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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: ClinicalTrials.gov
Last refreshed on: 19 February 2015
Main ID:  NCT00326339
Date of registration: 12/05/2006
Prospective Registration: Yes
Primary sponsor: Rigel Pharmaceuticals
Public title: Treatment of Arthritis With Syk Kinase Inhibition (TASKI-1)
Scientific 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
Date of first enrolment: August 2006
Target sample size: 189
Recruitment status: Completed
URL:  http://clinicaltrials.gov/show/NCT00326339
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  
Phase:  Phase 2
Countries of recruitment
Mexico United States
Contacts
Name:     Michael Weinblatt, M.D.
Address: 
Telephone:
Email:
Affiliation:  Brigham and Women's Hospital
Name:     Elliott Grossbard, M.D.
Address: 
Telephone:
Email:
Affiliation:  Rigel Pharmaceuticals
Name:     Arthur Kavanaugh, M.D.
Address: 
Telephone:
Email:
Affiliation:  University of California, San Diego
Key inclusion & exclusion 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.



Age minimum: 18 Years
Age maximum: 75 Years
Gender: Both
Health Condition(s) or Problem(s) studied
Rheumatoid Arthritis
Intervention(s)
Drug: Placebo
Drug: R788
Primary Outcome(s)
The Primary Efficacy parameter is ACR20 response rate at 3 months post dosing. [Time Frame: 12 weeks]
Secondary Outcome(s)
ACR 20/50 responses over time [Time Frame: 12 weeks]
Disease Activity Score (DAS) at baseline and endpoint [Time Frame: 12 Weeks]
Mean changes (SDs) from baseline in CRP [Time Frame: 12 Weeks]
Mean changes (SDs) from baseline in HAQ-DI [Time Frame: 12 Weeks]
Mean changes (SDs) from baseline in Patient assessment of pain by VAS [Time Frame: 12 Weeks]
Mean changes (SDs) from baseline in Patient global assessment of disease activity by VAS [Time Frame: 12 Weeks]
Mean changes (SDs) from baseline in Physician global assessment of disease activity by visual analog scale (VAS) [Time Frame: 12 Weeks]
Mean changes (SDs) from baseline in Swollen Joint Count (28 joint count) [Time Frame: 12 Weeks]
Mean changes (SDs) from baseline in Tender Joint Count (28 joint count) [Time Frame: 12 Weeks]
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]
The frequency and severity of hematopoietic cytopenias, principally effects on neutrophil, erythrocyte, and lymphocyte counts [Time Frame: 12 Weeks]
The frequency and severity of Liver Function Test abnormalities, especially ALT and alkaline phosphatase [Time Frame: 12 Weeks]
Secondary ID(s)
C-935788-006
Source(s) of Monetary Support
Please refer to primary and secondary sponsors
Secondary Sponsor(s)
Ethics review
Results
Results available:
Date Posted:
Date Completed:
URL:
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