Systemic Lupus Erythematosus (SLE) MedDRA version: 8.1 Level: LLT Classification code 10042945 Term: Systemic lupus erythematosus
Conditions
Interventions
Product Name: belimumab
Product Code: HGS1006
Pharmaceutical Form: Powder for solution for injection
INN or Proposed INN: belimumab
CAS
Sponsors
Human Genome Sciences, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
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 of greater than or equal to 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 of greater than or equal to 1:80 and/or a positive anti-dsDNA (greater than or equal to 30 IU/mL) serum antibody. OR • One positive historical test result and 1 positive test result during the screening period. Historical documentation of a positive test of ANA (eg, ANA by HEp-2 titer or ELISA) or anti-dsDNA (eg, anti-dsDNA by Farr assay or ELISA) must include the date and type of the test, the name of the testing laboratory, numerical reference range, and a key that explains values provided as positive vs negative OR negative, equivocal/borderline positive). 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 (prednisone or prednisone equivalent, up to 40 mg/day): - For subjects on SLE combination therapy, their stable steroid dose must be fixed within the range of 0 to 40 mg/day (prednisone or prednisone equivalent). 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 (prednisone or prednisone equivalent). 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 (inculing mycophenolate, mofetil, mycophenolate mofetil hydrochloride, and mycophenolate sodium), calcineurin inhibitors (eg, tacrolimus, cyclosporine), sirolimus, oral cyclophosphamide, 6-mercaptopurine or thalidomide. • Anti-malarials (eg, hydroxychloroquine, chloroquine, quinacrine). • Non-steroidal anti-inflammatory drugs. •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 (eg, ACE inhibitors, angiotensin receptor blockers [ARBs]) 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 (“statins”, such as simvastatin, rosuvastatin, atorvastatin, lovastatin, pravastatin, fluvastatin) 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 poten
Exclusion criteria
Exclusion criteria: 1. Have received treatment with any B cell targeted therapy (eg rituximab, other anti-CD20 agents, anti-CD22 [epratuzumab], anti-CD52 [alemtuzumab], BLyS-receptor fusion protein [BR3], TACI-Fc or belimumab) at any time 2. Have received any of the following within 364 days of Day 0: Abatacept; A biologic investigational agent other than B cell targeted therapy (eg abetimus sodium, anti-CD40L antibody [BG9588/ IDEC-131])(Investigational agent applies to any drug not approved for sale in the country in which it is being used) 3. Have required 3 or more courses of systemic corticosteroids for concomitant conditions (eg asthma, atopic dermatitis) within 364 days of Day 0 (Topical/inhaled steroids permitted) 4. Have received intravenous (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 (anakinra); Intravenous immunoglobulin (IVIG); High dose prednisone (>100 mg/day); 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 (eg statin) or angiotensin pathway antihypertensive (eg ACE inhibitor, angiotensin receptor blocker). (Inc Criteria 5, 6 & 7) Note: New inhaled steroids and new topical immunosuppressive agents (eg eye drops, topical creams) are allowed.Any NSAID use for 6g/24 hour or equivalent using spot urine protein to creatinine ratio, or serum creatinine >2.5mg/dL), have active nephritis, or have required hemodialysis or high-dose prednisone (>100 mg/day) within 90 days of Day 0 9. Have active central nervous system (CNS) lupus (including seizures, psychosis, organic brain syndrome, cerebrovascular accident [CVA], cerebritis or CNS vasculitis) 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 (ie cardiovascular, pulmonary, hematologic, gastrointestinal, hepatic, renal, neurological, malignancy or infectious diseases) which in the opinion of the PI could confound the results of the study or put the subject at risk 12. Have a planned surgical procedure or a history of any other medical disease (eg cardiopulmonary), lab abnormality or condition that in the opinion of the PI 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 carcin
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): The primary efficacy endpoint is response rate at Week 52. • A response is defined as: • Greater than or equal to a 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). ; Main Objective: 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. ;Secondary Objective: | — |
Countries
Austria, Belgium, Czech Republic, France, Germany, Italy, Netherlands, Slovakia, Spain, Sweden, United Kingdom
Outcome results
None listed