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

NCT02641054 | Completed Phase 2

• 1 other identifier: CT-CVXL-0107-01
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

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) .

Conditions

Idiopathic Parkinson Disease

Outcome Measures

Primary Outcomes (2)

• 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.

• 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 Outcomes (7)

• Incidence of Clinical Treatment-Emergent Adverse Events [Safety and Tolerability]

  at visit 3 (day 14) and visit 4 (day 36)

• Hematology laboratory safety of CVXL-0107

  at visit 3 (day 14) and visit 4 (day 36)

• Hepatic laboratory safety of CVXL-0107

  at visit 3 (day 14) and visit 4 (day 36)

• 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)

• Area Under the Curve [AUC] of levodopa concentrations

  at visit 3 (day 15= challenge test day) and visit 4 (day 37= challenge test day)

Study Arms (2)

CVXL-0107 then cross-over to placebo

EXPERIMENTAL

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

Drug: CVXL-0107; Drug: Placebo; Drug: Levodopa

Placebo then cross-over to CVXL-0107

PLACEBO COMPARATOR

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

Drug: CVXL-0107; Drug: Placebo; Drug: Levodopa

Interventions

CVXL-0107 DRUG

CVXL-0107 then cross-over to placebo; Placebo then cross-over to CVXL-0107

Placebo DRUG

CVXL-0107 then cross-over to placebo; Placebo then cross-over to CVXL-0107

Levodopa DRUG

CVXL-0107 then cross-over to placebo; Placebo then cross-over to CVXL-0107

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed written Informed Consent
• Male and female patient aged 40 -75 years
• Clinical diagnosis of idiopathic PD according to the UK Parkinson's Disease Society Brain Bank Clinical Diagnosis Criteria
• Advanced PD with clear daily motor fluctuations and dyskinesia with optimal levodopa-based therapy
• At least 2 hours in "OFF" state per day including morning OFF
• Predictable "OFF" in the morning on awakening prior to receiving morning dose of levodopa
• 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
• Patient with dyskinesia: MDS-UPDRS items 4.1 ("time spent with dyskinesia") and 4.2 ("functional impact of dyskinesia") scores ≥ 1 at Screening
• Hoehn and Yahr stages of 2-4 in the "OFF" state at Screening
• 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))
• Anti-PD therapy intended to remain constant throughout the course of the study
• Normal platelets count
• Mini-mental state examination (MMSE)≥24 at Screening
• PD patient treated by DBS can be included if surgery occurred at least one year before the study
• Patient with health insurance

You may not qualify if:

• Any relevant neurologic or psychiatric disease, except idiopathic PD
• Any secondary causes for Parkinsonism or other neurodegenerative disorder with Parkinsonism symptoms
• Any neurosurgical intervention for PD planned during the study period
• Neuroleptics and any D2-receptor antagonists within the last 3 months before Screening
• Amantadine, Riluzole, dextromethorphan, apomorphine continuous infusion (pump), morphine, or memantine, during the last month before screening and during the study duration
• History of psychosis or treatment with any antipsychotic drugs within the last 2 years
• History of seizure or epilepsy, or treatment with anticonvulsant drugs within the last year
• Any clinically significant unstable medical illness in the last month before randomization (e.g. unstable angina, unstable vascular disease etc)
• Anti-cancer treatment within the 3 months before Screening
• Treatment with anticoagulant drugs
• Any clinically significant renal (serum creatinine level ≥1.5x ULN or dialysis) or hepatic (liver enzyme values≥2x ULN) disease
• Any clinically significant condition that may compromise the safety of patient or the conduct of the study protocol according to Investigators' opinion.
• Known genetic disorder of human UDP-glucuronosyltransferase
• Participation in another trial with any investigational product within the last month before randomization or intake of any investigational product
• Pregnant, breastfeeding or lactating female

Sponsors & Collaborators

• CleveXel Pharma: lead

Study Sites (1)

Clevexel Pharma

Maisons-Alfort, 94700, France

Location

MeSH Terms

Conditions

Parkinson Disease

Interventions

Levodopa

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Dihydroxyphenylalanine; Catecholamines; Amines; Organic Chemicals; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Tyrosine

Study Officials

• Jean-Christophe Corvol, MD, PhD

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 7, 2015
• First Posted: December 29, 2015
• Study Start: February 1, 2016
• Primary Completion: June 1, 2017
• Study Completion: July 1, 2017
• Last Updated: July 24, 2017

Record last verified: 2017-07

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)