NCT06072482招募中4 期
A Randomized, Double-blind, Placebo-controlled Phase 4 Clinical Trial to Evaluate the Long-term Safety and Efficacy of Avacopan in Participants With Antineutrophil Cytoplasmic Antibody (ANCA)-Associated Vasculitis
适应症
干预措施
相关药物
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- Amgen
- 入组人数
- 300
- 试验地点
- 158
- 主要终点
- Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
研究概览
简要总结
The primary objective of this study is to evaluate the long-term safety of avacopan in participants with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV).
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants has provided informed consent before initiation of any study-specific activities/procedures.
- •Newly diagnosed or relapse of granulomatosis with polyangiitis or microscopic polyangiitis, consistent with Chapel-Hill Consensus Conference definitions (Jennette et al, 2013), where induction treatment with cyclophosphamide or rituximab is needed.
- •Age >/= 18 years (or >/= legal age within the country if it is older than 18 years).
- •Positive test for anti-positive antiproteinase 3 or antimyeloperoxidase (current or historic) antibodies.
- •At least 1 Birmingham Vasculitis Activity Score (BVAS) major item, or at least 3 BVAS nonmajor items, or at least the 2 renal items of proteinuria and hematuria.
- •eGFR >/= 15 mL/min/1.73 m^2 (using Chronic Kidney Disease Epidemiology Collaboration equations).
排除标准
- •Alveolar hemorrhage requiring invasive pulmonary ventilation support anticipated to last beyond the screening period of the study.
- •Any other known multisystem autoimmune disease that may confound study assessments and study conclusions including but not limited to eosinophilic granulomatosis with polyangiitis (GPA [Churg-Strauss]), systemic lupus erythematosus, immunoglobulin (Ig) A vasculitis (Henoch-Schönlein), rheumatoid vasculitis, Sjogren's syndrome, anti-glomerular basement membrane disease, or cryoglobulinemic vasculitis.
- •Any other medical condition requiring or expected to require continued use of immunosuppressive therapies, including corticosteroids that may cause confoundment with study assessments and study conclusions.
- •Received dialysis or plasma exchange within 16 weeks before Day 1 randomization.
- •Have had a kidney transplant.
- •Malignancy (except curatively treated nonmelanoma skin cancers, curatively treated cervical carcinoma in situ, or breast ductal carcinoma in situ) within the last 5 years before Day 1 randomization.
- •Acute or chronic, active hepatitis B virus or hepatitis C virus, or human immunodeficiency virus infection during screening.
- •Any known exposure to a case of active tuberculosis (TB) within the last 12 weeks before Day 1 randomization.
- •Positive test for active or latent TB during screening.
- •White blood cell count < 3500/µL, neutrophil count < 1500/µL, or lymphocyte count < 500/µl. Note: Complete Blood Count can be repeated once in the screening period at the investigator discretion. In such instances, eligibility will be determined based on the repeat complete blood count.
- •Evidence of clinically significant hepatic disease including prior diagnosis of cirrhosis.
- •Aspartate aminotransferase (AST), alanine aminotransferase (ALT), or alkaline phosphatase (ALP) >2.0 times the upper limit of normal (ULN).
- •Total bilirubin > 1.5 times the ULN. Note: A participant with documented Gilbert's syndrome with total bilirubin < 2 x ULN may be eligible.
- •Any of the following within 6 weeks prior to Day 1 randomization: serious infection, infection requiring treatment with intravenous (IV) anti-infective agents, any other infection (including active infection, chronic infection, opportunistic infection, or history of recurrent infection) that in the opinion of the investigator would pose a risk to participant safety or interfere with the study evaluation, procedures, or completion. Oral or vaginal candidiasis and cutaneous or nail fungal infections do not constitute an exclusion.
- •Any of the following within 12 weeks prior to Day 1 randomization: myocardial infarction, stroke, unstable angina, symptomatic congestive heart failure requiring prescription medication, any other clinically significant cardiovascular disease that in the opinion of the investigator would pose a risk to participant safety or interfere with the study evaluation, procedures, or completion.
- •Received cyclophosphamide (CYC) within 12 weeks before signing the informed consent; if on azathioprine (AZA), mycophenolate, or methotrexate (MTX) at the time of screening, these drugs must be withdrawn before receiving CYC. Note: If induction therapy with CYC was started within 1 week before signing the informed consent for the current episode of newly diagnosed or relapse of GPA or microscopic polyangiitis (MPA), the participant may be eligible, provided no CYC was received within 12 weeks before the start of the current induction therapy and if on AZA, mycophenolate, or MTX, these were withdrawn prior to receiving the current induction therapy with CYC.
- •Have been taking an oral daily dose of a glucocorticoid of more than 10 mg prednisone equivalent for more than 6 weeks continuously before signing of the informed consent.
- •Received RTX or other B-cell depleting therapies within 26 weeks before signing of the informed consent; if on AZA, mycophenolate, or MTX at the time of screening, these drugs must be withdrawn before receiving rituximab (RTX). Note: If induction therapy with RTX was started within 1 week before signing the informed consent for the current episode of newly diagnosed or relapse of GPA or MPA, the participant may be eligible, provided no RTX was received within 26 weeks before the start of the current induction therapy and if on AZA, mycophenolate, or MTX, these were withdrawn prior to receiving the current induction therapy with RTX.
- •Received any of the following within 16 weeks before Day 1 randomization:
- •antitumor necrosis factor treatment
- •abatacept
- •alemtuzumab
- •belimumab
- •anti interleukin-6 agent (eg, tocilizumab, sarilumab).
- •Taking a strong or moderate inducer of the cytochrome P450 3A4 (CYP3A4) enzyme unless the strong or moderate CYP3A4 inducer can be changed to an alternative medicine at least 1 week before Day 1 randomization.
- •Received an investigational drug within 30 days or within 5 half-lives (whichever is longer) before Day 1 randomization.
- •Previously received avacopan without clinical benefit per the Investigator's opinion or received avacopan within 60 days before Day 1 randomization.
研究组 & 干预措施
Group B: Avacopan/Placebo + SoC
Experimental
Avacopan 30 mg twice daily for 1 year, followed by placebo twice daily for 4 years + SoC background immunosuppressive therapy.
干预措施: Standard of Care (Drug)
Group C: Placebo + SoC
Placebo Comparator
Placebo twice daily for 5 years + SoC background immunosuppressive therapy.
干预措施: Placebo (Drug)
Group A: Avacopan + Standard of Care (SoC)
Experimental
Avacopan 30 mg twice daily for 5 years + SoC background immunosuppressive therapy.
干预措施: Standard of Care (Drug)
Group B: Avacopan/Placebo + SoC
Experimental
Avacopan 30 mg twice daily for 1 year, followed by placebo twice daily for 4 years + SoC background immunosuppressive therapy.
干预措施: Placebo (Drug)
Group C: Placebo + SoC
Placebo Comparator
Placebo twice daily for 5 years + SoC background immunosuppressive therapy.
干预措施: Standard of Care (Drug)
Group A: Avacopan + Standard of Care (SoC)
Experimental
Avacopan 30 mg twice daily for 5 years + SoC background immunosuppressive therapy.
干预措施: Avacopan (Drug)
Group B: Avacopan/Placebo + SoC
Experimental
Avacopan 30 mg twice daily for 1 year, followed by placebo twice daily for 4 years + SoC background immunosuppressive therapy.
干预措施: Avacopan (Drug)
结局指标
主要结局
Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs)
时间窗: Up to Month 60
Percentage of Participants Experiencing Adverse Events of Special Interest
时间窗: Up to Month 60
Percentage of Participants Experiencing Adverse Events Leading to Withdrawal
时间窗: Up to Month 60
Number of Participants Experiencing Clinical Significant Changes from Baseline in Hematology Assessments
时间窗: Up to Month 60
Number of Participants Experiencing Clinical Significant Changes from Baseline in Serum Chemistry Assessments
时间窗: Up to Month 60
Number of Participants Experiencing Clinical Significant Changes from Baseline in Urinalysis Assessments
时间窗: Up to Month 60
Number of Participants Experiencing Clinical Significant Changes from Baseline in Vital Signs Measurements
时间窗: Up to Month 60
Percentage of Participants Experiencing Serious Adverse Events
时间窗: Up to Month 60
Percentage of Participants Experiencing Adverse Events Leading to Death
时间窗: Up to Month 60
次要结局
- Group A and B Participants who Achieved Remission at Month 12: Percentage of Participants who Relapse After Achieving Remission at Month 12(Month 12 to Month 60)
- Group A and B Participants who Achieved Remission at Month 12: Time to Relapse in AAV Between Month 12 and Month 60(Month 12 to Month 60)
- Groups A and C: Percentage of Participants who Achieved Sustained Remission at Month 60(Month 60)
- Group A and C Participants with Overt Renal Disease at Baseline: Change from Baseline to Month 60 in Estimated Glomerular Filtration Rate (eGFR)(Baseline and Month 60)
- Groups A and C: Change from Baseline to Month 60 in Short Form 36 Health Survey Version 2 (SF-36 v2) General Health Perception Score(Baseline and Month 60)
- Groups A and C: Change from Baseline to Month 60 in EuroQoL-5 Dimension 5 Levels (EQ-5D-5L) Visual Analogue Scale (VAS)(Baseline and Month 60)
- Percentage of Participants who Achieved Remission at Month 6(Month 6)
- Groups A and C: Change from Baseline to Month 60 in Vasculitis Damage Index (VDI)(Baseline and Month 60)
- Groups A and C: Percentage of Participants with Composite Outcome of Initiation of Maintenance Dialysis, Kidney Transplantation, or Death(Up to Month 60)
- Percentage of Participants With Glucocorticoid Use(Up to Month 60)
- Percentage of Participants With Immunosuppressant Use(Up to Month 60)
研究者
研究点 (158)
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