PR001 for Parkinson's Disease

Recruiting at 11 trial locations

Overseen By Prevail Therapeutics

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Prevail Therapeutics

Must be taking: ERT, SRT

Must not be taking: Ambroxol, Blood thinners

Disqualifiers: CNS disease, Cancer, Diabetes, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

32 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate a new treatment, PR001 (also known as LY3884961 or PR001A), for individuals with moderate to severe Parkinson's disease, particularly those with a specific genetic mutation called GBA1. Researchers are testing two different doses to assess their safety and effectiveness. The study will span five years, with the first year concentrating on patient tolerance and any effects on symptoms. Patients diagnosed with Parkinson's disease and maintaining stable medication use might be suitable candidates for this trial. As a Phase 1, Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial requires that you have been on a stable dose of your current medications for at least 8 weeks before starting the study. If you are taking treatments for Gaucher Disease, you need to be on a stable regimen for at least 3 months before screening. Some medications, like ambroxol and certain blood thinners, must be stopped before the study.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that PR001, the treatment under study, is in the early testing stages to determine its safety for people. Researchers are testing two different doses, focusing on ensuring the treatment's safety and tolerability. As a Phase 1/2a study, the treatment has not undergone extensive testing in humans. This phase aims to observe the body's response and identify any major safety issues.

Available sources have not reported specific side effects or safety problems. Since this is the first human trial, close monitoring of participants is crucial to detect any potential side effects early. Ongoing monitoring over several years demonstrates a commitment to understanding long-term safety. In summary, while detailed safety information is not yet available, the study is designed to carefully assess and ensure the treatment's safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Parkinson's disease?

Researchers are excited about PR001 for Parkinson's Disease because it offers a fresh approach compared to traditional treatments like Levodopa or dopamine agonists, which often focus on managing symptoms. PR001 is unique as it targets the genetic roots of the disease by delivering a modified gene directly to brain cells. This gene therapy aims to address the underlying causes of Parkinson's rather than just alleviating symptoms, potentially offering more lasting benefits. This innovative mechanism could revolutionize how we approach treating this condition, offering hope for more effective long-term management.

What evidence suggests that PR001 might be an effective treatment for Parkinson's disease?

Research shows that PR001, also known as LY3884961, is a gene therapy under study for its potential to treat Parkinson's disease in patients with a specific GBA1 mutation. This trial evaluates different dose levels of PR001 to determine its effectiveness. The treatment aims to restore normal levels of an enzyme called GCase, which may help slow the progression of Parkinson's disease. Early findings suggest that targeting this enzyme could support brain cell function. By boosting GCase activity, PR001 might reduce symptoms and improve the quality of life for those affected. While researchers are still collecting human data, the treatment appears promising based on its intended mechanism. ^{1 2 3 6 7}

Who Is on the Research Team?

Travis B. Lewis, MD, PhD

Principal Investigator

Prevail Therapeutics

Are You a Good Fit for This Trial?

This trial is for adults with Parkinson's Disease who have a specific GBA1 mutation, weigh between 88-242 lbs with a BMI of 18-34, and are in moderate to severe stages (Hoehn and Yahr Stage III-IV). They must be on stable medications for Parkinson's or Gaucher Disease treatments if applicable. Participants need a reliable informant, updated vaccinations, and agree to use effective contraception if necessary. Exclusions include other significant CNS diseases, certain MRI findings, hypersensitivity to study drugs, uncontrolled health conditions like hypertension or diabetes.

Inclusion Criteria

My weight is between 88 and 242 lbs, and my BMI is between 18 and 34.

My weight is between 88 and 242 lbs, and my BMI is between 18 and 34.

I have had the pneumococcal and shingles vaccines within the last 10 years.

Exclusion Criteria

Criterion: You have any of the following conditions or diseases that could interfere with the study, pose a safety risk, or make it difficult for you to follow the study procedures: liver problems, unstable autoimmune disease, uncontrolled diabetes, heart issues, uncontrolled high blood pressure, recent history of certain cancers, recent alcohol or drug abuse, current psychiatric diagnosis that may interfere with study procedures, risk of self-harm, spinal diseases, bleeding problems, recent stroke, recent seizures, active or severe infections, severe allergies, history of certain infections, abnormal lab test results, recent participation in another study with disease-modifying effects on PD, recent gene or cell therapy, recent live vaccinations, recent use of certain medications, contraindications or intolerance to imaging methods, contraindications to anesthesia or sedation, positive urine test for drugs of abuse without prescription, frailty or medical condition that may not be in your best interest to participate in the study.

I don't have allergies or reasons I can't use corticosteroids or sirolimus, including recent severe osteoporosis, uncontrolled high blood pressure, diabetes, or cholesterol.

I have a brain condition that is not Parkinson's but could be causing my symptoms.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intracisternal administration of LY3884961 and are evaluated for safety, tolerability, immunogenicity, biomarkers, and clinical efficacy measures

12 months

Follow-up

Participants are monitored for safety and selected biomarker and efficacy measures

48 months

What Are the Treatments Tested in This Trial?

Interventions

• PR001

Trial Overview The PROPEL trial tests the safety of PR001 (LY3884961), an investigational drug administered into the spinal fluid for those with Parkinson's linked to GBA1 mutations. It includes two dosage levels over five years—initially focusing on safety and efficacy within the first year followed by long-term effects monitoring.

How Is the Trial Designed?

Group I: Dose Level 2 Experimental Treatment 3 Interventions

Group II: Dose Level 1 Experimental Treatment 3 Interventions

Who Is Running the Clinical Trial?

Prevail Therapeutics

Lead Sponsor

Trials

5

Recruited

190+

Eli Lilly and Company

Industry Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Published Research Related to This Trial

A precision medicine approach that tailors treatments based on individual genetic profiles may improve outcomes in Parkinson's disease, as many traditional trials have failed due to a generic treatment strategy.

The review identifies six ongoing clinical trials targeting GBA-associated Parkinson's disease and two targeting LRRK2-associated Parkinson's disease, highlighting the importance of focusing on specific genetic forms for potential disease modification.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Precision medicine in Parkinson's disease: emerging treatments for genetic Parkinson's disease. Schneider, SA., Alcalay, RN.[2021]

A phase 1 clinical trial has been conducted to evaluate kinase inhibitors that target LRRK2, which is a promising approach for treating Parkinson's disease.

This trial lays the groundwork for future studies to assess the effectiveness of LRRK2 inhibitors in managing Parkinson's disease symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A step forward for LRRK2 inhibitors in Parkinson's disease. Lewis, PA.[2022]

A new drug has demonstrated potential in delaying the onset of Parkinsonism, which is a significant advancement for patients at risk of developing this condition.

The findings suggest that this drug could improve the quality of life for individuals by postponing the debilitating symptoms associated with Parkinson's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delaying the onset of parkinson's disease. [2016]

The LRRK2 gene has been linked to Parkinson's disease, suggesting that targeting its kinase activity could lead to new treatments that may slow or prevent disease progression.

Current therapies only address symptoms of Parkinson's disease, highlighting the urgent need for innovative approaches like LRRK2 kinase inhibition, which could change the treatment landscape for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ten years and counting: moving leucine-rich repeat kinase 2 inhibitors to the clinic. West, AB.[2021]

The LRRK2 inhibitor BIIB122 was found to be safe and well-tolerated in both healthy participants and patients with Parkinson's disease, with no serious adverse events reported during the studies involving 186 healthy participants and 36 patients.

BIIB122 demonstrated significant reductions in LRRK2 activity and engagement of lysosomal pathways, indicating its potential effectiveness in treating Parkinson's disease, with evidence of good central nervous system distribution.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

LRRK2 Inhibition by BIIB122 in Healthy Participants and Patients with Parkinson's Disease. Jennings, D., Huntwork-Rodriguez, S., Vissers, MFJM., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04127578

Study Details | NCT04127578 | Phase 1/2a Clinical Trial of ... 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, ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04127578?cond=%22Parkinson's%20Disease%22&intr=%22Mometasone%20furoate%22&viewType=Table&rank=1

Phase 1/2a Clinical Trial of PR001 (LY3884961) in ... 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.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8543272/

Gene Therapy for Parkinson's Disease Associated with GBA1 ... These findings support the view that re-establishing normal levels of GCase enzyme activity may reduce the progression of Parkinson's disease in patients ...

4. clinicaltrial.be clinicaltrial.be/en/details/4608?per_page=20&recruiting=1&enrolling_by_invitation=1&active_not_recruiting=1&not_yet_recruiting=0&completed=0&only_recruiting=0&only_eligible=0

Phase 1/2a Clinical Trial of PR001 (LY3884961) in Patient... Clinically significant abnormalities in laboratory test results at Screening. Participation within 3 months prior to Screening in another ...

5. withpower.com withpower.com/trial/phase-2-parkinson-disease-2020-8d993

PR001 for Parkinson's Disease This trial is testing a new treatment called LY3884961 for people with moderate to severe Parkinson's disease who have a specific genetic mutation.

6. cgtlive.com cgtlive.com/view/prevail-therapeutics-seeking-bring-gene-therapy-pr001-parkinson-disease-phase-propel-clinical-trial

Prevail Therapeutics Seeking to Bring Gene Therapy ... The study's secondary end points include the change in glycolipid, GCase, and enzyme activity levels in the blood from baseline to 7 days, 14 ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12263715/

Investigational Gene Therapies for Parkinson's Disease - PMC Results at 6 months showed significant motor improvement and reduction of levodopa dose, and a 56% increase in PET signal using 6-[18F]fluoro-l- ...