Last updated 4 months ago
A Study of PBFT02 in Patients With Frontotemporal Dementia and Progranulin Mutations (FTD-GRN)
15 patients around the world
Available in United States, Brazil
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.
Passage Bio, Inc.
2Research sites
15Patients around the world
Requirements for the patient
To 75 Years
All Gender
Medical requirements
- Documented to be a pathogenic GRN mutation carrierClinical diagnosis of frontotemporal dementiaHave a reliable informant / caregiver (and back-up informant / caregiver) who personally speaks with or sees the subject at least weeklyLiving in the community (i.e., not in a nursing home); assisted living may be permitted at the discretion of the investigator
- Classification of the GRN mutation as "not pathogenic," "likely benign variant," "benign variant," or "pathogenic nature unclear"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 studyHomozygous GRN mutation carrierRosen-modified Hachinski Ischemic Scale score > 7Known presence of a structural brain lesion (eg, tumor, cortical infarct) that could reasonably explain symptoms in a symptomatic subjectKnown 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 onsetHistory of untreated vitamin B12 deficiencyPresence 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 oxygenInability to provide full consent or the lack of a legally authorized caregiver with adequate contact who can provide consentAny contraindication to MRI or lumbar puncture (LP) (eg, local infection, history of thrombocytopenia, coagulopathy)Any contraindication to the ICM administration procedureMedical 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)Immunocompromised statusPeripheral axonal sensory neuropathyReceipt of a vaccine within 14 days of dosingA 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 screeningMalignant neoplasia (except localized skin cancer) or a documented history of hereditary cancer syndromeAny 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 deficiencyCurrent or recent history of clinically significant suicidal ideation within the past 6 monthsFor 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 postdoseWomen who are breastfeedingFor 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 postdoseAny 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 resultsAny acute illness requiring hospitalization within 30 days of enrollmentFailure to meet the protocol-specified coagulation test criteria:Platelet count over 100,000 per uLINR less than 1.5aPTT less than 40 secondsUse of anticoagulants in the 2 weeks prior to screening, or anticipated use of anticoagulants during the study. Antiplatelet therapies may be acceptableHypersensitivity or contraindications to corticosteroid useKnown or suspected intolerance or hypersensitivity to PBFT02 or any of its ingredients or to closely related compounds
Sites
Hospital Das Clínicas Da Universidade Federal de Minas Gerais - UFMG
Recruiting
Hospital das Clínicas da Faculdade de Medicina da São Paulo - USP
Recruiting
StudyupliFT-D
SponsorPassage Bio, Inc.
Study typeInterventional
Requirements
To 75 YearsAll Gender
Unique study IDclinicaltrials.gov
NCT04747431
