Study of Safety Tolerability and Efficacy of PBGM01 in Pediatric Subjects With GM1 Gangliosidosis

  • End date
    Feb 19, 2029
  • participants needed
  • sponsor
    Passage Bio, Inc.
Updated on 22 August 2021


PBGM01 is a gene therapy for GM1 gangliosidosis intended to deliver a functional copy of the GLB1 gene to the brain and peripheral tissues. This study will assess in a 2-stage design the safety, tolerability and efficacy of this treatment in patients with early onset infantile (Type 1) and late onset infantile (Type 2a) GM1 gangliosidosis. Results from the Type 1 and Type 2a groups will be assessed separately.


PBGM01 is an adeno-associated viral vector serotype Hu68 carrying GLB1, the gene encoding for human beta-galactosidase, formulated as a solution for injection into the cisterna magna. This is a global interventional, multicenter, single-arm, dose escalation, adaptive design study of PBGM01 delivered as a one-time dose administered into the cisterna magna to patients with infantile GM1 gangliosidosis. There are two infantile subtypes of GM1 gangliosidosis: early onset infantile (Type 1) and late onset infantile (Type 2a) which are defined by the age of onset of disease symptoms.

Early Onset Infantile (Type 1):

  • Onset <6 months of age
  • Age at enrollment: >4 to <24 months of age

Late Onset Infantile (Type 2a):

  • Onset >6 to 18 months of age
  • Age at enrollment: >6 to <36 months of age (except Cohort 1 will be >12 to <36 months of age)

In Part 1 of the study, two dose levels of PBGM01 will be studied separately in patients with either Type 1 or Type 2a GM1 gangliosidosis (see table below). The cohorts for patients with Type 1 and Type 2a will be assessed independently from each other. Part 1 will enroll a total of four cohorts, enrolled sequentially with separate dose-escalation cohorts for Type 1 GM1 and Type 2a GM1. Enrollment will initiate in Cohort 1. Following completion of Cohort 1, simultaneous enrollment in Cohort 2 and Cohort 3 will occur. Cohort 4 will follow completion of cohort 3.

Part 2 of the study will test the safety and efficacy of PBGM01 in confirmatory cohorts for Types 1 and Type 2a GM1 gangliosidosis with a dose chosen based on the data obtained in part 1 of the study. This will be a 2-year study with a 3-year safety extension.

Condition GM1 gangliosidosis
Treatment PBGM01
Clinical Study IdentifierNCT04713475
SponsorPassage Bio, Inc.
Last Modified on22 August 2021


Yes No Not Sure

Inclusion Criteria

All Patients: Documented GM1 gangliosidosis diagnosis based on genotyping confirming 2 mutations in the GLB1 gene and documented deficiency of beta-galactosidase enzyme by laboratory testing
Age: 4 to 36 months (first cohort will be 12-36 months)
Early onset infantile (Type 1): Subjects who have signs and/or symptoms of GM1 gangliosidosis that started at or before 6 months of age and have specific developmental milestones remaining
Late onset infantile (Type 2a): Subjects who have signs and/or symptoms of GM1 gangliosidosis that started between 6 and 18 months of age and have specific developmental milestones remaining

Exclusion Criteria

Any clinically significant neurocognitive deficit not attributable to GM1 gangliosidosis or any other condition that may, in the opinion of the investigator, confound interpretation of study results
If a subject had an acute illness requiring hospitalization within 30 days of enrollment, the history must be discussed with the sponsor's medical monitor before allowing the subject to be enrolled
History of ventilation assisted respiratory support or a need for tracheostomy as a result of their disease
Intractable seizure or uncontrolled epilepsy defined as having had an episode of status epilepticus, or seizures requiring hospitalization within 30 days prior to dosing of PBGM01
Any contraindication to the ICM administration procedure, including contraindications to fluoroscopic imaging 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 a space occupying lesion causing mass effects or signs of increased intracranial pressure, space occupying lesion in the posterior fossa or foramen magnum, aberrant vascular anatomy such as a large midline posterior inferior cerebellar artery, aberrant venous anatomy such as a large cerebellar vein or occipital sinus, or congenital anatomical abnormalities such as a Chiari malformation
Any contraindication to MRI or lumbar puncture (LP)
Prior gene therapy
Use of miglustat within 48 hours prior to dosing of PBGM01. The use of miglustat is prohibited throughout the study
Use of enzyme replacement therapy or other investigational therapy within 5 half-lives prior to dosing of PBGM01. The use of enzyme replacement is prohibited throughout the study
Receipt of a vaccine within 14 days of dosing
Estimate glomerular filtration rate (eGFR) <30 mL/minute based on creatinine
Coagulopathy (INR > 1.5) or activated partial thromboplastin time [aPTT] > 40 seconds
Thrombocytopenia (platelet count < 100,000 per L
AST or ALT > 3 times the upper limit of normal (ULN) or total bilirubin > 1.5x ULN
Cardiomyopathy (screening troponin level above the ULN)
Peripheral neuropathy
Medical conditions or laboratory or vital sign abnormalities that would increase risk of complications from intra-cisterna magna injection, anesthesia, fluoroscopy, LP, and/or MRI including temperature over 38C, oxygen saturation below 95% on room air or baseline oxygen requirement, heart rate or respiratory rate abnormal for age of the subject, abnormal blood pressure for age, or evidence of infection
Any condition (e.g., 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 put the subject at undue risk during the administration procedure or would interfere with evaluation of PBGM01 or interpretation of subject safety or study results
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