A Study to Evaluate the Efficacy and Safety of Rituximab in Patients With Severe Systemic Lupus Erythematosus (EXPLORER)
This study is ongoing, but not recruiting participants.
Sponsor:
Genentech
Information provided by:
Genentech
ClinicalTrials.gov Identifier:
NCT00137969
First received: August 26, 2005
Last updated: November 17, 2011
Last verified: November 2011
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Purpose
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 Systemic Lupus Erythematosus (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.
| Condition | Intervention | Phase |
|---|---|---|
|
Lupus Erythematosus, Systemic |
Drug: placebo Drug: prednisone Drug: rituximab |
Phase 2 Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment |
| 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 |
Resource links provided by NLM:
Further study details as provided by Genentech:
Primary Outcome Measures:
- Participants Achieving Either a Major Clinical Response (MCR) or Partial Clinical Response (PCR) Defined by British Isles Lupus Assessment Group (BILAG) Scores Over the 52-week Treatment Period [ Time Frame: From baseline to 52 weeks ] [ Designated as safety issue: No ]The BILAG Index is used for measuring clinical disease activity in Systemic Lupus Erythematosus(SLE)and uses a single score for each of the 8 domains and the range is from severe to less severe (A to E). MCR = BILAG C score or better at 24 wks and maintained response without a flare to 52 wks; PCR = BILAG C score or better at 24 wks and maintained response without a flare for 16 consecutive weeks, or maximum of one BILAG B score at 24 weeks and maintains response without a flare to 52 wks, or maximum of 2 BILAG B scores at 24 wks without development of BILAG scores of A or B until Week 52
Secondary Outcome Measures:
- Time-adjusted Area Under the Curve Minus Baseline (AUCMB) of BILAG Score Over 52 Weeks [ Time Frame: From baseline to 52 weeks ] [ Designated as safety issue: No ]
The BILAG Index measures clinical disease activity in SLE. A single alphabetic score (A through E) is used to denote disease severity for each of the 8 domains. The global BILAG score is the sum of a converted numerical score (A=9, B=3, C=1, D=0, E=0) over 8 domains. The AUCMB of BILAG Score Over 52 Weeks is calculated as:
- Calculate the AUC of the BILAG global score versus time (in days) by 52 weeks.
- Calculate the Time-Adjusted AUC by dividing the AUC by the number of days a patient was on the study.
- Minus the Time-Adjusted AUC by the baseline BILAG global score
- Participants Achieving an MCR (Excluding PCR) [ Time Frame: From baseline to 52 weeks ] [ Designated as safety issue: No ]The BILAG Index is used for measuring clinical disease activity in SLE and uses a single alphabetic score for each of the 8 domains and the range is from more severe to less severe (A through E). MCR = participants who achieve BILAG C scores or better at 24 weeks, maintain this response without developing a flare to 52 weeks, and do not experience a severe flare from Day 1 to Week 24
- Participants Achieving a PCR (Including MCR) [ Time Frame: From baseline to 52 Weeks ] [ Designated as safety issue: No ]The BILAG Index is used for measuring clinical disease activity in SLE and uses a single alphabetic score for each of the 8 domains and the range is from more severe to less severe (A through E). BILAG C scores or better at 24 wks and maintain without developing a flare for 16 wks; or only one domain with a BILAG B score at 24 wks and maintain without developing a flare to 52 wks; or a max of 2 BILAG Bs at 24 wks and no BILAG A or B in new domain until Wk 52 if the baseline BILAG score is 1A+>=2Bs, or>=2 As, or>=4 Bs
- Participants Achieving a BILAG C or Better in All Domains [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]The BILAG Index is used for measuring clinical disease activity in SLE and uses a single alphabetic score for each of the 8 domains and the range is from more severe to less severe (A through E).
- Time to First Moderate or Severe Flare [ Time Frame: 52 weeks ] [ Designated as safety issue: No ]The BILAG Index is used for measuring clinical disease activity in SLE and uses a single alphabetic score for each of the 8 domains and the range is from more severe to less severe (A through E). A severe flare = having BILAG A score(s) present in one or more domains or BILAG B scores present in three or more domains at the same visit following a visit of inactive disease state defined above. A moderate flare = having only BILAG B scores present in two domains at the same visit following a visit of inactive disease state.
- Change in SLE Expanded Health Survey Physical Function Score From Baseline [ Time Frame: From baseline to 52 weeks ] [ Designated as safety issue: No ]Short Form (36) with additional questions specific to lupus (scale = 0-100; with 100 representing the highest level of functioning possible) to measure the ability of rituximab to improve quality of life.
- Participants Who Achieved an MCR in the ITT Population [ Time Frame: From Weeks 24 to 52 ] [ Designated as safety issue: No ]The BILAG Index is used for measuring clinical disease activity in SLE and uses a single alphabetic score for each of the 8 domains and the range is from more severe to less severe (A through E). MCR = participants who achieve BILAG C scores or better at 24 weeks, maintain this response without developing a flare to 52 weeks
| Enrollment: | 257 |
| Study Start Date: | May 2005 |
| Primary Completion Date: | February 2008 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Experimental: 1 |
Drug: prednisone
Initial prednisone dose (0.5 mg/kg/day, 0.75 mg/kg/day, or 1.0 mg/kg/day) with tapering beginning at Day 16
Drug: rituximab
Intravenously at a dose of 1000 mg on Days 1, 15, 168, and 182
|
| Placebo Comparator: 2 |
Drug: placebo
Intravenously at a dose of 1000 mg on Days 1, 15, 168, and 182
Drug: prednisone
Initial prednisone dose (0.5 mg/kg/day, 0.75 mg/kg/day, or 1.0 mg/kg/day) with tapering beginning at Day 16
|
Eligibility| Ages Eligible for Study: | 16 Years to 75 Years |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Diagnosis of Systemic Lupus Erythematosus (SLE)
- Active disease at screening
- Stable use of one immunosuppressive drug
- Use of an antimalarial drug
- For subjects of reproductive potential (males and females), use of a reliable means of contraception throughout their study participation
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
- 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 that in the investigator's opinion would preclude subject participation
- Concomitant conditions that required oral or systemic corticosteroid use
- 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
- History of deep space infection 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
- Major surgery
- Previous treatment with CAMPATH-1H
- Previous treatment with any B cell-targeted 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 prior to screening or change in dose of ongoing immunosuppressive drug prior to screening
- Prednisone dose of≥ 1 mg/kg/day prior to screening
- Treatment with cyclophosphamide or a calcineurin inhibitor
- Treatment with a second immunosuppressive or immunomodulatory drug
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 x the upper limit of normal
Contacts and Locations More Information
Additional Information:
No publications provided by Genentech
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Clinical Trials Posting Group, Genentech, Inc. |
| ClinicalTrials.gov Identifier: | NCT00137969 History of Changes |
| Other Study ID Numbers: | U2971g |
| Study First Received: | August 26, 2005 |
| Results First Received: | June 5, 2009 |
| Last Updated: | November 17, 2011 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Genentech:
|
Rituxan SLE Lupus |
Additional relevant MeSH terms:
|
Lupus Erythematosus, Systemic Connective Tissue Diseases Autoimmune Diseases Immune System Diseases Prednisone Rituximab Glucocorticoids Hormones Hormones, Hormone Substitutes, and Hormone Antagonists |
Physiological Effects of Drugs Pharmacologic Actions Antineoplastic Agents, Hormonal Antineoplastic Agents Therapeutic Uses Anti-Inflammatory Agents Immunologic Factors Antirheumatic Agents |
ClinicalTrials.gov processed this record on May 19, 2013