Lupus - SLE MedDRA version: 21.1 Level: PT Classification code 10042945 Term: Systemic lupus erythematosus System Organ Class: 10028395 - Musculoskeletal and connective tissue disorders
Conditions
Sponsors
GlaxoSmithKline Research & Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Participants are eligible to be included in Parts A and B of the study only if all of the following criteria apply: Age 1. Participant must be between 5 and 17 years of age inclusive, at the time of Day 1. Type of Participant and Disease Characteristics 2. Participants who meet the 1997 American College of Rheumatology (ACR) criteria for the classification of SLE (Appendix 8) of the protocol a. Have or have had in series 4 or more of the 11 ACR criteria for the classification of SLE 3. Have active SLE disease defined as a SELENA SLEDAI score =6 at screening (Appendix 9) of the protocol. 4. Have documented positive autoantibody test results within the study screening period, defined as an ANA titre = 1:80 and/or a positive anti-dsDNA (=30 IU/mL) serum antibody test based on EITHER the study’s central laboratory results OR the local laboratory results. Only unequivocally positive values as defined in the laboratory’s reference range are acceptable; borderline values will not be accepted. 5. Are on a stable SLE treatment regimen. “Stable treatment at baseline” consists of any of the following medications (alone or in combination) administered for a period of at least 30 days prior to Day 1: - Corticosteroids (prednisone or prednisone equivalent up to 0.5 mg/kg/day): - For those participants 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 (including mycophenolate mofetil, mycophenolate mofetil hydrochloride, and mycophenolate sodium), calcineurin inhibitors (e.g. tacrolimus, cyclosporine), sirolimus, oral cyclophosphamide, 6- mercaptopurine or thalidomide. - Anti-malarials (e.g. hydroxychloroquine, chloroquine, quinacrine) - Non-steroidal anti-inflammatory drugs (NSAIDs) - New SLE therapy must not be added within 30 days of Day 1. Weight 6. Body weight =15 kg. Sex 7. Male and/or female Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Male Participants No contraceptive measures are required for male participants. Female participants: A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: - Is not a woman of childbearing potential (WOCBP) (See Appendix 4) of the protocol OR - Is a WOCBP and is using a contraceptive method that is highly effective, with a failure rate of <1%, as described in Appendix 4 during the belimumab treatment period and for at least 16 weeks, corresponding to the time needed to eliminate any study intervention(s) (e.g., 5 terminal half-lives), after the last dose of study intervention. The investigator should evaluate the effectiveness of the contraceptive method in relationship to the first dose of study intervention. - A WOCBP must have a negative highly sensitive [Appendix 2] of the protocol pregnancy test (serum or as required by local regulations) within 35 days before the first dose of belimumab. - The investigator is responsible for review of medical history, menstrual history, and recent sexual activity to decrease the risk for inclusion of a woman with an early undetected pregnancy. Informed Consent 8. Participant signs and dates a written age appropriate assent form (in accordance with
Exclusion criteria
Exclusion criteria: Participants are excluded from Parts A and B of the study if any of the following criteria apply: Medical Conditions 1. Have an estimated glomerular filtration rate (eGFR) as calculated by Schwartz Formula [Schwartz, 2009] of less than 30 mL/min. 2. Have acute severe nephritis defined as significant renal disease (e.g., the presence of urinary sediments and other lab abnormalities) that, in the opinion of the study investigator, may lead to the participant requiring induction therapy during the first 12 weeks of the trial. Note: Clinically stable lupus nephritis which can be managed with medications allowed in the study will not exclude participants from participating in the trial (nor will any maximum level of proteinuria exclude participants). Clinical assessment and medical management of nephritis will be at the discretion of the study investigator. 3. Have a history of a major organ transplant (e.g., heart, lung, kidney, liver) or hematopoetic stem cell/marrow transplant. 4. Have clinical evidence of significant, unstable or uncontrolled, acute or chronic diseases not due to SLE (i.e., cardiovascular, pulmonary, hematologic, gastrointestinal, hepatic, renal, neurological, malignancy or infectious diseases) which, in the opinion of the investigator, could confound the results of the study or put the participant at undue risk. 5. Have a planned surgical procedure or a history of any other medical disease (e.g., cardiopulmonary), laboratory abnormality, or condition (e.g., poor venous access) that, in the opinion of the investigator, makes the participant unsuitable for the study. 6. Have a history of malignant neoplasm within the last 5 years. 7. Have evidence of serious suicide risk including any history of suicidal behavior in the last 6 months, or who in the investigator’s opinion, pose a significant suicide risk. 8. Have a history of a primary immunodeficiency. 9. Have an IgA deficiency (IgA level <10 mg/dL). 10. Have acute or chronic infections requiring management, as follows: -Currently on any suppressive therapy for a chronic infection (such as tuberculosis, pneumocystis, cytomegalovirus, herpes simplex virus, herpes zoster and atypical mycobacteria). -Use of parenteral (IV or IM) antibiotics (antibacterials, antivirals, anti-fungals, or anti-parasitic agents) for infection within 60 days of Day 1. 11. Have a Grade 3 or greater laboratory abnormality based on the protocol defined Adverse Event and Laboratory Value Severity Grade scale (Appendix 2, Section 10.2.1) of the protocol except for the following that are allowed: - Stable Grade 3 prothrombin time (PT) secondary to warfarin treatment. -Stable Grade 3 partial thromboplastin time (PTT) due to lupus anticoagulant and not related to liver disease or anti-coagulant therapy. - Stable Grade 3 hypoalbuminemia due to lupus nephritis, and not related to liver disease or malnutrition. - Any grade proteinuria. - Stable Grade 3 gamma glutamyl transferase (GGT) elevation due to lupus hepatitis, and not related to alcoholic liver disease, uncontrolled diabetes or viral hepatitis. If present, any abnormalities in the ALT and or AST must be = Grade 2. - Stable Grade 3 neutropenia; or stable Grade 3 lymphopenia; or stable Grade 3 leukopenia, due to SLE. 12. Have a history of an anaphylactic reaction to parenteral administration of contrast agents, human or murine proteins or monoclonal antibodies or to any of the excipients of the study drug. Prior/Concomitant
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To characterize the PK profile of belimumab 200 mg SC in pediatric SLE participants.;Secondary Objective: - To evaluate the safety and tolerability of belimumab 200 mg SC in pediatric SLE participants. -To characterize the pharmacodynamic profile of belimumab 200 mg SC in pediatric SLE participants.;Primary end point(s): - Observed belimumab concentrations at Week 12. - Steady-state PK parameters: Cavg (AUC), Cmax, Cmin (based on population PK estimates).;Timepoint(s) of evaluation of this end point: Week 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): -Incidence of adverse events, serious adverse events and adverse events of special interest through Week 52. -Change from baseline in biomarkers (C3/C4, anti-dsDNA, B cell subsets, and immunoglobulins) at Weeks 12 and 52.;Timepoint(s) of evaluation of this end point: - Biomarkers: Weeks 12 and 52 -AEs: through week 52 | — |
Countries
Argentina, Germany, Japan, Mexico, Netherlands, Spain, United States
Contacts
Public ContactGSK Clinical Support Help Desk
GlaxoSmithKline Research & Development Ltd
Outcome results
None listed