Efficacy and Safety Study of R935788 Tablets to Treat Systemic Lupus Erythematosus

Study Overview
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Brief Summary
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Approximately 225 patients meeting study entry requirements will be enrolled and randomized (2:1, active versus placebo superimposed on background treatment) to R788 or placebo. Patients will be followed for efficacy and safety parameters for 6 months. The investigator should taper corticosteroids if clinically warranted.

Detailed Description
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This study is a multi-center, multinational, randomized, double-blind, placebo-controlled Phase II clinical trial. Study enrollment will comprise approximately 225 patients meeting study inclusion requirements. The study will be conducted at up to 80 multinational investigational sites. Eligible patients will be randomized (2:1) into one of two 6 month treatment groups. One group (approximately 150 patients) will receive R788 150 mg PO bid; the other treatment group (approximately 75 patients) will receive placebo.

Official Title
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A Phase II, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel Dose Study of R935788 in Systemic Lupus Erythematosus Patients With Active Disease

Conditions
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Systemic Lupus Erythematosus

Intervention / Treatment
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* Drug: Fostamatinib Disodium (R935788)
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must give written informed consent to participate in this study 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 SLE diagnosed at least 6 months prior to Day 1 dosing. Active SLE is defined as having fulfilled the ACR criteria for SLE. Patients 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 an effective method of birth control during the study (oral contraceptive, mechanical barrier, long acting hormonal agent). 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. In the investigator's opinion, the patient has the ability to understand the nature of the study and any anticipated risks of participation, communicate satisfactorily with the investigator, and participate in and comply with the requirements of the entire protocol. Exclusion Criteria: The patient has a history of, or a concurrent, clinically significant illness, medical condition or laboratory abnormality that, in the investigator's opinion, could affect the conduct of the study. Clinically significant or uncontrolled medical disease in any organ system, other than due to SLE. Background immunosuppressive therapy that has not remained stable ≤ 4 weeks prior to baseline. Severe active or unstable renal disease. Active severe neuropsychiatric SLE. Female patients must not be breastfeeding and must have a negative urine pregnancy test per the Schedule of Study Activities. The patient has a history of substance abuse, drug addiction, or alcoholism.

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: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>150 mg tablet, oral, twice-a-day | Drug: Fostamatinib Disodium (R935788)<br>* 150 mg tablet, oral, twice-a-day<br>* Other names: R788;|
| Placebo Comparator: B<br>Placebo tablet, oral, twice-a-day | Drug: Placebo<br>* Placebo tablet, oral, twice-a-day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary efficacy endpoint is defined as the decrease from baseline in the SELENA-SLEDAI score at 6 months. |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite Responder analysis defined as ≥4 points improvement in SELENA-SLEDAI and no 'Severe SLE flare' after Week 6. No worsening (≤10 mm on VAS) of Physician Global Assessment, or, no worsening of SF 36 PCS (not >-0.8) or PFI (not >2.5) |  | 3 and 6 months | 
| Attainment of daily prednisone dose decrease in those patients on daily corticosteroids by 50% or to ≤ 7.5 mg prednisone (or equivalent for other corticosteroids) at 3 and 6 months. |  | 3 and 6 months | 
| Decrease from baseline in SELENA-SLEDAI score at each post baseline visit. |  | At each post baseline visit | 
| Attainment of improvement in SELENA-SLEDAI by ≥ 2 points at Weeks 2 and 4. |  | Weeks 2 and 4 | 
| Attainment of improvement in SELENA-SLEDAI by ≥ 4 points at each post baseline visit. |  | At each post baseline visit | 
| Change from baseline of Physician Global Assessment by VAS over 6 months. |  | 6 months | 
| Time to rescue medication. |  | At each post baseline visit | 
| Time to severe SLE flare by SELENA Flare Index. |  | At each post baseline visit | 
| Change from baseline in the component scores of the SF 36 at Month 3 and Month 6. |  | Month 3 and 6 | 
| Effects on liver function tests, clinically significant reductions in peripheral neutrophil counts, G-I adverse effects, new onset or aggravated hypertension, and other adverse effects as they may appear. |  | At each post baseline visit | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SLE, Lupus