A Study of PBFT02 in Participants With FTD and Mutations in the Granulin Precursor (GRN) or C9ORF72 Genes

Running, not enrolling · Phase 1/Phase 2

Conditions studied: Frontotemporal Dementia, FTD, FTD-GRN, Dementia Frontotemporal, C9orf72

In brief

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 granulin precursor (GRN) or chromosome 9 open reading frame 72 (C9ORF72) genes

Key facts

Study ID

NCT04747431

Run by

Passage Bio, Inc.

People needed

30

Starts

2021-09-14

Expected to finish

2031-08-01

Last updated by the study team

2026-05-15

Who can join

Age: 35 and older, up to 75. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Documented to be a pathogenic carrier of GRN or C9orf72 mutation
• Clinical diagnosis of frontotemporal dementia
• Have a reliable informant / caregiver (and back-up informant / caregiver) who personally speaks with or sees the subject at least weekly
• Living in the community (i.e., not in a nursing home); assisted living may be permitted at the discretion of the investigator

You may not qualify if…

• Classification of the GRN mutation as "not pathogenic," "likely benign variant," "benign variant," or "pathogenic nature unclear" (FTD- GRN Cohorts 1-3) or C9orf72 HRE length ≤ 30 (FTD-C9orf72 Cohorts 4-5).
• 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
• Homozygous GRN mutation carrier (FTD-GRN Cohorts 1-3) or homozygous C9orf72 mutation carrier (FTD-C9orf72 Cohorts 4-5).
• Rosen-modified Hachinski Ischemic Scale score > 7
• Known presence of a structural brain lesion (eg, tumor, cortical infarct) that could reasonably explain symptoms in a symptomatic subject
• Known presence of an AD-causing mutation in PSEN1, PSEN2 or APP based on genetic testing history (if performed)
• 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
• History of untreated vitamin B12 deficiency
• Presence of untreated hypothyroidism (thyroid stimulating hormone [TSH] > ULN and free T4 < LLN)
• eGFR ≤ 30 ml/min (as calculated using the CKD-EPI equation)
• Alanine aminotransferase [ALT] or aspartate aminotransferase [AST] > 2 × ULN, or total bilirubin > ULN)
• Respiratory failure that requires supplemental oxygen, tracheostomy, or reliance on non-invasive ventilation for >2 hours during waking hours
• Inability to provide full consent or the lack of a legally authorized caregiver with adequate contact who can provide consent
• Any contraindication to MRI or lumbar puncture (LP) (eg, local infection, history of thrombocytopenia, coagulopathy)
• Any contraindication to the ICM administration procedure
• 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)
• Immunocompromised status
• Peripheral axonal sensory neuropathy
• Receipt of a vaccine within 14 days of dosing
• 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
• Malignant neoplasia (except localized skin cancer) or a documented history of hereditary cancer syndrome
• 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
• Current or recent history of clinically significant suicidal ideation within the past 6 months
• 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
• Women who are breastfeeding

Where it is running

• 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

Full record on ClinicalTrials.gov

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