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A Study of CH-4051 in Patients With Rheumatoid Arthritis (RA) (MOTION)

Primary Purpose

Rheumatoid Arthritis

Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
CH-4051
Methotrexate (MTX)
Folic Acid
Sponsored by
Chelsea Therapeutics
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Rheumatoid Arthritis focused on measuring rheumatoid arthritis, MTX, CH-405, antifolates

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients must be between the ages of 18 and 80;
  • Have diagnosed active rheumatoid arthritis according to ACR criteria functional class I-III;
  • Have at least 6 swollen joints (max = 66) and 6 tender joints (max = 68) at screening and baseline visits;
  • Patients must have at least one of the following:
  • C-reactive protein > 1.0 mg/dl at screening;
  • erythrocyte sedimentation rate > 28 mm/Hr;
  • Patients must have been taking methotrexate between 15 and 25 mg/week for at least 3 months and at a stable dose for at least 6 weeks;
  • Patients must be either Rheumatoid Factor (RF) or anti-cyclic citrullinated peptide (anti-CCP) positive;
  • Patients must have voluntarily signed the informed consent.

Exclusion Criteria:

  • Patients who received previous therapy with any biologic agent;
  • Patients currently taking any disease modifying anti-rheumatic drug (DMARD) other than MTX;
  • Previous non-biologic DMARD therapy is permitted as long as their last dose was at least 30 days prior to baseline;
  • Female patients of child bearing potential who are pregnant or who are not using two methods of contraception (at least one barrier: i.e. condom) with their partner;
  • Male patients who are sexually active and not using two methods of contraception (at least one barrier: i.e. condom) with their partner;
  • Patients with any current active infection or infections requiring IV drug therapy within 30 days of baseline or oral therapy within 15 days of Baseline;
  • Patients that have had any surgical procedures within 30 days of baseline;
  • Patients with a history of HIV;
  • Patients with Hepatitis B surface antigen positive and/or Hepatitis C antibody positive;
  • Patients who consume more than 4 units of alcohol per week (1 unit = 5 ounces/150 ml of wine = 1.5 ounces/45 ml spirits = 12 ounces/360 ml of beer);
  • Patients currently receiving any investigational drug or have received an investigational drug within 30 days of baseline or 5 half-lives of the investigational drug (whichever is longer);
  • Patients with a history of cancer within the past 5 years other than a successfully treated, non-metastatic cutaneous squamous cell or basal cell carcinoma or cervical cancer in situ;
  • Patients with a history of, or any, disease associated with an inflammatory arthritis other than RA;
  • Patients with pulmonary fibrosis (Chest x-ray must be taken within 28 days of screening);
  • Patients receiving probenecid;
  • Patients who have received any steroid injections within 30 days of baseline;
  • Patients with concomitant diseases that are unstable (i.e. cardiac, pulmonary) or that may affect drug activity (i.e. absorption, reactions, change in kinetics);
  • Patients, in the investigator's opinion, that have any significant renal or hepatic impairment;
  • Patients with a serum creatinine level > 1.5 mg/dl at screening;
  • Patients with an ALT >1.5 ULN at screening;
  • Patients considered by the investigator to be an unsuitable candidate to receive CH-4051;
  • Wheelchair or bed-bound patients.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm 4

    Arm 5

    Arm Type

    Active Comparator

    Experimental

    Experimental

    Experimental

    Experimental

    Arm Label

    Methotrexate (MTX) + Folic Acid

    0.3 mg CH-4051

    1.0 mg CH-4051

    3.0 mg CH-4051

    3.0 mg CH-4051 + folic acid

    Arm Description

    20 mg MTX weekly + 1 mg folic acid daily

    0.3 mg CH-4051 daily

    1.0 mg CH-4051 daily

    3.0 mg CH-4051 daily

    3.0 mg CH-4051 + 1.0 mg folic acid daily

    Outcomes

    Primary Outcome Measures

    Co-primary: Hybrid American College of Rheumatology response criteria (hACR)followed by the ACR20
    The hybrid ACR (hACR) response was developed by the American College of Rheumatology to provide an improvement measure more sensitive to change than many other currently used measures, e.g., traditional ACR 20, 50 and 70 responses, while still maintaining clinical meaning. While traditional ACR 20, 50 and 70 response criteria are dichotomous measures (responder = yes/no), the hACR is a semi-continuous variable based upon the traditional ACR response but incorporating additional information on patient response into the outcome measure.

    Secondary Outcome Measures

    DAS28
    The disease activity score (DAS) is a combined index that was developed in Nijmegen in the 1980s to measure the disease activity in patients with RA. It has been extensively validated for its use in clinical trials in combination with the European League Against Rheumatism (EULAR) response criteria.
    ACR response criteria
    ACR assessment criteria is a widely accepted composite index of improvement in RA proposed by the American College of Rheumatology (ACR). ACR20 refers to a composite improvement of 20% in swollen joint count, tender joint count, and 3 or more of the following 5 measures: patient's own global assessment of RA disease activity; physician's global assessment of disease activity; patient's own assessment of pain due to RA; acute-phase reactant (erythrocyte sedimentation rate (ESR) or CRP); and patient's self-assessed disability (Health Assessment Questionnaire).
    Morning stiffness
    Morning stiffness is a common complaint of patients suffering from rheumatoid arthritis. Severity and joints involves varies from patient to patient. Patients will be asked, "Over the past 7 days, what has been the duration of stiffness of your joints in the morning?" The amount of time it takes a patient's morning stiffness to subside will be captured in hours and minutes.
    Safety and tolerability of CH-4051 in RA patients as determined by the frequency and severity of adverse events, laboratory abnormalities, and dropouts due to AEs
    Safety will be assessed by physical exams, vital signs, laboratory safety (blood and urine) and AEs. Liver functions tests will be identified as laboratory values of particular interest.

    Full Information

    First Posted
    May 3, 2010
    Last Updated
    April 9, 2013
    Sponsor
    Chelsea Therapeutics
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    1. Study Identification

    Unique Protocol Identification Number
    NCT01116141
    Brief Title
    A Study of CH-4051 in Patients With Rheumatoid Arthritis (RA)
    Acronym
    MOTION
    Official Title
    A Phase II, Multi-center, Randomized, Parallel Group, Double-blind, MTX Controlled Study to Assess the Clinical Efficacy, Safety and Tolerability of CH-4051 in Patients With Active RA Who Have Shown an Inadequate Response to MTX Monotherapy
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    April 2013
    Overall Recruitment Status
    Completed
    Study Start Date
    September 2010 (undefined)
    Primary Completion Date
    April 2012 (Actual)
    Study Completion Date
    May 2012 (Actual)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Chelsea Therapeutics

    4. Oversight

    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    The purpose of this study is to determine if CH-4051 is a safe and effective treatment for rheumatoid arthritis.
    Detailed Description
    Multi-center, multi-national, double-blind, randomized, active-controlled (MTX), 3-month study with 4 doses of CH-4051 (0.3 mg, 1.0 mg, 3.0 mg and 3.0 mg with 1mg of folic acid supplementation p.o. daily) compared to a "standard" dose of MTX at 20 mg per week with 1 mg of folic acid supplementation p.o. daily. This study will be conducted in two parts: Part A: Patients will be randomized to 0.3 mg CH-4051, 1.0 mg CH-4051 or MTX. Part B: Patients will not be randomized into Part B until the Data Monitoring Committee has reviewed safety data from the Part A when approximately 25 patients (10 patients in each CH-4051 dose groups and 5 patients in the MTX groups) have completed 3 months of treatment. At this time the DMC will make a recommendation whether or not to commence randomization to 3.0 mg CH-4051, 3.0 mg CH-4051 with 1.0 mg of folic acid.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Rheumatoid Arthritis
    Keywords
    rheumatoid arthritis, MTX, CH-405, antifolates

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantCare ProviderInvestigator
    Allocation
    Randomized
    Enrollment
    250 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Methotrexate (MTX) + Folic Acid
    Arm Type
    Active Comparator
    Arm Description
    20 mg MTX weekly + 1 mg folic acid daily
    Arm Title
    0.3 mg CH-4051
    Arm Type
    Experimental
    Arm Description
    0.3 mg CH-4051 daily
    Arm Title
    1.0 mg CH-4051
    Arm Type
    Experimental
    Arm Description
    1.0 mg CH-4051 daily
    Arm Title
    3.0 mg CH-4051
    Arm Type
    Experimental
    Arm Description
    3.0 mg CH-4051 daily
    Arm Title
    3.0 mg CH-4051 + folic acid
    Arm Type
    Experimental
    Arm Description
    3.0 mg CH-4051 + 1.0 mg folic acid daily
    Intervention Type
    Drug
    Intervention Name(s)
    CH-4051
    Intervention Description
    Different doses CH-4051 to be compared
    Intervention Type
    Drug
    Intervention Name(s)
    Methotrexate (MTX)
    Other Intervention Name(s)
    amethopterin
    Intervention Description
    20 mg MTX weekly
    Intervention Type
    Drug
    Intervention Name(s)
    Folic Acid
    Other Intervention Name(s)
    folate
    Intervention Description
    1 mg folic acid daily
    Primary Outcome Measure Information:
    Title
    Co-primary: Hybrid American College of Rheumatology response criteria (hACR)followed by the ACR20
    Description
    The hybrid ACR (hACR) response was developed by the American College of Rheumatology to provide an improvement measure more sensitive to change than many other currently used measures, e.g., traditional ACR 20, 50 and 70 responses, while still maintaining clinical meaning. While traditional ACR 20, 50 and 70 response criteria are dichotomous measures (responder = yes/no), the hACR is a semi-continuous variable based upon the traditional ACR response but incorporating additional information on patient response into the outcome measure.
    Time Frame
    12 weeks
    Secondary Outcome Measure Information:
    Title
    DAS28
    Description
    The disease activity score (DAS) is a combined index that was developed in Nijmegen in the 1980s to measure the disease activity in patients with RA. It has been extensively validated for its use in clinical trials in combination with the European League Against Rheumatism (EULAR) response criteria.
    Time Frame
    12 weeks
    Title
    ACR response criteria
    Description
    ACR assessment criteria is a widely accepted composite index of improvement in RA proposed by the American College of Rheumatology (ACR). ACR20 refers to a composite improvement of 20% in swollen joint count, tender joint count, and 3 or more of the following 5 measures: patient's own global assessment of RA disease activity; physician's global assessment of disease activity; patient's own assessment of pain due to RA; acute-phase reactant (erythrocyte sedimentation rate (ESR) or CRP); and patient's self-assessed disability (Health Assessment Questionnaire).
    Time Frame
    12 weeks
    Title
    Morning stiffness
    Description
    Morning stiffness is a common complaint of patients suffering from rheumatoid arthritis. Severity and joints involves varies from patient to patient. Patients will be asked, "Over the past 7 days, what has been the duration of stiffness of your joints in the morning?" The amount of time it takes a patient's morning stiffness to subside will be captured in hours and minutes.
    Time Frame
    12 weeks
    Title
    Safety and tolerability of CH-4051 in RA patients as determined by the frequency and severity of adverse events, laboratory abnormalities, and dropouts due to AEs
    Description
    Safety will be assessed by physical exams, vital signs, laboratory safety (blood and urine) and AEs. Liver functions tests will be identified as laboratory values of particular interest.
    Time Frame
    12 weeks

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    80 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Patients must be between the ages of 18 and 80; Have diagnosed active rheumatoid arthritis according to ACR criteria functional class I-III; Have at least 6 swollen joints (max = 66) and 6 tender joints (max = 68) at screening and baseline visits; Patients must have at least one of the following: C-reactive protein > 1.0 mg/dl at screening; erythrocyte sedimentation rate > 28 mm/Hr; Patients must have been taking methotrexate between 15 and 25 mg/week for at least 3 months and at a stable dose for at least 6 weeks; Patients must be either Rheumatoid Factor (RF) or anti-cyclic citrullinated peptide (anti-CCP) positive; Patients must have voluntarily signed the informed consent. Exclusion Criteria: Patients who received previous therapy with any biologic agent; Patients currently taking any disease modifying anti-rheumatic drug (DMARD) other than MTX; Previous non-biologic DMARD therapy is permitted as long as their last dose was at least 30 days prior to baseline; Female patients of child bearing potential who are pregnant or who are not using two methods of contraception (at least one barrier: i.e. condom) with their partner; Male patients who are sexually active and not using two methods of contraception (at least one barrier: i.e. condom) with their partner; Patients with any current active infection or infections requiring IV drug therapy within 30 days of baseline or oral therapy within 15 days of Baseline; Patients that have had any surgical procedures within 30 days of baseline; Patients with a history of HIV; Patients with Hepatitis B surface antigen positive and/or Hepatitis C antibody positive; Patients who consume more than 4 units of alcohol per week (1 unit = 5 ounces/150 ml of wine = 1.5 ounces/45 ml spirits = 12 ounces/360 ml of beer); Patients currently receiving any investigational drug or have received an investigational drug within 30 days of baseline or 5 half-lives of the investigational drug (whichever is longer); Patients with a history of cancer within the past 5 years other than a successfully treated, non-metastatic cutaneous squamous cell or basal cell carcinoma or cervical cancer in situ; Patients with a history of, or any, disease associated with an inflammatory arthritis other than RA; Patients with pulmonary fibrosis (Chest x-ray must be taken within 28 days of screening); Patients receiving probenecid; Patients who have received any steroid injections within 30 days of baseline; Patients with concomitant diseases that are unstable (i.e. cardiac, pulmonary) or that may affect drug activity (i.e. absorption, reactions, change in kinetics); Patients, in the investigator's opinion, that have any significant renal or hepatic impairment; Patients with a serum creatinine level > 1.5 mg/dl at screening; Patients with an ALT >1.5 ULN at screening; Patients considered by the investigator to be an unsuitable candidate to receive CH-4051; Wheelchair or bed-bound patients.
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Arthur A Kavanaugh, MD
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Learn more about this trial

    A Study of CH-4051 in Patients With Rheumatoid Arthritis (RA)

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