Phase 1/2 Clinical Trial of LY3884963 in Patients With Frontotemporal Dementia With Progranulin Mutations (FTD-GRN)
NCT ID: NCT04408625
Last Updated: 2025-12-15
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
PHASE1/PHASE2
35 participants
INTERVENTIONAL
2020-11-09
2031-04-30
Brief Summary
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Detailed Description
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Conditions
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Study Design
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NON_RANDOMIZED
SEQUENTIAL
TREATMENT
NONE
Study Groups
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Initial Cohort - Low dose
LY3884963
Participants will receive a single dose of LY3884963, administered intra cisterna magna
Methylprednisolone
IV pulses every 2 weeks in the first 3 months.
Optional Sirolimus
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 Prednisone
If needed and at the investigator discretion, Oral Prednisone may be added to the immunosuppression regimen
Initial Cohort - Medium dose
LY3884963
Participants will receive a single dose of LY3884963, administered intra cisterna magna
Methylprednisolone
IV pulses every 2 weeks in the first 3 months.
Optional Sirolimus
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 Prednisone
If needed and at the investigator discretion, Oral Prednisone may be added to the immunosuppression regimen
Bridging Cohort - Low dose
Participants enrolled in the Bridging Cohort will be assigned to either low or medium dose in an alternating manner
LY3884963
Participants will receive a single dose of LY3884963, administered intra cisterna magna
Methylprednisolone
IV pulses every 2 weeks in the first 3 months.
Optional Sirolimus
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 Prednisone
If needed and at the investigator discretion, Oral Prednisone may be added to the immunosuppression regimen
Bridging Cohort - Medium dose
Participants enrolled in the Bridging Cohort will be assigned to either low or medium dose in an alternating manner
LY3884963
Participants will receive a single dose of LY3884963, administered intra cisterna magna
Methylprednisolone
IV pulses every 2 weeks in the first 3 months.
Optional Sirolimus
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 Prednisone
If needed and at the investigator discretion, Oral Prednisone may be added to the immunosuppression regimen
Cohort 5-Medium Dose
Will enroll up to 10 participants with early phase of disease
LY3884963
Participants will receive a single dose of LY3884963, administered intra cisterna magna
Methylprednisolone
IV pulses every 2 weeks in the first 3 months.
Optional Sirolimus
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 Prednisone
If needed and at the investigator discretion, Oral Prednisone may be added to the immunosuppression regimen
Interventions
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LY3884963
Participants will receive a single dose of LY3884963, administered intra cisterna magna
Methylprednisolone
IV pulses every 2 weeks in the first 3 months.
Optional Sirolimus
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 Prednisone
If needed and at the investigator discretion, Oral Prednisone may be added to the immunosuppression regimen
Eligibility Criteria
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Inclusion Criteria
* 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.
* 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.
Exclusion Criteria
* 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.
* 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.
30 Years
85 Years
ALL
No
Sponsors
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Eli Lilly and Company
INDUSTRY
Prevail Therapeutics
INDUSTRY
Responsible Party
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Principal Investigators
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Travis Lewis, MD, PhD
Role: STUDY_DIRECTOR
Prevail Therapeutics
Locations
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k2 Medical Research-Maitland
Maitland, Florida, United States
PPD Phase 1 Clinic, 100 West Gore Street, Suite 202
Orlando, Florida, United States
Lahey Hospital & Medical Center, 41 Burlington Mall Road
Burlington, Massachusetts, United States
Hospital of the University of Pennsylvania, 3 West Gates Building, 3400 Spruce Street
Philadelphia, Pennsylvania, United States
Royal Prince Alfred Hospital, Brain & Mind Research Institute, 94 Mallet Street
Camperdown, New South Wales, Australia
UZ Leuven, Neurologie Herestraat 49
Leuven, , Belgium
AP-HM Hôpital de La Timone
Saint-Pierre, Marseille, France
Centre Mémoire de Ressources
Lille, , France
Le Ber, Institut du Cerveau et de la Moelle Epinière
Paris, , France
Hospital Clinic de Barcelona, Villaroel 170 Servicio de Neurología
Barcelona, , Spain
Hospital Universitario de Donostia, Servicio De Neurologia, Consultas Externas Neurologia, San Sebastian, Guipúzcoa
Donostia / San Sebastian, , Spain
University College London,Queen Square, Dementia Research Building, London,
London, , United Kingdom
Countries
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Central Contacts
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Facility Contacts
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References
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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.
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.
Related Links
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Progranulin AAV gene therapy for frontotemporal dementia
Other Identifiers
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J4B-MC-OKAA (PRV-FTD101)
Identifier Type: -
Identifier Source: org_study_id
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