Determining the Responses and Impact of Rituximab-instigated Cell Depletion on T Cells in People With SLE

Lupus Erythematosus, Systemic Clinical Trial

Official title:

Rituximab in SLE: Understanding of Long-term Responses and the Impact of B Cell Depletion on T Cells

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01702038
• Other study ID #: DAIT ALE01
• Status: Withdrawn
• Phase: Phase 2
• First received: October 3, 2012
• Last updated: October 4, 2012
• Start date: September 2009

Study information

• Verified date: October 2012
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Federal Government
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine how B cell subsets and autoantibodies are related to disease remission after rituximab treatment in subjects with Systemic Lupus Erythematosus (SLE).

Description:

Immune cells are an important part of the abnormal autoimmune response in SLE. The B cell is a significant part of this autimmune response because it produces the antibodies which can react with normal tissue of the body. B cells have the ability to accumulate and promote the development of SLE. The purpose of this study is to determine how B cell subsets and autoantibodies are related to disease remission after rituximab treatment in subjects with SLE.

This study will last approximately two years and consist of 15 study visits. These visits will occur at screening, baseline, Days 0 and 14, and Months 1, 2, 3, 4, 6, 9, 12, 15, 18, 21, and 24. Participants will receive a single rituximab injection on Days 0 and 14. Medication history and blood tests will occur at every study visit. A physical exam, medical history, and urine tests will occur at most visits. For females, a pregnancy test will occur at selected visits.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 19 Years to 65 Years

Eligibility

Inclusion Criteria:

• Diagnosis of SLE

• Positive ANA with a titer of at least 1:160

• Active disease (one or more modified BILAG A or B) or inability to lower steroids to leass than 20 mg/day. More information about this criterion can be found in the protocol.

• For females, must agree to use effective birth control methods for the duration of the study

Exclusion Criteria:

• Severe thrombocytopenia

• Active, moderate, or severe proliferative glomerulonephritis

• Active CNS manifestations due to lupus other than migraines, mild cognitive dysfunction, or mood disorders. More information about this criterion can be found in the protocol.

• Poorly controlled anti-phospholipid syndrom

• Significant organ dysfunction

• Conditions, other than SLE, that are likely to require prolonged systemic steroids

• Chronic infections. More information about this criterion can be found in the protocol.

• Hepatitis B infection

• Hepatitis C infection

• Deep space infection within two years of study entry

• Severe bacterial infection within three months of study entry

• More than one severe bacterial infection within two years of study entry

• Positive purified protein derivative tuberculin skin test

• History of cancer, not including basal cell carcinomas and carcinoma in situ of the cervix with documentation of successful treatment

• Alcohol or drug abuse

• Surgery within three months of study entry

• Immunization with a live vaccine within two months of study entry

• Any immunization within one month of study entry

• Received cyclophosphamide or calcineurin inhibitors within six months of study entry

• Received anti-TNF alpha antibody within 3 months of study entry

• Received etanercept within one month of study entry

• Received anti-CD20 antibodies or other lymphocyte depleting antibodies

• Received Immunoglobin G infusion protein or monoclonal antibody

• Treatment with FDA non-approved agents within six months of study entry

• Transaminases greater than two times the upper limit of normal

• Pregnant or breastfeeding

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic

Intervention

Drug:
• Rituximab
1000 mg administered intravenously

Locations

Country	Name	City	State
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	University of Rochester	Rochester	New York

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Country where clinical trial is conducted

United States, 

References & Publications (2)

Eisenberg R. Targeting B cells in SLE: the experience with rituximab treatment (anti-CD20). Endocr Metab Immune Disord Drug Targets. 2006 Dec;6(4):345-50. Review. — View Citation

Pego-Reigosa JM, Isenberg DA. Systemic lupus erythematosus: pharmacological developments and recommendations for a therapeutic strategy. Expert Opin Investig Drugs. 2008 Jan;17(1):31-41. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Ratio of B and T cell subsets among those with and without a long-term response and those with and without baseline anti-RBP antibody		Day 0 through month 24	Yes
Secondary	Impact of prolonged B cell absence on the composition and activation status of helper T cell subsets and regulatory T cells		Day 0 through month 24	Yes
Secondary	Effect of B cell depletion on interferon-alpha activity		Day 0 through month 24	Yes