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
About this trial
This is an interventional treatment trial for Rheumatoid Arthritis focused on measuring rheumatoid arthritis, MTX, CH-405, antifolates
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.
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
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)
We'll reach out to this number within 24 hrs