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Frontotemporal DementiaPhase 1/2PROCLAIMNCT04408625

Phase 1/2 Clinical Trial of LY3884963 in Patients With Frontotemporal Dementia With Progranulin Mutations (FTD-GRN)

A Phase 1/2 study testing LY3884963, Methylprednisolone and Optional Sirolimus in people with Frontotemporal Dementia, run by Prevail Therapeutics at 12 sites in 6 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

Study J4B-MC-OKAA is a Phase 1/2, multi-center, open-label ascending dose, first-in-human study that will evaluate the safety and effect of intra-cisternal LY3884963 administration on progranulin protein (PGRN) levels in patients with frontotemporal dementia with progranulin mutations (FTD-GRN). Read more about this study

Who is it for?
Ages 30 to 85 years
Conditions the study is for
Frontotemporal Dementia
What is being tested?
LY3884963, Methylprednisolone and Optional Sirolimus
Could I receive a placebo?
No, everyone receives an active treatment
How many people
35 participants
Where
12 sitesin 6 countries
Study dates
9 Nov 2020to 30 Nov 2029
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

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 30 to 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Men or women aged 30 to 85 years (inclusive), at the time of informed consent.
  • Body weight range of ≥40 kg (88 lbs) to ≤110 kg (242 lb) and a BMI of 18 to 34 kg/m2.
  • Has symptomatic frontotemporal dementia (FTD), including mild behavioral, cognitive, motor or language impairment per Investigator's assessment (behavioral-variant FTD, primary progressive aphasia-FTD, FTD with corticobasal syndrome, or a combination of syndromes are allowed for enrollment).
  • Score ≥0.5 and ≤15 on CDR plus NACC FTLD sum of boxes (Cohorts 1-4 only). Note: In Cohort 5 only patients with CDR plus NACC FTLD with sum of boxes ≥0.5 and ≤9 AND global score of 0.5 or 1 will be enrolled.
  • Stable use of background medications at least 8 weeks prior to LY3884963 dosing.
  • Carrier of a pathogenic progranulin gene (GRN) mutation.
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  • Negative screening test for Mycobacterium tuberculosis (MTB) or documented negative MTB test within 1year prior to screening.
  • Age- and gender-appropriate cancer screenings are up-to-date and completed.
  • Patient and/or patient's legally authorized representative has the ability to understand the purpose and risks of the study, and provide written informed consent and authorization to use protected health information.
  • Women of nonchildbearing potential must be either surgically sterile (hysterectomy, bilateral tubal ligation, salpingectomy, and/or bilateral oophorectomy at least 26 weeks before Screening) or postmenopausal, defined as spontaneous amenorrhea for at least 2 years, with follicle stimulating hormone level in the postmenopausal range at Screening based on the central laboratory's range.
  • Men and women of childbearing potential (i.e., ovulating, premenopausal, and not surgically sterile) must use a highly effective method of contraception consistently and correctly for the duration of the study, including the long term follow up. Highly effective methods of contraception are those that, alone or in combination, result in a failure rate of less than 1% per year when used consistently and correctly (i.e., perfect use) and include the following for female patients of childbearing potential:
  • Combined (estrogen and progestogen containing) oral, intravaginal, or transdermal hormonal contraception associated with inhibition of ovulation.
  • Oral, injectable, or implantable progestogen-only hormonal contraception associated with inhibition of ovulation.
  • Intrauterine device.
  • Intrauterine hormone-releasing system.
  • Bilateral tubal ligation or bilateral tubal occlusion (performed at least 3 months prior to Screening).
  • Vasectomized partner (performed at least 3 months prior to Screening).
  • Sexual abstinence (no sexual intercourse), if in line with the patient's usual and preferred lifestyle.
  • Acceptable forms of contraception for male patients include:
  • Sexual abstinence (no sexual intercourse), if in line with the patient's usual and preferred lifestyle.
  • History of vasectomy (performed at least 3 months prior to Screening, with documented absence of sperm in the ejaculate) in combination with condom.
  • Condom with spermicide used together with highly effective female contraceptive methods if the female partner(s) is of childbearing potential (see above for list of acceptable female contraceptive methods).
  • Note: Individuals who are in exclusively same sex relationships (as their preferred and usual lifestyle) are not required to use contraception.
  • Men must agree to use a condom during any sexual intercourse (including male patients who have had a vasectomy) and abstain from sperm donation for the duration of the study, including long-term follow-up.
  • Women must agree to abstain from egg donation for the duration of the study, including long-term follow-up.
  • Women of childbearing potential cannot be pregnant or lactating/breastfeeding and must have a negative result for the serum pregnancy test (β-human chorionic gonadotropin) at Screening.
  • Patient must agree to abstain from blood donation for the first year following gene transfer.
  • Patient has a reliable study partner/informant (e.g. family member, friend) willing and able to participate in the study as a source of information on the patient's health status and cognitive and functional abilities.
  • Patient is not dependent on a walker or wheelchair.
  • Patient is living in the community (i.e. not in nursing home); some levels of assisted living may be permitted at the discretion of the investigator.
  • Pneumococcal pneumonia and shingles vaccines are required within 10 years of Screening allowed to be performed during Screening but must be given at least 4 weeks prior to initiation of immunosuppressant regimen.

Who cannot join

  • Diagnosis of a significant CNS (central nervous system) disease other than frontotemporal dementia (FTD) that may cause FTD symptoms or confound study objectives.
  • Brain or cervical spine magnetic resonance image (MRI)/MRA imaging showing clinically significant abnormality considered to prevent intracisternal magna (ICM) injection.
  • Hypersensitivity or contraindications to corticosteroid, and/or sirolimus use.
  • Clinical evidence of peripheral symmetric sensory polyneuropathy (stable sensory mononeuropathies and radiculopathies are not exclusionary).
  • Concomitant disease or condition within 6 months of screening that could interfere with, or treatment of which might interfere with, the conduct of the study or that would, in the opinion of the investigator, pose an unacceptable safety risk to the patient or interfere with the patient's ability to comply with study procedures
  • Clinically significant laboratory test result abnormalities assessed at screening.
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  • Participation within 3 months prior to screening in another therapeutic investigational drug or device study with purported disease-modifying effects on FTD, unless it can be documented that the patient received placebo only.
  • Any type of prior gene or cell therapy.
  • Live vaccines in the 4 weeks prior to Screening. NOTE: Pneumococcal vaccine and/or shingles vaccine administration is allowed at least 4 weeks prior to initiation of immunosuppressant regimen.
  • Use of blood thinners in the 2 weeks prior to screening, or anticipated use of blood thinners during the study. Antiplatelet therapies are acceptable if the patient is medically able to temporarily stop 48 hours to 7 days (depending on the antiplatelet medication used) prior to and at least 48 hours after ICM injection and LP. Note: the use of blood thinners as part of prophylaxis or treatment of an emergent VTE or another AE during the study does not exclude the patient, unless there is a baseline high risk of thromboembolic events, and use of blood thinners is highly anticipated in the opinion of the Investigator.
  • Contraindications or intolerance to imaging methods (MRA, MRI, and/or computed tomography [CT]), including claustrophobia and intolerance to contrast agents used for MRI, MRA, or CT (including, but not limited to, gadolinium contrast agents and iohexol).
  • Contraindications to general anesthesia or deep sedation.
  • Positive urine test for drugs of abuse (including opiates, amphetamines, cocaine, barbiturates, and phencyclidine) without prescription at Screening and on Day 1.
  • Other protocol-defined inclusion/exclusion criteria may apply

Trial locations and contacts

12 sites in 6 countries.

12 sites in 6 countries

United States4 sites

  • Lahey Hospital & Medical Center, 41 Burlington Mall Road

    Burlington, Massachusetts, 01805

  • k2 Medical Research-Maitland

    Maitland, Florida, 32751-5669

  • PPD Phase 1 Clinic, 100 West Gore Street, Suite 202

    Orlando, Florida, 32806

  • Hospital of the University of Pennsylvania, 3 West Gates Building, 3400 Spruce Street

    Philadelphia, Pennsylvania, 19104

Other trials in United States

France3 sites

  • Centre Mémoire de Ressources

    Lille, 59000

  • Le Ber, Institut du Cerveau et de la Moelle Epinière

    Paris, 75013

  • AP-HM Hôpital de La Timone

    Saint-Pierre, Marseille, 13386

Other trials in France

Spain2 sites

  • Hospital Clinic de Barcelona, Villaroel 170 Servicio de Neurología

    Barcelona, 08036

  • Hospital Universitario de Donostia, Servicio De Neurologia, Consultas Externas Neurologia, San Sebastian, Guipúzcoa

    Donostia / San Sebastian, 20014

Other trials in Spain

Australia1 site

  • Royal Prince Alfred Hospital, Brain & Mind Research Institute, 94 Mallet Street

    Camperdown, New South Wales, 2050

Other trials in Australia

Belgium1 site

  • UZ Leuven, Neurologie Herestraat 49

    Leuven, 3000

Other trials in Belgium

United Kingdom1 site

  • University College London,Queen Square, Dementia Research Building, London,

    London, WC1N 3BG

Other trials in United Kingdom

About this study

Official title: A Phase 1/2 Ascending Dose Study to Evaluate the Safety and Effects on Progranulin Levels of LY3884963 in Patients With Fronto-Temporal Dementia With Progranulin Mutations (FTD-GRN)

Study J4B-MC-OKAA is a Phase 1/2, multi-center, open-label ascending dose, first-in-human study that will evaluate the safety and effect of intra-cisternal LY3884963 administration on progranulin protein (PGRN) levels in patients with frontotemporal dementia with progranulin mutations (FTD-GRN). Two escalating dose (low dose and medium dose) cohorts are planned, as well as one bridging cohort which will allocate patients to receive either low or medium dose. The duration of the study is 5 years. During the first year, patients will be evaluated for the effect of LY3884963 on safety, tolerability, immunogenicity, biomarkers, and efficacy. Patients will follow up for an additional 4 years to monitor safety and changes on selected biomarkers and clinical outcomes.

Being tested
LY3884963, Methylprednisolone, Optional Sirolimus, Optional Prednisone
Keywords
Fronto-Temporal Dementia, Frontotemporal Dementia, Progranulin Mutations, FTD-GRN, Gene Therapy, Dementia Gene Therapy, AAV9
Medical subject headings
Frontotemporal Dementia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LY3884963Biological

    Participants will receive a single dose of LY3884963, administered intra cisterna magna

  • MethylprednisoloneDrug

    IV pulses every 2 weeks in the first 3 months.

  • Optional SirolimusDrug

    At the investigators discretion following steroid tolerability issues, patients may receive a loading dose, followed by maintenance dose, followed by dose tapering; administered as concomitant medication

  • Optional PrednisoneDrug

    If needed and at the investigator discretion, Oral Prednisone may be added to the immunosuppression regimen

Study groups in NCT04408625
Study groupRoleWhat they receive
Initial Cohort - Low doseExperimentalNot described
Receives: Biological: LY3884963; Drug: Methylprednisolone; Drug: Optional Sirolimus; Drug: Optional Prednisone
Initial Cohort - Medium doseExperimentalNot described
Receives: Biological: LY3884963; Drug: Methylprednisolone; Drug: Optional Sirolimus; Drug: Optional Prednisone
Bridging Cohort - Low doseExperimentalParticipants enrolled in the Bridging Cohort will be assigned to either low or medium dose in an alternating manner
Receives: Biological: LY3884963; Drug: Methylprednisolone; Drug: Optional Sirolimus; Drug: Optional Prednisone
Bridging Cohort - Medium doseExperimentalParticipants enrolled in the Bridging Cohort will be assigned to either low or medium dose in an alternating manner
Receives: Biological: LY3884963; Drug: Methylprednisolone; Drug: Optional Sirolimus; Drug: Optional Prednisone
Cohort 5-Medium DoseExperimentalWill enroll up to 10 participants with early phase of disease
Receives: Biological: LY3884963; Drug: Methylprednisolone; Drug: Optional Sirolimus; Drug: Optional Prednisone

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Adverse Events (AEs), Serious Adverse Events (SAEs), and Adverse Events Leading to discontinuation

    Measured: 5 Years

  2. Sum of adverse reactions (ARs) and suspected ARs

    Measured: 5 years

  3. Sum of serious ARs and serious suspected ARs

    Measured: 5 years

  4. Incidence of procedure or treatment-emergent AEs

    Measured by brain and spine MRI

    Measured: 5 years

  5. Change in AAV9, PGRN, and NfL immunogenicity in blood

    PGRN: progranulin protein. Measured by level of antibodies and ELISPOT

    Measured: Days 7, 14, and 21 and at Months 1, 1.5, 2, 3, 6, 9, 12, 18, and 24

  6. Change in AAV9, PGRN, and NfL immunogenicity in CSF

    Measured by levels of antibodies.

    Measured: Months 2, 6, 12, 18, and 24

  7. Change in PGRN levels in blood

    Measured: Days 7, 14, and 21 and at Months 1, 1.5, 2, 3, 6, 9, 12, 18, and 24

  8. Change in PGRN levels in CSF

    Measured: Months 2, 6, 12, 18, and 24

Secondary outcomes (3)

  1. Change in CDR plus NACC FTLD

    CDR: Clinical Dementia Rating staging instrument. NACC FTLD: National Alzheimer's Coordinating Center frontotemporal lobar degeneration domains

    Measured: Months 3, 6, 9, and 12

  2. Change in NfL levels in blood

    NfL: neurofilament light chain

    Measured: Days 7, 14, and 21 and at Months 1, 1.5, 2, 3, 6, 9, and 12

  3. Change in NfL levels in CSF

    Measured: Months 2, 6, and 12

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted29 May 2020
  2. Study start9 Nov 2020
  3. Primary completion30 Nov 2029 (estimated)
  4. Study completion30 Nov 2029 (estimated)

Resources

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
Masking
None (open label)
Enrolment
35 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04408625
Sponsor's protocol ID
J4B-MC-OKAA (PRV-FTD101)
Acronym
PROCLAIM
Status last verified
Jul 2026
First submitted
21 May 2020
Last updated
16 Jul 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Sevigny J, Uspenskaya O, Heckman LD, Wong LC, Hatch DA, Tewari A, Vandenberghe R, Irwin DJ, Saracino D, Le Ber I, Ahmed R, Rohrer JD, Boxer AL, Boland S, Sheehan P, Brandes A, Burstein SR, Shykind BM, Kamalakaran S, Daniels CW, David Litwack E, Mahoney E, Velaga J, McNamara I, Sondergaard P, Sajjad SA, Kobayashi YM, Abeliovich A, Hefti F. Progranulin AAV gene therapy for frontotemporal dementia: translational studies and phase 1/2 trial interim results. Nat Med. 2024 May;30(5):1406-1415. doi: 10.1038/s41591-024-02973-0. Epub 2024 May 14.

    PubMed 38745011

  • De BP, Rosenberg JB, Selvan N, Wilson I, Yusufzai N, Greco A, Kaminsky SM, Heier LA, Ricart Arbona RJ, Miranda IC, Monette S, Nair A, Khanna R, Crystal RG, Sondhi D. Assessment of Safety and Biodistribution of AAVrh.10hCLN2 Following Intracisternal Administration in Nonhuman Primates for the Treatment of CLN2 Batten Disease. Hum Gene Ther. 2023 Sep;34(17-18):905-916. doi: 10.1089/hum.2023.067.

    PubMed 37624739

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing LY3884963, Methylprednisolone and Optional Sirolimus in people with Frontotemporal Dementia, run by Prevail Therapeutics at 12 sites in 6 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 31 inclusion and 14 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: under way, not looking for participants, as of the sponsor's last update on 16 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 12 sites in United States, France, Spain, Australia, Belgium and 1 more country. 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?

This study is still under way. Results are not available in the source record yet.

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 Adverse Events (AEs), Serious Adverse Events (SAEs), and Adverse Events Leading to discontinuation (time frame: 5 Years). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04408625, which also lists 2 linked publications.

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 16 Jul 2026.

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