Clinical trial comparing the efficacy and safety of certolizumab pegol and belimumab in patients with moderate or severe activity of systemic lupus erythematosus (CERT-SLE)

Prior treatment

• Previous stroke, heart attack within 6 months prior to screening
• Active or significant history of infection, including treatment with intravenous antibiotics in the last 4 weeks or oral antibiotics in the 2 weeks prior to screening
• A positive SARS-CoV-2 test result during visit “0” is an exclusion criterion, while an infection more than 4 weeks before screening and confirmed by a negative SARS-CoV-2 test is not an exclusion criterion
• Patients who have ever received any of the study drugs in the past
• Active or past malignancy within 5 years prior to screening, except resected/cured localized basal cell or squamous cell carcinoma of the skin or cervical cancer in situ
• Active or past drug or alcohol abuse
• Patients who received any of the following medications and/or procedures during the indicated time period: ● Plasmapheresis or intravenous immunoglobulin within the last 12 weeks prior to screening ● Lymphatic depleting therapy. B (e.g., anti-CD20 or anti-CD19) within 24 weeks prior to screening ● blisibimod, tabalumab (or other anti-B cell activating factor [BAFF] agents), atacicept, epratuzumab (or other anti-CD22 agents) within 5 half-lives or 12 weeks (whichever is longer) prior to screening ● cyclophosphamide or other alkylating agents within 12 weeks prior to screening ● oral cyclosporine, anakinra, tacrolimus, sirolimus, or other calcineurin inhibitors, topical calcineurin inhibitors within 4 weeks prior to screening ● thalidomide or thalidomide derivatives within 24 weeks prior to screening ● tumor necrosis factor (TNF) antagonists, tocilizumab or other biologics not listed previously used in the past. ● Any other immunosuppressive drug used for SLE not listed in the inclusion criteria within 12 weeks or 5 half-lives prior to screening, whichever is longer
• Major surgery within 8 weeks prior to screening
• Immunization with a live or attenuated vaccine within 4 weeks prior to planned treatment

Other illness

• History of severe bronchial asthma or other clinically significant pulmonary abnormalities
• NYHA III/IV cardiovascular disease
• Patients with chronic liver disease (Child Pugh A, B, C liver dysfunction)
• Active confirmed tuberculosis or latent without chemoprophylaxis performed in accordance with applicable local recommendations
• Active HBV, HCV infection (acceptable history of HCV after treatment and virus elimination confirmed by PCR test)
• Human immunodeficiency virus (HIV) infection
• History of severe depression
• Rheumatic disease other than systemic lupus erythematosus (rheumatoid arthritis, mixed connective tissue disease, systemic sclerosis) acceptable diagnosis of secondary Sjögren's syndrome
• Known hypersensitivity to human, humanized or mouse monoclonal antibodies

Lab values

• Aspartate aminotransferase (AST), alanine aminotransferase (ALT) >2 x ULN, if normalization occurs the patient may be considered for a repeat screening visit
• Bilirubin >1.5 x GGN
• Hypogammaglobulinemia (IgG <400 mg/dl) or IgA (IgA <10 mg/dl) deficiency
• Patients with active lupus nephritis: ● Proteinuria > 2 g/24 h or equivalent based on albumin/creatinine ratio (ACR) ● Active proliferative lupus nephritis (class III or IV TZN) based on renal biopsy performed within 6 months prior to screening (or during the study). ● Hemodialysis or high-dose corticosteroids (>100 mg/d prednisone or equivalent) for lupus erythematosus renal disease within 90 days of screening ● Serum creatinine > 2.0 mg/dL or estimated glomerular filtration rate ≤ 30 mL/min or chronic renal replacement therapy

Other

• Pregnancy or breastfeeding
• Diagnosed primary or secondary immunodeficiency
• The inability to understand and comply with the protocol requirements (lack of compliance) also excludes from participation in the study.
• Severe active central nervous system lupus erythematosus within 52 weeks of screening

• Signed informed consent form
• Patients of childbearing potential should agree to abstinence or use a highly effective method of contraception during the entire study period and for at least 5 months after the last dose of certolizumab pegol or at least 4 months after the last dose of belimumab
• Age 18-65 years
• Ability to follow the study protocol
• Documented diagnosis of SLE according to the American College of Rheumatology (ACR) or Systemic Lupus International Collaborating Clinics (SLICC) classification criteria at any time before or during screening
• Positive antinuclear antibody (ANA) immunofluorescence test result with a titer of at least 1:80 AND Presence of at least one of the following serological markers of SLE at screening: ● Antibodies against double-stranded DNA (anti-dsDNA); OR ● Anti-Smith antibodies (anti-Sm)
• At least moderate SLE activity, defined as meeting all of the following criteria: ● SELENA-SLEDAI score ≥4 indicating active disease ● Physician Global Assessment (PGA) ≥1.0 (on a scale of 0-3)
• Acceptable medications and doses: ● Azathioprine: 1 to 2.5 mg/kg/day ● Methotrexate: 7.5 to 25 mg/week ● Mycophenolate mofetil: 500 to 3000 mg/day ● Hydroxychloroquine: 200 to 400 mg/day ● Chloroquine: 250 to 500 mg/day ● Leflunomide - 10-20 mg/day Patients treated with conventional medications should be on stable doses for ≥ 8 weeks prior to screening visit
• Patients may receive standard treatment but no new therapy has been initiated or therapy has been withdrawn in the 8 weeks prior to the screening visit
• If oral glucocorticosteroids (GCS) are used, the dose must be ≤20 mg/day prednisone (or equivalent) and must be stable for at least 2 weeks prior to study