A Double Blind, Randomized, Placebo Controlled, Multi-Center Trial of Anti-TNF-alpha Chimeric Monoclonal Antibody (Infliximab) and Azathioprine in Patients Suffering From Systemic Lupus Erythematosus (SLE) With WHO Class V Glomerulonephritis

Medical University of Vienna9 sites in 3 countries1 target enrollmentSeptember 2006

ConditionsLupus Erythematosus, Systemic Lupus Nephritis

Interventionsinfliximab placebo

Drugsinfliximab placebo

Overview

Phase: Phase 2
Intervention: infliximab
Conditions: Lupus Erythematosus, Systemic
Sponsor: Medical University of Vienna
Enrollment: 1
Locations: 9
Primary Endpoint: Comparison of time needed to reduce proteinuria to 1.5 g/day or less between the infliximab plus azathioprine and the azathioprine only group.
Status: Terminated
Last Updated: 16 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

Background:

Standard therapy is ill-defined for patients with systemic lupus erythematosus (SLE) suffering from the membraneous form of Lupus nephritis (WHO class V). Therapeutic options used at present include azathioprine.

In a small, open label safety study, patients with lupus nephritis, including patients with membraneous lupus nephritis, have experienced a long-lasting therapeutic response, with sustained reduction in proteinuria, following a 10 weeks course of 4 infusions of infliximab in combination with azathioprine. This short course appeared safe with regard to SLE activity, despite increases in autoantibody levels.

Study hypothesis:

The combination of four infusions of infliximab (5 mg/kg of body weight)administered at weeks 0, 2,6, and 10, with azathioprine will be faster than azathioprine alone in reducing proteinuria to less than 1.5 g/day in patients with active lupus nephritis WHO class V (proteinuria > 3g/day).
This combination therapy will show a tolerable safety profile with regard to SLE activity and infections.

Registry

clinicaltrials.gov

Start Date

September 2006

End Date

June 2009

Last Updated

16 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Medical University of Vienna

Eligibility Criteria

Inclusion Criteria

•SLE (ACR criteria fulfilled) with biopsy-proven membranous glomerulonephritis (WHO class V).
•Proteinuria \> 3 g/day despite adequate therapy with ACE inhibitors and steroids (at least 2 months treatment with steroids with a dose at any time of at least 50 mg prednisolone (or equivalent), and ACE inhibitors and/or AT II antagonists at their maximum daily dose or, if this cannot be reached, the maximum daily dose tolerated).
•Capacity to understand and sign an informed consent form.
•Men and women of childbearing potential must use adequate birth control measures for the duration of the study and should continue such precautions for 6 months after receiving the last infusion.
•No history of latent or active TB prior to screening.
•No signs or symptoms suggestive of active TB upon medical history and/or physical examination.
•No recent close contact with a person with active TB or, if there has been such contact, will be referred to a physician specializing in TB to undergo additional evaluation and, if warranted, receive appropriate treatment for latent TB prior to or simultaneously with the first administration of study agent.
•Within 1 month prior to the first administration of study agent, either have a negative tuberculin skin test, or have a newly identified positive tuberculin skin test during screening in which active TB has been ruled out and for which appropriate treatment for latent TB has been initiated either prior to or simultaneously with the first administration of study agent.
•Have a chest radiograph (both posterior-anterior and lateral views) with no evidence of current active TB or old inactive TB.
•Screening laboratory test results meet the following criteria:

Exclusion Criteria

•Active WHO class IV SLE nephritis.
•Treatment with Azathioprine within the previous 12 months.
•Treatment with cyclophosphamide within the previous 12 months.
•Treatment with cyclosporine within the previous 6 weeks.
•Active cerebral SLE
•Presence of anti-phospholipid-antibodies unless under adequate anticoagulation
•Women who are pregnant, nursing, or planning pregnancy within 6 months after the last infusion.
•Have had any previous treatment with monoclonal antibodies or antibody fragments.
•History of receiving human/murine recombinant products or a known allergy to murine products. A known allergy to murine product is definitely an exclusion criterion
•Documentation of seropositive for human immunodeficiency virus (HIV).

Arms & Interventions

1

azathioprine plus 4 infusions of infliximab (5 mg/kg)

Intervention: infliximab

2

azathioprine plus 4 placebo infusions

Intervention: placebo

Outcomes

Primary Outcomes

Comparison of time needed to reduce proteinuria to 1.5 g/day or less between the infliximab plus azathioprine and the azathioprine only group.

Secondary Outcomes

Percentage of patients reaching reduction in proteinuria to ≤ 1.5 g/day, at week 12 and week 52.
Percent reduction in proteinuria at 6 weeks, 12 weeks, 20 weeks, 36 weeks, and 52 weeks after the first infusion.
Absolute reduction in proteinuria at 6 weeks, 12 weeks, 20 weeks, 36 weeks, and 52 weeks after the first infusion.
Percent reduction in protein/ creatinine ratio.
Percent reduction in SLE disease activity (measured by SIS and SLEDAI).
Absolute reduction in SLE disease activity (measured by SIS and SLEDAI).
Changes in Quality of life as determined by the SF36 questionnaire.
Changes in Fatigue as determined by the FSS (Fatigue Severity Scale).