Idiopathic Parkinson Disease
Conditions
Brief summary
CVXL-0107 a glutamate release inhibitor, has shown evidence of antiparkinsonian and antidyskinetic activity in a macaque model and has shown a significant effect on the UPDRS-III (Movement Disorder Society - Unified Parkinson's Disease Rating Scale) while ON, as well as an increase of ON-time without dyskinesia or without troublesome dyskinesia in a previous phase 2a proof of concept study. This study will confirm the efficacy of CVXL-0107 in combination with optimal dose of levodopa on motor symptoms of Parkinson's disease (PD) .
Detailed description
Phase IIa study, 1:1 randomized, double blind placebo- controlled, with cross-over. Each volunteer patient will be randomly assigned to receive CVXL-0107 or placebo as add-on PD therapy and crossed-over to the other arm in the second sequence of the study. They will be assessed during an acute levodopa challenge test with one intake of the study drug or placebo with a supra-optimal dose of levodopa after 2 weeks of daily treatment with the same study drug or placebo. Patients will be cross-overed to the other treatment and reassessed during a second acute levodopa challenge test after 2 weeks of daily treatment with the study drug or the placebo. The study will evaluate the anti-PD and the anti-dyskinesia efficacy of CVXL-0107 as measured by MDS-UPDRS part III (Movement Disorder Society - Unified Parkinson's Disease Rating Scale) and on levodopa-induced dyskinesia as measured by the AIMS (Abnormal Involuntary Movement Scale).
Interventions
DRUGCVXL-0107
DRUGPlacebo
DRUGLevodopa
Sponsors
CleveXel Pharma
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Signed written Informed Consent 2. Male and female patient aged 40 -75 years 3. Clinical diagnosis of idiopathic PD according to the UK Parkinson's Disease Society Brain Bank Clinical Diagnosis Criteria 4. Advanced PD with clear daily motor fluctuations and dyskinesia with optimal levodopa-based therapy 5. At least 2 hours in OFF state per day including morning OFF 6. Predictable OFF in the morning on awakening prior to receiving morning dose of levodopa 7. During an acute levodopa challenge test : Motor improvement of at least 30% on the MDS-UPDRS part III and AIMS score ≥ 1 at least two time points 8. Patient with dyskinesia: MDS-UPDRS items 4.1 (time spent with dyskinesia) and 4.2 (functional impact of dyskinesia) scores ≥ 1 at Screening 9. Hoehn and Yahr stages of 2-4 in the OFF state at Screening 10. Stable doses and regimens of antiparkinsonian medications for at least the last month prior to randomization (levodopa, dopamine agonists and selective monoamine oxidase type B inhibitors (selegiline, rasagiline)) 11. Anti-PD therapy intended to remain constant throughout the course of the study 12. Normal platelets count 13. Mini-mental state examination (MMSE)≥24 at Screening 14. PD patient treated by DBS can be included if surgery occurred at least one year before the study 15. Patient with health insurance 16. Female of childbearing potential with an effective contraception
Exclusion criteria
1. Any relevant neurologic or psychiatric disease, except idiopathic PD 2. Any secondary causes for Parkinsonism or other neurodegenerative disorder with Parkinsonism symptoms 3. Any neurosurgical intervention for PD planned during the study period 4. Neuroleptics and any D2-receptor antagonists within the last 3 months before Screening 5. Amantadine, Riluzole, dextromethorphan, apomorphine continuous infusion (pump), morphine, or memantine, during the last month before screening and during the study duration 6. History of psychosis or treatment with any antipsychotic drugs within the last 2 years 7. History of seizure or epilepsy, or treatment with anticonvulsant drugs within the last year 8. Any clinically significant unstable medical illness in the last month before randomization (e.g. unstable angina, unstable vascular disease etc) 9. Anti-cancer treatment within the 3 months before Screening 10. Treatment with anticoagulant drugs 11. Any clinically significant renal (serum creatinine level ≥1.5x ULN or dialysis) or hepatic (liver enzyme values≥2x ULN) disease 12. Any clinically significant condition that may compromise the safety of patient or the conduct of the study protocol according to Investigators' opinion. 13. Known genetic disorder of human UDP-glucuronosyltransferase 14. Participation in another trial with any investigational product within the last month before randomization or intake of any investigational product 15. Pregnant, breastfeeding or lactating female
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in MDS-UPDRS part III (Movement Disorder Society - Unified Parkinson's Disease Rating Scale Part III) score. | at visit 3 (day 15= challenge test day) and visit 4 (day 37= challenge test day): at baseline (before L-Dopa administration), then every 20 minutes during the first hour and then every 30 minutes during 5 hours. | CVXL-0107 and placebo |
| Change in AIMS ( Abnormal Involuntary Movement Scale) score | at visit 3 (day 15= challenge test day) and visit 4 (day 37 = challenge test day): at baseline (before L-Dopa administration), then every 20 minutes during the first hour and then every 30 minutes during 5 hours | CVXL-0107 and placebo |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hepatic laboratory safety of CVXL-0107 | at visit 3 (day 14) and visit 4 (day 36) | aspartate transaminase, alanine transaminase, gamma-glutamyl-transpeptidase, alkaline phosphatase |
| Area Under the Curve [AUC] of CVXL-0107 concentrations | at visit 3 (day 15= challenge test day) and visit 4 (day 37= challenge test day) | Blood samples at L-dopa intake and after 20', 40', 60', 90', 120', 240'. |
| Hematology laboratory safety of CVXL-0107 | at visit 3 (day 14) and visit 4 (day 36) | complete blood count |
| Assessment of total daily ON time in Patients Diaries | During 3 days, prior to visit 3 (days 11-13) and prior to visit 4 (days 33, 34, 35) | Total ON-time |
| Assessment of daily ON time without dyskinesia in Patients Diaries | During 3 days; prior to visit 3 (days 11-13) and prior to visit 4 (days 33, 34, 35) | ON-time without dyskinesia |
| Area Under the Curve [AUC] of levodopa concentrations | at visit 3 (day 15= challenge test day) and visit 4 (day 37= challenge test day) | Blood samples at L-dopa intake and after 20', 40', 60', 90', 120', 240'. |
| Incidence of Clinical Treatment-Emergent Adverse Events [Safety and Tolerability] | at visit 3 (day 14) and visit 4 (day 36) | Physical examination, vital signs |
Countries
France
Outcome results
None listed