2024-516242-19-00招募中3 期
OBILUP. Induction therapy for lupus nephritis with no added oral corticosteroids : An open label randomised multicentre controlled trial comparing oral corticosteroids plus mycophenolate mofetil (MMF) versus Obinutuzumab and MMF.
适应症
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 196
- 试验地点
- 29
- 主要终点
- Complete renal response (CR) at week 52 is defined as: - Urine PCR (protein to creatinine ratio) < 0.5 g/g - AND: eGFR (estimated glomerular filtration rate using CKD-epi) ≥ 60 ml/min, or if < 60 ml/min at screening, no decline >20% compared to screening/randomisation (whichever worse) - AND: o In the obinutuzumab arm: with no corticosteroids or without receiving oral corticosteroids > 10 mg/day within the first 6 month, and then, without receiving oral corticosteroids > 7.5 mg/day between 6 an
研究概览
简要总结
To demonstrate that a regimen free of additional oral corticosteroids but with obinutuzumab and MMF is non-inferior to a regimen based on oral corticosteroids and MMF in achieving the primary outcome of complete renal response (CR) at week 52 without receiving corticosteroids above a prespecified dose
研究设计
- 分配方式
- Randomized
- 主要目的
- Obilup
- 盲法
- None
入排标准
- 年龄范围
- 0 years 至 65+ years（0-17 Years, 65+ Years, 18-64 Years）
- 接受健康志愿者
- 否
入选标准
- •Children aged 14-17 years old and adults (until 75 years old)
- •Active lupus nephritis, as defined by kidney biopsy within the preceding 8 weeks, assessed by the International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification: class III or IV (A or A/C) ± V with active lesions in at least 10% of the viable glomeruli
- •Urine protein-to-creatinine ratio (uPCR) ≥ 0.5 g/g at any time in the 21 days before inclusion
- •Ability to provide informed and signed consent
- •For child-bearing aged women, willingness to use appropriate and efficient contraception, as recommended when using MMF and obinutuzumab (18 months after inclusion)
- •Affiliation to a French social security system (beneficiary or legal)
排除标准
- •Severe "critical" SLE flare defined as any SLE manifestation requiring more immunosuppression than allowed within the protocol, in the physician's opinion
- •Receipt of a live-attenuated vaccine in the 4 weeks before study enrolment
- •Patient who has presented a malignant pathology in the previous 2 years (with the exception of cervical cancer in situ and of malignancy that are considered definitely cured, for instance some skin cancers), subject to confirmation by the oncologist.
- •In female patients, known 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) within the past 3 years. However, the patient will be eligible after the condition has resolved (e.g., follow-up HPV test is negative or cervical abnormality was effectively treated >1 year ago).
- •Patients with hepatic or pulmonary insufficiency
- •Progressive cardiac pathology
- •Patients with uncontrolled arterial hypertension or hypotension
- •Participation in another interventional study or being in the exclusion period at the end of a previous study.
- •Pregnancy and breast feeding
- •Patient under tutorship or guardianship, and unable to give informed consent
- •Patients who cannot be prescribed 10 mg prednisone/prednisolone corticosteroids "only", after inclusion according to their physician
- •Prior use within 6 months preceding inclusion of therapeutic monoclonal antibody for systemic lupus erythematosus and/or B- or T cell modulating 'biologic' except belimumab and and anifrolumab that can be used up to 7 days before inclusion
- •Contraindications to the use of IV methylprednisolone, MMF, oral corticosteroids or obinutuzumab, or its premedication drugs listed in the corresponding SmPCs
- •Hypersensitivity to the active substances or to any of the excipients
- •Obsolescence of >60% of the glomeruli or tubulointerstitial scarring of >60%
- •CKD stage 4 or stage 5 defined as eGFR <30 ml/min/1.73 m2 according to CKD-EPI (to be differentiated from acute renal injury)
- •Patients with gastro-intestinal ulcer with active bleeding
- •Active infections, including but not limited to human immunodeficiency virus (HIV), hepatitis B in the absence of a specific therapy, hepatitis C or tuberculosis
结局指标
主要结局
Complete renal response (CR) at week 52 is defined as: - Urine PCR (protein to creatinine ratio) < 0.5 g/g - AND: eGFR (estimated glomerular filtration rate using CKD-epi) ≥ 60 ml/min, or if < 60 ml/min at screening, no decline >20% compared to screening/randomisation (whichever worse) - AND: o In the obinutuzumab arm: with no corticosteroids or without receiving oral corticosteroids > 10 mg/day within the first 6 month, and then, without receiving oral corticosteroids > 7.5 mg/day between 6 an
Complete renal response (CR) at week 52 is defined as: - Urine PCR (protein to creatinine ratio) < 0.5 g/g - AND: eGFR (estimated glomerular filtration rate using CKD-epi) ≥ 60 ml/min, or if < 60 ml/min at screening, no decline >20% compared to screening/randomisation (whichever worse) - AND: o In the obinutuzumab arm: with no corticosteroids or without receiving oral corticosteroids > 10 mg/day within the first 6 month, and then, without receiving oral corticosteroids > 7.5 mg/day between 6 an
次要结局
- Efficacy - Partial renal response (PR) will be defined as: o 50% improvement in spot uPCR o AND uPCR between 0.5 and 3 g/g o AND eGFR (estimated glomerular filtration rate using CKD-epi) ≥ 60 ml/min, or if < 60 ml/min at screening, no decline >20% compared to screening/randomisation (whichever worse) - Complete renal response (independently of the treatment): see primary outcome - Proteinuria measurement: see primary outcome [1] - Extrarenal flare will be defined according to the SELENA-SLEDAI
- Safety - Toxicity of corticosteroids will be measured with the Glucocorticoid Toxicity Index (GTI) (see Appendix D) - The number of serious adverse events will be measured per patient according to the CTCAE (version 5.0) toxicity grading system for the following adverse events combined: death (all causes), grade 3 or higher infections, hospitalization resulting either from the disease or from a complication due to the study treatment. - The number of serious infectious episodes will be measured
- Non-adherence to treatment will be assessed with hydroxychloroquine blood levels and with questionnaires.
- Efficiency: incremental cost effectiveness ratio in cost per QALY.
研究者
Nathalie COSTEDOAT-CHALUMEAU
Scientific
Assistance Publique Hopitaux De Paris
研究点 (29)
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