or laboratory or vital sign abnormalities that would increase risk of complications from ICM injection, anesthesia,
fluoroscopy, LP, and/or MRI (Temp > 38°C, oxygen saturation < 95% on room air or baseline oxygen requirement, heart rate or respiratory rate
abnormal for age of the subject, abnormal blood pressure for age, evidence of infection)
18. Any condition (eg history of any disease, evidence of any current disease, any finding upon physical examination, or any laboratory abnormality) that, in the opinion of the Investigator, would interfere with evaluation of the investigational product or interpretation of subject safety or
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method