Frontotemporal DementiaPhase 1/2upliFT-DNCT04747431
A Study of PBFT02 in Participants With FTD and Mutations in the Granulin Precursor (GRN) or C9ORF72 Genes
A Phase 1/2 study testing PBFT02 in people with Frontotemporal Dementia and FTD, run by Passage Bio, Inc. at 10 sites in 5 countries.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 35 to 75 years
- Conditions the study is for
- Frontotemporal Dementia, FTD, FTD-GRN
- What is being tested?
- PBFT02
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 10 sitesin 5 countries
- Study dates
- 14 Sep 2021to 19 Jun 2026
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 35 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
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- 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
- 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
- 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
- Any acute illness requiring hospitalization within 30 days of enrollment
- Failure to meet the protocol-specified coagulation test criteria:
- Platelet count > 100,000 per uL
- INR < 1.5
- aPTT < 40 seconds
- Use of anticoagulants in the 2 weeks prior to screening
- Hypersensitivity or contraindications to corticosteroid use
- Known or suspected intolerance or hypersensitivity to PBFT02 or any of its ingredients or to closely related compounds
- Any condition expected to increase risk of thrombosis
- 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:
- ALSFRS-R < 35 at screening.
- SVC < 75% of predicted normal adjusted for sex, age, and height (from the sitting position).
- Bulbar-onset ALS.
- Current or anticipated need, in the opinion of the Investigator for a diaphragm pacing system (DPS) during the study period.
- 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.
Trial locations and contacts
10 sites in 5 countries.
10 sites in 5 countries
United States4 sites
Michigan Alzheimer's Disease Center
Ann Arbor, Michigan, 48105
University of Texas at Houston
Houston, Texas, 77030
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Brazil2 sites
Hospital das Clinicas da Universidade Federal de Minas Gerais (UFMG)
Minas Gerais
Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (HCFMUSP)
São Paulo
Canada2 sites
Montreal Neurological Institute-Hospital
Montreal, Quebec, H3A 2B4
University of Toronto, Toronto Western Hospital
Toronto, Ontario, M5T 2S8
About this study
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 ICM of Adults With FTD and Mutations in the GRN or C9ORF72 Genes
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
Read the detailed description
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 study of PBFT02 delivered as a one-time dose administered into the cisterna magna to participants with FTD-GRN or C9orf72. Participants aged ≥ 35 and ≤ 75 years with early symptomatic FTD-GRN or with symptomatic FTD-C9orf72 may be enrolled into the study.
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
- Frontotemporal Dementia, FTD, FTD-GRN, Dementia Frontotemporal, C9orf72
- Being tested
- PBFT02
- Keywords
- frontotemporal dementia, Progranulin Mutations, FTD-GRN, Gene Therapy, Dementia Gene Therapy, AAV1, Fronto-temporal Dementia, C9orf72
- Medical subject headings
- Frontotemporal Dementia, Pick Disease of the Brain, Frontotemporal Dementia With Motor Neuron Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PBFT02Drug
PBFT02
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | Drug: PBFT02 Dose 1; Single dose of PBFT02, via intra cisterna magna
*GC/g: gene copy per gram of estimated brain weight Receives: Drug: PBFT02 |
| Cohort 2, 3, 4 and 5 | Experimental | Drug: PBFT02 Dose 1 or 2; Single dose of PBFT02, via intra cisterna magna
*GC/g: gene copy per gram of estimated brain weight Receives: Drug: PBFT02 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants with Treatment-Related AEs and SAEs
Assess the number of treatment-related adverse events (AEs) and serious adverse events (SAEs)
Measured: Up to 5 years (multiple visits)
Change in Nerve Conduction Velocity and Amplitude from Baseline on Nerve Conduction Studies
Assess changes in nerve conduction velocity in the distal segments of the sural, radial, and median sensory nerves and peroneal motor nerve as measured on conventional nerve conduction studies.
Measured: From baseline to 5 years (multiple visits)
Change in Cellular and Humoral Response Against the Vector and Transgene in Serum
Assess ELISpot and antibody titers against AAV1 and against human progranulin
Measured: From baseline to 5 years (multiple visits)
Secondary outcomes (6)
Change from baseline in CSF and plasma PGRN levels
Assess effect of treatment with PBFT02 on CSF and plasma PGRN levels following administration of a single ICM dose.
Measured: From baseline to 5 years (multiple visits)
Change from baseline in plasma and CSF neurofilament light chain (NfL) levels
Assess the effect of treatment with PBFT02 on PGRN level in CSF and plasma
Measured: From baseline to 5 years (multiple visits)
Change in Brain anatomy as assessed by MRI
Assess the effect of treatment with PBFT02 on Brain volume, white matter integrity, and cortical thickness as assessed by MRI
Measured: From baseline to 5 years (multiple visits)
Change in FTLD disease progression
Assess changes in the Clinical Dementia Rating Scale for Frontotemporal Lobar Degeneration plus National Alzheimer's Coordinating Center FTLD Behavior \& Language Domains (CDR® plus NACC FTLD SB)
Measured: From baseline to 5 years (multiple visits)
Change in ALS disease progression in participants with FTD C9orf72
Assess changes in ALS disease progression using the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R), percent predicted slow vital capacity (SVC) and in muscle strength as measured by handheld dynamometry (HHD)
Measured: From baseline to 5 years (multiple visits)
Change in vital status
Assess the impact of PBFT02 on survival
Measured: From Baseline to 5 years (multiple years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2021
- Study start14 Sep 2021
- Primary completion19 Jun 2026
- Study completion19 Jun 2026
Why it stopped: The PBFT02-001 Study was terminated by the Sponsor, Passage Bio, Inc., due to strategic company resourcing decisions. The early closure is not related to safety, efficacy, or any change in the benefit-risk profile of the investigational product.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Frontotemporal DementiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- Open-label, multi-center, dose escalation
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Passage Bio, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Chief Medical Officer Chief Medical Officer, Study chair, Passage Bio, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04747431
- Sponsor's protocol ID
- PBFT02-001
- Other IDs
- 2020-004499-17
- Acronym
- upliFT-D
- Status last verified
- Oct 2026
- First submitted
- 2 Feb 2021
- Last updated
- 29 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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 ICM of Adults With FTD and Mutations in the GRN or C9ORF72 Genes
- ClinicalTrials.gov ID
- NCT04747431
- Acronym / sponsor ID
- upliFT-D / PBFT02-001
- Conditions
- Frontotemporal Dementia, FTD, FTD-GRN, Dementia Frontotemporal, C9orf72
- Keywords
- frontotemporal dementia, Progranulin Mutations, FTD-GRN, Gene Therapy, Dementia Gene Therapy, AAV1, Fronto-temporal Dementia, C9orf72
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The PBFT02-001 Study was terminated by the Sponsor, Passage Bio, Inc., due to strategic company resourcing decisions. The early closure is not related to safety, efficacy, or any change in the benefit-risk profile of the investigational product.
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Passage Bio, Inc.Industry (pharma, biotech, devices)
- Study start
- 14 Sep 2021 (actual)
- Primary completion
- 19 Jun 2026 (actual)
- Study completion
- 19 Jun 2026 (actual)
- First posted
- 10 Feb 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Detailed description
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 study of PBFT02 delivered as a one-time dose administered into the cisterna magna to participants with FTD-GRN or C9orf72. Participants aged ≥ 35 and ≤ 75 years with early symptomatic FTD-GRN or with symptomatic FTD-C9orf72 may be enrolled into the study.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Open-label, multi-center, dose escalation
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Drug: PBFT02Drug: PBFT02 Dose 1; Single dose of PBFT02, via intra cisterna magna *GC/g: gene copy per gram of estimated brain weight |
| Cohort 2, 3, 4 and 5 | Experimental | Drug: PBFT02Drug: PBFT02 Dose 1 or 2; Single dose of PBFT02, via intra cisterna magna *GC/g: gene copy per gram of estimated brain weight |
Who may qualify
- Ages
- 35 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (43 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PBFT02PBFT02 | Drug | Cohort 1, Cohort 2, 3, 4 and 5 |
Primary outcome
Number of Participants with Treatment-Related AEs and SAEs
Time frame: Up to 5 years (multiple visits)
Assess the number of treatment-related adverse events (AEs) and serious adverse events (SAEs)
Change in Nerve Conduction Velocity and Amplitude from Baseline on Nerve Conduction Studies
Time frame: From baseline to 5 years (multiple visits)
Assess changes in nerve conduction velocity in the distal segments of the sural, radial, and median sensory nerves and peroneal motor nerve as measured on conventional nerve conduction studies.
Change in Cellular and Humoral Response Against the Vector and Transgene in Serum
Time frame: From baseline to 5 years (multiple visits)
Assess ELISpot and antibody titers against AAV1 and against human progranulin
6 secondary outcomes
Change from baseline in CSF and plasma PGRN levels
Time frame: From baseline to 5 years (multiple visits)
Change from baseline in plasma and CSF neurofilament light chain (NfL) levels
Time frame: From baseline to 5 years (multiple visits)
Change in Brain anatomy as assessed by MRI
Time frame: From baseline to 5 years (multiple visits)
Change in FTLD disease progression
Time frame: From baseline to 5 years (multiple visits)
Change in ALS disease progression in participants with FTD C9orf72
Time frame: From baseline to 5 years (multiple visits)
Change in vital status
Time frame: From Baseline to 5 years (multiple years)
Results and safety
The study was stopped early (reason given: The PBFT02-001 Study was terminated by the Sponsor, Passage Bio, Inc., due to strategic company resourcing decisions. The early closure is not related to safety, efficacy, or any change in the benefit-risk profile of the investigational product.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Oct 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Chief Medical Officer Chief Medical Officer study chair
Passage Bio, Inc.
10 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing PBFT02 in people with Frontotemporal Dementia and FTD, run by Passage Bio, Inc. at 10 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 43 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 29 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States, Brazil, Canada, Australia, Portugal. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: The PBFT02-001 Study was terminated by the Sponsor, Passage Bio, Inc., due to strategic company resourcing decisions. The early closure is not related to safety, efficacy, or any change in the benefit-risk profile of the investigational product.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants with Treatment-Related AEs and SAEs (time frame: Up to 5 years (multiple visits)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Oct 2026.