A Study to Investigate The Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of RO7486967 in Participants With Early Idiopathic Parkinson's Disease
Study Details
Study Description
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| 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
|
| Placebo Comparator: Placebo Matching placebo |
Drug: Placebo
For up to approximately 28 days
|
Outcome Measures
Primary Outcome Measures
- 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
- 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]
Eligibility Criteria
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
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Use of any of symptomatic drug for PD other than levodopa pramipexole, ropinirole, or rotigotine within 60 days prior to the first dose
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Known carriers for mutations in the following genes: alpha-synuclein, LRRK2, GBA, PRKN, PINK1, or DJ1
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Unstable or clinically significant cardiovascular disease within the last year prior to screening
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Uncontrolled hypertension
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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)
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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
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History of immunodeficiency diseases
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Presence of hepatitis B surface antigen (HBsAg) or positive for total hepatitis B core antibody (HBcAb), or positive hepatitis C (HCV) at screening
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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
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Any previous administration of RO7486967 or other compound targeting NLRP3
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Enrollment in another investigational study
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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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Alabama at Birmingham | Birmingham | Alabama | United States | 35294 |
| 2 | Cedars Sinai Medical Center | Los Angeles | California | United States | 90048 |
| 3 | Georgetown University | Washington | District of Columbia | United States | 20007 |
| 4 | NeuroStudies.net, LLC | Decatur | Georgia | United States | 30033 |
| 5 | Weill Cornell Medical College | New York | New York | United States | 10065 |
| 6 | University Pennsylvania Hospital | Philadelphia | Pennsylvania | United States | 19104 |
| 7 | Brain Research Center B.V | Amsterdam | Netherlands | 1081 GN | |
| 8 | UMC St Radboud | Nijmegen | Netherlands | 6525 GA | |
| 9 | Brain Research Center Zwolle | Zwolle | Netherlands | 8025AZ | |
| 10 | Barts Health NHS Trust | London | United Kingdom | E1 2ES | |
| 11 | Imperial College Healthcare NHS Trust; Charing Cross Hospital | London | United Kingdom | W6 8RF | |
| 12 | National Hospital for Neurology and Neurosurgery; Leonard Wolfson Experimental Neurology Centre CRF | London | United Kingdom | WC1N 3BG | |
| 13 | Campus for Ageing & Vitality; Clincal Ageing Research Unit | Newcastle | United Kingdom | NE4 5PL |
Sponsors and Collaborators
- Hoffmann-La Roche
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- BP43176