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

NCT05924243 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: BP43176
• Study Type: interventional
• Target: 60
• Locations: 3 countries
• Sites: 17

Brief Summary

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).

Conditions

Parkinson Disease

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• 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

Study Arms (2)

RO7486967 Arm

EXPERIMENTAL

Participants will receive RO07486967 for approximately 28 days with 14 days of follow up after the last dose.

Drug: RO7486967

Placebo

PLACEBO COMPARATOR

Matching placebo

Drug: Placebo

Interventions

RO7486967 DRUG

For up to approximately 28 days

RO7486967 Arm

Placebo DRUG

For up to approximately 28 days

Placebo

Eligibility Criteria

• Age: 40 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (17)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Cedars Sinai Medical Center

Los Angeles, California, 90048, United States

Location

CenExel Rocky Mountain Clinical Research, LLC

Englewood, Colorado, 80113, United States

Location

Georgetown University

Washington D.C., District of Columbia, 20007, United States

Location

Advent Health Orlando

Orlando, Florida, 32804, United States

Location

Quest Research Institute

Farmington Hills, Michigan, 48334, United States

Location

Weill Cornell Medical College

New York, New York, 10065, United States

Location

The Movement Disorder Clinic of Oklahoma

Tulsa, Oklahoma, 74136, United States

Location

University Pennsylvania Hospital

Philadelphia, Pennsylvania, 19104, United States

Location

Brain Research Center B.V

Amsterdam, 1081 GN, Netherlands

Location

UMC St Radboud

Nijmegen, 6525 GA, Netherlands

Location

Brain Research Center Zwolle

Zwolle, 8025AZ, Netherlands

Location

University of Exeter

Exeter, EX4 4RN, United Kingdom

Location

Barts Health NHS Trust

London, E1 2ES, United Kingdom

Location

Imperial College Healthcare NHS Trust; Charing Cross Hospital

London, W6 8RF, United Kingdom

Location

National Hospital for Neurology and Neurosurgery; Leonard Wolfson Experimental Neurology Centre CRF

London, WC1N 3BG, United Kingdom

Location

Campus for Ageing & Vitality; Clincal Ageing Research Unit

Newcastle, NE4 5PL, United Kingdom

Location

MeSH Terms

Conditions

Parkinson Disease

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 21, 2023
• First Posted: June 29, 2023
• Study Start: September 22, 2022
• Primary Completion: July 18, 2024
• Study Completion: July 18, 2024
• Last Updated: September 19, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

NL (3); GB (5); US (9)