E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Systemic Lupus Erythematosus |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Classification code | 10042945 |
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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 |
The primary study objective is to demonstrate that epratuzumab is effective in the treatment of acute lupus flare.
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E.2.2 | Secondary objectives of the trial |
-To evaluate the effectiveness of epratuzumab in treating severe disease activity (acute flare) and in maintaining disease control -To evaluate the ability of epratuzumab to reduce the use of corticosteroids and other lupus medications. -To demonstrate the safety of epratuzumab in patients with SLE. -To assess the effect of adding epratuzumab to standard care on the quality of life of patients with SLE. Supplemental endpoints: -Time-to-reflare (new/recurrent BILAG A or B) among patients with no BILAG index B (or A) scores in any body/organ system at 4 weeks as well as the proportion of patients with these reflares. -Proportion of patients able to maintain successfull steroid-tapering from week 24 to week 48. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
-Male or female, 18 years and older; -Signed written informed consent obtained prior to study entry; -Has SLE by American College of Rheumatology revised criteria (meets at least 4 criteria); -Has had SLE for at least 6 months prior to study entry; -Has at least one elevated lupus-associated autoantibody level at or any time prior to study entry; -Has new onset of BILAG index A level activity in at least one body/organ system outside the renal and neurologic systems which developed within 4 weeks of study entry; -If initiated corticosteroids >20 mg/day prednisone (or equivalent) for treatment of the current flare, within 14 days of anticipated first infusion of study drug; -If on immunosuppresives, receiving a stable regimen for at least 8 weeks prior to study entry; and -If on antimalarials, receiving a stable regimenfor at least 12 weeks prior to study entry. |
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E.4 | Principal exclusion criteria |
-Pregnant or lactating women. Women of childbearing potential are required to have a negative pregnancy test; -Women of childbearing potential and fertile men who are not practicing or who are unwilling to practice birth control during and for a period of 6 months after the completion of the study; -Active severe CNS disease; -Active severe renal disease; -Treatment with Lymphostat B, or CTLA4-Ig within 6 months, or with rituximab or other anti-B-cell ABs within 12 months; -Allergy to murine or human ABs; -Experimental therapy or any therapy with human or murine ABs within 3 months; Cyclophosphamide, cyclosporin, intravenous, joint or IM injections of corticosteroids exceeding 120 mg methylprednisolone, 60 mg triamcinolone, or equivalent; IV immunoglobulins, or any IMPs within 4 weeks; -Thrombosis, spontaneous or induced abortion, stillbirth or live birth, within 4 weeks; -Patients with antiphospholipid ABs AND a history of thromboembolic events; -On oral anticoagulants within 4 weeks; -History of malignancy (except basal or squamous cell carcinoma, cervical CIS); -Active infection receiving antibiotics within 7 days of screening or infection requiring hospitalization or herpes zoster treatment within 4 weeks; long-term infectious diseases (tuberculosis, fungal infections) active within 2 years; -Known HIV, hepatitis B or C infection, or other immunosuppressive states; -Live vaccine within 4 weeks; -Hematological abnormalities not attributed to lupus; -Liver transaminases or alkaline phosphatase > 3X upper limit of normal and not attributed to SLE; -Serum creatinine > 2.5 mg/dL or clinically significant increases within 4 weeks, or proteinuria > 3.5 mg/day; and -Substance abuse or other concurrent medical conditions that, in the investigator's opinion, could confound study interpretation or affect the patient's ability to tolerate or complete the study. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint evaluated at 24 weeks is a patient response variable with three ordered categories; complete response (CR), partial response (PR) and non-response (NR). In order to be given a response status of CR or PR, a patient must meet two minimum conditionas: (i) not be considered a treatment failure and (ii) not have any BILAG Index A score in any body/organ system at any post-treatment evaluation time-point from weeks 4 to 24. In addition, if the patient also satisfies the protocol-defined steroid-tapering criterion at 24 weeks and does not have any BILAG Index B score, in any body/organ system at any post-treatment evaluation time-point from weeks 4 to 24, the patient will be assigned a CR status. Otherwise, the patient will be assigned a PR status provided the two minimum conditions are satisfied. Requirements for CR and PR are summarized in the protocol (page 22). A patient who fails to meet the two minimum conditions will be assigned a NR status. |
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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 | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
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 | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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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
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Last patient, last visit. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 11 |