Phase 1/2a Clinical Trial of PR001 (LY3884961) in Patients With Parkinson's Disease With at Least One GBA1 Mutation (PROPEL)

NCT ID: NCT04127578

Last Updated: 2026-01-20

Study Results

Results pending

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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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

32 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-01-03

Study Completion Date

2030-12-31

Brief Summary

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Study J3Z-MC-OJAA is a Phase 1/2a, multicenter, open-label, ascending dose, first in-human study that will evaluate the safety of intracisternal LY3884961 administration in patients with moderate to severe Parkinson's disease with at least 1 pathogenic GBA1 mutation. Two dose level cohorts of LY3884961 are planned (Dose Level 1 and Dose Level 2). The duration of the study is 5 years. During the first year, patients will be evaluated for the effect of LY3884961 on safety, tolerability, immunogenicity, biomarkers, and clinical efficacy measures. Patients will continue to be followed for an additional 4 years to continue to monitor safety as well as selected biomarker and efficacy measures.

Detailed Description

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Conditions

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Parkinson Disease

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Dose Level 1

Group Type EXPERIMENTAL

LY3884961

Intervention Type BIOLOGICAL

Participants will receive a single dose of LY3884961, administered intra-cisterna magna

Methylprednisolone

Intervention Type DRUG

6 IV pulses administered as concomitant medication over 3 months

Sirolimus

Intervention Type DRUG

Back-up treatment if corticosteroid is not well tolerated. Loading dose, followed by maintenance dose, followed by dose tapering; administered as concomitant medication

Dose Level 2

Group Type EXPERIMENTAL

LY3884961

Intervention Type BIOLOGICAL

Participants will receive a single dose of LY3884961, administered intra-cisterna magna

Methylprednisolone

Intervention Type DRUG

6 IV pulses administered as concomitant medication over 3 months

Sirolimus

Intervention Type DRUG

Back-up treatment if corticosteroid is not well tolerated. Loading dose, followed by maintenance dose, followed by dose tapering; administered as concomitant medication

Interventions

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LY3884961

Participants will receive a single dose of LY3884961, administered intra-cisterna magna

Intervention Type BIOLOGICAL

Methylprednisolone

6 IV pulses administered as concomitant medication over 3 months

Intervention Type DRUG

Sirolimus

Back-up treatment if corticosteroid is not well tolerated. Loading dose, followed by maintenance dose, followed by dose tapering; administered as concomitant medication

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Body weight range of ≥40 kg (88 lbs) to ≤110 kg (242 lbs) and a body mass index (BMI) of 18 to 34 kg/m2.
* Diagnosis of Parkinson's Disease (PD) per UK Parkinson's Disease Society Brain Bank Clinical Diagnostic Criteria.
* Hoehn and Yahr Stage III-IV (as determined in Practically Defined OFF state).
* Stable use of background medications at least 8 weeks prior to investigational product (IP) administration, including but not limited to those used for treatment of PD. Gaucher Disease-PD patients receiving GD treatments should be on a stable regimen of their ERT or substrate replacement therapy (SRT) medication for at least 3 months prior to screening.
* At least 1 pathogenic GBA1 mutation confirmed by the central laboratory
* Negative screening test for Mycobacterium tuberculosis (MTB), documented negative MTB test within 1 year prior to Screening, or clearance by an infectious disease specialist.
* Patient and/or patient's legally authorized representative (LAR) has the ability to understand the purpose and risks of the study and provide written informed consent and authorization to use protected health information in accordance with national and local privacy regulations.
* 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 (including providing input into the rating scales). The study partner should have regular contact with the patient (in person or via phone/video communication). The study partner must sign a separate partner informed consent form (ICF) indicating that she/he understands the study requirements and is willing to participate and attend study visits requiring study partner input.
* Women of nonchildbearing potential must be either surgically sterile or postmenopausal. Men and women of childbearing potential must use a highly effective method of contraception consistently and correctly for the duration of the study including the long-term follow-up. Individuals in an exclusively same sex relationship (as their preferred and usual lifestyle) are not required to use contraception.
* Men must agree to 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 serum pregnancy test at Screening.
* Patient is generally ambulatory, not dependent on 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 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 start of the immunosuppressant treatment).
* Patient is up to date with age and gender-appropriate cancer screening as per local standard of care based on Principal Investigator's (PI) judgment.

Exclusion Criteria

* Diagnosis of a significant CNS disease other than Parkinson's Disease (PD) that may be a cause for the patient's PD symptoms or may confound study objectives.
* MoCA (Montreal Cognitive Assessment) score of \<14
* Spinal, cervical, or brain MRI/magnetic resonance angiography (MRA) indicating clinically significant abnormality, including evidence of prior hemorrhage, infarct \>1 cm3 or \>3 lacunar infarcts, or a structural abnormality deemed a contraindication to intracisternal injection.
* Hypersensitivity or contraindications to corticosteroid and/or, sirolimus use (including but not limited to osteoporosis with vertebral fractures within 1 year prior to Screening, uncontrolled hypertension, poorly controlled diabetes, uncontrolled hyperlipidemia or hypercholesterolemia as per Investigator assessment.
* 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; including, but not limited to the following:

1. Evidence of clinically significant liver pathology;
2. Unstable autoimmune disease; autoimmune disease requiring chronic immunosuppression;
3. Poorly controlled/not adequately managed diabetes (Screening glycosylated hemoglobin \[HbA1C\] ≥ 7%);
4. History of unstable angina, myocardial infarction, chronic heart failure (New York Heart Association Class III or IV), or clinically significant conduction abnormalities (e.g., unstable atrial fibrillation) within 1 year prior to Screening;
5. Clinically significant 12-lead electrocardiogram (ECG) abnormalities at Screening, as determined by the Investigator;
6. Uncontrolled hypertension;
7. History of cancer, including B-cell cancers, within 5 years of Screening with the exception of fully excised non-melanoma skin cancers, non-metastatic prostate cancer, and full treated ductal carcinoma in situ, provided it has been stable for at least 6 months;
8. History or current alcohol or drug abuse within 2 years of Screening;
9. Any current psychiatric diagnosis that may interfere with patient's ability to perform study procedures and all assessments;
10. At imminent risk of self-harm;
11. Any medical disorders that, in the opinion of the Investigator, could interfere with study-related procedures (including safe performance of lumbar puncture \[LP\] or intracisternal injection), such as prohibitive spinal diseases, bleeding diathesis, clinically significant coagulopathy,, thrombocytopenia, or increased intracranial pressure;
12. Documented stroke or transient ischemic attack within 1 year prior to Screening;
13. History of seizure or unexplained blackouts within 10 years prior to Screening;
14. Currently active infection or a severe infection (e.g., pneumonia, septicemia, central nervous system infections \[e.g. meningitis, encephalitis\]) within 12 weeks prior to Screening;
15. History of severe allergic or anaphylactic reactions. History of hypersensitivity to any inactive ingredient of the IP or protocol-required immunosuppressant medications.
16. Acute or chronic: hepatitis B (HBV); hepatitis C (HCV) infection must have completed curative antiviral treatment with HCV viral load below the limit of quantification or be HCV RNA negative due to prior treatment or natural resolution to be eligible for enrollment.
* Clinically significant abnormalities in laboratory test results at Screening.
* Participation within 3 months prior to Screening in another therapeutic investigational drug or device study with purported disease-modifying effects on PD, unless it can be documented that the patient received placebo.
* History of deep brain stimulator placement, focused ultrasound, or surgery for PD
* Any type of prior gene or cell therapy.
* Immunizations (live vaccines) in the 4 weeks prior to Screening. Note: Pneumococcal and shingles vaccine administrations are allowed during the Screening period (patients not previously vaccinated should receive pneumococcal and/or shingles vaccine administration at least 4 weeks prior to initiation of Immunosuppression regimen).
* Use of ambroxol within 8 weeks of dosing.
* Use of blood thinners in the 2 weeks prior to Screening lumbar puncture (LP) or intra-cisterna magna (ICM) procedure, or the anticipated need to initiate blood thinners during the study. Antiplatelet therapies (e.g., prophylactic aspirin, clopidogrel) 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 intracisternal injection and lumbar puncture.
* Contraindications or intolerance to imaging methods (MRI, MRA, CT, DaT-SPECT) inducing claustrophobia and/or intolerance to contrast agents used for MRI, MRA or CT.
* Contraindications to general anesthesia or deep sedation.
* Positive urine test for drugs of abuse (including opiates, benzodiazepines, amphetamines, cocaine, barbiturates, and phencyclidine) without prescription, at Screening and Day -1. Note: Use of medical marijuana is permitted provided the patient is on a stable regimen. It is also permitted if the patient resides in a state in which the recreational use of marijuana is legalized, so long as the patient does not meet drug abuse criteria (as defined in the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition).
* Patient is generally frail or has any medical condition, for which, in view of the Investigator, participation in the study would not be in the best interest of the patient or is likely to prohibit further participation during the study.
Minimum Eligible Age

35 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Eli Lilly and Company

INDUSTRY

Sponsor Role collaborator

Prevail Therapeutics

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Travis B. Lewis, MD, PhD

Role: STUDY_DIRECTOR

Prevail Therapeutics

Locations

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Mayo Clinic, 13400 E. Shea Boulevard

Scottsdale, Arizona, United States

Site Status RECRUITING

Esperanza Clinical, 25220 Hancock Avenue

Murrieta, California, United States

Site Status RECRUITING

Rocky Mountain Clinical Research - CenExel - PPDS, 701 East Hampden Avenue Suite 510

Englewood, Colorado, United States

Site Status RECRUITING

K2 Medical Research, 101 Southhall Lane, Suite 150

Maitland, Florida, United States

Site Status RECRUITING

PPD, 100 West Gore Street, Suite 202

Orlando, Florida, United States

Site Status COMPLETED

Northwestern University Feinberg School of Medicine, Dept. of Neurology, Parkinson's Disease & Movement Disorders Center, 710 N. Lake Shore Drive, 11th Floor

Chicago, Illinois, United States

Site Status ACTIVE_NOT_RECRUITING

Mayo Clinic, 200 First Street SW

Rochester, Minnesota, United States

Site Status NOT_YET_RECRUITING

Mount Sinai Beth Israel, 10 Union Square East, Suite 5H

New York, New York, United States

Site Status COMPLETED

Joan and Sanford I. Weill Department of Medicine, 525 E 68th Street

New York, New York, United States

Site Status ACTIVE_NOT_RECRUITING

Hospital of the University of Pennsylvania, 330 S. 9th Street

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

Vanderbilt University Medical Center, 1500 21st Avenue South Suite 2600

Nashville, Tennessee, United States

Site Status NOT_YET_RECRUITING

Shaare Zedek Medical Center, 12 Shmuel Biet Street

Jerusalem, , Israel

Site Status COMPLETED

Hadassah Medical Center, Hadassah Ein Kerem, Dept. of Neurology, P.O. Box 12000

Jerusalem, , Israel

Site Status COMPLETED

Sheba Medical Center, Tel Hashomer

Ramat Gan, , Israel

Site Status COMPLETED

Tel Aviv Sourasky Medical Center, 6 Weizmann St.

Tel Aviv, , Israel

Site Status COMPLETED

Countries

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United States Israel

Central Contacts

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Prevail Therapeutics

Role: CONTACT

(917) 336-9310

Facility Contacts

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Haydee Renkas, BSN, RN

Role: primary

480-574-4490

Patricia Courville

Role: primary

951-417-4466

Gabriel Casareno

Role: primary

720-776-0092 ext. 2520

Gina Lagares

Role: primary

321-204-9552

Christina Pacheco

Role: backup

407-794-6598

Bridget Neja

Role: primary

507-266-9150

Alexandria Oliver

Role: primary

215-829-7104

Jacqueline Harris

Role: primary

615-936-3833

Keimora Wright

Role: backup

6159363833

References

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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.

Reference Type DERIVED
PMID: 37624739 (View on PubMed)

Other Identifiers

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J3Z-MC-OJAA formerly PRV-PD101

Identifier Type: -

Identifier Source: org_study_id

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