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Anti-CD20 in Systemic Lupus Erythematosus

This study has been completed.
Sponsor:
Collaborator:
Autoimmunity Centers of Excellence
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00036491
First received: May 10, 2002
Last updated: February 12, 2016
Last verified: February 2016
  Purpose

The purpose of this study is to determine the safety and effectiveness of rituximab (anti-CD20) in treating systemic lupus erythematosus (SLE).

White blood cells in the body called B cells give off substances that are active in promoting SLE disease. Researchers have found that anti-CD20 can block production of these substances in another disease. This study explores whether anti-CD20 will also be safe in people with SLE and whether it may be effective in treating SLE.


Condition Intervention Phase
Lupus Erythematosus, Systemic
Drug: Rituximab
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label Safety and Efficacy Study of an Anti-CD20 Antibody (Rituximab, Rituxan®) for Anti-B Cell Therapy in the Treatment of Systemic Lupus Erythematosus

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:
  • Serum Autoantibodies [ Time Frame: Baseline, Week 4, Week 12, Week 24, Week 36 and Week 56 ] [ Designated as safety issue: No ]
  • Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) [ Time Frame: Baseline, Week 4, Week 7, Week 11, Week 15, Week 19, Week 27, Week 39 and Week 55 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • C3 and C4 complement levels [ Designated as safety issue: Yes ]
  • Systemic Lupus Activity Measure (SLAM) [ Time Frame: Baseline, Week 4, Week 7, Week 11, Week 15, Week 19, Week 27, Week 39 and Week 55 ] [ Designated as safety issue: No ]
  • Erythrocyte Sedimentation Rate (ESR) [ Designated as safety issue: Yes ]
  • Prednisone Dose [ Time Frame: Baseline, Week 4, Week 12, Week 24, Week 36 and Week 56 ] [ Designated as safety issue: No ]
  • Renal Function [ Designated as safety issue: Yes ]
    Measured by creatinine clearance and total protein.

  • Modified Health Assessment Questionnaire (HAQ) [ Designated as safety issue: No ]
  • Short Form-36 Health Survey (SF-36) [ Designated as safety issue: No ]
  • Physician Global Assessment (VAS) [ Designated as safety issue: No ]
  • Patient Global Assessment (VAS) [ Designated as safety issue: No ]
  • Systemic Lupus Erythematosus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) Damage Index for SLE [ Designated as safety issue: No ]
  • Adverse Events [ Designated as safety issue: Yes ]

Enrollment: 24
Study Start Date: January 2001
Study Completion Date: January 2006
Primary Completion Date: January 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: rituximab
375 mg/m^2 administered intravenously
Drug: Rituximab
Subjects received four weekly infusions of rituximab at a dose of 375 mg/m^2
Other Name: Rituxan®

Detailed Description:

B cells clearly play an essential role in the pathogenesis of SLE since they produce autoantibodies. Clinical observations support the contention that intervening in the production of autoantibodies by the B lymphocyte will be effective therapy. Current approved therapy for B-cell non-Hodgkin's lymphoma includes anti-CD20. The results of anti-CD20 administration in SLE are anticipated to be similar to those in lymphoma patients. The current proposal explores the mechanisms and applicability of B-cell depletion as a potential treatment for SLE.

Participants receive 4 weekly infusions of study medication. Each participant is enrolled in the study for a total of 1 year with protocol visits weekly for the first 3 months, then every other week for the next 2 months, every month for the next 4 months, and every other month for the remaining 5 months of the study (Weeks 0, 1, 2, 3, 4, 5, 6, 7, 9, 11, 13, 15, 19, 23, 27, 31, 39, 47, and 55). Responses to exogenous antigens are measured; assessments for clinical response with SLE-disease activity score (SLEDEI) and systemic lupus activity measure (SLAM) score are performed. Participants complete a health questionnaire and a health survey and laboratory parameters are evaluated.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

People may be eligible for this study if they:

  • Are 18 to 70 years of age
  • Agree to use a reliable method of birth control during treatment and for 6 months after treatment ends
  • Have SLE (by the American College of Rheumatology criteria)
  • Have had SLE for at least 6 months prior to screening
  • Have active SLE disease at the screening visit
  • Have organ disease (lung, stomach, intestinal, blood, kidney, and/or heart)
  • Have failed standard therapy, including at least 1 immunosuppressive agent, or have experienced side effects from an immunosuppressive agent that required discontinuation of treatment
  • Meet blood, liver, and kidney laboratory values set by the protocol
  • Have not taken an immunosuppressive agent for 2 weeks prior to the first treatment
  • Have been on a stable dose of oral corticosteroids, if taking them, for 4 weeks before the first week's visit. Oral corticosteroids may be altered as medically necessary after enrollment.
  • Have at least 1 elevated autoantibody level at screening visit.

Exclusion Criteria

People will not be eligible for this study if they:

  • Are pregnant or breast-feeding
  • Have heart, lung, nervous system, kidney, liver, stomach, intestinal, or other diseases that may place the patient at risk if participating in the trial
  • Have cranial neuropathy (a condition affecting the head region)
  • Are on blood-thinning agents to prevent blood clotting
  • Have a serious skin disease
  • Have a certain class of heart disease
  • Have had cancer, unless surgically cured basal cell carcinoma or cervical dysplasia
  • Have a long term serious infectious disease such as tuberculosis or a fungal infection that is now active, or active within 2 years of the baseline visit
  • Have had HIV infection or another immunosuppressive state (chemotherapy or radiation therapy)
  • Have received any experimental drug within 30 days of baseline visit
  • Have received any monoclonal antibody or similar medication within 3 months of the baseline visit
  • Received any intravenous, joint, or muscle injection of corticosteroids within 4 weeks of the baseline visit
  • Abuse alcohol or drugs
  • Are unwilling or unable to follow the protocol
  • Have poor veins for receiving injections.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00036491

Locations
United States, Colorado
University of Colorado
Denver, Colorado, United States, 80045
United States, New York
University of Rochester
Rochester, New York, United States, 14623
United States, Pennsylvania
University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Autoimmunity Centers of Excellence
Investigators
Study Chair: Robert A. Eisenberg, MD University of Pennsylvania
  More Information

Additional Information:
Publications:
Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00036491     History of Changes
Other Study ID Numbers: DAIT AC002  SACCC #ASL02  UPenn #U1131s  ACE Study #AC002 
Study First Received: May 10, 2002
Last Updated: February 12, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Systemic Lupus Erythematosus
SLE
B-Lymphocytes
anti-CD20
rituximab

Additional relevant MeSH terms:
Lupus Erythematosus, Systemic
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Rituximab
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents

ClinicalTrials.gov processed this record on September 26, 2016