A Study of PBFT02 in Participants With FTD and Mutations in the Granulin Precursor (GRN) or C9ORF72 Genes
NCT ID: NCT04747431
Last Updated: 2025-12-31
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE1/PHASE2
30 participants
INTERVENTIONAL
2021-09-14
2031-08-31
Brief Summary
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Detailed Description
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PBFT02 will be studied in three cohorts of FTD-GRN participants and two cohorts of FTD-C9orf72 participants.
This is a 5-year study, with a 2-year main study, followed by a 3-year safety extension.
Conditions
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Keywords
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Study Design
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NON_RANDOMIZED
SEQUENTIAL
TREATMENT
NONE
Study Groups
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Cohort 1
Drug: PBFT02 Dose 1; Single dose of PBFT02, via intra cisterna magna
\*GC/g: gene copy per gram of estimated brain weight
PBFT02
PBFT02
Cohort 2, 3, 4 and 5
Drug: PBFT02 Dose 1 or 2; Single dose of PBFT02, via intra cisterna magna
\*GC/g: gene copy per gram of estimated brain weight
PBFT02
PBFT02
Interventions
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PBFT02
PBFT02
Eligibility Criteria
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Inclusion Criteria
2. Clinical diagnosis of frontotemporal dementia
3. Have a reliable informant / caregiver (and back-up informant / caregiver) who personally speaks with or sees the subject at least weekly
4. Living in the community (i.e., not in a nursing home); assisted living may be permitted at the discretion of the investigator
Exclusion Criteria
2. Previous treatment with any gene therapy. Any other therapies with the potential to alter PGRN levels must be washed out for at least 5 half-lives prior to entry into this study
3. Homozygous GRN mutation carrier (FTD-GRN Cohorts 1-3) or homozygous C9orf72 mutation carrier (FTD-C9orf72 Cohorts 4-5).
4. Rosen-modified Hachinski Ischemic Scale score \> 7
5. Known presence of a structural brain lesion (eg, tumor, cortical infarct) that could reasonably explain symptoms in a symptomatic subject
6. Known presence of an AD-causing mutation in PSEN1, PSEN2 or APP based on genetic testing history (if performed)
7. Previous history of Korsakoff encephalopathy, severe alcohol or substance dependence (within 5 years of onset of dementia), except where onset of increased alcohol consumption occurs at the time of FTD disease onset
8. History of untreated vitamin B12 deficiency
9. Presence of untreated hypothyroidism (thyroid stimulating hormone \[TSH\] \> ULN and free T4 \< LLN)
10. eGFR ≤ 30 ml/min (as calculated using the CKD-EPI equation)
11. Alanine aminotransferase \[ALT\] or aspartate aminotransferase \[AST\] \> 2 × ULN, or total bilirubin \> ULN)
12. Respiratory failure that requires supplemental oxygen, tracheostomy, or reliance on non-invasive ventilation for \>2 hours during waking hours
13. Inability to provide full consent or the lack of a legally authorized caregiver with adequate contact who can provide consent
14. Any contraindication to MRI or lumbar puncture (LP) (eg, local infection, history of thrombocytopenia, coagulopathy)
15. Any contraindication to the ICM administration procedure
16. Medical conditions or laboratory or vital sign abnormalities that would increase risk of complications from ICM injection, anesthesia, LP, and/or MRI (e.g., fever, hypoxia, tachycardia, or evidence of active infection)
17. Immunocompromised status
18. Peripheral axonal sensory neuropathy
19. Receipt of a vaccine within 14 days of dosing
20. A positive test result for human immunodeficiency virus (HIV), human T cell leukemia virus (HTLV) type 1 or type 2, or Hepatitis B or C; a Mycobacterium tuberculosis positive test within 1 year of or determined at screening
21. Malignant neoplasia (except localized skin cancer) or a documented history of hereditary cancer syndrome
22. Any concurrent disease that, in the opinion of the investigator, may cause cognitive impairment unrelated to GRN or C9orf72 mutations, including other causes of dementia, neurosyphilis, hydrocephalus, stroke, small vessel ischemic disease, uncontrolled hypothyroidism, or vitamin deficiency
23. Current or recent history of clinically significant suicidal ideation within the past 6 months
24. For women of childbearing potential, a positive serum pregnancy test at the screening visit, a positive serum result on Day 1 prior to administration of the investigational product, or unwillingness to have additional pregnancy tests during the study. Women of childbearing potential must use a highly effective method of birth control or engage in abstinence until 90 days postdose
25. Women who are breastfeeding
26. For sexually active men, unwillingness to use a medically accepted method of double-barrier contraception (such as a condom/diaphragm used with spermicide) or engage in abstinence from the date of screening until 90 days postdose
27. 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 put the subject at undue risk or would interfere with evaluation of the investigational product or interpretation of subject safety or study results
28. Any acute illness requiring hospitalization within 30 days of enrollment
29. Failure to meet the protocol-specified coagulation test criteria:
* Platelet count \> 100,000 per uL
* INR \< 1.5
* aPTT \< 40 seconds
30. Use of anticoagulants in the 2 weeks prior to screening
31. Hypersensitivity or contraindications to corticosteroid use
32. Known or suspected intolerance or hypersensitivity to PBFT02 or any of its ingredients or to closely related compounds
33. Any condition expected to increase risk of thrombosis
34. Hypersensitivity or contraindications to apixaban
Additional Criteria for FTD-C9orf72 (Cohorts 4-5) ONLY: Presence of concurrent ALS is permitted provided the following criteria are NOT met:
35. ALSFRS-R \< 35 at screening.
36. SVC \< 75% of predicted normal adjusted for sex, age, and height (from the sitting position).
37. Bulbar-onset ALS.
38. Current or anticipated need, in the opinion of the Investigator for a diaphragm pacing system (DPS) during the study period.
39. If taking riluzole or edaravone, participant's dose has not been stable for ≥ 30 days prior to Day 1 and/or dose adjustments are anticipated before the Day 60 study visit.
35 Years
75 Years
ALL
No
Sponsors
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Passage Bio, Inc.
INDUSTRY
Responsible Party
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Principal Investigators
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Tiffini Voss, MD, PhD
Role: STUDY_DIRECTOR
Passage Bio, Inc.
Locations
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Michigan Alzheimer's Disease Center
Ann Arbor, Michigan, United States
University of Pennsylvania
Philadelphia, Pennsylvania, United States
Vanderbilt University Medical Center
Nashville, Tennessee, United States
University of Texas at Houston
Houston, Texas, United States
Eastern Health-Box Hill Hospital
Melbourne, Victoria, Australia
Hospital das Clinicas da Universidade Federal de Minas Gerais (UFMG)
Minas Gerais, , Brazil
Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HCFMUSP)
São Paulo, , Brazil
University of Toronto, Toronto Western Hospital
Toronto, Ontario, Canada
Montreal Neurological Institute-Hospital
Montreal, Quebec, Canada
Centro Hospitalar e Universitário de Coimbra
Coimbra, , Portugal
Countries
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Central Contacts
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Facility Contacts
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Kiren A Chaudhry
Role: primary
Arijit K Bhaumik, CCRP
Role: backup
Alexandra Tavani
Role: primary
Catherine Cerroni
Role: primary
Omar Hasan
Role: primary
Claire McCarthy
Role: primary
Cassandra Yankoff
Role: backup
Leonardo Cruz de Souza, MD
Role: primary
Leonel Tadao Takada, MD
Role: primary
Luzia Lima Carreira
Role: backup
Behnaz Ghazanfari, MD
Role: primary
Elisabeth Sylvain
Role: primary
Mariana Gomes
Role: primary
Other Identifiers
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2020-004499-17
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
PBFT02-001
Identifier Type: -
Identifier Source: org_study_id