E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Systemic Lupus Erythematosus (SLE) |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 19.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10025134 |
E.1.2 | Term | Lupus erythematosus |
E.1.2 | System Organ Class | 100000004859 |
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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 |
• To evaluate the efficacy of belimumab in adult SLE subjects of black race.
• To evaluate the safety and tolerability of belimumab in adult SLE subjects of black race. |
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E.2.2 | Secondary objectives of the trial |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Title: Pharmacogenetic Research
Date: 20 June 2012
Objectives:
• Relationship between genetic variants and the pharmakokinetics of belimumab.
• Relationship between genetic variants and safety and/or tolerability of belimumab.
• Relationship between genetic variants and efficacy of belimumab.
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E.3 | Principal inclusion criteria |
• Black race.
• Clinical diagnosis of SLE by American College of Rheumatology (ACR) criteria.
• Active SLE disease.
• Autoantibody-positive.
• On stable SLE treatment regimen which may include corticosteroids (for example, prednisone), antimalarial (for example, hydroxychloroquine) and/or immunosuppressants (for example, azathioprine, methotrexate, mycophenolate). |
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E.4 | Principal exclusion criteria |
• Pregnant or nursing.
• Have received treatment with belimumab at any time
• Have received treatment with any other B cell targeted therapy (for example, rituximab) in the past year.
• Have received treatment with an investigational biological agent in the past year.
• Have received intravenous (IV) cyclophosphamide within the past 90 days.
• Have severe active lupus kidney disease.
• Have severe active central nervous system (CNS) lupus.
• Have required management of acute or chronic infections within the past 60 days.
• Have current drug or alcohol abuse or dependence.
• Tested positive for human immunodeficiency virus (HIV), hepatitis B, or hepatitis C.
• Have a history of severe allergic reaction to contrast agents or biological medicines. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is the systemic lupus erythematosus
responder index (SRI) response rate with the modified SLEDAI-2K
scoring for proteinuria at Week 52
A participant that has an SRI response has all 3 of the following:
• ≥4 point reduction from baseline in Safety of Estrogen in Lupus National Assessment SLE Disease Activity Index (SELENA SLEDAI) score (with the modified SLEDAI-2K scoring for proteinuria), AND
• No worsening (increase of <0.30 points from baseline) in Physician's Global Assessment (PGA), AND
• No new British Isles Lupus Assessment Group (BILAG) A organ domain score or 2 new BILAG B organ domain scores compared with baseline at the time of assessment (ie, at Week 52). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• SRI response rate with the SELENA SLEDAI for scoring of proteinuria at
Week 52.
• Time to first severe flare (SLE Flare Index) with SLEDAI-2K and
SELENA SLEDAI as the SLEDAI criterion of the SFI.
• Reduction in prednisone
• Number of participants who experienced adverse events |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Baseline to 52 weeks
Baseline, weeks 40 to 52
Up to 84 weeks |
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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 | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | Yes |
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) | Yes |
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.8.2.4 | Number of treatment arms in the trial | 2 |
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.8.4.1 | Number of sites anticipated in Member State concerned | 5 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 8 |
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 | No |
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 |
Brazil |
Colombia |
France |
Martinique |
South Africa |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | Yes |
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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 5 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |