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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01116141
Recruitment Status : Completed
First Posted : May 4, 2010
Last Update Posted : April 15, 2013
Information provided by (Responsible Party):
Chelsea Therapeutics

Brief Summary:
The purpose of this study is to determine if CH-4051 is a safe and effective treatment for rheumatoid arthritis.

Condition or disease Intervention/treatment Phase
Rheumatoid Arthritis Drug: CH-4051 Drug: Methotrexate (MTX) Drug: Folic Acid Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 250 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
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 Start Date : September 2010
Actual Primary Completion Date : April 2012
Actual Study Completion Date : May 2012

Arm Intervention/treatment
Active Comparator: Methotrexate (MTX) + Folic Acid
20 mg MTX weekly + 1 mg folic acid daily
Drug: Methotrexate (MTX)
20 mg MTX weekly
Other Name: amethopterin

Drug: Folic Acid
1 mg folic acid daily
Other Name: folate

Experimental: 0.3 mg CH-4051
0.3 mg CH-4051 daily
Drug: CH-4051
Different doses CH-4051 to be compared

Experimental: 1.0 mg CH-4051
1.0 mg CH-4051 daily
Drug: CH-4051
Different doses CH-4051 to be compared

Experimental: 3.0 mg CH-4051
3.0 mg CH-4051 daily
Drug: CH-4051
Different doses CH-4051 to be compared

Experimental: 3.0 mg CH-4051 + folic acid
3.0 mg CH-4051 + 1.0 mg folic acid daily
Drug: CH-4051
Different doses CH-4051 to be compared

Drug: Folic Acid
1 mg folic acid daily
Other Name: folate

Primary Outcome Measures :
  1. Co-primary: Hybrid American College of Rheumatology response criteria (hACR)followed by the ACR20 [ Time Frame: 12 weeks ]
    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 :
  1. DAS28 [ Time Frame: 12 weeks ]
    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.

  2. ACR response criteria [ Time Frame: 12 weeks ]
    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).

  3. Morning stiffness [ Time Frame: 12 weeks ]
    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.

  4. 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 [ Time Frame: 12 weeks ]
    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.

Information from the National Library of Medicine

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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

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01116141

Sponsors and Collaborators
Chelsea Therapeutics
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Principal Investigator: Arthur A Kavanaugh, MD

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Responsible Party: Chelsea Therapeutics Identifier: NCT01116141     History of Changes
Other Study ID Numbers: CH-4051-RA202
First Posted: May 4, 2010    Key Record Dates
Last Update Posted: April 15, 2013
Last Verified: April 2013
Keywords provided by Chelsea Therapeutics:
rheumatoid arthritis
Additional relevant MeSH terms:
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Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Folic Acid
Vitamin B Complex
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors