A Study to Investigate The Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of RO7486967 in Participants With Early Idiopathic Parkinson's Disease

A Phase 1b, Adaptive, Multi-Center, Randomized, Double Blind, Placebo-Controlled, Parallel Design Study to Investigate The Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of RO7486967 in Participants With Early Idiopathic Parkinson's Disease

This is a multi-center, randomized, double blind, adaptive, parallel-group, placebo controlled Phase 1b study to evaluate the safety, tolerability, pharmacokinetic (PK) and pharmacodynamics of RO7486967 in participants with idiopathic PD at the early stage of the disease (modified H&Y stage ≤2.5) who are either treatment-naïve or on stable treatment with symptomatic therapy (levodopa and/or pramipexole, ropinirole, rotigotine).

Study Overview

• Status: Recruiting
• Conditions: Parkinson Disease
• Intervention / Treatment: Drug: RO7486967; Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 72
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Reference Study ID Number: BP43176 https://forpatients.roche.com/; Phone Number: 888-662-6728 (U.S. Only); Email: global-roche-genentech-trials@gene.com

Study Locations

• Netherlands
  • Amsterdam, Netherlands, 1081 GN
    • Recruiting
    • Brain Research Center B.V
  • Nijmegen, Netherlands, 6525 GA
    • Recruiting
    • UMC St Radboud
  • Zwolle, Netherlands, 8025AZ
    • Recruiting
    • Brain Research Center Zwolle
• United Kingdom
  • Exeter, United Kingdom, EX4 4RN
    • Recruiting
    • University of Exeter
  • London, United Kingdom, SW17 0RE
    • Withdrawn
    • St Georges University Hospitals NHS Foundation Trust
  • London, United Kingdom, WC1N 3BG
    • Recruiting
    • National Hospital for Neurology and Neurosurgery; Leonard Wolfson Experimental Neurology Centre CRF
  • London, United Kingdom, E1 2ES
    • Completed
    • Barts Health NHS Trust
  • London, United Kingdom, W6 8RF
    • Suspended
    • Imperial College Healthcare NHS Trust; Charing Cross Hospital
  • Newcastle, United Kingdom, NE4 5PL
    • Recruiting
    • Campus for Ageing & Vitality; Clincal Ageing Research Unit
  • Plymouth, United Kingdom, PL6 8BT
    • Withdrawn
    • Derriford Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Recruiting
      • University of Alabama at Birmingham
  • California
    • Los Angeles, California, United States, 90048
      • Recruiting
      • Cedars Sinai Medical Center
  • Colorado
    • Englewood, Colorado, United States, 80113
      • Recruiting
      • CenExel Rocky Mountain Clinical Research, LLC
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Recruiting
      • Georgetown University
  • Florida
    • Orlando, Florida, United States, 32804
      • Recruiting
      • Advent Health Orlando
  • Georgia
    • Decatur, Georgia, United States, 30033
      • Withdrawn
      • NeuroStudies.net, LLC
  • Michigan
    • Farmington Hills, Michigan, United States, 48334
      • Recruiting
      • Quest Research Institute
  • New York
    • New York, New York, United States, 10065
      • Recruiting
      • Weill Cornell Medical College
    • New York, New York, United States, 10032
      • Withdrawn
      • Columbia University Medical Center; The Neurological Institute of New York
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74136
      • Recruiting
      • The Movement Disorder Clinic of Oklahoma
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • University Pennsylvania Hospital
  • Tennessee
    • Nashville, Tennessee, United States, 37212
      • Withdrawn
      • Vanderbilt University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Key Criteria:

• Male or post-menopausal female
• Diagnosis of clinically probable idiopathic PD based on MDS criteria with bradykinesia plus one of the other cardinal signs of PD (resting tremor, rigidity)
• A time from diagnosis of PD of at least 3 to maximum 60 months (5 years) at screening
• Modified H&Y Stage ≤2.5 (in ON state)
• Dopaminergic imaging consistent with dopamine transporter deficit
• "High-affinity binder" or "mixed-affinity binder" genotype for TSPO
• Either treatment naïve or treatment with symptomatic PD therapy (levodopa and/or pramipexole, ropinirole, rotigotine) given for at least 90 days, with stable doses for at least 30 days prior to the first dose
• No anticipated changes in PD therapy throughout the study duration
• SARS-CoV-2 vaccination completed at least 60 days prior to the first dose.

Exclusion Key Criteria:

• Medical history indicating a Parkinsonian syndrome other than idiopathic PD
• CNS or psychiatric disorders other than idiopathic PD (mild depression or anxiety arising in the context of PD is not exclusionary)
• History of brain surgery for PD
• Use of any of symptomatic drug for PD other than levodopa pramipexole, ropinirole, or rotigotine within 60 days prior to the first dose
• Known carriers for mutations in the following genes: alpha-synuclein, LRRK2, GBA, PRKN, PINK1, or DJ1
• Unstable or clinically significant cardiovascular disease within the last year prior to screening
• Uncontrolled hypertension
• Use of oral anticoagulants, low-molecular-weight heparin, warfarin (Coumadin), acenocoumarol, and phenprocoumon is not allowed within 10 days before the first Lumbar Puncture and during the study (low dose aspirin is permitted as monotherapy)
• Concomitant disease or unstable medical condition within 6 months of screening that could interfere with the study or treatment that might interfere with the conduct of the study, including but not limited to autoimmune disease, immunodeficiency diseases, any active infectious disease
• History of immunodeficiency diseases
• Presence of hepatitis B surface antigen (HBsAg) or positive for total hepatitis B core antibody (HBcAb), or positive hepatitis C (HCV) at screening
• Vaccine(s) other than SARS-CoV2 vaccine within 28 days prior to the first dose, or plans to receive vaccines during the study or within 28 days of the last dose
• History of chronic liver disease
• Clinically significant abnormalities in laboratory test results at screening, including hepatic and renal panels, complete blood count, chemistry panel and urinalysis
• Any previous administration of RO7486967 or other compound targeting NLRP3
• Enrollment in another investigational study
• Use of any of other investigational therapy (other than protocol-mandated study treatment) within 90 days or 5 drug elimination half-lives (whichever is longer) prior to the first dose

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Matching placebo	Drug: Placebo; For up to approximately 28 days
Experimental: RO7486967 Arm; Participants will receive RO07486967 for approximately 28 days with 14 days of follow up after the last dose.	Drug: RO7486967; For up to approximately 28 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of Participants with adverse events (AEs)	Up to 45 Days
The change in Columbia-Suicide Severity Rating Scale (C-SSRS) Scores from baseline	From Baseline to Up to 45 Days

Secondary Outcome Measures

Outcome Measure	Time Frame
Time to maximum concentration of RO7486967 in Plasma	Day 1, Day 15, and Day 28
Maximum concentration (Cmax) of RO7486967 in Plasma	Day 1, Day 15, and Day 28
Area under the curve (AUC) RO7486967 in Plasma	Day 1, Day 15, and Day 28
Change from baseline in parametric bindings of [18F]-DPA-714 in different brain areas at Day 25 PET	From Baseline to Approximately Day 25

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): September 22, 2022
• Primary Completion (Estimated): January 30, 2025
• Study Completion (Estimated): January 30, 2025

Study Registration Dates

• First Submitted: June 21, 2023
• First Submitted That Met QC Criteria: June 21, 2023
• First Posted (Actual): June 29, 2023

Study Record Updates

• Last Update Posted (Actual): April 15, 2024
• Last Update Submitted That Met QC Criteria: April 12, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease
• Other Study ID Numbers: BP43176

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No