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 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10042945 |
E.1.2 | Term | Systemic lupus erythematosus |
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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 subjects with SLE. To evaluate the safety and tolerability of belimumab in subjects with SLE. To evaluate the impact of belimumab on quality of life in subjects with SLE. |
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E.2.2 | Secondary objectives of the trial | |
E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
1. Are at least 18 years of age. 2. Have a clinical diagnosis of SLE according to the American College of Rheumatology (ACR) criteria. 3. Have active SLE disease defined as a SELENA SLEDAI score >= 6 at screening. 4. Have unequivocally positive anti-nuclear antibody (ANA) test results from 2 independent time points as follows: Positive test results from 2 independent time points within the study screening period. Screening results must be based on the study's central laboratory results. A positive ANA test is defined as an ANA titer >= 1:80 and/or a positive anti-dsDNA (>= 30 IU/mL) serum antibody. OR One positive historical test result and 1 positive result during the screening period. 5. Are on a stable SLE treatment regimen consisting of any of the following medications (alone or in combination) for a period of at least 30 days prior to Day 0 (ie, day of 1st dose of study agent): Corticosteroids: For subjects on SLE combination therapy, their stable steroid dose must be fixed within the range of 0 to 40 mg/day For subjects whose only SLE treatment is steroids, their stable steroid dose must be fixed within the range of 7.5 to 40 mg/day For those subjects on alternating day doses of steroids, use the average of 2 daily doses to calculate the average daily steroid dose. Other immunosuppressive or immunomodulatory agents including methotrexate, azathioprine, leflunomide, mycophenolate mofetil, calcineurin inhibitors, sirolimus, oral cyclophosphamide, 6-mercaptopurine or thalidomide. Anti-malarials. Non-steroidal anti-inflammatory drugs (NSAIDs). Pre-existing SLE medications must be stable for at least 30 days prior to Day 0. Corticosteroids may be added as new medication or their doses adjusted only up to 30 days prior to Day 0. New SLE therapy other than corticosteroids must not be added within 60 days of Day 0. 6. Subjects on angiotensin pathway antihypertensives must be on a stable regimen for a period of at least 30 days prior to Day 0. 7. Subjects on HMG CoA reductase inhibitors must be on a stable regimen for a period of at least 30 days prior to Day 0. 8. A female subject is eligible to enter the study if she is: not pregnant or nursing; of non-childbearing potential or of childbearing potential. These women must have a negative serum pregnancy test at screening, and agree to 1 of the following: complete abstinence from intercourse from 2 weeks prior to administration of the 1st dose of study agent until 8 weeks after the last dose of study agent; or consistent and correct use of 1 of the following acceptable methods of birth control for 1 month prior to the start of the study agent and 8 weeks after the last dose of study agent: implants of levonorgestrel; injectable progesterone; any intrauterine device (IUD) with a documented failure rate of less than 1% per year; oral contraceptives (either combined or progesterone only); double barrier method: condom, cervical cap or diaphragm with spermicidal agent; transdermal contraceptive patch; male partner who is sterile prior to the female subject's entry into the study and is the sole sexual partner for the female subject. 9. A male subject is eligible to enter the study if he agrees to use effective contraception throughout the study and for 3 months after the last dose of study agent. 10. Have the ability to understand the requirements of the study, provide written informed consent. |
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E.4 | Principal exclusion criteria |
1. Have received treatment with any B cell targeted therapy. 2. Have received any of the following within 364 days of Day 0: Abatacept. A biologic investigational agent other than B cell targeted therapy 3. Have required 3 or more courses of systemic corticosteroids for concomitant conditions (within 364 days of Day 0. 4. Have received IV cyclophosphamide within 180 days of Day 0. 5. Have received any of the following within 90 days of Day 0: Anti-TNF therapy. Interleukin-1 receptor antagonist. Intravenous immunoglobulin. High dose prednisone. Plasmapheresis. 6. Have received any of the following within 60 days of Day 0: A non-biologic investigational agent. Any new immunosuppressive/immunomodulatory agent, anti-malarial, NSAID, HMG CoA reductase inhibitor or angiotensin pathway antihypertensive. Any steroid injection. 7. Have received any of the following within 30 days of Day 0: A live vaccine. A change in dose of a corticosteroid, other immunosuppressive/immunomodulatory agent, anti-malarial, NSAID, HMG CoA reductase inhibitor or angiotensin pathway antihypertensive 8. Have severe lupus kidney disease , or have active nephritis, or have required hemodialysis or high-dose prednisone within 90 days of Day 0. 9. Have active central nervous system (CNS) lupus requiring therapeutic intervention within 60 days of Day 0. 10. Have a history of a major organ transplant or hematopoietic stem cell/marrow transplant. 11. Have clinical evidence of significant unstable or uncontrolled acute or chronic diseases not due to SLE which, in the opinion of the principal investigator, could confound the results of the study or put the subject at undue risk. 12. Have a planned surgical procedure or a history of any other medical disease, laboratory abnormality, or condition that, in the opinion of the principal investigator, makes the subject unsuitable for the study. 13. Have a history of malignant neoplasm within the last 5 years, except for adequately treated cancers of the skin (basal or squamous cell) or carcinoma in situ of the uterine cervix. 14. Have required management of acute or chronic infections, as follows: Currently on any suppressive therapy for a chronic infection Hospitalization for treatment of infection within 60 days of Day 0. Use of parenteral (IV or IM) antibiotics within 60 days of Day 0. 15. Have current drug or alcohol abuse or dependence, or a history of drug or alcohol abuse or dependence within 364 days prior to Day 0. 16. Have a historically positive test or test positive at screening for HIV-1 antibody, hepatitis B surface antigen, or hepatitis C antibody. 17. Have an IgA deficiency 18. Have a Grade 3 or greater laboratory abnormality based on the protocol toxicity scale except for the following that are allowed: Stable Grade 3 prothrombin time (PT) secondary to warfarin treatment. Stable Grade 3/4 proteinuria. Stable Grade 3 neutropenia or stable Grade 3 white blood cell count. 19. Have a history of an anaphylactic reaction to parenteral administration of contrast agents, human or murine proteins or monoclonal antibodies. |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary efficacy endpoint is response rate at Week 52. A response is defined as: >=4 point reduction from baseline in SELENA SLEDAI score, AND No worsening (increase of < 0.30 points from baseline) in Physician's Global Assessment (PGA), AND No new 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.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 | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | No |
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) | 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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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |