Efficacy Phase IIa Study of CVXL-0107 in Advanced Parkinson's Disease

NCT ID: NCT02641054

Last Updated: 2017-07-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-02-29
• Study Completion Date: 2017-07-31

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).

Conditions

Idiopathic Parkinson Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

CVXL-0107 then cross-over to placebo

Study drug (CVXL-0107) 4 times per day for 2 weeks on top of usual treatment for Parkinson disease, followed by one challenge test day: one intake of study drug on top of supraoptimal dose of levodopa.

Cross-over to placebo 4 times per day for 2 weeks on top of usual treatment for Parkinson disease, followed by one challenge test day: one intake of placebo on top of supraoptimal dose of levodopa

Group Type: EXPERIMENTAL

CVXL-0107

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Levodopa

Intervention Type: DRUG

Placebo then cross-over to CVXL-0107

Placebo 4 times per day for 2 weeks on top of usual treatment for Parkinson disease, followed by one challenge test day: one intake of placebo on top of supraoptimal dose of levodopa.

Cross-over to study drug (CVXL-0107) 4 times per day for 2 weeks on top of usual treatment for Parkinson disease, followed by one challenge test day: one intake of study drug on top of supraoptimal dose of levodopa

Group Type: PLACEBO_COMPARATOR

CVXL-0107

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Levodopa

Intervention Type: DRUG

Interventions

CVXL-0107

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Levodopa

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 40 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

CleveXel Pharma

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jean-Christophe Corvol, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

CIC-Neurologie, bâtiment ICM, Hôpital Pitié-Salpêtrière, 47/83 Bd de l'Hôpital, 75013 Paris, France

Locations

Clevexel Pharma

Maisons-Alfort, , France

Countries

France

Other Identifiers

CT-CVXL-0107-01

Identifier Type: -

Identifier Source: org_study_id