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Lupus Erythematosus, SystemicPhase 2/3EXPLORERNCT00137969

A Study to Evaluate the Safety of Rituximab Retreatment in Subjects With Systemic Lupus Erythematosus

A Phase 2/3 study testing Rituximab, Prednisone and Acetaminophen in people with Lupus Erythematosus, Systemic, run by Genentech, Inc. at 65 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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). Read more about this study

Who is it for?
Ages 16 to 75 years
Conditions the study is for
Lupus Erythematosus, Systemic
What is being tested?
Rituximab, Prednisone and Acetaminophen
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
262 participants
Where
65 sitesin 2 countries
Study dates
10 May 2005to 25 Aug 2008
Phase
Phase 2/3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 16 to 75 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 25Show fewer
  • 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 require 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 intravenous (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 antibody.
  • 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.

Trial locations and contacts

65 sites in 2 countries.

65 sites in 2 countries

United States63 sites
  • Center for Rheumatology, State Uni. of New York

    Albany, New York, 12206

  • University Of Michigan

    Ann Arbor, Michigan, 48109

  • Emory Uni ; Division of Rheumatology

    Atlanta, Georgia, 30303

  • University of Colorado Denver

    Aurora, Colorado, 80045

  • Arthritis & Rheumatism; Disease Specialities

    Aventura, Florida, 33180

  • Johns Hopkins Uni

    Baltimore, Maryland, 21205

  • East Penn Rheumatology Associates, Pc

    Bethlehem, Pennsylvania, 18015

  • Univ of Alabama School of Med; Clinical Immun Rheumatology

    Birmingham, Alabama, 35294

  • Intermountain Research Center

    Boise, Idaho, 83702

  • Tufts - New England Medical Center

    Boston, Massachusetts, 02111

  • Dana-Farber Cancer Institute; Rheumatology

    Boston, Massachusetts, 02215-5501

  • Michigan Arthritis Rsrch Ctr

    Brighton, Michigan, 48116

  • SUNY Downstate Medical Center.

    Brooklyn, New York, 11203

  • University of North Carolina Hospitals Department of Pharmacy; Investigational Drug Services

    Chapel Hill, North Carolina, 27514

  • Medical Univ of South Carolina

    Charleston, South Carolina, 29425

  • University of Virginia Med Ctr; Div of Ped Respiratory Med

    Charlottesville, Virginia, 22908

  • Arthritis Associates PLLC

    Chattanooga, Tennessee, 37404

  • Northwestern University

    Chicago, Illinois, 60611

  • Rheumatology Associates

    Chicago, Illinois, 60612

  • University of Chicago

    Chicago, Illinois, 60637

  • Coeur D'Alene Arthritis Clinic

    Coeur d'Alene, Idaho, 83814

  • Ohio State University; Division of Nephrology

    Columbus, Ohio, 43210

  • Metroplex Clinical Research

    Dallas, Texas, 75231

  • Arthritis Centers of Texas

    Dallas, Texas, 75246

  • Altoona Arthritis & Osteo Center

    Duncansville, Pennsylvania, 16635

  • Duke Medical Center

    Durham, North Carolina, 27710

  • Tri-State Arth & Rheum Center

    Evansville, Indiana, 47714

  • Physicians East Pa

    Greenville, North Carolina, 27834

  • Houston Inst. For Clinical Research

    Houston, Texas, 77074

  • Rheumatology Assoc of North AL

    Huntsville, Alabama, 35801

  • Family Arthritis Center

    Jupiter, Florida, 33458

  • Univ of Kansas Medical Center; Allergy/Clin Imm/Rheum

    Kansas City, Kansas, 66160

  • Univ of California, San Diego

    La Jolla, California, 92037

  • NS-LIJ Health Systems; Rheum-Allergy Clin Immu

    Lake Success, New York, 11042

  • Univ of Calif., Los Angeles; Rheumatology

    Los Angeles, California, 90025

  • Cedars-Sinai Medical Center

    Los Angeles, California, 90048

  • Kentuckiana Cancer Institute

    Louisville, Kentucky, 40202

  • Arthritis & Osteoporosis Associates, LLP

    Lubbock, Texas, 79424

  • Feinstein Institute for Medical Research

    Manhasset, New York, 11030

  • NYU-Hosp for Joint Diseases; Rheum and Med

    New York, New York, 10003

  • Hospital for Special Surgery

    New York, New York, 10021

  • Bone and Joint Hospital at St. Anthony Research Department

    Oklahoma City, Oklahoma, 73103

  • Oklahoma Medical Research Foundation

    Oklahoma City, Oklahoma, 73104

  • Buffalo Rheumatology Associates

    Orchard Park, New York, 14127

  • Stanford University Med Ctr;Div of Immunology/Rheumatology

    Palo Alto, California, 94304

  • Arizona Arthritis & Rheumatology Research, Pllc

    Paradise Valley, Arizona, 85253

  • Uni of Pennslyvania Medical Center

    Philadelphia, Pennsylvania, 19104

  • Albert Einstein Medical Center

    Philadelphia, Pennsylvania, 19141

  • University of Pittsburgh

    Pittsburgh, Pennsylvania, 15213

  • Long Island Osteo/Arth Center

    Plainview, New York, 11803

  • Portland Medical Associates

    Portland, Oregon, 97224

  • Virginia Commonwealth University

    Richmond, Virginia, 23298

  • University of Rochester - Strong Memorial Hospital

    Rochester, New York, 14642

  • Univ of Calif, San Francisco; Rheumatology

    San Francisco, California, 94143-0111

  • Eden Medical Center San Leandro Hospital

    San Leandro, California, 94578

  • Seattle Rheumatology Assoc; Swedish Rheumatology Research

    Seattle, Washington, 98104

  • Seattle Cancer Care Alliance

    Seattle, Washington, 98109

  • LA State Univ; Medicine

    Shreveport, Louisiana, 71103

  • Arthritis Northwest, Spokane

    Spokane, Washington, 99204

  • Washington University; Rheumatology Division

    St Louis, Missouri, 63110

  • Texas Research Center

    Sugar Land, Texas, 77479

  • Oklahoma Center For Arthritis Therapy & Research

    Tulsa, Oklahoma, 74104

  • Center For Rheumatology & Bone Research

    Wheaton, Maryland, 20902

Other trials in United States

Canada2 sites
  • St. Joseph'S Health Care Centre

    London, Ontario, N6A 4V2

  • Univ of Manitoba, Health Scien; Arthritis Centre

    Winnipeg, Manitoba, R3A1M4

Other trials in Canada

About this study

Official title: 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

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.

Being tested
Rituximab, Placebo, Prednisone, Acetaminophen, Diphenhydramine
Keywords
Rituxan, SLE, Lupus
Medical subject headings
Lupus Erythematosus, Systemic

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RituximabDrug

    Also called Rituxan, MabThera, Zytux

    Rituximab will be supplied as a sterile liquid for IV administration.

  • PlaceboDrug

    Placebo will be supplied as a sterile liquid for IV administration.

  • PrednisoneDrug

  • AcetaminophenDrug

  • DiphenhydramineDrug

Study groups in NCT00137969
Study groupRoleWhat they receive
Rituximab 1000 mg + prednisoneExperimentalParticipants will receive rituximab 1000 mg intravenously on Days 1, 15, 168, and 182. Participants will also receive an initial dose of prednisone (0.5, 0.75, or 1.0 mg/kg orally once a day) with tapering beginning at Day 16 for 10 weeks to a dose of ≤ 10 mg/day. Participants will also receive acetaminophen 1000 mg orally and diphenhydramine 50 mg orally prior to study drug infusion.
Receives: Drug: Rituximab; Drug: Prednisone; Drug: Acetaminophen; Drug: Diphenhydramine
Placebo + prednisonePlacebo comparatorParticipants will receive placebo intravenously on Days 1, 15, 168, and 182. Participants will also receive an initial dose of prednisone (0.5, 0.75, or 1.0 mg/kg orally once a day) with tapering beginning at Day 16 for 10 weeks to a dose of ≤ 10 mg/day. Participants will also receive acetaminophen 1000 mg orally and diphenhydramine 50 mg orally prior to study drug infusion.
Receives: Drug: Placebo; Drug: Prednisone; Drug: Acetaminophen; Drug: Diphenhydramine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants Who Achieved a Major Clinical Response (MCR), Partial Clinical Response (PCR), or Nonclinical Response (NCR) Defined by British Isles Lupus Assessment Group (BILAG) Scores Over The 52-week Treatment Period

    The BILAG Index measures clinical disease activity in Systemic Lupus Erythematosus (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. MCR = participants who achieved BILAG C scores or better at 24 weeks, maintained this response without developing a flare to 52 weeks, and did not experience a severe flare from Day 1 to Week 24; PCR = participants who achieved 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 maintained 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 if the baseline BILAG score was 1A+>=2Bs, or>=2 As, or>=4 Bs, or participants who enrolled with scores of severe disease and did not achieve a single BILAG B at Month 6.

    Measured: From baseline to 52 weeks

Secondary outcomes (7)
  1. Time-adjusted Area Under The Curve Minus Baseline (AUCMB) of BILAG Score Over The 52-week Treatment Period

    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 was calculated as: 1. Calculate the AUC of the BILAG global score versus time (in days) by 52 weeks. 2. Calculate the Time-Adjusted AUC by dividing the AUC by the number of days a patient was on the study. 3. Minus the Time-Adjusted AUC by the baseline BILAG global score

    Measured: From baseline to 52 weeks

  2. Number of Participants Who Achieved an MCR (Excluding PCR)

    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. MCR = participants who achieved BILAG C scores or better at 24 weeks, maintained this response without developing a flare to 52 weeks, and did not experience a severe flare from Day 1 to Week 24. PCR = participants who achieved 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 maintained 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 if the baseline BILAG score was 1A+>=2Bs, or>=2 As, or>=4 Bs, or participants who enrolled with scores of severe disease and did not achieve a single BILAG B at Month 6.

    Measured: From baseline to 52 weeks

  3. Number of Participants Who Achieved a PCR (Including MCR)

    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. PCR = participants who achieved 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 maintained 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 if the baseline BILAG score was 1A+>=2Bs, or>=2 As, or>=4 Bs, or participants who enrolled with scores of severe disease and did not achieve a single BILAG B at Month 6. MCR = participants who achieved BILAG C or better at 24 weeks, maintained this response without developing a flare to 52 weeks, and did not experience a severe flare from Day 1 to Week 24.

    Measured: From baseline to 52 Weeks

  4. Number of Participants Who Achieved a BILAG C or Better in All Domains

    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.

    Measured: 24 weeks

  5. Time to First Moderate or Severe Flare

    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. A severe flare = participants had 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 = participants had only BILAG B scores present in two domains at the same visit following a visit of inactive disease state.

    Measured: 52 weeks

  6. Change in SLE Expanded Health Survey Physical Function Score From Baseline

    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. A positive value for this outcome measure indicates that symptoms have improved.

    Measured: From baseline to 52 weeks

  7. Number of Participants Who Achieved an MCR in The ITT Population

    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. MCR = participants who achieved BILAG C scores or better at 24 weeks, maintained this response without developing a flare to 52 weeks, and did not experience a severe flare from Day 1 to Week 24.

    Measured: From Weeks 24 to 52

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Aug 2005 (estimated)
  2. Study start10 May 2005
  3. Primary completion25 Aug 2008
  4. Study completion25 Aug 2008

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
262 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00137969
Sponsor's protocol ID
U2971g
Acronym
EXPLORER
Status last verified
Jun 2017
First submitted
26 Aug 2005
Last updated
20 Aug 2019
Data monitoring committee
No

Publications

  • Merrill JT, Neuwelt CM, Wallace DJ, Shanahan JC, Latinis KM, Oates JC, Utset TO, Gordon C, Isenberg DA, Hsieh HJ, Zhang D, Brunetta PG. Efficacy and safety of rituximab in moderately-to-severely active systemic lupus erythematosus: the randomized, double-blind, phase II/III systemic lupus erythematosus evaluation of rituximab trial. Arthritis Rheum. 2010 Jan;62(1):222-33. doi: 10.1002/art.27233.

    PubMed 20039413

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Rituximab, Prednisone and Acetaminophen in people with Lupus Erythematosus, Systemic, run by Genentech, Inc. at 65 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 65 sites in United States, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 10 Dec 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants Who Achieved a Major Clinical Response (MCR), Partial Clinical Response (PCR), or Nonclinical Response (NCR) Defined by British Isles Lupus Assessment Group (BILAG) Scores Over The 52-week Treatment Period (time frame: From baseline to 52 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00137969, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Aug 2019.

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