Efficacy and Safety Study of R935788 Tablets to Treat Rheumatoid Arthritis

Rigel Pharmaceuticals457 enrolled

Overview

The purpose of this study is to determine whether the Spleen Tyrosine Kinase (Syk) inhibitor, R935788 (R788), at a dose of 100 mg, orally, twice-a-day, and/or a dose of of 150 mg, orally, once-a-day is effective in the treatment of Rheumatoid Arthrits in patients who have had an inadequate clinical response to methotrexate.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

457

Conditions

Rheumatoid Arthritis

Interventions

Fostamatinib disodium (R935788)DRUG

100 mg tablet, orally, twice-a-day

Fostamatinib disodium (R935788)DRUG

150 mg tablet, orally, once a day

PlaceboDRUG

Placebo, orally, either once a day, or twice a day

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * 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 6 months prior to Day 1 dosing. * Patients must have been receiving weekly methotrexate 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 must be receiving a 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. Exclusion Criteria: * 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: 1. uncontrolled or poorly controlled hypertension; 2. other autoimmune disease (psoriatic arthritis, lupus, mixed connective disorder) or arthritis syndromes (gout, Lyme disease, Reiter's syndrome); 3. recent (within past 2 months prior to Day 1 dosing) serious surgery or infectious disease; 4. recent history (past 5 years prior to Day 1 dosing) of, or treatment for, a malignancy other than nonmelanomatous skin cancer, or any history of lymphoma; 5. Hepatitis B ; 6. Hepatitis C ; 7. interstitial pneumonitis or active pulmonary infection on chest x-ray; 8. Tuberculosis (TB): the TB skin test should be negative. 9. 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.

Locations (65)

Outcomes

Primary Outcomes

American College of Rheumatology 20 (ACR20) Response at 6 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, HAQ-DI; and C-Reactive Protein (CRP) or erythrocyte sedimentation rate (ESR), after 6 months

Time frame: 6 months

Secondary Outcomes

American College of Rheumatology 20 (ACR20) Response at 1 Week

Time frame: 1 week

American College of Rheumatology 20 (ACR20) Response at 2 Weeks

Time frame: 2 weeks

American College of Rheumatology 20 (ACR20) Response at 1 Month

Time frame: 1 month

American College of Rheumatology 20 (ACR20) Response at 6 Weeks

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Divison of Rheumatology Allergy and Immunology

La Jolla, California, United States

Desert Medical Advances

Palm Desert, California, United States

Arthritis & Osteoporosis Center, PC

Hamden, Connecticut, United States

Cynthia Morgan

Washington D.C., District of Columbia, United States

Florida Medical Research Institute

Gainsville, Florida, United States

Paddock Park Clinical Research

Ocala, Florida, United States

Jeffrey Poiley, MD

Orlando, Florida, United States

Lovelace Scientific Resources

Sarasota, Florida, United States

Rheumatology Associates, SC

Chicago, Illinois, United States

Memorial Medical Group Clinical Research Inst

South Bend, Indiana, United States

...and 55 more locations

American College of Rheumatology 20 (ACR20) Response at 2 Months

Time frame: 2 months

American College of Rheumatology 20 (ACR20) Response at 3 Months

Time frame: 3 months

American College of Rheumatology 20 (ACR20) Response at 4 Months

Time frame: 4 months

American College of Rheumatology 20 (ACR20) Response at 5 Months

Time frame: 5 months

American College of Rheumatology 50 (ACR50) Response at 1 Week

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 C-Reactive Protein (CRP) or erythrocyte sedimentation rate (ESR), after 1 week

Time frame: 1 week

American College of Rheumatology 50 (ACR50) Response at 2 Weeks

Time frame: 2 weeks

American College of Rheumatology 50 (ACR50) Response at 1 Month

Time frame: 1 month

American College of Rheumatology 50 (ACR50) Response at 6 Weeks

Time frame: 6 weeks

American College of Rheumatology 50 (ACR50) Response at 2 Months

Time frame: 2 months

American College of Rheumatology 50 (ACR50) Response at 3 Months

Time frame: 3 months

American College of Rheumatology 50 (ACR50) Response at 4 Months

Time frame: 4 months

American College of Rheumatology 50 (ACR50) Response at 5 Months

Time frame: 5 months

American College of Rheumatology 50 (ACR50) Response at 6 Months

Time frame: 6 months

American College of Rheumatology 70 (ACR70) Response at 1 Week

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 C-Reactive Protein (CRP) or erythrocyte sedimentation rate (ESR), after 1 week

Time frame: 1 week

American College of Rheumatology 70 (ACR70) Response at 2 Weeks

Time frame: 2 weeks

American College of Rheumatology 70 (ACR70) Response at 1 Month

Time frame: 1 month

American College of Rheumatology 70 (ACR70) Response at 6 Weeks

Time frame: 6 weeks

American College of Rheumatology 70 (ACR70) Response at 2 Months

Time frame: 2 months

American College of Rheumatology 70 (ACR70) Response at 3 Months

Time frame: 3 months

American College of Rheumatology 70 (ACR70) Response at 4 Months

Time frame: 4 months

American College of Rheumatology 70 (ACR70) Response at 5 Months

Time frame: 5 months

American College of Rheumatology 70 (ACR70) Response at 6 Months

Time frame: 6 months

American College of Rheumatology Index of Improvement (ACRn) at 1 Week

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 1 week of treatment

Time frame: 1 week

American College of Rheumatology Index of Improvement (ACRn) at 2 Weeks

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 2 weeks of treatment

Time frame: 2 weeks

American College of Rheumatology Index of Improvement (ACRn) at 1 Month

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 1 month of treatment

Time frame: 1 month

American College of Rheumatology Index of Improvement (ACRn) at 6 Weeks

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 6 weeks of treatment

Time frame: 6 weeks

American College of Rheumatology Index of Improvement (ACRn) at 2 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 2 months of treatment

Time frame: 2 months

American College of Rheumatology Index of Improvement (ACRn) at 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

Time frame: 3 months

American College of Rheumatology Index of Improvement (ACRn) at 4 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 4 months of treatment

Time frame: 4 months

American College of Rheumatology Index of Improvement (ACRn) at 5 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 5 months of treatment

Time frame: 5 months

American College of Rheumatology Index of Improvement (ACRn) at 6 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 6 months of treatment

Time frame: 6 months

Disease Activity Score-C-Reactive Protein (DAS28-CRP) <2.6 at 1 Month

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

Time frame: 1 month

Disease Activity Score-C-Reactive Protein (DAS28-CRP) <2.6 at 2 Months

Time frame: 2 months

Disease Activity Score-C-Reactive Protein (DAS28-CRP) <2.6 at 3 Months

Time frame: 3 months

Disease Activity Score-C-Reactive Protein (DAS28-CRP) <2.6 at 4 Months

Time frame: 4 months

Disease Activity Score-C-Reactive Protein (DAS28-CRP) <2.6 at 5 Months

Time frame: 5 months

Disease Activity Score-C-Reactive Protein (DAS28-CRP) <2.6 at 6 Months

Time frame: 6 months

Disease Activity Score-C-Reactive Protein (DAS28-CRP) <3.2 at 1 Month

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

Time frame: 1 month

Disease Activity Score-C-Reactive Protein (DAS28-CRP) <3.2 at 2 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

Time frame: 2 months

Disease Activity Score-C-Reactive Protein (DAS28-CRP) <3.2 at 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

Time frame: 3 months

Disease Activity Score-C-Reactive Protein (DAS28-CRP) <3.2 at 4 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

Time frame: 4 months

Disease Activity Score-C-Reactive Protein (DAS28-CRP) <3.2 at 5 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

Time frame: 5 months

Disease Activity Score-C-Reactive Protein (DAS28-CRP) <3.2 at 6 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

Time frame: 6 months

Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) <2.6 at 1 Month

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

Time frame: 1 month

Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) <2.6 at 2 Months

Time frame: 2 months

Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) <2.6 at 3 Months

Time frame: 3 months

Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) <2.6 at 4 Months

Time frame: 4 months

Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) <2.6 at 5 Months

Time frame: 5 months

Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) <2.6 at 6 Months

Time frame: 6 months

Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) <3.2 at 1 Month

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

Time frame: 1 month

Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) <3.2 at 2 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

Time frame: 2 months

Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) <3.2 at 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

Time frame: 3 months

Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) <3.2 at 4 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

Time frame: 4 months

Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) <3.2 at 5 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

Time frame: 5 months

Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) <3.2 at 6 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

Time frame: 6 months

Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) at 6 Months

Change from baseline in FACIT-F, which is a patient-reported 13-item questionnaire that assesses fatigue, calculated as the score at 6 months minus the score at baseline. The FACIT-F runs from 0 to 52 with lower scores indicating higher fatigue. A positive change from baseline indicates an improvement in fatigue after treatment.

Time frame: Baseline to 6 months

Short Form Health Survey (SF-36) Physical Component Summary (PCS) at 6 Months

Change from baseline in the PCS of the SF-36 (which assesses health and wellbeing), calculated as the score at 6 months minus the score at baseline. The PCS ranges from 0 to 100 with 100 indicating the highest level of functioning possible. A positive change indicates an improvement in PCS after treatment

Time frame: Baseline to 6 months

Short Form Health Survey (SF-36) Mental Component Summary (MCS) at 6 Months

Change from baseline in the MCS of the SF-36 (which assesses health and wellbeing), calculated as the score at 6 months minus the score at baseline. The MCS ranges from 0 to 100 with 100 indicating the highest level of functioning possible. A positive change indicates an improvement in MCS after treatment

Time frame: Baseline to 6 months

Alanine Aminotransferase (ALT) >1.5x Upper Limit of Normal (ULN)

The number of participants with ALT (a test of liver function) values greater than 1.5 times the ULN