A Study to Evaluate the Efficacy of Prasinezumab (RO7046015/PRX002) in Participants With Early Parkinson's Disease (PASADENA)

• ClinicalTrials.gov Identifier: NCT03100149
• Recruitment Status: Active, not recruiting
• First Posted: April 4, 2017
• Last Update Posted: April 26, 2019
• Sponsor: Hoffmann-La Roche
• Collaborator: Prothena Biosciences Limited
• Information provided by (Responsible Party): Hoffmann-La Roche

Tracking Information

• First Submitted Date: March 29, 2017
• First Posted Date: April 4, 2017
• Last Update Posted Date: April 26, 2019
• Actual Study Start Date: June 27, 2017
• Estimated Primary Completion Date: December 10, 2019 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: March 29, 2017): 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: Baseline and Week 52 ]
• Original Primary Outcome Measures: Same as current
• Change History: Complete list of historical versions of study NCT03100149 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: March 29, 2017)

• Change From Baseline in Dopamine Transporter Imaging With Single Photon Emission Computed Tomography (DaT-SPECT) Signal at Week 52 [ Time Frame: Baseline and Week 52 ]
• Change From Baseline in the MDS-UPDRS Motor Subscale (Part III) Score [ Time Frame: Baseline and Week 52 ]
• Clinical Global Impression of Improvement (CGI-I) Score at Weeks 24 and 52 [ Time Frame: Week 24 and Week 52 ]
• Patient Global Impression of Change (PGIC) Score at Weeks 24 and 52 [ Time Frame: Week 24 and Week 52 ]
• Time to Start of Dopaminergic Symptomatic Treatment [ Time Frame: From Baseline to Week 52 ]
• Percentage of Participants With Adverse Events (AEs) and Serious AEs (SAEs) [ Time Frame: From Day 1 to Week 104 ]
• Percentage of Participants With Anti-Drug Antibodies (ADAs) Against RO7046015 [ Time Frame: 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) ]
• Systemic Clearance (CL) of RO7046015 [ Time Frame: Predose (0 hours) and end of infusion (infusion length=2 hours or less) on Day 1, 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) ]
• Apparent Volume of Distribution (Vz/F) of RO7046015 [ Time Frame: Predose (0 hours) and end of infusion (infusion length=2 hours or less) on Day 1, 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 [ Time Frame: Predose (0 hours) and end of infusion (infusion length=2 hours or less) on Day 1, 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) ]
• Maximum Observed Serum Concentration (Cmax) of RO7046015 [ Time Frame: Predose (0 hours) and end of infusion (infusion length=2 hours or less) on Day 1, 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) ]
• Minimum Observed Serum Trough Concentration (Ctrough) of RO7046015 [ Time Frame: Predose (0 hours) and end of infusion (infusion length=2 hours or less) on Day 1, 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) ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study to Evaluate the Efficacy of Prasinezumab (RO7046015/PRX002) in Participants With Early Parkinson's Disease
• Official Title: A Randomized, Double-Blind, Placebo-Controlled, 52-Week Phase II Study to Evaluate the Efficacy of Intravenous RO7046015 (PRX002) in Participants With Early Parkinson's Disease With a 52-Week Blinded Extension
• 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 2 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).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Parkinson's Disease

Intervention

• Drug: RO7046015
  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.
  Other Name: PRX002; prasinezumab
• Drug: RO7046015
  RO7046015 will be administered at dose of 1500 mg to all participants in the indicated arm.
  Other Name: PRX002; prasinezumab
• Drug: Placebo
  RO7046015 placebo will be administered to all participants in the indicated arm.

Study Arms

• Experimental: Part 1: RO7046015 High Dose
  Participants will receive RO7046015 at high dose level as intravenous infusion every 4 weeks (Q4W) up to 52 weeks in Part 1.
  Intervention: Drug: RO7046015
• Experimental: Part 1: RO7046015 Low Dose
  Participants will receive RO7046015 at low dose level as intravenous infusion Q4W up to 52 weeks in Part 1.
  Intervention: Drug: RO7046015
• Placebo Comparator: Part1: Placebo
  Participants will receive placebo as intravenous infusion Q4W up to 52 weeks in Part 1.
  Intervention: Drug: Placebo
• Experimental: 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 intravenous infusion Q4W for additional 52 weeks in Part 2.
  Intervention: Drug: RO7046015
• Experimental: 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 intravenous infusion Q4W for additional 52 weeks in Part 2.
  Intervention: Drug: RO7046015

• Publications *: Jankovic J, Goodman I, Safirstein B, Marmon TK, Schenk DB, Koller M, Zago W, Ness DK, Griffith SG, Grundman M, Soto J, Ostrowitzki S, Boess FG, Martin-Facklam M, Quinn JF, Isaacson SH, Omidvar O, Ellenbogen A, Kinney GG. Safety and Tolerability of Multiple Ascending Doses of PRX002/RG7935, an Anti-α-Synuclein Monoclonal Antibody, in Patients With Parkinson Disease: A Randomized Clinical Trial. JAMA Neurol. 2018 Oct 1;75(10):1206-1214. doi: 10.1001/jamaneurol.2018.1487.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: December 14, 2018): 316
• Original Estimated Enrollment (submitted: March 29, 2017): 300
• Estimated Study Completion Date: February 18, 2021
• Estimated Primary Completion Date: December 10, 2019 (Final data collection date for primary outcome measure)

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

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 40 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Austria, France, Germany, Spain, United States

Administrative Information

• NCT Number: NCT03100149
• Other Study ID Numbers: BP39529; 2017-000087-15 ( EudraCT Number )
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Responsible Party: Hoffmann-La Roche
• Study Sponsor: Hoffmann-La Roche
• Collaborators: Prothena Biosciences Limited
• Investigators: Not Provided
• PRS Account: Hoffmann-La Roche
• Verification Date: April 2019