TNF Blockade With Remicade in Active Lupus Nephritis WHO Class V (TRIAL )

NCT00368264 | Terminated Phase 2

• 4 other identifiers: TRIAL VEudract-Nr. 2005-004067-30Protocol EU-116EK Nr:110/2006
• Study Type: interventional
• Target: 1
• Locations: 3 countries
• Sites: 9

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:

1. 1.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).
2. 2.This combination therapy will show a tolerable safety profile with regard to SLE activity and infections.

Conditions

Lupus Erythematosus, Systemic; Lupus Nephritis

Keywords

lupus; nephritis; membraneous; proteinuria; TNF; infliximab; azathioprine; autoantibodies

Outcome Measures

Primary Outcomes (1)

• 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 (8)

• 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).

Study Arms (2)

1

EXPERIMENTAL

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

Drug: infliximab

2

PLACEBO COMPARATOR

azathioprine plus 4 placebo infusions

Drug: placebo

Interventions

infliximab DRUG

azathioprine (2 mg/lkg) plus four infusions of infliximab (5mg/kg)

1

placebo DRUG

azathioprine (2 mg/kg) plus four placebo infusions

2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• WBC (white blood cell count): \> 3.0 109/L
• Hemoglobin: \> 6 mmol/L (9,6 g/dL)
• Platelets: 100-350 109/L
• Serum Creatinine: 1.5 times the upper limit of normal range
• ALAT / ASAT within twice the upper normal range.

You may not qualify if:

• 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.
• Documentation of seropositive for human immunodeficiency virus (HIV).
• A positive test for hepatitis B surface antigen or hepatitis C.
• Alcohol or substance abuse
• Known history of serious infections in the previous 3 months.
• Opportunistic infection within 6 months prior to screening.
• History of latent or active granulomatous infection.
• Bacille Calmette-Guerin (BCG) vaccination within 12 months of screening.

Sponsors & Collaborators

• Medical University of Vienna: lead
• Hospital Hietzing: collaborator
• Medical University of Graz: collaborator
• Charite University, Berlin, Germany: collaborator
• University of Erlangen-Nürnberg: collaborator
• Heinrich-Heine University, Duesseldorf: collaborator
• University Medical Center Groningen: collaborator
• Leiden University Medical Center: collaborator
• Radboud University Medical Center: collaborator

Study Sites (9)

Departments of Rheumatology, Internal Medicine, Medical University of Graz

Graz, A-8036, Austria

Location

Rheumatology, Internal Medicine III, Medical University of Vienna

Vienna, A-1090, Austria

Location

Internal Medicine II, Hietzing Hospital

Vienna, A-1130, Austria

Location

Rheumatology, Charite

Berlin, D-10117, Germany

Location

Rheumatology, University of Düsseldorf

Düsseldorf, D-40225, Germany

Location

Internal Medicine III, University of Erlangen

Erlangen, D-91023, Germany

Location

Clinical Immunology, Groningen University Hospital

Groningen, 9713 GZ, Netherlands

Location

Leiden University Medical Center, Netherlands

Leiden, 2300 RC, Netherlands

Location

Nephrology, University of Nymegen, Netherlands

Nijmegen, G6525 GA, Netherlands

Location

Related Publications (1)

• Aringer M, Graninger WB, Steiner G, Smolen JS. Safety and efficacy of tumor necrosis factor alpha blockade in systemic lupus erythematosus: an open-label study. Arthritis Rheum. 2004 Oct;50(10):3161-9. doi: 10.1002/art.20576.

  PMID: 15476222 BACKGROUND

MeSH Terms

Conditions

Lupus Erythematosus, Systemic; Lupus Nephritis; Nephritis; Proteinuria

Interventions

Infliximab

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases; Glomerulonephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urination Disorders; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Josef S Smolen, MD

  Head, Department of Rheumatology, Internal Medicine III, Medical University of Vienna, Austria

  STUDY CHAIR

• Martin Aringer, MD

  Department of Rheumatology, Internal Medicine III, Medical University of Vienna, Austria

  PRINCIPAL INVESTIGATOR

• Falk Hiepe, MD

  Rheumatology, Charite, Berlin, Germany

  PRINCIPAL INVESTIGATOR

• Marc Bijl, MD

  Clinical Immunology, Groningen University Hospital, Netherlands

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: August 23, 2006
• First Posted: August 24, 2006
• Study Start: September 1, 2006
• Primary Completion: June 1, 2009
• Study Completion: June 1, 2009
• Last Updated: October 5, 2009

Record last verified: 2009-10

Locations

AU (3); DE (3); NL (3)