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

Parkinson Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05924243
• Other study ID #: BP43176
• Status: Recruiting
• Phase: Phase 1
• Start date: September 22, 2022
• Est. completion date: January 30, 2025

Study information

• Verified date: June 2024
• Source: Hoffmann-La Roche
• Contact: Reference Study ID Number: BP43176 https://forpatients.roche.com
• Phone: 888-662-6728 (U.S. Only)
• Email: global-roche-genentech-trials[@]gene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 72
• Est. completion date: January 30, 2025
• Est. primary completion date: January 30, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Parkinson Disease

Intervention

Drug:
• RO7486967
For up to approximately 28 days
• Placebo
For up to approximately 28 days

Locations

Country	Name	City	State
Netherlands	Brain Research Center B.V	Amsterdam
Netherlands	UMC St Radboud	Nijmegen
Netherlands	Brain Research Center Zwolle	Zwolle
United Kingdom	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	St Georges University Hospitals NHS Foundation Trust	London
United Kingdom	Campus for Ageing & Vitality; Clincal Ageing Research Unit	Newcastle
United Kingdom	Derriford Hospital	Plymouth
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	NeuroStudies.net, LLC	Decatur	Georgia
United States	CenExel Rocky Mountain Clinical Research, LLC	Englewood	Colorado
United States	Quest Research Institute	Farmington Hills	Michigan
United States	Cedars Sinai Medical Center	Los Angeles	California
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Columbia University Medical Center; The Neurological Institute of New York	New York	New York
United States	Weill Cornell Medical College	New York	New York
United States	Advent Health Orlando	Orlando	Florida
United States	University Pennsylvania Hospital	Philadelphia	Pennsylvania
United States	The Movement Disorder Clinic of Oklahoma	Tulsa	Oklahoma
United States	Georgetown University	Washington	District of Columbia

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Netherlands,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants with adverse events (AEs)		Up to 45 Days
Primary	The change in Columbia-Suicide Severity Rating Scale (C-SSRS) Scores from baseline		From Baseline to Up to 45 Days
Secondary	Time to maximum concentration of RO7486967 in Plasma		Day 1, Day 15, and Day 28
Secondary	Maximum concentration (Cmax) of RO7486967 in Plasma		Day 1, Day 15, and Day 28
Secondary	Area under the curve (AUC) RO7486967 in Plasma		Day 1, Day 15, and Day 28
Secondary	Change from baseline in parametric bindings of [18F]-DPA-714 in different brain areas at Day 25 PET		From Baseline to Approximately Day 25