A Randomized, Double-blind, Double-dummy, Active-controlled, Multicenter, 2-part Phase II Study on Replacement of Steroids by IFX-1 in Active Granulomatosis With Polyangiitis (GPA) and Microscopic Polyangiitis (MPA)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- InflaRx GmbH
- 入组人数
- 57
- 试验地点
- 2
- 主要终点
- Percentage of Subjects Achieving Clinical Response
研究概览
简要总结
The purpose of the study is to evaluate the efficacy of IFX-1 treatment as replacement for glucocorticoid (GC) therapy in subjects with polyangiitis (GPA) or microscopic polyangiitis (MPA).
详细描述
Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) is a group of potentially life-threatening autoimmune diseases. Preclinical data demonstrate that primed neutrophils are activated by anti-neutrophil cytoplasmic antibody (ANCA) and generate C5a that engages C5a receptors on neutrophils. Patients with ANCA-related disease have elevated plasma and urine levels of C5a in active disease but not in remission. IFX-1 is as a monoclonal antibody specifically binding to the soluble human complement split product C5a, which results in nearly complete blockade of C5a induced biological effects. Therefore, IFX-1 may be effective in the treatment of subjects with AAV.
In this Phase II study of 20 to 55 subjects with granulomatosis with GPA and MPA, IFX-1 will be administered in combination with reduced dose glucocorticoids or a placebo glucocorticoid compared with standard dose glucocorticoids.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA)
- •Have ≥ 1 "major" item, or ≥ 3 other items, or ≥ 2 renal items on the Birmingham Vasculitis Activity Score Version 3 (BVASv3).
- •Newly diagnosed or relapsed GPA or MPA that requires treatment with Cyclophosphamide (CYC) or Rituximab (RTX) plus GCs.
- •Glomerular filtration rate ≥ 20 mL/min/1.73 m².
排除标准
- •Any other multi-system autoimmune disease.
- •Require mechanical ventilation at screening.
- •Known hypersensitivity to any investigational medicinal product and/or any excipient.
- •Rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption.
- •Have required management of infections, as follows (a) Chronic infection requiring anti-infective therapy within 3 months before screening. (b) Use of intravenous antibacterials, antivirals, anti-fungals, or anti-parasitic agents within 30 days of screening
- •Current and/or history (within the previous 5 years) of drug and/or alcohol abuse and/or dependence.
- •Evidence of Hep B, C and/ or HIV infection. Only subjects with documented negative historical results (within 4 weeks before screening) for Hep B,C Virus and HIV or a negative test by Screening can be included into the study.
- •Abnormal laboratory findings at screening
- •Current or history of malignancy, lymphoproliferative, or myeloproliferative disorder
- •Received CYC or RTX within 12 weeks before screening or within 12 weeks before CYC or RTX is started for remission induction within 2 weeks before screening.
- •Received > 3 g cumulative intravenous GCs within 4 weeks before screening.
- •Received an oral daily dose of a GC of > 10 mg prednisone-equivalent for more than 6 weeks continuously prior to screening.
- •Received an oral daily dose of a GC of > 80 mg prednisone equivalent within 2 weeks before screening.
- •Received a CD20 inhibitor, anti-tumor necrosis factor treatment, abatacept, alemtuzumab, any other experimental or biological therapy, intravenous immunoglobulin (Ig) or plasma exchange, antithymocyte globulin, or required renal dialysis within 12 weeks before screening.
- •Received a live vaccination within 4 weeks before screening
- •Either active or latent tuberculosis treatment is ongoing.
- •Pregnant or lactating.
- •Abnormal electrocardiogram.
- •Female subjects of childbearing potential unwilling or unable to use a highly effective method of contraception
- •Participation in an investigational clinical study during the 12 weeks before screening.
- •Male subjects with female partners of childbearing potential unwilling to use contraception
研究组 & 干预措施
Group A Experimental + active comparator
IFX-1 + reduced dose GC
干预措施: IFX-1 (Drug)
Group A Experimental + active comparator
IFX-1 + reduced dose GC
干预措施: Glucocorticoid (GC) (Drug)
Group B Placebo + active comparator
Placebo-IFX-1 + standard dose GC
干预措施: Placebo-IFX-1 (Drug)
Group B Placebo + active comparator
Placebo-IFX-1 + standard dose GC
干预措施: Glucocorticoid (GC) (Drug)
Group C Experimental + placebo comparator
IFX-1 + Placebo-GC
干预措施: IFX-1 (Drug)
Group C Experimental + placebo comparator
IFX-1 + Placebo-GC
干预措施: Placebo-Glucocorticoid (Placebo-GC) (Drug)
结局指标
主要结局
Percentage of Subjects Achieving Clinical Response
时间窗: Baseline, Week 16
Efficacy Endpoint: Percentage of subjects achieving clinical response (reduction in Birmingham Vasculitis Activity Score version 3 \[BVASv3\] of ≥50% compared to baseline and no worsening in any body system). Subjects who received rescue therapy after Day 1 or discontinued due to related adverse event, lack of efficacy or progressive disease are considered as non-responders at all subsequent visits. The BVASv3 score ranges from 0 to 63 with higher values representing higher disease activity.
次要结局
- Vasculitis Damage Index (VDI)(Week 16)
- Estimated Glomerular Filtration Rate(Week 16)
- Plasma Concentrations of C5a(Week 16)
- Percentage of Subjects With Clinical Remission(Week 16)
- IFX-1 Blocking Activity 10 nM(Week 16)
- Physician Global Assessment (PGA)(Week 16)
- IFX-1 Plasma Concentrations (Pre-dose)(Week 16 (pre-dose))
- Change From Baseline in BVASv3 Total Score(Baseline, Week 16)
- Number and Percentage of Subjects Who Had a Treatment-emergent Adverse Event (TEAE)(Week 24)
- Glucocorticoid Toxicity Index (GTI)(Week 16)
- IFX-1 Blocking Activity 2.5 nM(Week 16)