A Randomized, Controlled Double-blind Study Comparing the Efficacy and Safety of Voclosporin (23.7 mg BID, or 39.5 mg BID) With Placebo in Achieving Remission in Patients With Active Lupus Nephritis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 265
- 试验地点
- 5
- 主要终点
- Number of Subjects Achieving Complete Renal Remission at 24 Weeks
研究概览
简要总结
To assess the efficacy of 2 doses of voclosporin compared to placebo in achieving complete remission after 24 weeks of therapy in subjects with active lupus nephritis.
详细描述
Voclosporin is a next generation CNI intended for use in the prevention of organ graft rejection and for the treatment of autoimmune diseases. The aim of the current study is to investigate whether voclosporin added to the standard of care treatment in active LN is able to reduce disease activity, as measured by a reduction in proteinuria. Two doses of voclosporin will be studied and compared in a placebo controlled trial on a background of MMF and corticosteroids. Patients with active, flaring LN will be eligible to enter the study. They are required to have a diagnosis of LN according to established diagnostic criteria (American College of Rheumatology) and clinical and biopsy features suggestive of active nephritis. Efficacy will be assessed by the ability of the drug combination to reduce the level of proteinuria while demonstrating an acceptable safety profile.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female subjects aged 18 to 75 years.
- •Diagnosis of systemic lupus erythematosus (SLE) according to the American College of Rheumatology criteria.
- •Kidney biopsy within 6 months prior to Screening (Visit 1) with a histologic diagnosis of lupus nephritis (International Society of Nephrology/Renal Pathology Society 2003 classification of lupus nephritis) Classes III, IV-S or IV-G, (A) or (A/C); or Class V, alone or in combination with Class III or IV.
- •Laboratory evidence of active nephritis at screening, defined as:
- •Class III, IV-S or IV-G: Confirmed proteinuria ≥1,500 mg/24 hours when assessed by 24 hour urine collection, defined by a UPCR of ≥1.5 mg/mg assessed in a first morning void urine specimen (2 samples).
- •Class V (alone or in combination with Class III or IV): Confirmed proteinuria ≥2,000 mg/24 hours when assessed by 24 hour urine collection, defined by a UPCR of ≥2 mg/mg assessed in a first morning void urine specimen (2 samples).
排除标准
- •Estimated glomerular filtration rate (eGFR) as calculated by the Chronic Kidney Disease Epidemiology Collaboration equation of ≤45 mL/min/1.73 m
- •Currently requiring renal dialysis (hemodialysis or peritoneal dialysis) or expected to require dialysis during the study period.
- •A previous kidney transplant or planned transplant within study treatment period.
- •In the opinion of the Investigator, subject does not require long-term immunosuppressive treatment (in addition to corticosteroids).
- •Current or medical history of:
- •Pancreatitis or gastrointestinal hemorrhage within 6 months prior to screening.
- •Active unhealed peptic ulcer within 3 months prior to screening. If an ulcer has healed and the subject is on adequate therapy, the subject may be randomized.
- •Congenital or acquired immunodeficiency.
- •Clinically significant drug or alcohol abuse 2 years prior to screening.
- •Malignancy within 5 years of screening, with the exception of basal and squamous cell carcinomas treated by complete excision. Subjects with cervical dysplasia that is cervical intraepithelial neoplasia 1, but have been treated with conization or loop electrosurgical excision procedure, and have had a normal repeat PAP are allowed.
- •Lymphoproliferative disease or previous total lymphoid irradiation.
- •Severe viral infection (such as CMV, HBV, HCV) within 3 months of screening; or known human immunodeficiency virus infection.
- •Active tuberculosis (TB), or known history of TB/evidence of old TB if not taking prophylaxis with isoniazid.
- •Other known clinically significant active medical conditions, such as:
- •Severe cardiovascular disease including congestive heart failure, history of cardiac dysrhythmia or congenital long QT syndrome.
- •Liver dysfunction (aspartate aminotransferase, alanine aminotransferase, or bilirubin greater than 2.5 times the upper limit of normal) at screening and confirmed before randomization.
- •Chronic obstructive pulmonary disease or asthma requiring oral steroids.
- •Bone marrow insufficiency unrelated to active SLE (according to Investigator judgment) with white blood cell count <2,500/mm3; absolute neutrophil count <1.3 x 103/μL; thrombocytopenia (platelet count <50,000/mm3).
- •Active bleeding disorders.
- •Current infection requiring IV antibiotics.
- •Any overlapping autoimmune condition for which the condition or the treatment of the condition may affect the study assessments or outcomes. Overlapping conditions for which the condition or treatment is not expected to affect assessments or outcomes are not excluded.
- •Subjects who are pregnant, breast feeding or, if of childbearing potential, not using adequate contraceptive precautions.
研究组 & 干预措施
Placebo
Low dose: Voclosporin placebo, oral, 3 capsules BID
High dose: Voclosporin placebo, oral, 3 capsules BID until Week 2 then voclosporin placebo, oral, 5 capsules BID
干预措施: Placebo (Drug)
Voclosporin Low Dose
Voclosporin, oral, 23.7 mg BID
干预措施: Voclosporin Low Dose (Drug)
Voclosporin High Dose
Voclosporin, oral 23.7 mg BID until Week 2, then voclosporin, oral, 39.5 mg BID
干预措施: Voclosporin High Dose (Drug)
结局指标
主要结局
Number of Subjects Achieving Complete Renal Remission at 24 Weeks
时间窗: week 24
Complete remission is defined as: * Confirmed protein/creatinine ratio of ≤0.5 mg/mg and * eGFR ≥60 mL/min/1.73m2 or no confirmed decrease from baseline in eGFR of ≥20%. Subjects who received rescue medication for lupus nephritis or \>10 mg prednisone for \>3 consecutive days or \>7 days total from 56 days prior to remission assessment until the time of the remission assessment were considered not achieving complete remission.
次要结局
- Number of Subjects Achieving Complete Renal Remission at 48 Weeks(Week 48)
- Number of Subjects Achieving Complete Renal Remission at 24 and 48 Weeks in the Presence of Low Dose Steroids(Weeks 24 and 48)
- Time to Complete Remission (Number of Weeks)(week 48)
- Time to Sustained Early Complete Remission (Number of Weeks)(week 48)
- Number of Subjects Achieving Sustained Early Complete Remission(week 48)
- Time to Partial Remission (Number of Weeks)(week 48)
- Number of Subjects Achieving Partial Remission(week 48)
- Number of Subjects Achieving, and Remaining in, Complete Remission(week 48)
- Duration of Complete Remission (Number of Weeks)(week 48)
- Number of Subjects Achieving Partial Renal Remission at 24 and 48 Weeks(week 24 and 48)
- Time to Sustained Partial Remission (Number of Weeks)(week 48)
- Number of Subjects Achieving Sustained Partial Remission(week 48)
- Time to Sustained Early Partial Remission (Number of Weeks)(week 48)
- Number of Subjects Achieving Sustained Early Partial Remission(week 48)
- Change From Baseline in UPCR at Weeks 24 and 48(Baseline, Week 24 and Week 48)
- Change From Baseline in Safety of Estrogens in Systemic Lupus Erythematosus National Assessment Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) Score(Baseline, Week 24 and Week 48)