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

Idiopathic Parkinson Disease Clinical Trial

Official title:

Double-Blind Randomized Placebo-Controlled Cross-Over Phase IIa Trial to Evaluate Efficacy of CVXL-0107 on Parkinson-Related Symptoms and Levodopa-Induced Dyskinesia in Advanced Parkinson's Disease Patients Using a Levodopa Challenge Test

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02641054
• Other study ID #: CT-CVXL-0107-01
• Status: Completed
• Phase: Phase 2
• First received: December 7, 2015
• Last updated: July 20, 2017
• Start date: February 2016
• Est. completion date: July 2017

Study information

• Verified date: July 2017
• Source: CleveXel Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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) .

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: July 2017
• Est. primary completion date: June 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 40 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Idiopathic Parkinson Disease
• Parkinson Disease

Intervention

Drug:
• CVXL-0107

• Placebo

• Levodopa

Locations

Country	Name	City	State
France	Clevexel Pharma	Maisons-Alfort

Sponsors (1)

Lead Sponsor	Collaborator
CleveXel Pharma

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in MDS-UPDRS part III (Movement Disorder Society - Unified Parkinson's Disease Rating Scale Part III) score.	CVXL-0107 and placebo	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.
Primary	Change in AIMS ( Abnormal Involuntary Movement Scale) score	CVXL-0107 and placebo	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
Secondary	Incidence of Clinical Treatment-Emergent Adverse Events [Safety and Tolerability]	Physical examination, vital signs	at visit 3 (day 14) and visit 4 (day 36)
Secondary	Hematology laboratory safety of CVXL-0107	complete blood count	at visit 3 (day 14) and visit 4 (day 36)
Secondary	Hepatic laboratory safety of CVXL-0107	aspartate transaminase, alanine transaminase, gamma-glutamyl-transpeptidase, alkaline phosphatase	at visit 3 (day 14) and visit 4 (day 36)
Secondary	Area Under the Curve [AUC] of CVXL-0107 concentrations	Blood samples at L-dopa intake and after 20', 40', 60', 90', 120', 240'.	at visit 3 (day 15= challenge test day) and visit 4 (day 37= challenge test day)
Secondary	Area Under the Curve [AUC] of levodopa concentrations	Blood samples at L-dopa intake and after 20', 40', 60', 90', 120', 240'.	at visit 3 (day 15= challenge test day) and visit 4 (day 37= challenge test day)
Secondary	Assessment of total daily "ON" time in Patients Diaries	Total "ON-time"	During 3 days, prior to visit 3 (days 11-13) and prior to visit 4 (days 33, 34, 35)
Secondary	Assessment of daily "ON" time without dyskinesia in Patients Diaries	"ON-time" without dyskinesia	During 3 days; prior to visit 3 (days 11-13) and prior to visit 4 (days 33, 34, 35)