Treatment of Arthritis With Syk Kinase Inhibition (TASKI-1)

This study has been completed.
Sponsor:
Information provided by:
Rigel Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00326339
First received: May 12, 2006
Last updated: April 16, 2009
Last verified: March 2008
  Purpose

This is a Phase II, multicenter, randomized, double-blind, placebo-controlled, ascending dose, dose ranging study to evaluate up to three doses of R935788 (50 mg bid, 100 mg bid and 150 mg bid). Approximately 180 patients who have had rheumatoid arthritis for a minimum of 12 months and who have been receiving a weekly methotrexate (MTX) dose for a minimum of 6 months will be enrolled into the study.


Condition Intervention Phase
Rheumatoid Arthritis
Drug: R788
Drug: Placebo
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, Ascending Dose, Dose Ranging Study to Evaluate Up to Three Doses of R935788 in Rheumatoid Arthritis Patients Failing to Respond to Methotrexate

Resource links provided by NLM:


Further study details as provided by Rigel Pharmaceuticals:

Primary Outcome Measures:
  • The Primary Efficacy parameter is ACR20 response rate at 3 months post dosing. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • ACR 20/50 responses over time [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Disease Activity Score (DAS) at baseline and endpoint [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
  • Mean changes (SDs) from baseline in Swollen Joint Count (28 joint count) [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
  • Mean changes (SDs) from baseline in Tender Joint Count (28 joint count) [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
  • Mean changes (SDs) from baseline in Physician global assessment of disease activity by visual analog scale (VAS) [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
  • Mean changes (SDs) from baseline in Patient global assessment of disease activity by VAS [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
  • Mean changes (SDs) from baseline in Patient assessment of pain by VAS [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
  • Mean changes (SDs) from baseline in HAQ-DI [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
  • Mean changes (SDs) from baseline in CRP [ Time Frame: 12 Weeks ] [ Designated as safety issue: No ]
  • The frequency and severity of Liver Function Test abnormalities, especially ALT and alkaline phosphatase [ Time Frame: 12 Weeks ] [ Designated as safety issue: Yes ]
  • The frequency and severity of hematopoietic cytopenias, principally effects on neutrophil, erythrocyte, and lymphocyte counts [ Time Frame: 12 Weeks ] [ Designated as safety issue: Yes ]
  • The frequency and severity of clinically significant adverse events, especially skin rash, postural dizziness, and alterations in blood pressure and other relevant clinical outcomes [ Time Frame: 12 Weeks ] [ Designated as safety issue: Yes ]

Enrollment: 189
Study Start Date: August 2006
Study Completion Date: December 2007
Primary Completion Date: October 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
R788 50 mg PO bid
Drug: R788
R788 50 mg, 100 mg, or 150 mg PO bid
Other Name: tamatinib fosdium
Experimental: 2
R788 100 mg PO bid
Drug: R788
R788 50 mg, 100 mg, or 150 mg PO bid
Other Name: tamatinib fosdium
Experimental: 3
R788 150 mg PO bid
Drug: R788
R788 50 mg, 100 mg, or 150 mg PO bid
Other Name: tamatinib fosdium
Placebo Comparator: 4
Placebo PO bid
Drug: Placebo
Placebo PO bid

Detailed Description:

The primary objective of this study is to assess the preliminary efficacy of up to three different dosage regimens of R788 as determined by ACR 20 responder rates at 12 weeks The secondary objectives of this study are to assess the safety of up to three different dosage regimens of R788 as determined by ACR 20 responder rates at 12 weeks, and to assess the general clinical and laboratory safety evaluations throughout the study.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients must give written informed consent by signing an IRB-approved Informed Consent Form (ICF) prior to admission to this study.
  2. Males and females, 18 to 75 years of age, with active RA for at least 12 months (functional class I-III, e.g., not bed or wheelchair-bound) who have been receiving weekly doses of methotrexate (10-25 mg/week) for a minimum of 180 days, and who have been receiving a stable MTX dose of at least 15 mg without any change in route or change in folic acid supplementation for at least 30 days.

    Active RA is defined as the presence of (a)6 swollen joints (28 joint count); AND (b)6 tender joints (28 joint count); AND (c) CRP level > ULN for the central reference laboratory.

    Patient may receive up to 10 mg per day of oral prednisone or steroid equivalent, NSAID therapy, hydroxychloroquine, chloroquine, minocycline, sulfasalazine, and doxycycline. The dose(s) must have been stable for at least 30 days and must not be changed during the washout, screening and treatment periods, unless dictated by tolerability requirements.

  3. Females of childbearing potential must be fully informed of the potential for methotrexate and R788 to adversely affect the fetus and must agree to use adequate (2 methods) contraception during the study. These patients must not be lactating and must have a negative urine pregnancy test at the time of randomization and at each laboratory determination.
  4. The patient is in otherwise good health as determined by the Investigator on the basis of medical history, physical examination, and laboratory screening tests during the screening period, including the absence of clinically significant findings, such as HIV, HBV or HCV, interstitial pneumonitis or active pulmonary infection, on chest X-ray taken within 6 months prior to screening and a negative TB skin test, or abnormal liver function defined as known ALT >1.2xULN within the past 90 days.
  5. 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:

  1. 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 (these will be included in an exclusion log).
  2. The patient has a history of substance abuse, drug addiction or alcoholism.
  3. The patient is unable to abstain from alcohol during the study.
  4. The patient has a recent (past 5 years) history of, or treatment for, a malignancy other than basal skin cancer.
  5. The patient has received any investigational medication within 30 days prior to admission to the study.
  6. Any patient who has received any of the following treatments must abide by the indicated washout period:

    1. oral or injectable gold, azathioprine, penicillamine, anakinra require a 30 day washout period prior to Day 1 dosing
    2. cyclosporine, abatacept, etanercept, infliximab or adalimumab require a 60 day washout period prior to Day 1 dosing
    3. leflunomide requires a 60 day washout period prior to screening, unless the patient has undergone cholestyramine washout at least 30 days prior to Day 1 dosing
    4. cyclophosphamide requires a 180 day washout period prior to Day 1 dosing
    5. Rituxan requires a 180 day washout period and normal CD19 count prior to Day 1 dosing
    6. parenteral or intra-articular corticosteroids require a 30 day washout period prior to Day 1 dosing
  7. Patients with the following laboratory abnormalities: ALT > 1.2X ULN, creatinine > ULN, a neutrophil count < 2,500/mm3 or lymphocyte count < 800/mm3, Hgb < 10 g/dL, platelet count < 125,000/mm3 are excluded.
  8. Patients should not use CYP3A4 inhibitors from within 3 days of randomization until the end of study. R406 is metabolized by CYP3A4, and ketoconazole increases the R406 AUC of a dose of R788 by approximately 2 fold.
  9. Patients should not use CYP3A4 inducers from within 3 days of randomization until the end of the study. Although glucocorticoids are inducers, a stable dose of no more than 10 mg/day is allowed.
  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: NCT00326339

  Show 38 Study Locations
Sponsors and Collaborators
Rigel Pharmaceuticals
Investigators
Study Director: Elliott Grossbard, M.D. Rigel Pharmaceuticals
Principal Investigator: Michael Weinblatt, M.D. Brigham and Women's Hospital
Principal Investigator: Arthur Kavanaugh, M.D. University of California, San Diego
  More Information

No publications provided

Responsible Party: Elliott Grossbard/SVP Medical Development, Rigel Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT00326339     History of Changes
Other Study ID Numbers: C-935788-006
Study First Received: May 12, 2006
Last Updated: April 16, 2009
Health Authority: United States: Food and Drug Administration
Mexico: Ministry of Health

Keywords provided by Rigel Pharmaceuticals:
R935788
Rheumatoid Arthritis
Syk Kinase

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 14, 2014