Eliza Chakravarty
A Study to Evaluate the Efficacy and Safety of Rituximab in Patients With Severe Systemic Lupus Erythematosus (SLE)
Contact Information
Stanford University School of Medicine 300 Pasteur Drive Stanford, CA 94305Brief
This is a Phase II/III, randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy and safety of rituximab compared with placebo when combined with a single stable background immunosuppressive medication in subjects with moderate to severe SLE. The primary efficacy endpoint of the trial will be evaluated at 52 weeks. The study will enroll approximately 250 subjects at approximately 55 centers in the United States.
Recruiting Status:
No longer recruitingStanford Recruiting Status:
No longer recruitingCondition(s):
Intervention(s):
- Drug: Rituximab
Phase:
Phase 2/Phase 3Eligibility
Ages Eligible for Study:
18 years to 75 yearsGenders Eligible for Study:
Male and FemaleHealth of Volunteers:
People with the conditions listed in this trial can participate as controls.Key Inclusion Criteria:
* Ability and willingness to provide written informed consent and comply with the schedule of protocol assessments
* Diagnosis of Systemic Lupus Erythematosus (SLE) per the current American College of Rheumatology (ACR) criteria at any time prior to screening (at least four criteria must be present, one of which must be a positive antinuclear antibody [ANA])
* Age 16-75 years
* Active disease at screening as defined by one or more domains with a BILAG A score or two or more domains with a BILAG B score that in the investigator's judgment is serious enough to warrant potential exposure to immunotherapy
* Stable use of one immunosuppressive drug (100-250 mg/day azathioprine, 50-250 mg/day 6-mercaptopurine, 1-4 gm/day mycophenolate mofetil [MMF], or 7.5-27.5 mg/wk methotrexate [MTX])
* Use of an antimalarial drug (hydroxychloroquine 200 mg every day or twice daily, chloroquine 500 mg every day or every other day, or quinacrine 100 mg every day) unless excluded by a history of antimalarial drug toxicity or not clinically indicated prior to trial screening
* For subjects of reproductive potential (males and females), use of a reliable means of contraception (e.g., hormonal contraceptive, patch, vaginal ring, intrauterine device, physical barrier) throughout their study participation
Key Exclusion Criteria:
* Unstable patients with thrombocytopenia experiencing or at high risk for developing clinically significant bleeding or organ dysfunction requiring therapies such as plasmapheresis or acute blood or platelet transfusions
* Active moderate to severe glomerulonephritis, as defined by proteinuria > 1 g/24 hr (or urinary protein to urinary creatinine ratio [Upr/Ucr] > 1) and either presence of red blood cell (RBC) casts ore 10 RBC/hpf (in the absence of infection or menstrual hematuria at screening)
* Retinitis, poorly controlled seizure disorder, acute confusional state, myelitis, stroke or stroke syndrome, cerebellar ataxia, or dementia that is currently active and resulting from SLE
* Lack of peripheral venous access
* Pregnant women or nursing (breast feeding) mothers
* History of severe, allergic, or anaphylactic reactions to humanized or murine monoclonal antibodies
* Significant, uncontrolled medical disease in any organ system not related to SLE (e.g., poorly controlled chronic obstructive pulmonary disease or asthma, cardiovascular disease, accelerated hypertension, major depression) that in the investigator's opinion would preclude subject participation
* Concomitant conditions (e.g., asthma, Crohn's disease, etc.) that required oral or systemic corticosteroid use within the 52 weeks prior to screening
* Known human immunodeficiency virus (HIV) infection
* Known active infection of any kind (excluding fungal infection of nail beds) or any major episode of infection requiring hospitalization or treatment with IV antibiotics within 8 weeks of screening or oral antibiotics within 2 weeks prior to screening
* History of deep space infection (i.e., fasciitis, abscess, osteomyelitis) within 1 year of screening
* History of serious recurrent or chronic infection
* History of cancer, including solid tumors, hematological malignancies, and carcinoma in situ
* Active alcohol or drug abuse, or history of alcohol or drug abuse within the past 52 weeks
* Major surgery within 4 weeks prior to screening
* Previous treatment with CAMPATH-1H
* Previous treatment with any B cell-targeted therapy (e.g., anti-CD20, anti-CD22, or anti-BlyS therapy)
* Treatment with any investigational agent within 28 days of screening (Day -7) or 5 half-lives of the investigational drug (whichever is longer)
* Receipt of a live vaccine within 28 days prior to screening
* Intolerance or contraindication to oral or IV corticosteroids
* Use of a new immunosuppressive drug within 90 days prior to screening or change in dose of ongoing immunosuppressive drug within 30 days prior to screening
* Prednisone dose ofe 1 mg/kg/day for more than 7 of the 30 days prior to screening
* Treatment with cyclophosphamide or a calcineurin inhibitor within 12 weeks of screening
* Treatment with a second immunosuppressive or immunomodulatory drug (e.g., sulfasalazine, leflunomide) within 30 days of screening
* Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 x the upper limit of normal
* Amylase or lipase > 2 x the upper limit of normal
* Neutrophils < 1500 uL
* Positive hepatitis surface antigen (BsAg) or hepatitis C serology
* Hemoglobin < 7 g/dL unless caused by autoimmune hemolytic anemia resulting from SLE
* Platelet count < 10,000/uL
* Serum creatinine > 2.5 mg/dL
Additional Study Details
Official Title:
A Randomized, Double Blind, Placebo-Controlled, Multicenter, Phase II/III Study to Evaluate the Efficacy and Safety of Rituximab in Subjects With Moderate to Severe Systemic Lupus Erythematosus (EXPLORER)Anticipated start date:
5/10/0005Lead Sponsor:
GenentechInvestigator(s):
Study Type:
InterventionalPurpose:
TreatmentAllocation:
RandomizedMasking:
Double BlindControl:
noneAssignment:
ParallelEndpoints:
Safety/EfficacyPrimary Outcomes:
- To assess the efficacy of rituximab compared with placebo in achieving and maintaining a major clinical response (MCR) or partial clinical response (PCR) in subjects with moderate to severe systemic lupus erythematosus (SLE)
Secondary Outcomes:
- To evaluate the ability of rituximab to decrease overall SLE disease activity as measured by time-adjusted area under the curve minus baseline (AUCMB) scoring with the British Isles Lupus Assessment Group (BILAG) assessment over 52 weeks
- to evaluate the ability of rituximab to induce MCRs (excluding PCRs) or PCRs (including MCRs)
- to evaluate the safety and tolerability of rituximab
- to evaluate the ability of rituximab-treated subjects to achieve a BILAG C or better at Week 24
- to evaluate the ability of rituximab to prolong the time to a moderate or severe flare
- to evaluate the ability of rituximab to improve quality of life as measured by SLE Expanded Health Survey (SF-36 index with additional elements specific to lupus)
- to evaluate corticosteroid-sparing in subjects receiving rituximab
- to evaluate the pharmacokinetics of rituximab in subjects with SLE
Total Number to be Enrolled:
250Total Number to be Enrolled at Stanford:
0More Information
Locations & Contacts
Stanford Locations & Contacts:
Stanford University School of Medicine 300 Pasteur Drive Stanford, CA 94305Non-Stanford Locations:
The Stanford website does not have any locations outside of Stanford listed for this trial. You may want to check clinicaltrials.gov for posible additional locations.
This listing was last updated:
11/7/2007PLEASE NOTE:
Study Coordinators and Research Nurses cannot give medical advice over the phone. Telephone numbers are provided for obtaining additional information on specific clinical research trials only. If you have specific questions which require clinical expertise, please call your primary care physician. If you do not have a primary care physician please feel free to call the SHC Physician Referral Service at (800) 756-9000 or send an email.
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