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Completed

NCT Number: NCT00665626

Efficacy and Safety Study of R935788 Tablets to Treat Rheumatoid Arthritis (Taski-3)

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.

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Key information

Conditions

Rheumatoid Arthritis Arthritis Arthritis, Rheumatoid Autoimmune Diseases Connective Tissue Diseases Immune System Diseases Joint Diseases Musculoskeletal Diseases Rheumatic Diseases Skin and Connective Tissue Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

ZNA Middelheim, Antwepen, Belgium

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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 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.

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:
  • 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.

Treatment and study plan

Fostamatinib disodium (R935788)

Drug

R935788 100 mg tablet, orally, twice-a-day

Placebo

Drug

Placebo, orally, twice-a-day

Primary outcomes

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

    Time frame: 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 outcomes

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

    Time frame: 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

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

    Time frame: 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

  3. American College of Rheumatology Index of Improvement (ACRn) at 3 Months

    Time frame: 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

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

    Time frame: 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

  5. Disease Activity Score-C-Reactive Protein (DAS28-CRP) <3.2 at 3 Months

    Time frame: 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.

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

    Time frame: 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

  7. Disease Activity Score-Erythrocyte Sedimentation Rate (DAS28-ESR) <3.2 at 3 Months

    Time frame: 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.

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

    Time frame: 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.

  9. American College of Rheumatology 20 (ACR20) Response at Week 2

    Time frame: 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

  10. Rheumatoid Arthritis Magnetic Resonance Imaging Scoring (RAMRIS) Erosion Score at 3 Months

    Time frame: 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.

  11. Rheumatoid Arthritis Magnetic Resonance Imaging Scoring (RAMRIS) Osteitis Score at 3 Months

    Time frame: 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.

  12. Rheumatoid Arthritis Magnetic Resonance Imaging Scoring (RAMRIS) Synovitis Score at 3 Months

    Time frame: 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.

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

    Time frame: 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

  14. Alanine Aminotransferase (ALT) >1.5-2x Upper Limit of Normal (ULN)

    Time frame: 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

  15. Alanine Aminotransferase (ALT) >2-3x Upper Limit of Normal (ULN)

    Time frame: 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

  16. Alanine Aminotransferase (ALT) >3x Upper Limit of Normal (ULN)

    Time frame: 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

  17. Alanine Aminotransferase (ALT) >3-5x Upper Limit of Normal (ULN)

    Time frame: 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

  18. Alanine Aminotransferase (ALT) >5-10x Upper Limit of Normal (ULN)

    Time frame: 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

  19. Alanine Aminotransferase (ALT) >10x Upper Limit of Normal (ULN)

    Time frame: 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

  20. Aspartate Aminotransferase (AST) >1.5x Upper Limit of Normal (ULN)

    Time frame: 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

  21. Aspartate Aminotransferase (AST) >1.5-2x Upper Limit of Normal (ULN)

    Time frame: 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

  22. Aspartate Aminotransferase (AST) >2-3x Upper Limit of Normal (ULN)

    Time frame: 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

  23. Aspartate Aminotransferase (AST) >3x Upper Limit of Normal (ULN)

    Time frame: 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

  24. Aspartate Aminotransferase (AST) >3-5x Upper Limit of Normal (ULN)

    Time frame: 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

  25. Aspartate Aminotransferase (AST) >5-10x Upper Limit of Normal (ULN)

    Time frame: 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

  26. Aspartate Aminotransferase (AST) >10x Upper Limit of Normal (ULN)

    Time frame: 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

  27. Alkaline Phosphatase >1.5x Upper Limit of Normal (ULN) and >1.5x Baseline

    Time frame: 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

  28. Bilirubin >1.5x Upper Limit of Normal (ULN)

    Time frame: 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

  29. Bilirubin >2x Upper Limit of Normal (ULN)

    Time frame: 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

  30. Absolute Neutrophil Count (ANC) <1500/mm3

    Time frame: Any time between baseline and 3 months

    The number of participants with ANC values less than 1500/mm3

Sponsors and collaborators

Lead sponsor

Rigel Pharmaceuticals

Industry

Registry information

Official study title

A Phase II, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Dose Study of R935788 in Patients With Rheumatoid Arthritis Who Have Failed at Least One Biologic

Acronym: Taski-3

Important dates

Study start
2008
Primary completion
2009
Study completion
2009
First posted
Apr 24, 2008
Registry last updated
May 1, 2017

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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