for people ages 35-75 (full criteria)
at San Francisco, California and other locations
study started
estimated completion



PBFT02 is a gene therapy for frontotemporal dementia intended to deliver a functional copy of the GRN gene to the brain. This study will assess the safety, tolerability and efficacy of this treatment in patients with frontotemporal dementia and mutations in the progranulin gene (FTD-GRN).

Official Title

A Phase 1b Open-Label, Multicenter, Dose-Escalation Study to Assess the Safety, Tolerability, and Pharmacodynamic Effects of a Single Dose of PBFT02 Delivered Into the Cisterna Magna of Adult Subjects With Frontotemporal Dementia and Mutations in the Progranulin Gene


PBFT02 is an adeno-associated viral vector serotype 1 carrying GRN, the gene encoding for human progranulin, formulated as a solution for injection into the cisterna magna. This is a global interventional, multicenter, open-label, single-arm, dose-escalation study of PBFT02 delivered as a one-time dose administered into the cisterna magna to patients with FTD-GRN. Subjects aged ≥ 35 and ≤ 75 years with early symptomatic FTD-GRN may be enrolled into the study. Two dose levels of PBFT02 will be studied in patients with FTD-GRN. The study will sequentially enroll 2 cohorts. An optional third dose level cohort may be enrolled based on the results of the first two cohorts. This is a 5-year study, with a 2-year main study, followed by a 3-year safety extension.


Frontotemporal Dementia, Progranulin Mutations, FTD-GRN, Gene Therapy, Dementia Gene Therapy, AAV1, Fronto-temporal Dementia, Dementia, Primary Progressive Aphasia, Pick Disease of the Brain, PBFT02


You can join if…

Open to people ages 35-75

  1. Documented to be a pathogenic GRN mutation carrier
  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

You CAN'T join if...

  1. Classification of the GRN mutation as "not pathogenic," "likely benign variant," "benign variant," or "pathogenic nature unclear"
  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
  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
  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 intra-cisterna magna 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 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 females 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. Females 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:
  30. Platelet count over 100,000 per uL
  31. INR less than 1.5
  32. aPTT less than 40 seconds
  33. . Use of anticoagulants in the 2 weeks prior to screening, or anticipated use of anticoagulants during the study. Antiplatelet therapies may be acceptable
  34. . Hypersensitivity or contraindications to corticosteroid use
  35. . Known or suspected intolerance or hypersensitivity to PBFT02 or any of its ingredients or to closely related compounds


  • University of California at San Francisco not yet accepting patients
    San Francisco California 94143 United States
  • University of Texas at Houston accepting new patients
    Houston Texas 77030 United States


accepting new patients at some sites,
but this study is not currently recruiting here
Start Date
Completion Date
Passage Bio, Inc.
Phase 1/2 research study
Study Type
Expecting 6 study participants
Last Updated