A study to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of selnofast in participants with early idiopathic Parkinson's disease
| ISRCTN | ISRCTN85338453 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN85338453 |
| EudraCT/CTIS number | 2023-504412-14-00 |
| IRAS number | 307220 |
| ClinicalTrials.gov number | NCT05924243 |
| Secondary identifying numbers | BP43176, CPMS 50823, IRAS 307220 |
- Submission date
- 07/12/2021
- Registration date
- 29/04/2022
- Last edited
- 26/07/2024
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Nervous System Diseases
Plain English Summary
Background and study aims:
Parkinson’s disease (PD) is a progressive and incurable disease that affects the nervous system. It is caused by the loss of brain cells that produce dopamine, a chemical that helps brain cells communicate and control movement. The main symptoms include decreased mobility, rigidity or stiffness of arms, legs and trunk, and resting tremors (shaking that occurs at rest). Evidence suggests that people with PD may have increased inflammation (swelling) in the brain. A protein called NLRP3 is thought to play a key role in this inflammatory process. Selnoflast is a new drug that has been developed to slow the progression of disease in people with early PD. Selnoflast acts by blocking NLRP3, which might lower the inflammation in the brain. Health authorities have not yet approved selnoflast for the treatment of PD or any other disease. The main
purpose of this study is:
-To determine how safe and tolerable selnoflast is when compared to a placebo (medicine without an active ingredient)
-To determine how selnoflast is absorbed, distributed and, eventually eliminated from the body
-To assess the effect of selnoflast on the inflammation in the brain using certain scans called the TSO-PET scans
Who can participate?
People aged between 40 to 85 years with PD.
What does the study involve?
Participants may be asked to be in the study for approximately 100 days. This includes: -
Screening Period of up to 60 days where tests will be done to check if the participants are eligible to take part in the study. Participants may have to visit the clinic approximately 3 times during the Screening Period.
Baseline Period of up to 3 days before the start of study wherein participants will be contacted over the phone to collect details about other medicines and changes to their health and life. MRI and TSPO PET scans will also be done at this time. The participants will have to report to a dedicated external PET center for the scans.
Treatment Period of approximately 28 days where participants will have to report 5 times to the clinic and 1 time to a dedicated external PET centre for tests, assessments, and procedures in addition to taking the study medication twice a day.
Follow-up Period where participants will have a check-up approximately 14 days after the last study treatment administration.
Participants will be placed in one of the following treatment groups:
Group 1 will receive selnoflast, given as capsules for about 28 days.
Group 2 will receive a placebo, given as capsules for about 28 days.
What are the possible benefits and risks of participating?
Participants' health may or may not improve from participation in the clinical trial. Still, the information collected may help other people with similar medical conditions in the future.
Participants may have side effects from the drugs or procedures used in this study that can be mild to severe or even life-threatening in nature, and they can vary from person to person.
Participants will be closely monitored during the clinical trial; safety assessments will be performed regularly.
Where is the study run from?
Roche (Switzerland)
When is the study starting and how long is it expected to run for?
September 2021 to July 2024
Who is funding the study?
Roche (Switzerland)
Who is the main contact?
global-roche-genentech-trials@gene.com
Contact information
Public
Building 1
Grenzacherstrasse 124
Basel
CH-4070
Switzerland
| Phone | +1 888-662-6728 |
|---|---|
| global-roche-genentech-trials@gene.com |
Study information
| Study design | Phase 1b adaptive multicentre double-blind randomized placebo-controlled parallel design study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised parallel trial |
| Study setting(s) | Other |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details to request a patient information sheet. |
| Scientific title | A phase 1b, adaptive, multi-center, randomized, double blind, placebo-controlled, parallel design study to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of selnofast in participants with early idiopathic Parkinson's disease |
| Study hypothesis | Current study hypothesis as of 24/07/2023: The aim of the study is to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of selnoflast in participants with early idiopathic Parkinson’s disease (PD). _____ Previous study hypothesis: The aim of the study is to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of RO7486967 in participants with early idiopathic Parkinson’s disease (PD). |
| Ethics approval(s) | Approved 11/04/2021, WCG IRB (1019 39th Avenue, SE Suite 120 Puyallup, WA 98374, USA; +1 855-818-2289; clientservices@wcgirb.com), ref: 20215051 |
| Condition | Parkinson’s disease |
| Intervention | 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 days. Randomisation is done using an Interactive Voice/Web Response System (IxRS) _____ Previous interventions: RO7486967: Participants will receive RO7486967 capsules, 200 mg, orally, twice daily, for 28 days. Placebo: Participants will receive a matching placebo to RO7486967 capsules, orally, twice daily, for 28 days. Randomisation is done using an Interactive Voice/Web Response System (IxRS) |
| Intervention type | Drug |
| Pharmaceutical study type(s) | |
| Phase | Phase I |
| Drug / device / biological / vaccine name(s) | Selnoflast |
| Primary outcome measure | 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 outcome measures | 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 |
| Overall study start date | 11/04/2021 |
| Overall study end date | 18/07/2024 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 40 Years |
| Upper age limit | 85 Years |
| Sex | Both |
| Target number of participants | 72 |
| Total final enrolment | 61 |
| Participant 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 |
| Participant 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: α-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, distribution, metabolism, or excretion of drugs, or which may jeopardize the participant in case of participation in the study 11. History of major vascular surgery within 6 months prior to screening 12. History of clinically significant Electrocardiogram (ECG) abnormalities, or ECG abnormalities at screening or baseline (Day 1) 13. Within the last year prior to screening, unstable or clinically significant cardiovascular disease (e.g., myocardial infarction, major vascular surgery) 14. Uncontrolled hypertension 15. Recent (within the last 3 years prior to screening) and/or recurrent history of clinically significant autonomic dysfunction 16. History of clinically significant severe drug allergies, multiple drug allergies, or anaphylaxis due to gelatine (a constituent of the capsule shell) |
| Recruitment start date | 22/09/2022 |
| Recruitment end date | 06/06/2024 |
Locations
Countries of recruitment
- England
- Netherlands
- United Kingdom
- United States of America
Study participating centres
Netherlands
United States of America
United States of America
Netherlands
Netherlands
United States of America
United States of America
United States of America
United States of America
United States of America
Mile End Road
London
E1 4NS
United Kingdom
Westgate Road
Newcastle upon Tyne
NE4 6BE
United Kingdom
Cranmer Terrace
London
SW17 0RE
United Kingdom
London
W6 8RF
United Kingdom
London
WC1N 3BG
United Kingdom
Exeter
EX4 4PY
United Kingdom
United States of America
Sponsor information
Industry
Building 1
Grenzacherstrasse 124
Basel
CH-4070
Switzerland
| Phone | +1 888-662-6728 |
|---|---|
| global-roche-genentech-trials@gene.com | |
| Website | http://www.roche.com/about_roche/roche_worldwide.htm |
"ROR" |
https://ror.org/00by1q217 |
Funders
Funder type
Industry
Private sector organisation / For-profit companies (industry)
- Alternative name(s)
- Hoffman-La Roche, F. Hoffmann-La Roche Ltd.
- Location
- Switzerland
Results and Publications
| Intention to publish date | 31/05/2026 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not expected to be made available |
| Publication and dissemination plan | Planned dissemination at the international congress (e.g. International Congress of Movement disorders) and publication in a high-impact peer-reviewed journal |
| IPD sharing plan | The datasets generated during and/or analysed during the current study are not expected to be made available due to participant-level data not being a regulatory requirement |
Editorial Notes
26/07/2024: The following changes were made:
1. The overall study end date was changed from 30/04/2025 to 18/07/2024.
2. The total final enrolment was added.
3. The recruitment end date was changed from 01/03/2025 to 06/06/2024.
04/12/2023: Study website added.
26/07/2023: The target number of participants was changed from 78 to 72.
25/07/2023: The following changes were made to the trial record:
1. The EudraCT number was added.
2. The ClinicalTrials.gov number was added.
3. The study participating centres Conquest Research, LLC and Derriford Hospital were removed.
4. The contact address was changed.
24/07/2023: The following changes were made to the trial record:
1. The public title was changed from "A study to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of RO7486967 in participants with early idiopathic Parkinson's disease" to "A study to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of selnofast in participants with early idiopathic Parkinson's disease".
2. The scientific title was changed from "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" to "A phase 1b, adaptive, multi-center, randomized, double blind, placebo-controlled, parallel design study to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of selnofast in participants with early idiopathic Parkinson's disease".
3. The study hypothesis was changed.
4. The overall end date was changed from 30/10/2023 to 30/04/2025.
5. The interventions were changed.
6. The drug name was changed from "RO7486967" to "Selnoflast".
7. The secondary outcome measures were changed.
8. The inclusion criteria were changed.
9. The target number of participants was changed from 48 to 78.
10. The exclusion criteria were changed.
11. The recruitment start date was changed from 15/07/2022 to 22/09/2022.
12. The recruitment end date was changed from 15/07/2023 to 01/03/2025.
13. The study participating centre Cedars Sinai Medical Center was added.
14. The plain English summary was updated to reflect these changes.
15. The intention to publish date was changed from 01/07/2024 to 31/05/2026.
16. The sponsor name was changed from Roche (United States) to Roche (Switzerland).
17. The sponsor details were updated.
05/05/2022: Internal review.
10/12/2021: Trial's existence confirmed by WCG IRB.
