Efficacy and Safety Study of R935788 Tablets to Treat Rheumatoid Arthritis (Taski-3)
- Conditions
- Rheumatoid Arthritis
- Interventions
- Drug: Placebo
- Registration Number
- NCT00665626
- Lead Sponsor
- Rigel Pharmaceuticals
- Brief Summary
The purpose of this study is to determine whether the Spleen Tyrosine Kinase (Syk) Inhibitor, R935788 (R788) at a dose of 100 mg, tablet, orally, twice-a-day is effective in the treatment of Rheumatoid Arthritis in patients who have 'failed' a biologic therapy.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 219
- Patients must give written informed consent by signing an IRB/EC-approved Informed Consent Form (ICF) prior to admission to this study.
- Males and females, 18 years of age or older, with active RA for at least 12 months prior to Day 1 dosing
- Are currently receiving or previously had received a biologic therapy with an inhibitor of TNF, rituximab, abatacept, or anakinra at an approved labeled dose for ≥3 months prior to Day 1 dosing and are designated as biologic therapy failures for lack of efficacy, safety, or tolerability.
- Patients may receive stable doses of methotrexate (MTX), azathioprine (not in combination with MTX), leflunomide (not in combination with MTX), sulfasalazine, chloroquine, hydroxychloroquine, gold, NSAIDs (including COX2 inhibitors), minocycline, or doxycycline. The dose must have been stable for at least 30 days prior to Day 1 dosing and must not be changed during the washout, screening and treatment periods, unless dictated by tolerability requirements. Patients who are taking MTX must have been receiving weekly MTX doses (7.5-25 mg/week) for a minimum of 3 months prior to Day 1 dosing and must be receiving a stable MTX dose, with no change in route, for the previous 6 weeks prior to Day 1 dosing. Patients who are receiving MTX must also be receiving folic or folinic acid supplementation at a stable dose for at least 6 weeks prior to Day 1 dosing.
- Females of childbearing potential must be fully informed of the potential for R788 to adversely affect the fetus and, if sexually active, must agree to use a well established method of birth control during the study (oral contraceptive, mechanical barrier, long acting hormonal agent). These patients must not be lactating and must have a negative urine pregnancy test at the time of randomization and at each laboratory determination.
- The patient must otherwise be in good health as determined by the Investigator on the basis of medical history, physical examination, and laboratory screening tests during the screening period. See exclusion criteria for specific exclusions.
- In the Investigator's opinion, the patient has the ability to understand the nature of the study and any hazards of participation, and to communicate satisfactorily with the Investigator and to participate in, and to comply with, the requirements of the entire protocol.
-
The patient has a history of, or a concurrent, clinically significant illness, medical condition (other than arthritis) or laboratory abnormality that, in the Investigator's opinion, could affect the conduct of the study. Specifically, excluded are patients with the following:
- uncontrolled or poorly controlled hypertension;
- other autoimmune disease (psoriatic arthritis, lupus, mixed connective disorder) or arthritis syndromes (gout, Lyme disease, Reiter's syndrome);
- recent serious surgery or infectious disease;
- recent history ( of, or treatment for, a malignancy other than nonmelanomatous skin cancer, or any history of lymphoma;
- Hepatitis B;
- Hepatitis C;
- interstitial pneumonitis or active pulmonary infection on chest x-ray
- Tuberculosis (TB)
- known laboratory abnormalities
-
The patient has a history of substance abuse, drug addiction or alcoholism. Patients may consume up to 4 units of alcohol per week; however, alcohol should be avoided in the 72 hours prior to lab assessments. Patients who cannot reliably comply with this should be excluded. A unit of alcohol is defined as the following: Beer=12 oz or 355 mL; wine = 5 oz or 148 mL; sweet dessert wine=3 oz or 89 mL; 80 proof distilled spirits= 1.5 oz or 44 mL.
-
The patient has been treated previously treated with R788 under a different protocol.
-
The patient has a pacemaker, aneurysm clip or other contraindication to MRI.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 1 Fostamatinib disodium (R935788) Fostamatinib disodium (R935788) 100 mg tablet, orally, twice-a-day Arm 2 Placebo Placebo, orally, twice-a-day
- Primary Outcome Measures
Name Time Method American College of Rheumatology 20 (ACR20) Response at 3 Months 3 months The number of participants with greater than or equal to 20% improvement in tender and swollen joint counts, AND in any 3 of the following: physician's assessment of disease activity, patient's assessment of disease activity, patient's assessment of pain, Health Assessment Questionnaire-Disability Index (HAQ-DI); and CRP or ESR, after 3 months
- Secondary Outcome Measures
Name Time Method Aspartate Aminotransferase (AST) >1.5-2x Upper Limit of Normal (ULN) Any time between baseline and 3 months The number of participants with AST (a test of liver function) values greater than 1.5 to 2 times the ULN
Disease Activity Score-C-Reactive Protein (DAS28-CRP) <2.6 at 3 Months 3 months Number of participants with DAS28-CRP (measuring RA symptoms including: tender joint count, swollen joint count, patient's assessment of disease activity, and CRP in patients with high CRP at baseline), of less than 2.6. The DAS runs from 0 to 10 - higher scores indicate worse symptoms. A score of less than 2.6 indicates remission of RA symptoms
Disease Activity Score-C-Reactive Protein (DAS28-CRP) <3.2 at 3 Months 3 months Number of participants with DAS28-CRP (measuring RA symptoms including: tender joint count, swollen joint count, patient's assessment of disease activity, and CRP in patients with high CRP at baseline), of less than 3.2. The DAS runs from 0 to 10 - higher scores indicate worse symptoms. A score of less than 3.2 indicates low disease activity.
Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) <2.6 at 3 Months 3 months Number of participants with DAS28-ESR (measuring RA symptoms including: tender joint count, swollen joint count, patient's assessment of disease activity, and ESR in patients with high ESR at baseline), of less than 2.6. The DAS runs from 0 to 10 - higher scores indicate worse symptoms. A score of less than 2.6 indicates remission of RA symptoms
Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) <3.2 at 3 Months 3 months Number of participants with DAS28-ESR (measuring RA symptoms including: tender joint count, swollen joint count, patient's assessment of disease activity, and ESR in patients with high ESR at baseline), of less than 3.2. The DAS runs from 0 to 10 - higher scores indicate worse symptoms. A score of less than 3.2 indicates low disease activity.
American College of Rheumatology 50 (ACR50) Response at 3 Months 3 months The number of participants with greater than or equal to 50% improvement in tender and swollen joint counts, AND in any 3 of the following: physician's assessment of disease activity, patient's assessment of disease activity, patient's assessment of pain, HAQ-DI; and CRP or ESR, whichever was elevated at baseline, after 3 months
American College of Rheumatology 70 (ACR70) Response at 3 Months 3 months The number of participants with greater than or equal to 70% improvement in tender and swollen joint counts, AND in any 3 of the following: physician's assessment of disease activity, patient's assessment of disease activity, patient's assessment of pain, HAQ-DI; and CRP or ESR, whichever was elevated at baseline, after 3 months
American College of Rheumatology Index of Improvement (ACRn) at 3 Months 3 months The index of improvement in RA, where 0 indicates no improvement and 100 indicates a 100% improvement across all signs and symptoms of RA after 3 months of treatment
American College of Rheumatology 20 (ACR20) Response at Week 1 1 week The number of participants with greater than or equal to 20% improvement in tender and swollen joint counts, AND in any 3 of the following: physician's assessment of disease activity, patient's assessment of disease activity, patient's assessment of pain, HAQ-DI; and CRP or ESR, whichever was elevated at baseline, after 1 week.
American College of Rheumatology 20 (ACR20) Response at Week 2 2 weeks The number of participants with greater than or equal to 20% improvement in tender and swollen joint counts, AND in any 3 of the following: physician's assessment of disease activity, patient's assessment of disease activity, patient's assessment of pain, HAQ-DI; and CRP or ESR, whichever was elevated at baseline, after 2 weeks
Rheumatoid Arthritis Magnetic Resonance Imaging Scoring (RAMRIS) Erosion Score at 3 Months Baseline to 3 months Change from baseline in RAMRIS erosion score (a measure of bone erosion in the hands and wrists), calculated as the score at 3 months minus the score at baseline. The erosion score runs from 0 to 250 with lower values indicating a better clinical condition. A negative change indicates an improvement in symptoms.
Rheumatoid Arthritis Magnetic Resonance Imaging Scoring (RAMRIS) Osteitis Score at 3 Months Baseline to 3 months Change from baseline in RAMRIS osteitis score (a measure of bone inflammation in the hands and wrists), calculated as the score at 3 months minus the score at baseline. The osteitis score runs from 0 to 75 with lower values indicating a better clinical condition. A negative change indicates an improvement in symptoms.
Rheumatoid Arthritis Magnetic Resonance Imaging Scoring (RAMRIS) Synovitis Score at 3 Months Baseline to 3 months Change from baseline in RAMRIS synovitis score (a measure of inflammation in the joints of the hands and wrists), calculated as the score at 3 months minus the score at baseline. The synovitis score runs from 0 to 24 with lower values indicating a better clinical condition. A negative change indicates an improvement in symptoms.
Alanine Aminotransferase (ALT) >1.5x Upper Limit of Normal (ULN) Any time between baseline and 3 months The number of participants with ALT (a test of liver function) values greater than 1.5 times the ULN
Alanine Aminotransferase (ALT) >1.5-2x Upper Limit of Normal (ULN) Any time between baseline and 3 months The number of participants with ALT (a test of liver function) values greater than 1.5 to 2 times the ULN
Alanine Aminotransferase (ALT) >2-3x Upper Limit of Normal (ULN) Any time between baseline and 3 months The number of participants with ALT (a test of liver function) values greater than 2 to 3 times the ULN
Alanine Aminotransferase (ALT) >3x Upper Limit of Normal (ULN) Any time between baseline and 3 months The number of participants with ALT (a test of liver function) values greater than 3 times the ULN
Alanine Aminotransferase (ALT) >3-5x Upper Limit of Normal (ULN) Any time between baseline and 3 months The number of participants with ALT (a test of liver function) values greater than 3 to 5 times the ULN
Alanine Aminotransferase (ALT) >5-10x Upper Limit of Normal (ULN) Any time between baseline and 3 months The number of participants with ALT (a test of liver function) values greater than 5 to 10 times the ULN
Alanine Aminotransferase (ALT) >10x Upper Limit of Normal (ULN) Any time between baseline and 3 months The number of participants with ALT (a test of liver function) values greater than 10 times the ULN
Aspartate Aminotransferase (AST) >1.5x Upper Limit of Normal (ULN) Any time between baseline and 3 months The number of participants with AST (a test of liver function) values greater than 1.5 times the ULN
Aspartate Aminotransferase (AST) >2-3x Upper Limit of Normal (ULN) Any time between baseline and 3 months The number of participants with AST (a test of liver function) values greater than 2 to 3 times the ULN
Aspartate Aminotransferase (AST) >3x Upper Limit of Normal (ULN) Any time between baseline and 3 months The number of participants with AST (a test of liver function) values greater than 3 times the ULN
Aspartate Aminotransferase (AST) >3-5x Upper Limit of Normal (ULN) Any time between baseline and 3 months The number of participants with AST (a test of liver function) values greater than 3 to 5 times the ULN
Aspartate Aminotransferase (AST) >5-10x Upper Limit of Normal (ULN) Any time between baseline and 3 months The number of participants with AST (a test of liver function) values greater than 5 to 10 times the ULN
Aspartate Aminotransferase (AST) >10x Upper Limit of Normal (ULN) Any time between baseline and 3 months The number of participants with AST (a test of liver function) values greater than 10 times the ULN
Bilirubin >1.5x Upper Limit of Normal (ULN) Any time between baseline and 3 months The number of participants with bilirubin (a test of liver function) values greater than 1.5 times the ULN
Alkaline Phosphatase >1.5x Upper Limit of Normal (ULN) and >1.5x Baseline Any time between baseline and 3 months The number of participants with alkaline phosphatase (a test of liver function) values greater than 1.5 times the ULN and greater than 1.5 times baseline
Bilirubin >2x Upper Limit of Normal (ULN) Any time between baseline and 3 months The number of participants with bilirubin (a test of liver function) values greater than 2 times the ULN
Absolute Neutrophil Count (ANC) <1500/mm3 Any time between baseline and 3 months The number of participants with ANC values less than 1500/mm3
Trial Locations
- Locations (43)
RASF-Clinical Research Center
🇺🇸Boca Raton, Florida, United States
The Osteoporosis & Clinical Trials Center
🇺🇸Hagerstown, Maryland, United States
Desert Medical Advances
🇺🇸Palm Desert, California, United States
Department of Rheumatology
🇺🇸Washington, District of Columbia, United States
Memorial Medical Group Clinical Research Inst
🇺🇸South Bend, Indiana, United States
Arthritis & Rheumatic Disease Specialties
🇺🇸Aventura, California, United States
Hopital Pellegrin
🇫🇷Bordeaux Cedex, France
CHU Liege
🇧🇪Liege, Belgium
Paddock Park Clinical Research
🇺🇸Ocala, Florida, United States
San Diego Arthritis & Medical Clinic
🇺🇸San Diego, California, United States
Rheumatology Associates, SC
🇺🇸Chicago, Illinois, United States
Houston Institute for Clinical Research
🇺🇸Houston, Texas, United States
Azienda Ospedaliera Santa Maria della Miseri
🇮🇹Udine, Italy
Florida Medical Research Institute
🇺🇸Gainsville, Florida, United States
Intermountain Orthopedics
🇺🇸Boise, Idaho, United States
Lovelace Scientific Resources
🇺🇸Sarasota, Florida, United States
Fiechtner Research, Inc.
🇺🇸Lansing, Michigan, United States
North Shore Long Island Jewich Health System
🇺🇸Lake Success, New York, United States
Andrew Porges, MD PC
🇺🇸Roslyn, New York, United States
Rheumatology Associates
🇺🇸Erie, Pennsylvania, United States
Clinical Research Division
🇺🇸Mayfield Village, Ohio, United States
Rheumatology Associates of Long Island
🇺🇸Smithtown, New York, United States
Clinical Research Center of Reading, LLP
🇺🇸West Reading, Pennsylvania, United States
Rheumatic Disease Associates
🇺🇸Willow Grove, Pennsylvania, United States
ZNA Middelheim
🇧🇪Antwepen, Belgium
Arthritis Northwest, PLLC
🇺🇸Spokane, Washington, United States
UZ Gent
🇧🇪Gent, Belgium
Reumalab S.A.
🇨🇴Medellin, Antioquia, Colombia
Reumatologos del Caribe
🇨🇴Barranquilla, Atlantico, Colombia
CIREEM
🇨🇴Bogota, Cundinamarca, Colombia
Dr. Renato Guzman
🇨🇴Bogota, Cundinamarca, Colombia
Riesgo de Fractura S.A.
🇨🇴Bogota, Cundinamarca, Colombia
Klinikum der J.W. Goethe Universitaet
🇩🇪Frankfurt, Germany
ClinPharm International GmbH Leipzig
🇩🇪Leipzig, Germany
Klinikum Eilbek
🇩🇪Hamburg, Germany
Rheumazentrum am Universitatsklinikum Leipzig
🇩🇪Leipzig, Germany
Reumatologia Azienda Ospedaliera Universitaria
🇮🇹Siena, Italy
Universitatsklinikum Wurzburg
🇩🇪Wurzburg, Germany
Instituto de Ginecologia y Reproduccion
🇵🇪Lima, Peru
Center for Arthritis & Osteoperosis
🇺🇸Elizabethtown, Kentucky, United States
Health Research of Oklahoma
🇺🇸Oklahoma City, Oklahoma, United States
Westroads Medical Group
🇺🇸Omaha, Nebraska, United States
Austin Rheumatology & Research
🇺🇸Austin, Texas, United States