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

NCT ID: NCT00368264

Last Updated: 2009-10-05

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 1 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-09-30
• Study Completion Date: 2009-06-30

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

Conditions

Lupus Erythematosus, Systemic; Lupus Nephritis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

1

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

Group Type: EXPERIMENTAL

infliximab

Intervention Type: DRUG

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

2

azathioprine plus 4 placebo infusions

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

azathioprine (2 mg/kg) plus four placebo infusions

Interventions

infliximab

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

Intervention Type: DRUG

placebo

azathioprine (2 mg/kg) plus four placebo infusions

Intervention Type: DRUG

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:

• 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.

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).
• 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.
• Chest radiograph within 3 months prior to randomization suggestive of malignancy or current active infection.
• Nontuberculous mycobacterial infection or opportunistic infection within 6 months prior to screening.
• History of lymphoproliferative disease.
• Any known malignancy or history of malignancy within the previous 5 years, with the exception of basal cell or squamous cell carcinoma of the skin that has been fully excised with no evidence of recurrence.
• Current signs or symptoms of severe, progressive or uncontrolled renal (other than disease under investigation), hepatic, hematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, or cerebral disease.
• Use of any investigational drug within 30 days prior to screening or within 5 half-lives of the investigational agent, whichever is longer.
• Previous treatment with drugs targeted at reducing TNF.
• Presence of a transplanted solid organ (with the exception of a corneal transplant > 3 months prior to screening).
• Concomitant diagnosis or history of congestive heart failure.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hospital Hietzing

OTHER

Sponsor Role: collaborator

Medical University of Graz

OTHER

Sponsor Role: collaborator

Charite University, Berlin, Germany

OTHER

Sponsor Role: collaborator

University of Erlangen-Nürnberg

OTHER

Sponsor Role: collaborator

Heinrich-Heine University, Duesseldorf

OTHER

Sponsor Role: collaborator

University Medical Center Groningen

OTHER

Sponsor Role: collaborator

Leiden University Medical Center

OTHER

Sponsor Role: collaborator

Radboud University Medical Center

OTHER

Sponsor Role: collaborator

Medical University of Vienna

OTHER

Sponsor Role: lead

Responsible Party

Department of Medicine III, Medical University of Vienna, Austria

Principal Investigators

Josef S Smolen, MD

Role: STUDY_CHAIR

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

Martin Aringer, MD

Role: PRINCIPAL_INVESTIGATOR

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

Falk Hiepe, MD

Role: PRINCIPAL_INVESTIGATOR

Rheumatology, Charite, Berlin, Germany

Marc Bijl, MD

Role: PRINCIPAL_INVESTIGATOR

Clinical Immunology, Groningen University Hospital, Netherlands

Locations

Departments of Rheumatology, Internal Medicine, Medical University of Graz

Graz, , Austria

Rheumatology, Internal Medicine III, Medical University of Vienna

Vienna, , Austria

Internal Medicine II, Hietzing Hospital

Vienna, , Austria

Rheumatology, Charite

Berlin, , Germany

Rheumatology, University of Düsseldorf

Düsseldorf, , Germany

Internal Medicine III, University of Erlangen

Erlangen, , Germany

Clinical Immunology, Groningen University Hospital

Groningen, , Netherlands

Leiden University Medical Center, Netherlands

Leiden, , Netherlands

Nephrology, University of Nymegen, Netherlands

Nijmegen, , Netherlands

Countries

Austria; Germany; Netherlands

References

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.

Reference Type: BACKGROUND

PMID: 15476222 (View on PubMed)

Other Identifiers

Eudract-Nr. 2005-004067-30

Identifier Type: -

Identifier Source: secondary_id

Protocol EU-116

Identifier Type: -

Identifier Source: secondary_id

EK Nr:110/2006

Identifier Type: -

Identifier Source: secondary_id

TRIAL V

Identifier Type: -

Identifier Source: org_study_id