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

NCT ID: NCT05924243

Last Updated: 2024-09-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-09-22
• Study Completion Date: 2024-07-18

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

RO7486967 Arm

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

Group Type: EXPERIMENTAL

RO7486967

Intervention Type: DRUG

For up to approximately 28 days

Placebo

Matching placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

For up to approximately 28 days

Interventions

RO7486967

For up to approximately 28 days

Intervention Type: DRUG

Placebo

For up to approximately 28 days

Intervention Type: DRUG

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

Cedars Sinai Medical Center

Los Angeles, California, United States

CenExel Rocky Mountain Clinical Research, LLC

Englewood, Colorado, United States

Georgetown University

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

Advent Health Orlando

Orlando, Florida, United States

Quest Research Institute

Farmington Hills, Michigan, United States

Weill Cornell Medical College

New York, New York, United States

The Movement Disorder Clinic of Oklahoma

Tulsa, Oklahoma, United States

University Pennsylvania Hospital

Philadelphia, Pennsylvania, United States

Brain Research Center B.V

Amsterdam, , Netherlands

UMC St Radboud

Nijmegen, , Netherlands

Brain Research Center Zwolle

Zwolle, , Netherlands

University of Exeter

Exeter, , United Kingdom

Barts Health NHS Trust

London, , United Kingdom

Imperial College Healthcare NHS Trust; Charing Cross Hospital

London, , United Kingdom

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

London, , United Kingdom

Campus for Ageing & Vitality; Clincal Ageing Research Unit

Newcastle, , United Kingdom

Countries

United States; Netherlands; United Kingdom

Other Identifiers

BP43176

Identifier Type: -

Identifier Source: org_study_id