Clinical trial NCT05924243: A Study to Investigate The Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of RO7486967 in Participants With Early Idiopathic Parkinson's Disease.
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Parkinson Disease
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2023-06-29
Enrollment: 60
Sex: ALL
Minimum age (years): 40
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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

Primary outcomes:
measure: Percentage of Participants with adverse events (AEs)
timeFrame: Up to 45 Days
measure: The change in Columbia-Suicide Severity Rating Scale (C-SSRS) Scores from baseline
timeFrame: From Baseline to Up to 45 Days
Secondary outcomes:
measure: Time to maximum concentration of RO7486967 in Plasma
timeFrame: Day 1, Day 15, and Day 28
measure: Maximum concentration (Cmax) of RO7486967 in Plasma
timeFrame: Day 1, Day 15, and Day 28
measure: Area under the curve (AUC) RO7486967 in Plasma
timeFrame: Day 1, Day 15, and Day 28
measure: Change from baseline in parametric bindings of [18F]-DPA-714 in different brain areas at Day 25 PET
timeFrame: From Baseline to Approximately Day 25
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center
state: California
city: Englewood
country: United States
facility: CenExel Rocky Mountain Clinical Research, LLC
state: Colorado
city: Washington
country: United States
facility: Georgetown University
state: District of Columbia
city: Orlando
country: United States
facility: Advent Health Orlando
state: Florida
city: Farmington Hills
country: United States
facility: Quest Research Institute
state: Michigan
city: New York
country: United States
facility: Weill Cornell Medical College
state: New York
city: Tulsa
country: United States
facility: The Movement Disorder Clinic of Oklahoma
state: Oklahoma
city: Philadelphia
country: United States
facility: University Pennsylvania Hospital
state: Pennsylvania
city: Amsterdam
country: Netherlands
facility: Brain Research Center B.V
city: Nijmegen
country: Netherlands
facility: UMC St Radboud
city: Zwolle
country: Netherlands
facility: Brain Research Center Zwolle
city: Exeter
country: United Kingdom
facility: University of Exeter
city: London
country: United Kingdom
facility: Barts Health NHS Trust
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust; Charing Cross Hospital
city: London
country: United Kingdom
facility: National Hospital for Neurology and Neurosurgery; Leonard Wolfson Experimental Neurology Centre CRF
city: Newcastle
country: United Kingdom
facility: Campus for Ageing & Vitality; Clincal Ageing Research Unit
Study officials:
References: