A Study to Evaluate the Efficacy of Prasinezumab (RO7046015/PRX002) in Participants With Early Parkinson's Disease
A Study to Evaluate the Efficacy of Prasinezumab (RO7046015/PRX002) in Participants With Early Parkinson's Disease
This multicenter, randomized, double-blind, placebo-controlled, Phase 2 study will evaluate
 the efficacy of intravenous prasinezumab (RO7046015/PRX002) versus placebo over 52 weeks in
 participants with early Parkinson's Disease (PD) who are untreated or treated with monoamine
 oxidase B (MAO-B) inhibitors since baseline. The study will consist of three parts: a
 52-week, double-blind, placebo-controlled treatment period (Part 1) after which eligible
 participants will continue into an all-participants-on-treatment blinded dose extension for
 an additional 52 weeks (Part 2). Participants who complete Part 2 (including the 12-week
 treatment-free follow up visit assessing long term safety and efficacy of RO7046015) will be
 offered participation in Part 3 (all-participants-on-RO7046015-treatment) for an additional
 260 weeks.
Inclusion Criteria:

 -  Idiopathic PD with bradykinesia plus one of the other cardinal signs of PD (resting
 tremor, rigidity) being present, without any other known or suspected cause of PD
 untreated or treated with MAO-B inhibitor

 -  Body weight range between: >/=45 kg/ 99 pounds (lbs) and less than or equal to (</=)
 110 kg/242 lbs

 -  Body mass index (BMI) of 18 to 34 kilograms per meter-squared (kg/m^2)

 -  A diagnosis of PD for 2 years or less at screening

 -  Hoehn and Yahr Stage I or II

 -  A screening brain DaT-SPECT consistent with PD (central reading)

 -  Clinical status does not require dopaminergic PD medication and is not expected to
 require dopaminergic treatment within 52 weeks from baseline

 -  If presently being treated for PD, a stable dose of MAO-B inhibitor (rasagiline or
 selegiline) for at least 90 days prior to baseline and not expected to change within
 52 weeks

 -  For women of childbearing potential: use of highly effective contraceptive methods
 (that result in a failure rate of <1 percent [%] per year) during the treatment period
 and for at least 30 days (or longer if required by local regulations) after the last
 dose of study drug

 -  For men with female partners of childbearing potential or pregnant female partners,
 must use a condom during the treatment period and for at least 30 days (or longer if
 required by local regulations) after the last dose of study drug to avoid exposing the
 embryo. Men 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 30 days (or longer if required by local
 regulations) after the last dose of study drug

 Exclusion Criteria:

 -  Medical history indicating a Parkinson syndrome other than idiopathic PD, including
 but not limited to, progressive supranuclear gaze palsy, multiple system atrophy,
 drug-induced parkinsonism, essential tremor, primary dystonia

 -  Known carriers of certain familial PD genes (as specified in study protocol)

 -  History of PD related freezing episodes or falls

 -  A diagnosis of a significant CNS disease other than Parkinson's disease; history of
 repeated head injury; history of epilepsy or seizure disorder other than febrile
 seizures as a child

 -  Mini Mental State Examination (MMSE) </=25

 -  Reside in a nursing home or assisted care facility

 -  History of or screening brain magnetic resonance imaging (MRI) scan indicative of
 clinically significant abnormality

 -  Concomitant disease or condition 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 risk to the participant in this study or interfere
 with the participant's ability to comply with study procedures or abide by study
 restrictions, or with the ability to interpret safety data

 -  Any significant cardiovascular condition

 -  Any significant laboratory abnormality

 -  Lactating women

 -  Prior treatment with dopaminergic medication (for example, levodopa or a dopaminergic
 agonist) with no clinical treatment response or a clinical treatment response
 inconsistent with PD (for example, absence of observable response to a sufficiently
 high-dose of levodopa [i.e., ≥ 600 mg/day])

 -  Use of any of the following: catechol-O-methyl transferase (COMT) inhibitors
 (entacapone, tolcapone), amantadine or anticholinergics, or dopaminergic medication
 (levodopa and both ergot and non-ergot [pramipexole, ropinirole, rotigotine] dopamine
 agonists) for more than a total of 60 days or within 60 days of baseline

 -  Anti-epileptic medication for non-seizure-related treatment which has not remained
 stable for at least 60 days prior to baseline

 -  Anti-depressant or anxiolytic use that has not remained stable for at least 90 days
 prior to baseline. The use of fluoxetine and fluvoxamine is not permitted. For
 patients treated with a MAO-B inhibitor and an antidepressant (except fluoxetine and
 fluvoxamine), a 6-month period of stable and tolerated dosing before baseline is
 required.

 -  Use of any of the following within 90 days prior to baseline: antipsychotics
 (including clozapine and olanzapine), metoclopramide, alpha methyldopa, clozapine,
 olanzapine, flunarizine, amoxapine, amphetamine derivatives, reserpine, bupropion,
 buspirone, cocaine, mazindol, methamphetamine, methylphenidate, norephedrine,
 phentermine, phenylpropanolamine, and modafinil

 -  Participated in an investigational drug, device, surgical , or stem cell study in PD

 -  Any prior treatment with an investigational PD-related vaccine (including active
 immunization or passive immunotherapy with monoclonal antibodies).

 -  Prior participation in any RO7046015 or PRX002 study

 -  Receipt of any non-PD investigational product or device, or participation in a non-PD
 drug research study within a period of 30 days (or 5 half-lives of the drug, whichever
 is longer) before baseline

 -  Receipt of any monoclonal antibody or an investigational immunomodulator within 180
 days (or 5 half-lives, whichever is longer) before baseline

 -  Immunomodulating drugs within 30 days prior to baseline

 -  Allergy to any of the components of RO7046015 such as citrate, trehalose and
 polysorbate (Tween) 20 or a known hypersensitivity or an Infusion-related reaction
 (IRR) to the administration of any other monoclonal antibody

 -  Any contraindications to obtaining a brain MRI. Patients with a hypersensitivity to
 iodine may receive an alternative thyroid blocking agent.

 -  For participants consenting to provide optional cerebrospinal fluid (CSF) samples by
 lumbar puncture (LP): LP will only be performed if the participant does not have any
 contraindication to undergoing an LP

 -  Donation of blood over 500 milliliters (mL) within three months prior to screening