A Randomized, Double-Blind, Placebo-Controlled, 52-Week Phase II Study to Evaluate the Efficacy of Intravenous RO7046015/Prasinezumab (PRX002) in Participants With Early Parkinson's Disease With a 11-Year All-Participants-on-Treatment Extension
Overview
- Phase
- Phase 2
- Intervention
- RO7046015
- Conditions
- Parkinson's Disease
- Sponsor
- Hoffmann-La Roche
- Enrollment
- 316
- Locations
- 57
- Primary Endpoint
- Change From Baseline in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Total Score (Sum of Parts I, II, and III) at Week 52
- Status
- Active, not recruiting
- Last Updated
- last month
Overview
Brief 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 520 weeks.
Investigators
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
Arms & Interventions
Part 1: RO7046015 High Dose
Participants will receive RO7046015 at high dose level as intravenous (IV) infusion every 4 weeks (Q4W) up to 52 weeks in Part 1.
Intervention: RO7046015
Part 1: RO7046015 Low Dose
Participants will receive RO7046015 at low dose level as IV infusion Q4W up to 52 weeks in Part 1.
Intervention: RO7046015
Part 1: Placebo
Participants will receive placebo as IV infusion Q4W up to 52 weeks in Part 1.
Intervention: Placebo
Part 2: RO7046015 High Dose
Part 1 RO7046015 high dose group participants and placebo group participants randomized to high dose level will receive RO7046015 at high dose level as IV infusion Q4W for additional 52 weeks in Part 2.
Intervention: RO7046015
Part 2: RO7046015 Low Dose
Part 1 RO7046015 low dose group participants and placebo group participants randomized to low dose level will receive RO7046015 at low dose level as IV infusion Q4W for additional 52 weeks in Part 2.
Intervention: RO7046015
Part 3: RO7046015 Low Dose
All participants who complete Part 1 and Part 2 will receive monthly IV infusions of RO7046015.
Intervention: RO7046015
Outcomes
Primary Outcomes
Change From Baseline in Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Total Score (Sum of Parts I, II, and III) at Week 52
Time Frame: From baseline to Week 52
The MDS-UPDRS is a multimodal scale consisting of four parts. Part I assessed non-motor experiences of daily living and has 2 components (Range 0-52). Part IA contains 6 questions and are assessed by the examiner (Range 0-24). Part IB contains 7 questions on non-motor experiences of daily living which was completed by the participant (Range 0-28). Part II assessed motor experiences of daily living (Range 0-52). It contained 13 questions completed by the participant. Part III assessed the motor signs of Parkinson's Disease (PD) and was administered by the rater (Range 0-132). Part III contained 33 scores based on 18 items. For each question a numeric score is assigned between 0-4, where 0 = Normal, 1 = Slight, 2 = Mild, 3 = Moderate, 4 = Severe. The MDS-UPDRS Total Score equals the sum of Parts I,II, and III (Range: 0-236). A higher score indicated more severe symptoms of Parkinson's disease.
Secondary Outcomes
- Change From Baseline in Montreal Cognition Assessment (MoCA) Total Score(From baseline to Week 52)
- Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs)(From baseline to Week 52)
- Percentage of Participants With Anti-Drug Antibodies (ADAs) Against RO7046015(Baseline, Pre-dose (0 hours) on Weeks 4, 20, 36, 52, 56, 68, 80, and 104; at early termination (up to Week 104), and follow-up (12 weeks after last dose up to Week 116))
- Maximum Observed Serum Concentration (Cmax) of RO7046015 at Steady-state(Baseline over the duration of the study)
- Change From Baseline in Clinical Global Impression of Improvement (CGI-I) Score(From baseline to Week 52)
- Change From Baseline in Patient Global Impression of Change (PGIC) Score(From baseline to Week 52)
- Time to Worsening in Motor or Non-Motor Symptoms(From baseline to Week 52)
- Systemic Clearance (CL) of RO7046015(Predose (0 hours) and end of infusion (infusion length=2 hours or less) on Baseline, Weeks 4, 20, 36, 52, 56, 68, 80, and 104; at Day 7, Day 14, early termination (up to Week 104), and follow-up (12 weeks after last dose up to Week 116))
- Change From Baseline in the MDS-UPDRS Part IA, Part IB, Part I Total, Part II Total, Part III Total and Part III Subscores(From baseline to Week 52)
- Change From Baseline in Dopamine Transporter Imaging With Single Photon Emission Computed Tomography (DaT-SPECT) Striatal Binding Ratio (SBR) in the Putamen Ipsilateral to the Clinically Most Affected Side(From baseline to Week 52)
- Minimum Observed Serum Concentration (Ctrough) of RO7046015 at Steady-state(Baseline over the duration of the study)
- Change From Baseline in Schwab and England Activity of Daily Living (SE-ADL) Score(From baseline to Week 52)
- Time to Start of Dopaminergic Parkinson's Disease Treatment(From baseline to Week 52)
- Apparent Volume of Distribution (Vz/F) of RO7046015(Predose (0 hours) and end of infusion (infusion length=2 hours or less) on Baseline, Weeks 4, 20, 36, 52, 56, 68, 80, and 104; at Day 7, Day 14, early termination (up to Week 104), and follow-up (12 weeks after last dose up to Week 116))
- Area Under the Serum Concentration-Time Curve (AUC) of RO7046015 Over the Dosing Interval(Baseline over the duration of the study)