| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Systemic Lupus Erythematosus |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 6.1 |
| E.1.2 | Level | HLT |
| E.1.2 | Classification code | 10025136 |
|
| 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 objective for this study will be to assess the proportion of subjects with new clinical flare of SLE BILAG A or B during the 1 year double-blind treatment period, comparing abatacept with placebo on a background of tapering glucocorticosteroids. |
|
| E.2.2 | Secondary objectives of the trial |
| 1 Assess the proportion of subjects with a new clinical flare of SLE BILAG A or B within the initial 6 months of the double-blind treatment period. 2 Evaluate the proportion of subjects who during the study experienced a BILAG A or B flare and/or had an increase in prednisone or prednisone equivalent dosage for clinical re-activation of SLE that did not meet BILAG A or B criteria for flare of SLE. 3 Assess the total number of BILAG A and BILAG B flares in the two treatment groups. 4 Evaluate the time to occurrence of a new clinical flare of SLE in the two treatment groups. 5 Assess the proportion of subjects in each study arm who have no flares of their lupus for at least 6 consecutive months. 6 Assess SLICC/ACR Damage Index at one year compared with baseline for the two treatment groups. 7 Assess the total exposure to glucocorticosteroids in the two groups, as measured by total prednisone or prednisone equivalent area under the curve AUC . |
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
| Subjects must have SLE as defined by meeting 4 of the 11 classification criteria of the American College of Rheumatology for the classification of Systemic Lupus Erythematosus, either sequentially or coincident. The 4 criteria need not be present at study entry, but have occurred at some time during the course of the disease. Within 28 days of the screening visit, subjects must have at least one of the following flare manifestations of SLE, as defined by the BILAG criteria as modified for use in this study. The flare manifestation may represent the initial activity within that organ system or may be a recurrence of activity in an organ system previously affected. a Active mucocutaneous discoid lesions i A severe active facial and/or extensive discoid lesions 2/9 of body surface area , scarring or causing disability recorded as 1. ii B localized active discoid lesions 1/9 total body surface area , including lupus profundus recorded as 1. The skin lesions must be actively inflamed; they cannot be solely chronic changes, e.g. scar with depigmentation. In order to satisfy inclusion rules, the currently active lesions cannot represent ongoing chronic and continuous activity - they must constitute a flare, either newly inflamed or previously inflamed but quiescent for at least 3 months. b Active polyarthritis i A severe polyarthritis as recorded as 1 with loss of function not responsive to steroids less than 10 mg per day, antimalarials, NSAIDs ii B Arthritis as recorded as 1 active joint inflammation without loss of functional range of motion. At least 3 actively inflamed joints--swollen, tender, erythematous--not isolated Jaccoud arthropathy although the presence of Jaccoud arthropathy in a subject with active inflammation will not preclude study entry. The inflamed joints cannot have been chronically and continuously inflamed- they must constitute a flare, either newly inflamed or previously inflamed but quiescent for at least 3 months. Activity in an organ system that was either minimally or not active for at least 3 months i now BILAG A in an organ system that was BILAG B, C, D, or E, OR ii now BILAG B in an organ system that was previously BILAG C, D, or E c Active serositis pleuritis/pericarditis i A Symptomatic effusion recorded as 1 plus two other criteria listed below 1 or four of the following criteria listed below recorded as 1 pleuropericardial pain; dyspnea; friction rub; chest x-ray revealing pleural or pericardial effusion; electrocardiogram changes of pericarditis; or cardiac arrhythmia including tachycardia 100 beats per minute in the absence of fever. ii B Two of the following criteria listed below each recorded as 1 pleuropericardial pain; dyspnea; friction rub; chest x-ray revealing pleural or pericardial effusion; electrocardiogram changes of pericarditis; or cardiac arrhythmia including tachycardia 100 beats per minute in the absence of fever. Disease Activity and Concomitant Medication Permitted steroid sparing agents, i.e. azathioprine, mycophenolate mofetil MMF , chloroquine, hydroxychloroquine or methotrexate and anti-proteinuria therapies ie. angiotension converting enzyme inhibitors or angiotensin receptor blockade agents , or statins should be continued. These drugs should have been maintained at a stable dose for at least the 1 month prior to signing consent. All other steroid sparing agents i.e. calcineurin inhibitors, leflunomide, thalidomide, retinoic acid derivatives, other immunosuppressant or immunomodulatory agents should have been discontinued at least 1 month prior to the time of signing. |
|
| E.4 | Principal exclusion criteria |
| Medical History and Concurrent Diseases Treatment of current SLE flare with corticosteroids prednisone or prednisone equivalent , for more than 14 days prior to randomization, or treatment of the flare at any time with a dose 8805; 30 mg prednisone or prednisone equivalent per day. Active anti-phospholipid antibody syndrome, i.e. recent untreated thromboses, cerebral or pulmonary emboli, pregnancy loss, pleurisy due to thromboembolic phenomena as the sole or primary feature of their SLE or SLE-like syndrome should be excluded. However, subjects currently controlled with anti-coagulation therapy, who have no disease activity may be included in the study. Subjects with drug-induced SLE, rather than idiopathic SLE. Subjects with other autoimmune disease as a main diagnosis other than SLE e.g.; RA, MS . Current symptoms of severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, non-SLE pulmonary, non-SLE cardiac, neurological, or cerebral disease; pulmonary and/or cardiac manifestations of SLE shall not constitute an exclusion to study entry. Concomitant medical conditions that, in the opinion of the Investigator, might place the subject at unacceptable risk for participation in this study. Concomitant illness that in the opinion of the investigator, is likely to require additional systemic glucocorticosteroid therapy during the study, e.g.; asthma is exculsionary. However, treatment for asthma with inhalational corticosteroid therapy is allowed. Female subjects with a breast cancer screening that is suspicious for malignancy and in whom the possibility of malignancy cannot be reasonably excluded following additional clinical, laboratory or other diagnostic evaluations. Subjects with a history of cancer within the last five years other than nonmelanoma skin cell cancers cured by local resection . Existing non-melanoma skin cell cancers must be removed prior to randomization Day 1 treatment . Carcinoma in situ, treated with definitive surgical intervention, is allowed. Subjects who have a history of clinically significant drug or alcohol abuse. Subjects currently taking methotrexate who admit to consumption of more than an average of 1 alcoholic drink per day. Subjects with any serious bacterial infection such as pneumonia, renal infection and sinusitis , unless treated and resolved with antibiotics or chronic bacterial infection such as pyelonephritis, osteomyelitis and lung infection with bronchiectasis in the previous 3 months. The following subjects will not be allowed in this study -Subjects with current clinical or laboratory evidence of active or latent tuberculosis TB . -Subjects with a history of active TB treated within the last 3 years. Subjects with herpes zoster that resolved less than 2 months prior to enrollment. Subjects with evidence as assessed by the Investigator of active or latent bacterial or viral infections at the time of potential enrollment, including subjects with evidence of Human Immunodeficiency Virus HIV infection. Subjects currently on hydroxychloroquine or chloroquine with evidence of retinopathy within 6 months of enrollment or who have had no ophthalmologic evaluation within one year of enrollment and will not have this examination done. |
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| E.5 End points |
| E.5.1 | Primary end point(s) |
|
| 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 | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | Information not present in EudraCT |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Information not present in EudraCT |
| 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) | 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 | No |
| 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 |
|
| 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 | 1 |
| E.8.9.1 | In the Member State concerned months | 9 |
| 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 | 9 |
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