Lupus Erythematosus, SystemicPhase 2/3NCT00368264
TNF Blockade With Remicade in Active Lupus Nephritis WHO Class V (TRIAL )
A Phase 2/3 study testing infliximab in people with Lupus Erythematosus, Systemic and Lupus Nephritis, run by Medical University of Vienna at 9 sites in 3 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lupus Erythematosus, Systemic, Lupus Nephritis
- What is being tested?
- infliximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1 participants
- Where
- 9 sitesin 3 countries
- Study dates
- Sep 2006to Jun 2009
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Show all 15Show fewer
- 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.
Who cannot join
- 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
Show all 25Show fewer
- 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.
Trial locations and contacts
9 sites in 3 countries.
9 sites in 3 countries
Austria3 sites
Departments of Rheumatology, Internal Medicine, Medical University of Graz
Graz, A-8036
Rheumatology, Internal Medicine III, Medical University of Vienna
Vienna, A-1090
Internal Medicine II, Hietzing Hospital
Vienna, A-1130
Germany3 sites
Rheumatology, Charite
Berlin, D-10117
Rheumatology, University of Düsseldorf
Düsseldorf, D-40225
Internal Medicine III, University of Erlangen
Erlangen, D-91023
Netherlands3 sites
Clinical Immunology, Groningen University Hospital
Groningen, 9713 GZ
Leiden University Medical Center, Netherlands
Leiden, 2300 RC
Nephrology, University of Nymegen, Netherlands
Nijmegen, G6525 GA
About this study
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
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.
Read more
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.
- Conditions
- Lupus Erythematosus, Systemic, Lupus Nephritis
- Being tested
- infliximab, placebo
- Keywords
- lupus, nephritis, membraneous, proteinuria, TNF, infliximab, azathioprine, autoantibodies
- Medical subject headings
- Lupus Erythematosus, Systemic, Lupus Nephritis, Nephritis, Proteinuria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
infliximabDrug
azathioprine (2 mg/lkg) plus four infusions of infliximab (5mg/kg)
placeboDrug
azathioprine (2 mg/kg) plus four placebo infusions
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | azathioprine plus 4 infusions of infliximab (5 mg/kg) Receives: Drug: infliximab |
| 2 | Placebo comparator | azathioprine plus 4 placebo infusions Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
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).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Aug 2006 (estimated)
- Study startSep 2006
- Primary completionJun 2009
- Study completionJun 2009
Why it stopped: Failure to recruit patients with membranous lupus nephritis not previously treated with azathioprine .
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Lupus Erythematosus, SystemicStudies of the same condition, open and under way.
- More trials run by Medical University of ViennaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical University of Vienna
- Sponsor type
- University, hospital or other
- Collaborators
- Hospital Hietzing, Medical University of Graz, Charite University, Berlin, Germany, University of Erlangen-Nürnberg, Heinrich-Heine University, Duesseldorf, University Medical Center Groningen, Leiden University Medical Center, Radboud University Medical Center
- Investigators
- Josef S Smolen, MD, Study chair, Head, Department of Rheumatology, Internal Medicine III, Medical University of Vienna, AustriaMartin Aringer, MD, Principal investigator, Department of Rheumatology, Internal Medicine III, Medical University of Vienna, AustriaFalk Hiepe, MD, Principal investigator, Rheumatology, Charite, Berlin, GermanyMarc Bijl, MD, Principal investigator, Clinical Immunology, Groningen University Hospital, Netherlands
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00368264
- Sponsor's protocol ID
- TRIAL V
- Other IDs
- Eudract-Nr. 2005-004067-30, Protocol EU-116, EK Nr:110/2006
- Status last verified
- Oct 2009
- First submitted
- 23 Aug 2006
- Last updated
- 5 Oct 2009
- Results posted
- No
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. doi: 10.1002/art.20576.
PubMed 15476222
Study at a glance
From the registry record, last updated by the sponsor on 5 Oct 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00368264
- Acronym / sponsor ID
- TRIAL V
- Conditions
- Lupus Erythematosus, Systemic, Lupus Nephritis
- Keywords
- lupus, nephritis, membraneous, proteinuria, TNF, infliximab, azathioprine, autoantibodies
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Failure to recruit patients with membranous lupus nephritis not previously treated with azathioprine .
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Medical University of ViennaUniversity, hospital or other
- Collaborators
- Hospital Hietzing, Medical University of Graz, Charite University, Berlin, Germany, University of Erlangen-Nürnberg, Heinrich-Heine University, Duesseldorf, University Medical Center Groningen, Leiden University Medical Center, Radboud University Medical Center
- Study start
- Sep 2006
- Primary completion
- Jun 2009 (actual)
- Study completion
- Jun 2009 (actual)
- First posted
- 24 Aug 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: infliximabazathioprine plus 4 infusions of infliximab (5 mg/kg) |
| 2 | Placebo comparator | Drug: placeboazathioprine plus 4 placebo infusions |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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.
Key exclusion criteria (25 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| infliximabazathioprine (2 mg/lkg) plus four infusions of infliximab (5mg/kg) | Drug | 1 |
| placeboazathioprine (2 mg/kg) plus four placebo infusions | Drug | 2 |
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.
8 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).
Results and safety
The study was stopped early (reason given: Failure to recruit patients with membranous lupus nephritis not previously treated with azathioprine .). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Oct 2009.
- Background: PubMed 15476222Aringer 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.
Related trials for Lupus Erythematosus, Systemic
RecruitingObservational study
Deciphering the Genetic Architecture of Autoimmune Diseases
Autoimmune Diseases
RecruitingPhase 1
To Evaluate the Effects of Cevostamab in Participants With Systemic Lupus Erythematosus With or Without Active Lupus Nephritis
Lupus Erythematosus, Systemic
RecruitingPhase 1
A Trial in Healthy Adult Participants and Adults With Autoimmune Diseases to Test How HBM7020 is Tolerated and How it Behaves in the Body
Rheumatoid Arthritis, Systemic Lupus Erythematosus
RecruitingObservational study
Pain Phenotyping of Rheumatic Diseases - An Observational Study
Rheumatic Diseases, Lupus Erythematosus, Systemic
RecruitingPhase 3
A Study of Enpatoran in Participants With Cutaneous Manifestations of Lupus With or Without Systemic Disease
Systemic Lupus Erythematosus (SLE), Cutaneous Lupus Erythematosus (CLE)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Josef S Smolen, MD study chair
Head, Department of Rheumatology, Internal Medicine III, Medical University of Vienna, Austria
Martin Aringer, MD principal investigator
Department of Rheumatology, Internal Medicine III, Medical University of Vienna, Austria
Falk Hiepe, MD principal investigator
Rheumatology, Charite, Berlin, Germany
9 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing infliximab in people with Lupus Erythematosus, Systemic and Lupus Nephritis, run by Medical University of Vienna at 9 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 5 Oct 2009. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Austria, Germany, Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Failure to recruit patients with membranous lupus nephritis not previously treated with azathioprine .). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Comparison of time needed to reduce proteinuria to 1.5 g/day or less between the infliximab plus azathioprine and the azathioprine only group.. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00368264, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Oct 2009; AzTrials last refreshed its copy on 6 Nov 2026.