Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Phase II Efficacy and Safety Study of IFX-1 in Add-On to Standard of Care in Granulomatosis With Polyangiitis (GPA) and Microscopic Polyangiitis (MPA)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- InflaRx GmbH
- 入组人数
- 20
- 试验地点
- 38
- 主要终点
- Number and Percentage of Participants With at Least One TEAE Per Treatment Group.
研究概览
简要总结
The purpose of this study is to investigate the safety and tolerability of two dose regimens of IFX-1 as add-on to standard of care (SOC) in subjects with GPA and MPA compared with placebo.
详细描述
Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) are related systemic v anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), a potentially life-threatening disease.
GPA is a necrotizing vasculitis predominantly involving small- to medium-sized vessels (e.g., capillaries, venules, arterioles, arteries, and veins). MPA is a necrotizing vasculitis that primarily affects capillaries, venules, or arterioles, most commonly manifesting as necrotizing glomerulonephritis and/or pulmonary capillaritis. MPA.
Primed neutrophils are activated by ANCA and generate C5a that engages C5a receptors on neutrophils. Therefore, patients with ANCA-related disease have elevated plasma and urine levels of C5a in active disease and not in remission.
IFX-1 is a monoclonal antibody specifically binding to the soluble human complement split product C5a and the resulting nearly complete blockade of C5a-induced biological effects may be effective in the treatment of subjects with 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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female, ≥18 years of age.
- •Diagnosis of GPA or MPA according to the definitions of the Chapel Hill Consensus Conference.
- •Have at least one "major" item, or at least three other items, or at least two renal items on the Birmingham Vasculitis Activity Score (BVAS) Version 3.
- •New or relapsed GPA or MPA that require treatment with CYC or RTX plus GCs.
排除标准
- •Any other multisystem autoimmune disease
- •Requires mechanical ventilation because of alveolar hemorrhage at Screening.
- •Human immunodeficiency virus, hepatitis B, or hepatitis C viral screening test showing evidence of active or chronic viral infection at Screening or a documented history of the human immunodeficiency virus, hepatitis B, or hepatitis C.
- •Received CYC or RTX 12 weeks before Screening; if on azathioprine (AZA), methotrexate (MTX), mycophenolate mofetil (MMF), or mycophenolate sodium (MPS) at the time of Screening, these drugs must be withdrawn prior to receiving CYC or RTX.
- •Received more than 3 g cumulative high dose intravenous GCs within 4 weeks before Screening.
- •On an oral dose of a GC of more than 10 mg prednisone equivalent at Screening or for more than 6 weeks before Screening.
- •Received a CD20 inhibitor, anti-tumor necrosis factor treatment, abatacept, alemtuzumab, any other experimental or biological therapy, intravenous immunoglobulin or plasma exchange, antithymocyte globulin, or required dialysis within 12 weeks before Screening.
- •Received a live vaccination within 4 weeks before Screening or planned between Screening and Week
- •Female subjects of childbearing potential unwilling or unable to use a highly effective method of contraception (pearl index <1%) such as complete sexual abstinence, combined oral contraceptive, vaginal hormone ring, transdermal contraceptive patch, contraceptive implant, or depot contraceptive injection in combination with a second method of contraception such as condom, cervical cap, or diaphragm with spermicide during the study and for at least 4 weeks after last administration of IFX-1 (timeframes for SOC have to be considered as described in the respective Prescribing Information).
研究组 & 干预措施
IFX-1 low dose
Will receive IFX-1 low dose regimen diluted in sodium chloride solution
干预措施: IFX-1 low dose (Drug)
IFX-1 high dose
Will receive IFX-1 high dose regimen diluted in sodium chloride solution
干预措施: IFX-1 high dose (Drug)
Placebo
Will receive placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Number and Percentage of Participants With at Least One TEAE Per Treatment Group.
时间窗: Week 24
Number and percentage of participants who experience at least one treatment-emergent adverse event (TEAE) per treatment group.
次要结局
- Percentage of Participants Achieving Clinical Response(Week 16)
- Percentage of Participants With Clinical Remission (BVAS = 0)(Week 16)
- IFX-1 Concentration Pre-dose(Week 16)
- IFX 1 Concentration at Predose (0 Hours), After the End of the Infusion (+10minutes), and at 2, 6, 24, and 48 Hours After the Start of the Infusion for Participants in the PK Substudy(Weeks 1, 4 and 16)
- C5a Plasma Concentration(Week 16)
- IFX-1 Blocking Activity 2.5 nM(Week 16)
- IFX-1 Blocking Activity 10 nM(Week 16)