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

• Register: ClinicalTrials.gov
• Last refreshed on: 25 March 2024
• Main ID: NCT04127578
• Date of registration: 14/10/2019
• Prospective Registration: Yes
• Primary sponsor: Prevail Therapeutics
• Public title: Phase 1/2a Clinical Trial of PR001 (LY3884961) in Patients With Parkinson's Disease With at Least One GBA1 Mutation (PROPEL)
• Scientific title: A Phase 1/2a Open-Label Ascending Dose Study to Evaluate the Safety and Effects of LY3884961 in Patients With Parkinson's Disease With at Least One GBA1 Mutation (PROPEL)
• Date of first enrolment: January 3, 2020
• Target sample size: 20
• Recruitment status: Recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT04127578
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Sequential Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1/Phase 2

Countries of recruitment

Israel, United States

Contacts

• Name: Travis B. Lewis, MD, PhD
• Affiliation: Prevail Therapeutics

• Name: Prevail Therapeutics

Key inclusion & exclusion criteria

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



Age minimum: 35 Years
Age maximum: 80 Years
Gender: All

Health Condition(s) or Problem(s) studied

Parkinson Disease

Intervention(s)

Drug: Sirolimus

Drug: Methylprednisolone

Biological: LY3884961

Primary Outcome(s)

Cumulative number of Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [Time Frame: 5 years]

Change from baseline in immunogenicity of Nfl in blood [Time Frame: Baseline and Month 24]

Change in immunogenicity of AAV9 in CSF [Time Frame: Baseline and Month 12]

Treatment emergent immunogenicity of GCase in CSF [Time Frame: Thru Month 24]

Incidence of procedure or treatment-emergent AEs measured by brain MRI, spine MRI and nerve conduction study (NCS) [Time Frame: 5 years]

Treatment emergent immunogenicity of AAV9 in blood [Time Frame: Thru month 24]

Change from baseline in immunogenicity of AAV9 in blood [Time Frame: Baseline and Month 24]

Treatment emergent immunogenicity of GCase in blood [Time Frame: Thru Month 24]

Treatment emergent immunogenicity of Nfl in blood [Time Frame: Thru Month 24]

Treatment emergent immunogenicity of AAV9 in CSF [Time Frame: Thru Month 24]

Change from baseline in immunogenicity of GCase in blood [Time Frame: Baseline and Months 24]

Change in immunogenicity of GCase in CSF [Time Frame: Baseline, and Months 12]

Secondary Outcome(s)

GCase enzyme activity levels in blood [Time Frame: Days 7, 14, and 21, and Months 1, 1.5, 2, 3, 6, 9 and 12]

Change in glycolipid levels in blood [Time Frame: Baseline, Days 7, 14, and 21, and Months 1, 1.5, 2, 3, 6, 9 and 12]

Change in GCase levels in CSF [Time Frame: Baseline, and Months 2, 6, and 12]

Change in glycolipid levels in CSF [Time Frame: Baseline, and Months 2, 6, and 12]

Change in GCase levels [Time Frame: Baseline, Days 7, 14, and 21, and Months 1, 1.5, 2, 3, 6, 9 and 12]

GCase enzyme activity levels in CSF [Time Frame: Months 2, 6, and 12]

Secondary ID(s)

J3Z-MC-OJAA formerly PRV-PD101

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Eli Lilly and Company