| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Systemic Lupus Erythematosus (SLE) with WHO Class V Glomerulonephritis |
|
| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To prove that infliximab in combination with azathioprine is superior to azathioprine alone in rapidly inducing a meaningful renal improvement, defined as a reduction in proteinuria of at least 50%, in patients with membranous SLE glomerulonephritis not adequately responding to ACE inhibitors and glucocorticoids. |
|
| E.2.2 | Secondary objectives of the trial |
| Secondary objectives of the study include lab studies on renal markers, disease activity measurements, safety evaluation of infliximab for this population, general quality of life and fatigue. |
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
1. SLE (ACR criteria fulfilled) with biopsy-proven membranous glomerulonephritis (WHO class V), biopsy should have been done within the 12 months prior to signing the informed consent.
2. Proteinuria > 3 g/day (2 separate measurements) 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)
3. Have the capacity to understand and sign an informed consent form.
4. Individuals, with the age of 18 years or older.
5. Men and women of childbearing potential must use adequate birth control measures (e.g., abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, implantable or injectable contraceptives or surgical sterilization) for the duration of the study and should continue such precautions for 6 months after receiving the last infusion.
6. Are considered eligible according to the following tuberculosis (TB) screening criteria:
6.1. Have no history of latent or active TB prior to screening.
6.2. Have no signs or symptoms suggestive of active TB upon medical history and/or physical examination.
6.3. Have had 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.
6.4. Within 1 month prior to the first administration of study agent, either have a negative tuberculin skin test, as outlined in Section 19, 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.
6.5. Have a chest radiograph (both posterior-anterior and lateral views), taken within 3 months prior to the first administration of study agent and read by a qualified radiologist, with no evidence of current active TB or old inactive TB.
7. The screening laboratory test results must 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: ≤ 132 μmol/L (≤ 1,5 mg/dl) or 1.5 times the upper limit of normal range
ALAT / ASAT within twice the upper normal range.
|
|
| E.4 | Principal exclusion criteria |
1. Active WHO class IV SLE nephritis.
2. Treatment with Azathioprine within the previous 12 months.
3. Treatment with cyclophosphamide within the previous 12 months.
4. Treatment with cyclosporine within the previous 6 weeks.
5. Active cerebral SLE
6. Presence of anti-phospholipid-antibodies unless under adequate anticoagulation (coumadin or low molecular weight heparin for APLAS, low dose aspirin for ACLA without symptoms)
7. Women who are pregnant, nursing, or planning pregnancy within 6 months after the last infusion.
8. Have had any previous treatment with monoclonal antibodies or antibody fragments.
9. 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
10. Documentation of seropositive for human immunodeficiency virus (HIV).
11. A positive test for hepatitis B surface antigen or hepatitis C.
12. Have a history of alcohol or substance abuse within the preceding 6 months that, in the opinion of the investigator, may increase the risks associated with study participation or study agent administration, or may interfere with interpretation of results.
13. Have a known history of serious infections (eg, hepatitis, pneumonia) in the previous 3 months.
14. Have or have had an opportunistic infection (eg, herpes zoster [shingles], cytomegalovirus, Pneumocystis carinii, aspergillosis, histoplasmosis, or mycobacteria other than TB) within 6 months prior to screening.
15. Have a history of latent or active granulomatous infection, including TB, histoplasmosis, or coccidioidomycosis, prior to screening.
16. Have had a Bacille Calmette-Guerin (BCG) vaccination within 12 months of screening.
17. Have a chest radiograph within 3 months prior to randomization that shows an abnormality suggestive of a malignancy or current active infection, including TB.
18. Have had a nontuberculous mycobacterial infection or opportunistic infection (eg, cytomegalovirus, Pneumocystis carinii, aspergillosis) within 6 months prior to screening.
19. Have a history of lymphoproliferative disease, including lymphoma or signs suggestive of possible lymphoproliferative disease such as lymphadenopathy of unusual size or location (eg, nodes in the posterior triangle of the neck, infraclavicular, epitrochlear, or periaortic area), or splenomegaly.
20. Currently have any known malignancy or have a 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.
21. Have 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.
22. Are unable or unwilling to undergo multiple venipunctures because of poor tolerability or lack of easy access.
23. Use of any investigational drug within 30 days prior to screening or within 5 half-lives of the investigational agent, whichever is longer.
24. Previous treatment with drugs targeted at reducing TNF (pentoxifylline, thalidomide, etanercept, or other agents) as well as previous treatment with infliximab.
25. Presence of a transplanted solid organ (with the exception of a corneal transplant > 3 months prior to screening).
26. Have a concomitant diagnosis or history of congestive heart failure.
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| Comparison of time needed to reduce proteinuria to 1.5 g/day or less between the infliximab plus azathioprine and the azathioprine only group. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | Information not present in EudraCT |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 2 |
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