A Phase 2 study of VQ-101 in participants with Parkinson’s disease and GBA1 mutation

Prior treatment

• (Part A and B) History of or active substance use disorder (including alcohol) in the 12 months prior to screening, or positive urine drug screen for illicit drugs or drugs of abuse at screening and/or Day 1 pre-dose, or an unwillingness to abstain from these substances during in-clinic visit days. Marijuana and cannabinoids are allowed during the study, however participants should abstain from their ingestion at least 24 hours prior to study visits.
• (Part A and B) Has a significant risk of suicide according to the C-SSRS at Screening or Baseline (Day 0) or has attempted suicide within 12 months prior to the screening visit.
• (Part A and B) Participants who took any medications specifically used for treating memory dysfunction, such as, but not limited to cholinesterase inhibitors or memantine, within 30 days or 5 half-lives of these medications prior to randomization, whichever is longer
• (Part A and B) Current participation in or within 5 half-lives (or correspondent washout time for monoclonal antibody therapies) from another investigational interventional trial. Participants from another investigational interventional trial who are more than 5 half-lives or 2 weeks post-dose at the start of Part B, whichever is longer, are permitted in the trial.
• (Part A and B) Current or prior participation in an investigational trial of cell or gene therapy.
• (Part A and B) Current use of ambroxol use at doses >120 mg/day. Prior use of ambroxol (>120 mg/day) is permitted if participant is more than 2 weeks post-dose at the start of Part B.

Other illness

• (Part A and B) Atypical parkinsonism (e.g., diagnoses of progressive supranuclear palsy, cortico-basal syndrome, or multiple system atrophy) or secondary parkinsonism (e.g., due to drug(s) and/or toxin(s), vascular parkinsonism) as assessed by medical history or in the opinion of the Investigator.
• (Part A and B) Participants with regular presence of L-dopa-induced motor complications or with clinical signs of L-dopa dysregulation syndrome.
• (Part A and B) Participants with GD as defined by clinical signs and symptoms (i.e., hepatosplenomegaly, cytopenia, skeletal disease).
• (Part A and B) Participants with history of any surgical treatment for PD (e.g., deep brain stimulation, pallidotomy, thalamotomy, cell transplant).

Lab values

• (Part A and B) Any medical disorders and/or clinically relevant findings in the physical examination, medical history, or laboratory assessments that, in the opinion of the Investigator, could interfere with trial-related procedures including but not limited to: a. Diagnosis of a significant neurologic disease other than PD (e.g., Huntington’s disease, normal pressure hydrocephalus, cerebrovascular disease including stroke, frontotemporal dementia, Alzheimer’s disease). b. Unstable or clinically significant cardiovascular disease (e.g., myocardial infarction within 12 months from baseline, unstable angina, congestive heart failure, arrhythmias, confirmed bradycardia [<45 bpm] or tachycardia [>100 bpm at rest]). c. Uncontrolled hypertension. d. Total bilirubin, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2 times the upper limit of normal (ULN). e. Serum creatinine > 1.5 times the ULN. f. History of (within 60 days before initiation of screening) or planned upcoming major surgery that could interfere with, or for which the treatment might interfere with the conduct of the study or that would pose an unacceptable risk to the subject in the opinion of the Investigator. g. Other clinically significant abnormalities in laboratory tests, complete blood count, chemistry panel, and/or urinalysis results at the screening visit. Minor deviations in laboratory values from the normal range may be acceptable if judged by the Investigator to have no/minor clinical relevance.
• (Part A and B) For participants consenting to the optional lumbar puncture, participant has contraindication to lumbar dural puncture, including coagulopathy, concomitant anticoagulation medication (except for a platelet inhibitor such as aspirin), thrombocytopenia, or other factor(s) that precludes safe lumbar puncture.

Other

• (Part A and B) Participants with psychosis.
• (Part A and B) Participants with freezing and severe symptomatic orthostatic hypotension.
• (Part A and B) Participants with a known LRRK2 risk variant, homozygous or compound heterozygous GBA1 mutations.
• (Part A and B) CCI
• (Part A and B) Montreal Cognitive Assessment (MoCA) score of <22.
• (Part A and B) CCI
• (Part A and B) CCI

• (Part A and B) Able to provide a signed written informed consent.
• (Part A and B) Age 35 to 80 years inclusive, male or female.
• (Part A and B) Clinical diagnosis of Parkinson’s disease <5 years at time of screening according to the Movement Disorder Society (MDS) Clinical Diagnostic Criteria.
• (Part B) Modified Hoehn and Yahr stage ≤2.5 [CCI] at screening and at baseline.
• (Part B) Known carrier of a heterozygous mutation in GBA1 as determined in Part A or with documented positivity from an accredited laboratory (e.g., CLIA-certified or ISO 15189-accredited, or equivalent national accreditation).
• (Part B) If receiving levodopa or any other symptomatic medication for PD (such as a dopamine agonist), therapy must have been initiated at least 90 days prior to Part B screening, and the medication regimen must be stable for at least 30 days (at least 60 days for rasagiline) prior to Part B screening.
• (Part B) Able to ingest oral medication.
• (Part B) Able to complete all aspects of the trial alone, according to the Investigator’s judgment.
• (Part B) Agree to trial contraception requirements: Males with female partners of childbearing potential or pregnant female partners must use a condom during the treatment period and for at least 28 days (or longer if required by local regulations) after the last dose of trial intervention to avoid exposing the embryo. Males must refrain from donating sperm during this same period. The female partners should use a contraception method with a failure rate of <1% per year during the treatment period and for at least 28 days (or longer if required by local regulations) after the last dose of trial intervention. The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation methods) and withdrawal are not acceptable methods of contraception.