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

This study has been completed.
Sponsor:
Information provided by:
Rigel Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00665626
First received: April 22, 2008
Last updated: June 17, 2009
Last verified: June 2009
  Purpose

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.


Condition Intervention Phase
Rheumatoid Arthritis
Drug: Fostamatinib disodium (R935788)
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official 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

Resource links provided by NLM:


Further study details as provided by Rigel Pharmaceuticals:

Primary Outcome Measures:
  • The primary objective of this study is to assess the efficacy of R788 100 mg PO bid compared with placebo, as determined by ACR20 responder rates at Month 3. [ Time Frame: Month 3 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To assess the response rate of R788 100 mg PO bid as determined by ACR50, ACR70, ACRn, DAS28-CRP, and DAS28-ESR at Month 3 [ Time Frame: Month 3 ] [ Designated as safety issue: No ]
  • To assess the rapidity of onset of clinical effect of R788 100 mg PO bid compared with placebo as determined by ACR20 response rates at Weeks 1 and 2 [ Time Frame: Week 1 and Week 2 ] [ Designated as safety issue: No ]
  • To assess the radiologic response of R788 100 mg PO bid compared with placebo as determined by Magnetic Resonance Imaging (MRI) using the modified RAMRIS scoring system of hands and wrists at baseline and Month 3 [ Time Frame: Month 3 ] [ Designated as safety issue: No ]
  • To assess and compare the safety profiles of R788 100 mg PO bid dose with placebo for effects on liver function tests, clinically significant reduction in peripheral neutrophil counts, G-I side effects and other adverse effects as they may appear. [ Time Frame: Study ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 195
Study Start Date: May 2008
Study Completion Date: June 2009
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
R935788 100 mg tablet, orally, twice-a-day
Drug: Fostamatinib disodium (R935788)
R935788 100 mg tablet, orally, twice-a-day
Placebo Comparator: 2
Placebo, orally, twice-a-day
Drug: Fostamatinib disodium (R935788)
R935788 100 mg tablet, orally, twice-a-day

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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:

    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 serious surgery or infectious disease;
    4. recent history ( 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)
    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.
  • The patient has a pacemaker, aneurysm clip or other contraindication to MRI.
  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: NCT00665626

  Show 77 Study Locations
Sponsors and Collaborators
Rigel Pharmaceuticals
Investigators
Study Director: Daniel B Magilavy, MD Rigel Pharmaceuticals
  More Information

No publications provided

Responsible Party: Daniel B. Magilavy, MD, Rigel Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00665626     History of Changes
Other Study ID Numbers: C-935788-011
Study First Received: April 22, 2008
Last Updated: June 17, 2009
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board
Belgium: Federal Agency for Medicinal Products and Health Products
Belgium: Institutional Review Board
Brazil: Ethics Committee (Ethic Committee of each institution)
Brazil: Ministry of Health (Conselho Nacional de Saude, CNS)
Brazil: National Committee of Ethics in Research (Comissao Nacional de Etica em Pesquisa, CONEP)
Brazil: National Health Surveillance Agency (Agencia Nacional de Vigilancia Sanitaria, ANVISA)
Colombia: Ministry of Health (INVIMA: Instituto Nacional de Vigilancia de Medicamentos y Alimentos)
Colombia: Ethics Committee (Ethic Committee of each institution)
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
France: Institutional Ethical Committee
Germany: Ethics Commission
Germany: Federal Institute for Drugs and Medical Devices
Italy: Ethics Committee
Italy: National Monitoring Centre for Clinical Trials - Ministry of Health
Peru: Ethics Committee (19 registered IECs, the one used for this study is Comite de Etica de la Universidad de San Martin de Porres, CEUSMP).
Peru: General Directorate of Pharmaceuticals, Devices, and Drugs (Dirección general de medicamentos, insumos y drogas, DIGEMID)
Peru: Ministry of Health (Instituto Nacional de Salud, INS)

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on September 29, 2014