Systemic lupus erythematosus Skin and Connective Tissue Diseases
Conditions
Interventions
Participants will be randomised to receive belimumab or placebo (normal saline, sodium chloride 0.9%) using Sealed Envelope. Intravenous administration of belimumab or placebo will be given from rando
a physical exam and urine test
vital signs and weight change check
blood samples taken for safety monitoring
complete questionnaires about their lupus activity and how they feel during the trial and the collection of optional blood and stool samples.
Sponsors
University College London
Eligibility
Sex/Gender
All
Age
16 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Aged between 16 and 75 years inclusive at screening. 2. Participants who meet the 2019 criteria for SLE according to the European League Against Rheumatism/American College of Rheumatology Classification Criteria for Systemic Lupus Erythematosus. 3. Positive serum IgA2 anti-dsDNA antibodies (=12.5 AU) at time of screening measured in UCL laboratory. IgA2 results defined in UCL Central laboratory. 4. Participants are due to be treated with the first infusion of B-cell depletion therapy (e.g. Rituximab) 4-8 weeks before randomisation (Day 0, see participant timeline) for active SLE. Previous use of rituximab is allowed prior to this cycle. 5. No contraindications to the use of belimumab. 6. Participants willing and able to provide informed consent.
Exclusion criteria
Exclusion criteria: 1. Pregnant or planned pregnancy during the trial and/or breastfeeding. 2. Women of childbearing potential (WOCBP) not willing to use highly effective contraception or abstinence for the duration of the trial and for at least 4 months following the last dose of the study drug. 3. Prior use of biologic/advanced therapy (except rituximab given as part of this trial after screening) less than 3 months before randomisation. 4. Participation in any other interventional trial within the last 6 months before randomisation. 5. eGFR 2 years prior to screening. 13. History of cervical dysplasia CIN Grade III cervical high risk human papillomavirus or abnormal cervical cytology other than abnormal squamous cells of undetermined significance (ASCUS) in the last 3 years prior to randomisation. The participant will be eligible after the condition has resolved (e.g., follow-up HPV test is negative, or cervical abnormality has been effectively treated >1 year ago). 14. Severe, progressive, or uncontrolled renal, hepatic, haematological, gastrointestinal, pulmonary, cardiac, or neurological disease or, in the investigator’s opinion, any other concomitant medical condition or significant abnormal laboratory value that places the participant at risk by participating in this study except for diseases or conditions related to active SLE. 15. Comorbidities not lupus related currently requiring systemic corticosteroid or immunosuppressant therapy. 16. Evidence of serious suicide risk including having any history of suicidal behaviour in the last 6 months and/or suicidal ideation in the last 2 months, or who in the investigator’s judgement, pose a significant suicide risk. 17. History of an anaphylactic reaction to parenteral administration of contrast agents, human or murine proteins or monoclonal antibodies. 18. IgG levels <4.0 g/L or IgA level <1 mg/dL tested no more than 10 days before randomisation. 19. White blood cells (WBC) <1.5 x 10e9/L or Neutrophils <1.0 x 10e9/L measured no more than 10 days before randomi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Modified Major Clinical Response (MCR) at 52 weeks. Modified MCR is defined as a reduction in BILAG–2004 (British Isles Lupus Assessment Group-2004) index A/B scores to BILAG–2004 C/D or remain E in all domains, a reduction in steroid dose to =7.5 mg daily and a modified SLEDAI (Systemic Lupus Erythematosus Disease Activity Index 2000) –2K score =2 (without including the IgG anti-dsDNA antibody component) and no increase in immunosuppressant dose in the last 3 months before 52 weeks. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Modified Major Clinical Response (MCR) at 24 weeks: Reduction in BILAG–2004 (British Isles Lupus Assessment Group-2004) index A/B scores to BILAG–2004 C/D or remain E in all domains, a reduction in steroid dose to =7.5 mg daily and a modified SLEDAI (Systemic Lupus Erythematosus Disease Activity Index 2000) –2K score =2 (without including the IgG anti-dsDNA antibody component). 2. Major Clinical Response (MCR) at 24 and 52 weeks: Reduction in BILAG–2004 (British Isles Lupus Assessment Group-2004) index A/B scores to BILAG–2004 C/D or remain E in all domains, a reduction in steroid dose to =7.5mg daily and a modified SLEDAI (Systemic Lupus Erythematosus Disease Activity Index 2000) –2K score =4. For the 52- week outcome: no increase in immunosuppressant in the last 3 months. 3. Time to first incidence of: 3.1. Severe BILAG-2004 A flare (severe flare: a BILAG-2004 A score due to items which are “new” or “worse”; or, in the renal or haematological systems, an A score due to items which didn’t result in an A score last month). 3.2. Severe or moderate BILAG-2004 flares (moderate flare: 2 BILAG-2004 B scores due to items which are either “new” or “worse”; or, in the renal or haematological systems, B scores due to items which didn’t result in a B score last month) accompanied by an increase in concomitant lupus medication: glucocorticoids, or immunosuppressant through to 24 and 52 weeks. 3.3. Severe or moderate BILAG-2004 flare (moderate flare: 2 BILAG-2004 B scores due to items which are either “new” or “worse”; or, in the renal or haematological systems, B scores due to items which didn’t result in a B score last month). 3.4. BILAG-2004 low disease activity with prednisolone i) =5 mg/day (BILAG-2004 LDA-5); ii) =7.5 mg/day (BILAG-2004 LDA-7.5), and stable dose of immunosuppressive drugs. 4. Time to achieve: 4.1. BILAG-2004 low disease activity with prednisolone i) =5 mg/day; ii) =7.5 mg/day and stable dose of immunosuppressive drugs 4.2. Lupus Low Disease Activity | — |
Countries
England, United Kingdom, Wales
Contacts
Public ContactSTRATIFY lupus Trial Team
Outcome results
None listed