Efficacy of belimumab to improve subclinical cardiovascular abnormalities using imaging endpoints with cardiac magnetic resonance in patients with systemic lupus erythematosus
Conditions
Interventions
Trade Name: Benlysta®
Pharmaceutical Form: Solution for injection in pre-filled pen
Sponsors
Fraunhofer Institut für Translationale Medizin und Pharmakologie (ITMP)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Established diagnosis of SLE as per American College of Rheumatology revised classification criteria 2. Stable disease (SLEDAI =65 years) yes F.1.3.1 Number of subjects for this age range 5
Exclusion criteria
Exclusion criteria: Main exclusion criteria 1. Previous use of belimumab 2. Contraindications for treatment with belimumab (e.g., hypersensitivity to IMP) 3. Use of Rituximab and other B-cell-targeting therapies (e.g., anti-CD20 antibodies) within 12 months before BL 4. Use of Cyclophosphamide within 90 days before BL 5. Concomitant cortisone with dosages >10 mg/day 6. Vaccination with live vaccine within 30 days prior to BL 7. History of malignant neoplasm within the last 5 years except basal cell or squamous cell carcinoma of the skin treated with local resection only or carcinoma in situ of the uterine cervix treated locally and with no evidence of metastatic disease for 3 years 8. Any other clinically significant abnormal laboratory value in the opinion of the investigator 9. Any intercurrent significant medical or psychiatric illness that the investigator considers would make the candidate unsuitable for the study (e.g. severe depression) 10. Clinically manifest cardiovascular symptoms, e.g.: o Severe congestive heart failure (NYHA III-IV), EF < 35%, AV block, Mobitz type II o Established severe ischaemic heart disease, peripheral arterial disease and/or cerebrovascular disease o History of bypass surgery or triple vessel disease, presence of flow limiting obstructive coronary artery disease, congenital or clinically relevant vavular heart disease 11. Significant IgG deficiency (IgG level < 400 mg/dL) 12. IgA deficiency (IgA level < 10 mg/dL) 13. Renal disease with a current estimated GFR < 30 mL/min/1.73 m² 14. Patients with a history of a major organ transplant (i.e., heart, lung, kidney, liver) or hematopoetic stem cell/marrow transplant within the last 5 years 15. Patients with lupus nephritis 16.Evidence of significant uncontrolled concomitant diseases or serious and/or uncontrolled diseases that are likely to interfere with the evaluation of the patient’s safety and of the study outcome 17. History of primary immunodeficiency 18. Current suppressive therapy for a chronic infection (such as tuberculosis, pneumocystis, cytomegalovirus, herpes simplex virus, herpes zoster and atypical mycobacteria), hospitalization for treatment of infection within 60 days before SCR, or use of parenteral (IV or IM) antiobiotics (anti-bacterial, antiviral, anti-fungal, or anti-parasitic agents) within 60 days before SCR 19. History of an anaphylactic reaction to parenteral administration of contrast agents, human or murine proteins or monoclonal antibodies 20. History of or active status of Hepatitis (positive testing for HBsAG/HBcAb/Hepatitis C) and/or positive HIV test 21. Evidence of serious suicide risk including any history of suicidal behaviour in the last 6 months and/or any suicidal ideation in the last 2 months or who in the investigator's judgment poses a significant suicide risk 22. Contraindications to contrast material-enhanced CV magnetic resonance (MR) imaging 23. Current alcohol, drug or chemical abuse or dependence or within 1 year before SCR 24. Males or females of reproductive potential as well as menopausal women not willing to use effective contraception for the duration of the study period (defined as PEARL index <1 - e.g. contraceptive pill, IUD, or true sexual abstinence within the last 4 weeks and the study period, bilateral tubal occlusion or male partner with vasectomy; also see chapter 7.4.4 for guidance) 25. Current participation in another interventional clinical trial or participation within the last 3 months for non-biologi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •To determine myocardial changes due to diffuse inflammatory involvement measured by T1 and T2 mapping and first pass perfusion imaging under maximal vasodilation in SLE patients with new initiation of belimumab or continued standard-of care therapy at W24 compared to BL;Secondary Objective: Assess. of cardiovasc. risk factors and funct. (deform. and cardiac function (longitudinal strain, left ventricular (LV) volume and mass, ejection fraction, LGE, ECG, aortic stiffness (pulse wave velocity), myocardial triglyeride an creatine content (subgroup of patients) Assess.of cardiovas. risk factors and cardiac biomarkers measured in blood (lipids, triglycerides, VLDL, cholesterine, HDL, LDL, glucose, HbA1c, (apo)lipoproteine levels, hs-troponin T, NT-BNP, hsCRP) Assess. of antiphospholipid profile (lupus anticoagulant, anticardiolipin and anti-beta 2 GPI) Measurement of vital signs Assess. of cardiac echocardiography Determin. of SLE disease activity and damage (SLEDAI 2k, S2k Responder Index-50, SLICC damage index, CRP/ESR, PGA) Incidence of cardiovas. abnormalities PGIC LupusQoL Facit-Fatigue subscale CSSRS Compliance of belimumab/SLE Assess. of treatment changes Safety Parameters Rise in cardiac biomarkers/frequency of worsening of disease Subgroup analysis;Primary end point(s): •Treatment group difference in change in diffuse myocardial inflammation and myocardial blood flow using T1 and T2 mapping and first pass perfusion imaging at W24 compared to baseline;Timepoint(s) of evaluation of this end point: •Primary endpoint will be analysed after 24 weeks (Visit 4) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints will be analysed at all available visits for both treatment groups. For all continuous endpoints, “changes” refer to the difference between the visit measurement and baseline (absolute and in %): •T1 and T2 values and change thereof compared to BL •Longitudinal strain and change thereof compared to BL •Left ventricular (LV) volume and mass and change thereof compared to BL •Ejection fraction and change thereof compared to BL •Late gadolinium enhancement (LGE) and change thereof compared to BL •Pulse wave velocity and change thereof compared to BL •Changes in values in cardiac echocardiography and ECG •Presence and extent of coronary artery calcification and soft plaques •SLEDAI-2k score and change to BL •Sledai-2k responder index-50 (S2k RI-50) and change to BL •Proportion of patients with partial and complete recovery according to Sledai-2k and S2k RI-50 •SLICC score and change to BL •Proportion of patients that fulfil SLICC criteria (The SLICC criteria for SLE classification requires: 1) Fulfillment of at least four criteria, with at least one clinical criterion AND one immunologic criterion OR 2) Lupus nephritis as the sole clinical criterion in the presence of ANA or anti-dsDNA antibodies) •Physicians global assessment (PGA) and change to BL •Changes in cardiovascular risk factors and cardiac biomarkers in blood (lipids, triglycerides, VLDL, cholesterine, HDL, LDL, glucose, HbA1c, (apo)lipoproteine levels, hs-troponin T, NT-BNP) and CRP (+hsCRP) and ESR compared to BL •Blood pressure, heart rate and change thereof compared to BL •Patient global impression of change (PGIC/SGIC) score •Lupus Quality of Life score and change to BL •Facit-Fatigue subscale score and change to BL •CSSRS score and change to BL •Oral corticosteroid dose •Benlysta®/ SOC intake (empty syringes/pens) and patient diary information for drug accountability / compliance •Proportion of patients with a treatment change and proportion of patients who sw | — |
Countries
Germany
Contacts
Public ContactClinical Research
Fraunhofer Institut für Translationale Medizin und Pharmakologie (ITMP)
Outcome results
None listed