A Study to Evaluate the Efficacy of Prasinezumab (RO7046015/PRX002) in Participants With Early Parkinson's Disease
Condition: Parkinson's Disease
MeSH terms: Parkinson Disease
Intervention: RO7046015; RO7046015; Placebo
Intervention description: RO7046015 will be administered at dose of 4500 milligrams (mg) for participants with body-weight greater than or equal to (>/=) 65 kilograms (kg) or 3500 mg for participants with body-weight less than (<) 65 kg.; RO7046015 will be administered at dose of 1500 mg to all participants in the indicated arm.; RO7046015 placebo will be administered to all participants in the indicated arm.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 316.0
Sex: All
Minimum age: 40 Years
Maximum age: 80 Years
Healthy volunteers: No

Summary:

      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 open-label extension
      (all-participants-on-RO7046015-treatment) for an additional 260 weeks.
    

Eligibility criteria:

        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. Use of contraceptive measures is not
             required for male participants enrolled in Part 3.

        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