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出境医 / 临床实验 / A Study in Parkinson's Disease in Patients With Moderate to Severe Dyskinesia (ASTORIA)

A Study in Parkinson's Disease in Patients With Moderate to Severe Dyskinesia (ASTORIA)

Study Description
Brief Summary:
The current study will explore the efficacy, safety and tolerability of 2 dose combinations of JM-010 to determine the optimal doses of each component to be studied in confirmatory clinical trials.

Condition or disease Intervention/treatment Phase
Dyskinesias Parkinson Disease Drug: JM-010 group A Drug: JM-010 group B Drug: Placebos Phase 2

Detailed Description:

This is a Phase 2, double-blind, double-dummy, placebo-controlled, randomized, parallel group, multicentre study.

Subjects with a diagnosis of moderate to severe dyskinesia in Parkinson's disease (PD) will complete a Screening Visit to assess eligibility to participate in the study.

Subjects will continue with their usual levodopa treatment regimen for the duration of study participation.

The screening assessment period will be a minimum of 1 week up to a maximum of 6 weeks. Subjects deemed to be eligible at the end of the Screening Visit will be randomly assigned in a 1:1:1 ratio to receive either 1 of the 2 dose combinations of JM-010 and 1 placebo, or 2 placebos as per the double-dummy study design. The randomized subjects will be followed treatment periods for 12 weeks and safety follow periods for 2 weeks, including pharmacokinetic (PK) sub-study.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 81 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Double-blind, double-dummy.
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study in Parkinson's Disease Patients With Moderate to Severe Dyskinesia to Assess the Efficacy and Safety/Tolerability of Two Dose Combinations of JM-010
Actual Study Start Date : July 22, 2019
Estimated Primary Completion Date : March 2022
Estimated Study Completion Date : March 2022
Arms and Interventions
Arm Intervention/treatment
Experimental: JM-010 group A
As JM-010 4/0.8mg dose fixed combination drug(tablet) +Placebo 2
Drug: JM-010 group A
JM-010 fixed combination drug(4/0.8mg) + Placebo 2
Other Name: JM-010

Experimental: JM-010 group B
As JM-010 8/0.8mg dose fixed combination drug(tablet) + Placebo 1
Drug: JM-010 group B
JM-010 fixed combination drug (8/0.8mg) + Placebo 1
Other Name: JM-010

Placebo Comparator: Placebo
Double-dummy - 2 tablets = Placebo 1 +Placebo 2
Drug: Placebos
Placebo 1 + Placebo 2
Other Name: Placebo

Outcome Measures
Primary Outcome Measures :
  1. Unified Dyskinesia Rating Scale (UDysRS) [ Time Frame: 12 Weeks ]
    To compare the efficacy of JM-010 to that of placebo therapy in reducing dyskinesia severity in Parkinson's Disease by evaluating the total score mean change from Baseline to Week 12 in the sum of the items comprising UDysRS. The scoring range is 0-104, and a higher score indicates more severe dyskinesia.


Secondary Outcome Measures :
  1. Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) [ Time Frame: 2 Weeks, 4 Weeks, 8 Weeks, 12 Weeks ]
    To compare the efficacy of JM-010 to that of placebo therapy as measured by the sum of the MDS-UPDRS Part III score changes from Baseline to Weeks 2, 4, 8, 12. The score range is 0-132, where a higher score means more severe motor impairment.

  2. Clinician's Global Impression-Change (CGI-C) score [ Time Frame: 12 Weeks ]
    To compare the efficacy of JM-010 to that of placebo therapy in relation to improvement in clinician-reported PD symptoms as measured by CGI-C score at Week 12. The CGI-C uses the following ratings: 0=not assessed; 1=very much improved; 2=much improved; 3=a little improved; 4=no change; 5=minimally worse; 6=much worse; and 7=very much worse.

  3. Hauser diary [ Time Frame: 2 Weeks, 4 Weeks, 8 Weeks, 12 Weeks ]
    To compare the efficacy of JM-010 to that of placebo therapy as measured by ON time without troublesome dyskinesia changes, OFF time changes, ON time with troublesome dyskinesia changes, Total time with dyskinesia changes from Baseline to Week 2, 4, 8, 12 in Hauser diary

  4. Unified Dyskinesia Rating Scale (UDysRS) [ Time Frame: 2 Weeks, 4 Weeks, 8 Weeks ]

    To compare the efficacy of JM-010 to that of placebo therapy in reducing dyskinesia severity in Parkinson's Disease by evaluating the total score mean change from Baseline to Week 2, 4, 8.

    The scoring range is 0-104, and a higher score indicates more severe dyskinesia.



Eligibility Criteria
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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Is able to read, understand, and provide written, dated informed consent prior to Screening Visit.
  • Is male or female, between 18 and 80 years of age at Screening Visit.
  • Is diagnosed with idiopathic PD that meets UK Parkinson's Disease Society (UKPDS) Brain Bank Clinical Diagnostic Criteria and requires treatment with and shows responsiveness to levodopa.
  • Has experienced dyskinesia over a period of at least 3 months prior to Screening Visit
  • Has stable peak-effect dyskinesia
  • Has more than one hour of "ON" time with troublesome dyskinesia during daily waking hours on a 24-hour PD subject diary
  • Is on a stable levodopa dosing regimen requiring at least 3 dose administrations but no more than 6 dose administrations per day

Exclusion Criteria:

  • Has undergone surgery for the treatment of PD
  • Has a current diagnosis of Substance Use (including alcohol) Disorder (Abuse or Dependence, as defined by Diagnostic and Statistical Manual, Fifth Edition [DSM 5]),
  • Has psychiatric diagnosis of acute psychotic disorder or other psychiatric diagnoses
  • Has a significant risk for suicidal behaviour in the opinion of the investigator during the course of their participation in the study
  • Has current seizure disorders (other than febrile seizures in childhood) requiring treatment with anticonvulsants.
  • Has known serious ongoing symptomatic cerebral disease or cerebrovascular disease or any acute brain trauma requiring treatment with anti-convulsant therapy within 5 years prior Visit 2, Week 0 (Baseline Visit).
  • Has a history of exclusively diphasic, OFF state, myoclonic, dystonic, or akathetic dyskinesia without peak-dose dyskinesia.

Other criteria related to other medical conditions to be referred to the protocol.

Contacts and Locations

Contacts
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Contact: Serena Hyun 82-2-828-8114 cp.e103@conterapharma.co.kr

Locations
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France
Contera Investigational site_FR Recruiting
Toulouse, France
Contact: Contera         
Germany
Contera Investigational site_DE Recruiting
Rostock, Germany
Contact: Contera         
Italy
Contera Investigational site_IT Recruiting
Roma, Italy
Contact: Contera         
Spain
Contera Investigational site_ES Recruiting
Madrid, Spain
Contact: Contera         
Sponsors and Collaborators
Contera Pharma
Bukwang Pharmaceutical
Investigators
Layout table for investigator information
Study Director: Serena Hyun Contera Pharma
Tracking Information
First Submitted Date  ICMJE May 17, 2019
First Posted Date  ICMJE May 21, 2019
Last Update Posted Date May 24, 2021
Actual Study Start Date  ICMJE July 22, 2019
Estimated Primary Completion Date March 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 30, 2019)
Unified Dyskinesia Rating Scale (UDysRS) [ Time Frame: 12 Weeks ]
To compare the efficacy of JM-010 to that of placebo therapy in reducing dyskinesia severity in Parkinson's Disease by evaluating the total score mean change from Baseline to Week 12 in the sum of the items comprising UDysRS. The scoring range is 0-104, and a higher score indicates more severe dyskinesia.
Original Primary Outcome Measures  ICMJE
 (submitted: May 20, 2019)
Efficacy of JM-010 to that of placebo therapy in reducing dyskinesia severity in PD: Unified Dyskinesia Rating Scale (UDysRS) [ Time Frame: 12 Weeks ]
evaluating the mean change from Baseline to Week 12 through the Unified Dyskinesia Rating Scale (UDysRS).
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 17, 2020)
  • Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) [ Time Frame: 2 Weeks, 4 Weeks, 8 Weeks, 12 Weeks ]
    To compare the efficacy of JM-010 to that of placebo therapy as measured by the sum of the MDS-UPDRS Part III score changes from Baseline to Weeks 2, 4, 8, 12. The score range is 0-132, where a higher score means more severe motor impairment.
  • Clinician's Global Impression-Change (CGI-C) score [ Time Frame: 12 Weeks ]
    To compare the efficacy of JM-010 to that of placebo therapy in relation to improvement in clinician-reported PD symptoms as measured by CGI-C score at Week 12. The CGI-C uses the following ratings: 0=not assessed; 1=very much improved; 2=much improved; 3=a little improved; 4=no change; 5=minimally worse; 6=much worse; and 7=very much worse.
  • Hauser diary [ Time Frame: 2 Weeks, 4 Weeks, 8 Weeks, 12 Weeks ]
    To compare the efficacy of JM-010 to that of placebo therapy as measured by ON time without troublesome dyskinesia changes, OFF time changes, ON time with troublesome dyskinesia changes, Total time with dyskinesia changes from Baseline to Week 2, 4, 8, 12 in Hauser diary
  • Unified Dyskinesia Rating Scale (UDysRS) [ Time Frame: 2 Weeks, 4 Weeks, 8 Weeks ]
    To compare the efficacy of JM-010 to that of placebo therapy in reducing dyskinesia severity in Parkinson's Disease by evaluating the total score mean change from Baseline to Week 2, 4, 8. The scoring range is 0-104, and a higher score indicates more severe dyskinesia.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 20, 2019)
  • Change in parkinsonian disability/disease progression [ Time Frame: 2 Weeks, 4 Weeks, 8 Weeks ]
    UDysRS total score changes from Baseline to Weeks 2, 4, 8
  • Change in parkinsonian disability/disease progression [ Time Frame: 2 Weeks, 4 Weeks, 8 Weeks, 12 Weeks ]
    MDS-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I to IV from Baseline to Week 2, 4, 8, 12
  • Clinician's Global Impression-Change (CGI-C) score at Week 12 [ Time Frame: 12 Weeks ]
    Clinical Global Impression - Change assessed by investigator
  • Change from baseline through Hauser's patients diary [ Time Frame: 2 Weeks, 4 Weeks, 8 Weeks, 12 Weeks ]
    Change in ON time with troublesome dyskinesia, ON time with non-troublesome dyskinesia, ON time without dyskinesia, and OFF time as measured by Hauser's diary
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study in Parkinson's Disease in Patients With Moderate to Severe Dyskinesia
Official Title  ICMJE A Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study in Parkinson's Disease Patients With Moderate to Severe Dyskinesia to Assess the Efficacy and Safety/Tolerability of Two Dose Combinations of JM-010
Brief Summary The current study will explore the efficacy, safety and tolerability of 2 dose combinations of JM-010 to determine the optimal doses of each component to be studied in confirmatory clinical trials.
Detailed Description

This is a Phase 2, double-blind, double-dummy, placebo-controlled, randomized, parallel group, multicentre study.

Subjects with a diagnosis of moderate to severe dyskinesia in Parkinson's disease (PD) will complete a Screening Visit to assess eligibility to participate in the study.

Subjects will continue with their usual levodopa treatment regimen for the duration of study participation.

The screening assessment period will be a minimum of 1 week up to a maximum of 6 weeks. Subjects deemed to be eligible at the end of the Screening Visit will be randomly assigned in a 1:1:1 ratio to receive either 1 of the 2 dose combinations of JM-010 and 1 placebo, or 2 placebos as per the double-dummy study design. The randomized subjects will be followed treatment periods for 12 weeks and safety follow periods for 2 weeks, including pharmacokinetic (PK) sub-study.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Double-blind, double-dummy.
Primary Purpose: Treatment
Condition  ICMJE
  • Dyskinesias
  • Parkinson Disease
Intervention  ICMJE
  • Drug: JM-010 group A
    JM-010 fixed combination drug(4/0.8mg) + Placebo 2
    Other Name: JM-010
  • Drug: JM-010 group B
    JM-010 fixed combination drug (8/0.8mg) + Placebo 1
    Other Name: JM-010
  • Drug: Placebos
    Placebo 1 + Placebo 2
    Other Name: Placebo
Study Arms  ICMJE
  • Experimental: JM-010 group A
    As JM-010 4/0.8mg dose fixed combination drug(tablet) +Placebo 2
    Intervention: Drug: JM-010 group A
  • Experimental: JM-010 group B
    As JM-010 8/0.8mg dose fixed combination drug(tablet) + Placebo 1
    Intervention: Drug: JM-010 group B
  • Placebo Comparator: Placebo
    Double-dummy - 2 tablets = Placebo 1 +Placebo 2
    Intervention: Drug: Placebos
Publications * McFarthing K, Prakash N, Simuni T. CLINICAL TRIAL HIGHLIGHTS - DYSKINESIA. J Parkinsons Dis. 2019;9(3):449-465. doi: 10.3233/JPD-199002. Review.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 20, 2019)
81
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 2022
Estimated Primary Completion Date March 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Is able to read, understand, and provide written, dated informed consent prior to Screening Visit.
  • Is male or female, between 18 and 80 years of age at Screening Visit.
  • Is diagnosed with idiopathic PD that meets UK Parkinson's Disease Society (UKPDS) Brain Bank Clinical Diagnostic Criteria and requires treatment with and shows responsiveness to levodopa.
  • Has experienced dyskinesia over a period of at least 3 months prior to Screening Visit
  • Has stable peak-effect dyskinesia
  • Has more than one hour of "ON" time with troublesome dyskinesia during daily waking hours on a 24-hour PD subject diary
  • Is on a stable levodopa dosing regimen requiring at least 3 dose administrations but no more than 6 dose administrations per day

Exclusion Criteria:

  • Has undergone surgery for the treatment of PD
  • Has a current diagnosis of Substance Use (including alcohol) Disorder (Abuse or Dependence, as defined by Diagnostic and Statistical Manual, Fifth Edition [DSM 5]),
  • Has psychiatric diagnosis of acute psychotic disorder or other psychiatric diagnoses
  • Has a significant risk for suicidal behaviour in the opinion of the investigator during the course of their participation in the study
  • Has current seizure disorders (other than febrile seizures in childhood) requiring treatment with anticonvulsants.
  • Has known serious ongoing symptomatic cerebral disease or cerebrovascular disease or any acute brain trauma requiring treatment with anti-convulsant therapy within 5 years prior Visit 2, Week 0 (Baseline Visit).
  • Has a history of exclusively diphasic, OFF state, myoclonic, dystonic, or akathetic dyskinesia without peak-dose dyskinesia.

Other criteria related to other medical conditions to be referred to the protocol.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Serena Hyun 82-2-828-8114 cp.e103@conterapharma.co.kr
Listed Location Countries  ICMJE France,   Germany,   Italy,   Spain
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03956979
Other Study ID Numbers  ICMJE JM-010CS03
2017-003415-19 ( EudraCT Number )
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Bukwang Pharmaceutical ( Contera Pharma )
Study Sponsor  ICMJE Contera Pharma
Collaborators  ICMJE Bukwang Pharmaceutical
Investigators  ICMJE
Study Director: Serena Hyun Contera Pharma
PRS Account Bukwang Pharmaceutical
Verification Date May 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP