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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Chelsea Therapeutics
ClinicalTrials.gov Identifier:
NCT01116141
First received: May 3, 2010
Last updated: April 9, 2013
Last verified: April 2013
  Purpose

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


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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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

Resource links provided by NLM:


Further study details as provided by Chelsea Therapeutics:

Primary Outcome Measures:
  • Co-primary: Hybrid American College of Rheumatology response criteria (hACR)followed by the ACR20 [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
    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 [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 250
Study Start Date: September 2010
Study Completion Date: May 2012
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01116141

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

No publications provided

Responsible Party: Chelsea Therapeutics
ClinicalTrials.gov Identifier: NCT01116141     History of Changes
Other Study ID Numbers: CH-4051-RA202
Study First Received: May 3, 2010
Last Updated: April 9, 2013
Health Authority: United States: Food and Drug Administration
Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Bulgaria: Ministry of Health
Czech Republic: State Institute for Drug Control
Mexico: Ministry of Health
Poland: Ministry of Health
Spain: Ministry of Health

Keywords provided by Chelsea Therapeutics:
rheumatoid arthritis
MTX
CH-405
antifolates

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Folic Acid
Vitamin B Complex
Methotrexate
Hematinics
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents

ClinicalTrials.gov processed this record on August 28, 2014