Parkinson’s disease Nervous System Diseases
Conditions
Interventions
Current interventions as of 24/07/2023:
Selnoflast: Participants will receive selnoflast capsules for 28 days.
Placebo: Participants will receive a matching placebo to selnoflast capsules for 28 day
Sponsors
Roche (Switzerland)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 24/07/2023: 1. Male or post-menopausal female 2. Diagnosis of clinically probable idiopathic PD based on movement disorder society (MDS) criteria with bradykinesia plus one of the other cardinal signs of PD (resting tremor, rigidity) 3. A time from diagnosis of PD of at least 3 to maximum 60 months (5 years) at screening 4. Modified Hoehn and Yahr (H&Y) Stage =2.5 (in ON state) 5. Dopaminergic imaging consistent with dopamine transporter deficit 6. “High-affinity binder” or “mixed-affinity binder” for TSPO 7. 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 8. No anticipated changes in PD therapy throughout the study duration 9. SARS-CoV-2 vaccination completed at least 60 days prior to the first dose. _____ Previous inclusion criteria: 1. Males and post-menopausal females aged 50-85 years at the time of signing Informed Consent Form (ICF) 2. Diagnosis of clinically probable idiopathic PD based on Movement Disorder Society (MDS) criteria with bradykinesia plus one of the other cardinal signs of PD (resting tremor, rigidity), at least 3 to maximum 36 months prior to screening 3. No motor complications, assessed by a score of 0 on the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part IV at screening (for participants on levodopa treatment) 4. Modified Hoehn and Yahr (H&Y) Stage =2.5 (for participants on levodopa treatment in ON state) 5. Dopaminergic imaging is consistent with dopamine transporter deficit. A previously performed dopaminergic imaging scan (e.g., DAT-SPECT or FDOPA-PET) is also accepted if it was indicative of a dopaminergic deficit typical of Parkinson’s disease 6. “High-affinity binder” or “mixed-affinity binder” for TSPO, as confirmed by prospective genotyping of TSPO polymorphism during screening 7. Able to swallow capsules whole 8. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination completed at least 60 days prior to the first dose. Individual vaccination complete status to be defined as per local regulations at the time of screening 9. Agree to reduce the use of tobacco and alcohol products to a minimum throughout the study and to refrain from using tobacco or alcohol during study visits 10. Body weight ranging from 45-110 kg (99-242 lbs.) and a body mass index (BMI) of 18-32 kg/m^2 inclusive 11. Prior or Concomitant therapy must be Either monotherapy treatment with levodopa of maximum 600 mg levodopa immediate release or 800 mg levodopa controlled or 1000 mg levodopa dual release, given for at least 90 days, with stable doses for at least 30 days prior to the first dose OR treatment naïve
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 24/07/2023: 1. Medical history indicating a Parkinsonian syndrome other than idiopathic PD 2. CNS or psychiatric disorders other than idiopathic PD (mild depression or anxiety arising in the context of PD is not exclusionary) 3. History of brain surgery for PD 4. Use of any of symptomatic drug for PD other than levodopa pramipexole, ropinirole, or rotigotine within 60 days prior to the first dose 5. Known carriers for mutations in the following genes: alpha-synuclein, LRRK2, GBA, PRKN, PINK1, or DJ1 6. Unstable or clinically significant cardiovascular disease within the last year prior to screening 7. Uncontrolled hypertension 8. 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) 9. 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 10. History of immunodeficiency diseases 11. Presence of hepatitis B surface antigen (HBsAg) or positive for total hepatitis B core antibody (HBcAb), or positive hepatitis C (HCV) at screening 12. 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 13. History of chronic liver disease 14. Clinically significant abnormalities in laboratory test results at screening, including hepatic and renal panels, complete blood count, chemistry panel and urinalysis 15. Any previous administration of selnoflast or other compound targeting NLRP3 16. Enrollment in another investigational study 17. 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 _____ Previous exclusion criteria: 1. Medical history indicating a Parkinsonian syndrome other than idiopathic PD, including but not limited to progressive supranuclear palsy, multiple system atrophy, drug induced Parkinsonism, essential tremor, vascular Parkinsonism, primary dystonia 2. History of brain surgery for PD 3. Known carriers for mutations in the following genes: a-synuclein, LRRK2, GBA, PRKN, PINK1, or DJ1 4. Diagnosis of dementia or another significant central nervous system (CNS) disease other than PD 5. History of clinically significant abnormality in a Magnetic Resonance Imaging (MRI) scan, including but not limited to prior haemorrhage or infarct 6. Presence of any psychiatric condition (e.g., major depression, schizophrenia, delusion, delirium) at screening or baseline 7. Acute suicidality, as evidenced by answering “yes” for Question 3 or 4 on the C-SSRS scale 8. History of suicidal behaviour such that a determination of “yes” is made on the Suicidal Behaviour section of the C-SSRS for “Actual Attempt”, “Interrupted Attempt”, “Aborted Attempt”, or “Preparatory Acts or Behaviour 9. History of malignancy prior to screening, except for appropriately treated, nonmelanoma skin carcinoma, non-metastatic prostate cancer, treated carcinoma in situ of the cervix or Stage I uterine cancer 10. Any surgical or medical condition which might significantly alter the absorption, dist
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Percentage of Participants with Adverse Events, Serious Adverse Events and Severity per National Cancer Institute-Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE V5.0) from Screening up to Approximately 6 Weeks 2. Percentage of Participants with Abnormal Laboratory Findings in Blood and Urine from Screening up to Approximately 6 Weeks 3. Percentage of Participants with Abnormal Vital Signs and ECG Parameters Using Manual Techniques and Instrument Respectively from Screening up to Approximately 6 Weeks 4. Change from Baseline in Columbia Suicide Severity Rating Scale (C-SSRS) Using Interview-Based Instrument from Screening up to Approximately 6 Weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Current secondary outcome measures as of 24/07/2023: 1. Time to Maximum Concentration of Selnoflast using Blood Samples on Days 1, 15 and 28 2. Area Under the Curve (AUC) of Selnoflast using Blood samples on Days 1, 15 and 28 3. Maximum Concentration (Cmax) of Selnoflast using Blood Samples on Days 1, 15 and 28 4. Change from Baseline in Parametric Bindings of [18F]-DPA-714 in Different Brain Areas Using TSPO positron emission tomography [PET] Imaging from Baseline to Day 25 _____ Previous secondary outcome measures: 1. Serum Concentration of RO7486967 Using Blood and Cerebrospinal Fluid (CSF) Samples at Predose, 0.5 h, 1 h, 2 h, 4 h, 6 h on Days 1, 15 and 28 2. Area Under the Curve 0-6 hr [AUC(0-6h)] of RO7486967 Using Blood and CSF Samples at Predose, 0.5 h, 1 h, 2 h, 4 h, 6 h on Days 1, 15 and 28 3. AUC (12h) of RO7486967 Using Blood and CSF Samples at Predose, 0.5 h, 1 h, 2 h, 4 h, 6 h on Days 1, 15 and 28 4. Maximum Concentration (Cmax) of RO7486967 Using Blood and CSF Samples at Predose, 0.5 h, 1 h, 2 h, 4 h, 6 h on Days 1, 15 and 28 5. Time to Achieve Maximum Concentration (Tmax) of RO7486967 Using Blood and CSF Samples at Predose, 0.5 h, 1 h, 2 h, 4 h, 6 h on Days 1, 15 and 28 6. Terminal Half-Life (t1/2) of RO7486967 Using Blood and CSF Samples at Predose, 0.5 h, 1 h, 2 h, 4 h, 6 h on Days 1, 15 and 28 7. Total Clearance (CL/F) of RO7486967 Using Blood and CSF Samples at Predose, 0.5 h, 1 h, 2 h, 4 h, 6 h on Days 1, 15 and 28 8. Volume of Distribution at Steady-State (Vss/F) of RO7486967 Using Blood and CSF Samples at Predose, 0.5 h, 1 h, 2 h, 4 h, 6 h on Days 1, 15 and 28 9. Change from Baseline in Parametric Bindings of [18F]-DPA-714 in Different Brain Areas Using TSPO positron emission tomography [PET] Imaging at Day 25 | — |
Countries
England, Netherlands, United Kingdom, United States of America
Contacts
Public ContactClinical Trials
Outcome results
None listed