CTRI/2022/02/040015招募中3 期
A Multicenter Randomized Double-Blind Placebo-Controlled Phase 3 Study to Evaluate the Efficacy and Safety of Anifrolumab in Adult Patients with Active Proliferative Lupus Nephritis
AstraZeneca AB and AstraZeneca KK15 个研究点 分布在 1 个国家目标入组 360 人开始时间: 2022年2月15日最近更新:
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 360
- 试验地点
- 15
- 主要终点
- Efficacy of anifrolumab compared with placebo as added
研究概览
简要总结
Phase 3 Study of Anifrolumab in Adult Patients with Active Proliferative Lupus Nephritis to evaluate the efficacy and safety of anifrolumab as compared with placebo. The primary and secondary objectives: 1 To evaluate the efficacy of anifrolumab compared with placebo as added to SOC in active proliferative LN on the proportion of participants achieving CRR 2. To evaluate the effect of anifrolumab as compared with placebo as added to SOC on: Sustained OCS reduction, Onset of sustained CRR, Proteinuria, Onset of renal-related event or death through Week 52, Onset of renal-related event or death through Week 104 along with the other efficacy and safety objectives. A total of 360 participants will be randomized 1:1 to receive anifrolumab or placebo and includes:
Screening Period: Up to 30 days
Treatment Period: 104-week double-blind treatment period with:
Study intervention administration (anifrolumab or placebo) IV Q4W from Week 0 to Week 100 for a total of 26 doses
Follow-up Period: Up to 8 weeks after last efficacy assessment at Week 104 (ie, 12 weeks after last dose of study intervention)
研究设计
- 研究类型
- Interventional
- 分配方式
- Stratified block randomization
- 盲法
- Participant and Investigator Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 70.00 Year(s)（—）
- 性别
- All
入选标准
- •Informed consent-
- •Capable of giving signed informed consent prior to performing any protocol-related procedures, including Screening evaluations
- •Completion of Screening procedures within 30 days after signing the ICF. Age and Sex- Males and females aged 18 to 70 years of age. Disease Characteristics-
- •Fulfills updated 2019 SLE criteria
- •Have positive ANA, anti-dsDNA, or anti-Sm test result in sample obtained during Screening
- •Urine protein to creatinine ratio > 1 mg/mg (113.17 mg/mmol)
- •Have active proliferative LN Class III or IV either with or without the presence of Class V 5.Adequate peripheral venous access
- •eGFR ≥ 35 mL/min/1.73 m2 (as calculated by the Chronic Kidney Disease Epidemiology Collaboration formula) Tuberculosis
- •Chest radiograph or a CT scan of the chest that meets all of the following criteria:No evidence of current active infection (eg, pneumonia, TB) or previous TB; and No evidence of malignancy; and No CS abnormalities (unless due to SLE)
- •Meets all of the following TB criteria: No signs or symptoms of active TB prior to or during any Screening visit No medical history or past physical examinations suggestive of active TB A chest radiograph during the Screening Period or within 12 weeks prior to signing the ICF with no evidence of active or signs of prior TB infection No recent contact with a person with active TB OR if there has been such contact, referral to a physician specializing in TB to undergo additional evaluation prior to Week 0 (Day 1) and, if warranted, receipt of appropriate treatment for latent TB at or before the first administration of study intervention No history of latent TB prior to signing the ICF, with the exception of latent TB with documented completion of appropriate treatment. COVID-
- •Negative SARS-Cov-2 RT-PCR test result at Screening and no known or suspected COVID-19 infection or exposure between signing the ICF and Week 0 (Day 1). Weight Body weight ≥ 40.0 kg Pap Smear- Females with an intact cervix must have documentation of a Pap smear with no documented malignancy (eg, CIN III, carcinoma in situ, or adenocarcinoma in situ) within 2 years prior to Week 0 (Day 1) Contraceptive Requirements Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies Male participants: All males (sterilized or non-sterilized) who are sexually active must use condom (with spermicide, where commercially available for contraception) from Day 1 until at least 12 weeks after receipt of the final dose of study intervention and until at least 90 days after the last dose of Sponsor-provided MMF Male participants must not donate sperm during the course of the study and for 12 weeks after the last dose of the study intervention and 90 days after the last dose of Sponsor-provided MMF Female participants: females of childbearing potential must have Negative serum β-hCG test at Screening. Women of childbearing potential must have a negative urine pregnancy test at Week 0 (Day 1), prior to administration of study intervention and prior to the first dose of Sponsor-provided MMF. Females of childbearing potential must use 2 effective methods of avoiding pregnancy, only one of which is a barrier method, from Screening until 12 weeks after the final dose of study intervention and from the first dose of Sponsor-provided MMF until 6 weeks after the last dose of Sponsor-provided MMF unless the participant is surgically sterile (eg, bilateral oophorectomy or complete hysterectomy), has a sterile male partner, is at least one year postmenopausal, or practices sustained abstinence consistent with the participant’s customary lifestyle.
排除标准
- •Medical Conditions-
- •A diagnosis of pure Class V LN based on the renal biopsy obtained within 6 months prior to signing the ICF or during Screening
- •History of dialysis within 12 months prior to signing the ICF or expected need for renal replacement therapy 3 History of, or current renal diseases (other than LN) that, in the opinion of the Investigator, could interfere with the LN assessment and confound the disease activity assessment (eg, diabetic nephropathy) infection and malignancy risk factors- 1.History of recurrent infection requiring hospitalization and/or IV antibiotics
- •Known history of a primary immunodeficiency, splenectomy, or any underlying condition that predisposes the participant to infection, or a positive result for HIV infection confirmed by the central laboratory at Screening
- •At Screening, confirmed positive test for hepatitis B serology, as confirmed by central laboratory,
- •Positive test for hepatitis C antibody as confirmed by the central laboratory
- •Any clinical CMV or EBV infection that has not completely resolved within 12 weeks prior to signing the ICF
- •Opportunistic infection requiring hospitalization or IV antimicrobial treatment within 3 years prior to signing the ICF
- •Any severe case, of HZ infection at any time prior to Week 0 Systemic HZ such as herpes encephalitis, ophthalmic herpes involving the retina at any time prior to Week 0 (Day 1)
- •Clinically significant chronic infection (ie, osteomyelitis, bronchiectasis, etc
- •Any infection requiring oral anti-infectives
- •History of cancer, apart from: Squamous or basal cell carcinoma of the skin treated with documented success of curative therapy ≥ 3 months prior to Week 0 (Day 1) Cervical cancer in situ treated with apparent success with curative therapy ≥ 1 year prior to Week 0 (Day 1) COVID-19:
- •Any history of severe COVID-19 infection, eg, requiring hospitalization, intensive care unit care, or assisted ventilation, or any prior COVID-19 infection with unresolved sequelae
- •Confirmed or probable COVID-19 infection
- •Failure to comply with all required Screening procedures due to circumstances related to pandemic or public health emergency.
- •Prior/Concomitant Therapy-
- •Prior receipt of anifrolumab
- •Previous receipt of >â—¦2 investigation treatments (other than anifrolumab) for LN or SLE since time of diagnosis and through signing the ICF
- •Known intolerance to ≤ 1.0 g/day of MMF
- •Receipt of any commercially available biologic agent within 5 half-lives prior to signing of the ICF
- •Receipt of any of the following prior to signing the ICF: Receipt of B cell-depleting therapy (eg, rituximab or obinutuzumab):
- •A known history of allergy or reaction to any component of the study intervention formulation or history of anaphylaxis to any human gamma globulin therapy, human proteins, or monoclonal antibodies
- •Receipt of any of the following: Any live or attenuated vaccine within 8 weeks prior to signing the ICF Any restricted medication Blood transfusion within 4 weeks prior to signing the ICF Any of the following for the current LN flare (ie, since the qualifying renal biopsy): o IV cyclophosphamide > 2 pulses of high-dose (≥ 0.5 g/m2) or > 4 doses of low-dose (500 mg every 2 weeks) or o Average MMF > 2.5 g/day (or > 1800 mg/day of enteric coated mycophenolate sodium) for more than 8 weeks or o Tacrolimus > 4 mg/day for more than 8 weeks.
- •Cyclosporine for more than 8 weeks or during last 8 weeks prior to signing the ICF.
- •o Voclosporin for more than 8 weeks or during last 8 weeks prior to signing the ICF.
- •Receipt of any commercially available Janus kinase inhibitor (eg, tofacitinib or baricitinib) or Bruton’s tyrosine kinase inhibitor (eg, ibrutinib, acalabrutinib, zanubrutinib) 9.Any new medicinal cannabinoid should not be started during the course of the study.
- •Prior/Concurrent Clinical Study Experience-Participation in another clinical study with another study intervention (besides anifrolumab) administered within 4 weeks prior to ICF signing or within 5 half-lives of the study intervention used in that clinical study.
- •Diagnostic Assessments- Within 4 weeks of Week 0 (Day 1), any of the following (note: retesting of laboratory test results during Screening may be repeated once): AST > 2.5 × ULN ALT > 2.5 × ULN TBL > ULN (unless due to Gilbert’s syndrome [based on Investigator’s judgment]) Glycosylated hemoglobin > 8% (or > 0.08) at Screening (diabetic participants only) Neutrophil count < 1 × 103/μL (or < 1.0 × 109/L) Platelet count < 25 × 103/μL (or < 25 × 109/L) Hemoglobin < 8 g/dL (or < 80 g/L) Other Exclusions-
- •Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
- •Any condition that, in the opinion of the Investigator, would interfere with evaluation of the study intervention or interpretation of participant safety or study results
- •Lactating or pregnant females or females who intend to become pregnant or begin breastfeeding anytime from initiation of Screening through the Follow-up Period
- •weeks following last dose of study intervention and 6 weeks after the last dose of Sponsor-provided MMF (whichever is later) 30 Spontaneous or induced abortion, still or live birth, or pregnancy ≤ 4 weeks prior to signing the ICF
- •Current alcohol, drug or chemical abuse, or a history of such abuse within one year before Week 0 (Day 1)
- •Major surgery within 8 weeks before signing the ICF or elective major surgery planned during the study period
- •History of, or current diagnosis of, catastrophic antiphospholipid syndrome within one year prior to signing the ICF.
- •Participants with other degrees of antiphospholipid syndrome adequately controlled by anticoagulants or aspirin for at least 12 weeks can be recruited to the study.
- •History or evidence of suicidal ideation within the past 6 months; or any suicidal behavior within the past 12 months or recurrent behavior in the lifetime of the participant.
结局指标
主要结局
Efficacy of anifrolumab compared with placebo as added
时间窗: Week 52
to SOC in participants with active proliferative LN on the proportion of participants achieving CRR at Week 52
时间窗: Week 52
次要结局
- The efficacy of anifrolumab compared with placebo as added to SOC in(participants with active proliferative LN)
研究者
研究点 (15)
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