TNF Blockade With Remicade in Active Lupus Nephritis WHO Class V (TRIAL )
Information source: Medical University of Vienna
Information obtained from ClinicalTrials.gov on November 03, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Lupus Erythematosus, Systemic; Lupus Nephritis
Intervention: infliximab (Drug); placebo (Drug)
Phase: Phase 2/Phase 3
Status: Recruiting
Sponsored by: Medical University of Vienna Official(s) and/or principal investigator(s):
Josef S Smolen, MD, Study Chair, Affiliation: Head, Department of Rheumatology, Internal Medicine III, Medical University of Vienna, Austria
Martin Aringer, MD, Principal Investigator, Affiliation: Department of Rheumatology, Internal Medicine III, Medical University of Vienna, Austria
Falk Hiepe, MD, Principal Investigator, Affiliation: Rheumatology, Charite, Berlin, Germany
Marc Bijl, MD, Principal Investigator, Affiliation: Clinical Immunology, Groningen University Hospital, Netherlands
Overall contact:
Martin Aringer, MD, Phone: 43-1-40400, Ext: 4300, Email: martin.aringer@meduniwien.ac.at
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.
Clinical Details
Official title: 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
Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Primary outcome: 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 outcome: 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).
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
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.
Locations and Contacts
Martin Aringer, MD, Phone: 43-1-40400, Ext: 4300, Email: martin.aringer@meduniwien.ac.at
Rheumatology, Internal Medicine III, Medical University of Vienna, Vienna A-1090, Austria; Recruiting
Martin Aringer, MD, Principal Investigator
Clemens Scheinecker, MD, Principal Investigator
Internal Medicine II, Hietzing Hospital, Vienna A-1130, Austria; Recruiting
Peter Petera, MD, Principal Investigator
Departments of Rheumatology, Internal Medicine, Medical University of Graz, Graz A-8036, Austria; Recruiting
Winfried B Graninger, MD, Principal Investigator
Rheumatology, Charite, Berlin D-10117, Germany; Recruiting
Falk Hiepe, MD, Email: falk.hiepe@charite.de
Falk Hiepe, MD, Principal Investigator
Internal Medicine III, University of Erlangen, Erlangen D-91023, Germany; Recruiting
Reinhard Voll, MD, Principal Investigator
Rheumatology, University of Düsseldorf, Düsseldorf D-40225, Germany; Recruiting
Matthias Schneider, MD, Principal Investigator
Rheumatology, University of Schleswig-Holstein, Campus Lübeck, Lübeck D-23538, Germany; Not yet recruiting
Wolfgang L Gross, MD, Principal Investigator
Clinical Immunology, Groningen University Hospital, Groningen 9713 GZ, Netherlands; Recruiting
Marc Bilj, MD, Email: m.bijl@int.umcg.nl
Marc Bijl, MD, Principal Investigator
Leiden University Medical Center, Netherlands, Leiden 2300 RC, Netherlands; Recruiting
Stefan P Berger, MD, Principal Investigator
Nephrology, University of Nymegen, Netherlands, Nijmegen G6525 GA, Netherlands; Recruiting
Jo H Berden, MD, Principal Investigator
Additional Information
Related publications: 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.
Starting date: September 2006
Last updated: May 28, 2008
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