An Open-Label, Phase 2, Pilot Study Investigating the Safety, Clinical Activity, Pharmacokinetics, and Pharmacodynamics of Oral Treatment With the BTK Inhibitor PRN1008 in Patients With Newly Diagnosed or Relapsing Pemphigus Vulgaris
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 42
- 试验地点
- 13
- 主要终点
- Percentage of Participants With Treatment-emergent Adverse Events
研究概览
简要总结
Open-label cohort study in adult patients with newly diagnosed or relapsing pemphigus vulgaris, with intra-patient dose-adjustment based on clinical response and BTK occupancy, and with conventional immunosuppressive "rescue treatment", if indicated. The duration of therapy in Part A will be 12 weeks, followed by 12 weeks of follow up. The extension phase, Part B includes 24 weeks of therapy, followed by 4 weeks of follow-up.
详细描述
Primary Objectives:
To evaluate the safety of PRN1008 in patients with pemphigus vulgaris (PV)
To evaluate the clinical activity of PRN1008 in patients with PV, per criteria in the European Academy of Dermatology and Venereology (EADV) 2014 Pemphigus S2 Guideline (Hertl et al. 2015)
Secondary Objectives
To evaluate the pharmacokinetics (PK) and the pharmacodynamics (PD) of multiple doses of PRN1008 in patients with PV
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
盲法说明
Open Label
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female patients, aged 18 to 80 years old, with biopsy-proven, mild-moderate PV (PDAI 8 to 45) in Part A and mild to severe PV in Part B (PDAI 8 to 60) that are either:
- •newly diagnosed patients (i.e. naïve to an effective induction treatment regimen) for whom an initial period of PRN1008 monotherapy is judged clinically acceptable, or
- •relapsing patients, for whom an initial period of PRN1008 monotherapy, or combination therapy with any of low dose corticosteroid, ie.0.5 mg/kg of prednis(ol)one per day
排除标准
- •Pregnant or lactating women
- •A history of malignancy of any type, other than surgically excised non-melanoma skin cancers or in situ cervical cancer within 5 years before the day of dosing
- •Use of immunologic response modifiers with the following periods prior to Day 1: 1 week: cyclophosphamide; 4 weeks: intravenous immunoglobulin, Kinaret (anakinra) and Enbrel (etanercept); 12 weeks: Remicade (infliximab), Humira (adalimumab), Simponi (golimumab), Orencia (abatacept), Actemra (tocilizumab), Cimzia (certolizumab), Cosentyx (secukinumab), plasmapheresis; 6 months: Rituxan/MabThera (rituximab), ofatumumab, any other anti-CD20 antibody, other long acting biologics
- •More than 0.5 mg/kg of prednis(ol)one per day ("low dose corticosteroids") within the two weeks prior to Day 1
- •Use of proton pump inhibitor drugs such as omeprazole and esomeprazole
- •Has received any investigational drug (or is currently using an investigational device) within the 30 days before receiving the first dose of study medication, or at least 5 times the respective elimination half-life time (whichever is longer)
- •History of drug abuse within the precious 12 months
- •Alcoholism or excessive alcohol use, defined as regular consumption of more than approximately 3 standard drinks per day
- •Refractory nausea and vomiting, malabsorption, external biliary shunt, significant bowel resection that would preclude adequate study drug absorption
- •History of anorexia nervosa or periods of three months or more of low body weight in the past 5 years
- •Donation of a unit or more of blood or blood products within 4 weeks prior to Day 1
- •History of solid organ transplant
- •History of epilepsy or other forms of seizures in the last 5 years
- •Positive for screening for human immunodeficiency virus, hepatitis B (surface and core antibodies unrelated to vaccination), or hepatitis C (anti-HCV antibody confirmed with Hep C RNA)
- •History of active or latent tuberculosis (TB) infection (must test negative using the QuantiFERON test to be eligible)
- •History of serious infections requiring intravenous (by catheter that delivers antibiotics into your blood) treatment
- •Live vaccine within 28 days prior to baseline or plan to receive one during the study
研究组 & 干预措施
PRN1008
Part A: Open-label PRN1008, 12 weeks; 12 weeks follow-up; Part B: Open-label PRN1008, 24 weeks; 4 weeks follow-up
干预措施: PRN1008 (Drug)
结局指标
主要结局
Percentage of Participants With Treatment-emergent Adverse Events
时间窗: Part A: until 24 weeks and Part B: until 28 weeks
Treatment-emergent adverse events (TEAEs) including clinically significant changes in physical examination, laboratory tests, and vital signs. An AE was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily had to have a causal relationship with the treatment. TEAEs were defined as AEs that developed or worsened or became serious during on-treatment phase that was defined as the time from the start of study drug up to study completion.
Percentage of Participants Who Are Able to Achieve Control of Disease Activity (CDA) Within 4 Weeks of Starting PRN1008 Treatment Without the Need for Doses of Prednisone or Prednisolone >0.5 mg/kg
时间窗: 4 weeks
CDA was defined as the time at which new lesions cease to form and established lesions begin to heal.
次要结局
- Time to End of Consolidation Phase (ECP)(Part A: until 24 weeks and Part B: until 28 weeks)
- Time to Control of Disease Activity (CDA)(Part A: until 24 weeks and Part B: until 28 weeks)
- Time to Complete Remission (CR)(Part A: until 24 weeks and Part B: until 28 weeks)
- Time to Relapse After PRN1008 Treatment Discontinuation(Part A: until 24 weeks and Part B: until 28 weeks)
- Change From Baseline in Treatment of Autoimmune Bullous Diseases Quality of Life (TABQOL) Scores(Part A: until 24 weeks and Part B: until 28 weeks)
- Percentage of Participants Able to Achieve Control of Disease Activity (CDA) Without Corticosteroids Within 4 Weeks(4 weeks)
- Percentage of Participants Able to Achieve a Complete Response (CR) Without Corticosteroids(Part A: 12 weeks treatment and Part B: 24 weeks treatment)
- Percentage of Participants Able to Achieve Complete Remission (CR) Without the Need for Doses of Prednisone or Prednisolone of Greater Than 0.5mg/kg(Part A: 12 weeks treatment and Part B: 24 weeks treatment)
- Change From Baseline in Appetite (SNAQ Score)(Part A: until 24 weeks and Part B: until 28 weeks)
- Cumulative Corticosteroid Usage(Part A: until 24 weeks and Part B: until 28 weeks)
- Percentage Change From Baseline in Pemphigus Disease Area Index (PDAI) Total Activity Scores(Part A: until 24 weeks and Part B: until 28 weeks)
- Change From Baseline in Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) Total Activity Score(Part A: until 24 weeks and Part B: until 28 weeks)
- Change From Baseline in Autoimmune Bullous Diseases Quality of Life (ABQOL)(Part A: until 24 weeks and Part B: until 28 weeks)