An Exploratory, Randomized, Double-blind, Multicenter, Placebo-controlled Study to Assess the Safety, Tolerability, Pharmacokinetics, and Efficacy of AP1189 Versus Placebo Administered for 12 Weeks as an add-on to Patients, in ACE Inhibitor or Angiotensin II Receptor Blocker Treatment, With Idiopathic Membranous Nephropathy and Severe Proteinuria
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 23
- 试验地点
- 1
- 主要终点
- Serious Adverse Events
研究概览
简要总结
This study is an exploratory, randomized, double-blind, multicenter, placebo-controlled study with repeated doses of AP1189. The study population will consist of patients with idiopathic membranous nephropathy (iMN) and severe proteinuria who are on ACE inhibitor or angiotensin II receptor blocker treatment.
详细描述
This study is an exploratory, randomized, double-blind, multicenter, placebo-controlled study with repeated doses of AP1189. The study population will consist of patients with idiopathic membranous nephropathy (iMN) and severe proteinuria who are on ACE inhibitor or angiotensin II receptor blocker treatment.
Following a successful screening, subjects who fulfill the enrollment criteria will be randomized in a 2:1 ratio in group A and B:
- Group A (12 subjects): AP1189 dose 100 mg, once daily for 12 weeks (28 days) as an add-on to any ongoing treatment, including ACE inhibitors/ angiotensin II receptor blocker
- Group B (6 subjects): placebo for 12 weeks (28 days) as an add-on to any ongoing treatment including ACE inhibitors/ angiotensin II receptor blocker.
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, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent has been obtained prior to initiating any study-specific procedures
- •Male and female subjects, 18 to 85 years of age diagnosed with iMN within 6 months prior to inclusion
- •Diagnosed as anti-PLA2-Receptor positive by local laboratory within 6 months prior to inclusion
- •Severe proteinuria defined by a U-protein/creatinine ratio >3.0 g/g and/or U-albumin/creatinine ratio >2.0 g/g and a P-albumin below the lower normal limit
- •eGFR > 30 ml/min/1.73m2
- •Treated with ACE- inhibitors or angiotensin II receptor blocker for a minimum of 1 months with a stable systemic arterial blood pressure OR treatment with ACE inhibitors and/or angiotensin receptor blocker was excluded or discontinued due to hypotension, intolerance or other side effect
- •Only Denmark and Norway:
- •Females of child-bearing potential using reliable means of contraception or are post-menopausal
- •Females of childbearing potential with negative pregnancy test at screening and baseline
- •Only Sweden:
- •Post-menopausal women or women who are surgically sterilized.
排除标准
- •Participation in any other study involving investigational drug(s) during the study and within 4 weeks prior to study entry
- •Clinicial findings that in the opinion of the investigator would suggest condition(s) other than iMN as a major cause of severe proteinuria
- •Major surgery within 8 weeks prior to screening or planned surgery within 1 month following randomization
- •Blood pressure with systolic pressure above 160 mmHg and/or diastolic pressure above 100 mmHg despite antihypertensive treatment will in all cases be considered "uncontrolled"
- •Treated with systemic corticosteroids, or other immune suppressive, or immune modulating compounds within 4 weeks prior to screening and during the entire treatment period and until the final visit
- •Treated with rituximab within 12 months of screening
- •Evidence of active malignant disease
- •Uncontrolled disease states, such as asthma, psoriasis, or inflammatory bowel disease where flares are commonly treated with oral or parenteral corticosteroids
- •Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary, renal, hepatic, endocrine or gastrointestinal disease
- •Pregnant women or nursing mothers
- •History of alcohol, drug, or chemical abuse within the 6 months prior to screening
- •Any condition that in the view of the investigator would suggest that the patient is unable to comply with study protocol and procedures
- •Only Sweden:
- •Females of child-bearing potential.
研究组 & 干预措施
100 mg AP1189
100 mg AP1189. The treatment is a 12-weeks treatment. Each daily dose will be administered as a tablet
干预措施: 100 mg AP1189 (Drug)
Placebo
Placebo. The treatment is a 12-weeks treatment. Each daily dose will be administered as a tablet
干预措施: Placebo (Drug)
结局指标
主要结局
Serious Adverse Events
时间窗: Week 12
Evaluation of Serious Adverse Events
Alkaline phosphatase change in plasma samples
时间窗: Week 12
Evaluation of alkaline phosphatase compared with baseline
Adverse Event
时间窗: Week 12
Evaluation of Adverse Event
ALAT change in plasma samples
时间窗: Week 12
Evaluation of ALAT compared with baseline
ASAT change in plasma samples
时间窗: Week 12
Evaluation of ASAT compared with baseline
Total bilirubin change in plasma samples
时间窗: Week 12
Evaluation of total bilirubin compared with baseline
Protein change in 24 hours urinary protein excretion
时间窗: Week 12
Change of protein in urine excretion compared to baseline measured in 24 h urinary protein excretion
次要结局
- Albumin change in 24 hours urinary protein excretion(Week 12)