Open-Label, Multicenter Extension Study for Patients Completing Treatment Phase of a Rigel-Sponsored R935788 Studies

Study Overview
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Brief Summary
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The purpose of this new research study is to gain additional information about how safe and effective R935788 is over a longer period of time.

Official Title
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An Open-Label, Multicenter Extension Study to Evaluate the Safety of R935788 in Patients With Rheumatoid Arthritis Who Have Completed the Treatment Phase of a Rigel-Sponsored R935788 Study

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: Fostamatinib Disodium (R935788)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must give written informed consent by signing an IRB/EC-approved Informed Consent Form (ICF) prior to admission to this study Patients who are being treated in Study C-788-006X Patients who completed Studies C-788-010 or C-788-011 and did not withdraw due to adverse events Patients who withdrew from Study C-788-010 at Month 4 or Month 5 because of a pre-defined lack of efficacy 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 pregnancy test at the time of entry and at each laboratory determination. 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: unresolved Grade 2 or greater toxicity in a RA protocol studying R788 uncontrolled or poorly controlled hypertension; recent (within past 2 months) serious surgery or infectious disease; recent history (since enrollment in prior R788 study) of, or treatment for, a malignancy other than non-melanomatous skin cancer, or any history of lymphoma; known to be positive for Hepatitis B, Hepatitis C, HIV or Tuberculosis; interstitial pneumonitis or active pulmonary infection; known laboratory abnormalities: ALT > 1.2 x ULN, creatinine >1.5x ULN, an ANC <2,500/mm3 or 2.5 x 109/L, lymphocyte count < 600/mm3 or 0.6 x 109L, Hgb < 9 g/dL or 5 mmol/L, platelet count <125,000/mm3 or 125 x 109/L are excluded. 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 is unable to report for clinical and laboratory monitoring as per protocol.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>R935788 50 mg tablet, orally, twice-a-day | Drug: Fostamatinib Disodium (R935788)<br>* 50 mg PO BID; 100 mg PO BID; 100 mg PO QD; 150 mg tablet PO QD<br>* Other names: R935788;|
| Experimental: 2<br>R935788 100 mg tablet, orally, twice-a-day | Drug: Fostamatinib Disodium (R935788)<br>* 50 mg PO BID; 100 mg PO BID; 100 mg PO QD; 150 mg tablet PO QD<br>* Other names: R935788;|
| Experimental: 3<br>R935788 100 mg tablet, orally, once-a-day | Drug: Fostamatinib Disodium (R935788)<br>* 50 mg PO BID; 100 mg PO BID; 100 mg PO QD; 150 mg tablet PO QD<br>* Other names: R935788;|
| Experimental: 4<br>R935788 150 mg tablet, orally, once-a-day | Drug: Fostamatinib Disodium (R935788)<br>* 50 mg PO BID; 100 mg PO BID; 100 mg PO QD; 150 mg tablet PO QD<br>* Other names: R935788;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Patients Who Had at Least 1 Treatment Emergent Adverse Event in Any Category | AE = adverse event, bid = twice daily, IP = investigational product, qd = once daily, SAE = serious adverse event | Entry in extension to end of study, up to a maximum of 5 years. (Variable by subject - median duration of 3 years) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DAS28-CRP Score | The Disease Activity Score 28 using C-Reactive Protein (DAS28-CRP) is a measure of disease activity in rheumatoid arthritis (RA) and assesses the 28 joints RA commonly affects; the score includes the number of tender and swollen joints (out of 28), CRP level (a measure of inflammation in the blood), and the patient's global assessment of health (ranging from very good to very bad). These measures are then fed into a complex mathematical formula to produce the overall DAS on a scale from 1 to 10, where scores greater than 5.1 are considered to indicate active disease, scores less than 3.2 are considered to indicate with well controlled disease, and scores less than 2.6 are considered to indicate remission. bid = twice daily, CRP = C-reactive protein, DAS28 = Disease Activity Score based on a 28 joint count, n/a = not applicable, qd = once daily | 3 years | 
| HAQ-DI Score | Health Assessment Questionnaire - Disability Index, a measure of physical function. The HAQ-DI score is calculated by summing the category scores from 8 sub-categories (ie, scores for patient ability in dressing and grooming, rising, eating, walking, hygeine, reach, grip and common daily activities) and dividing by the number of categories completed. The HAQ-DI score takes values between 0 and 3, with a higher score indicating greater disability. A HAQ-DI response is a reduction from baseline in HAQ-DI greater than or equal to the minimally important difference (0.22). BID = twice daily, DMARD = disease-modifying anti-rheumatic drug, OR = odds ratio, PO = orally, QD = once a day. | 3 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RA