An Investigator-initiated, Randomized, Double-blind, Placebo Controlled Study of Apremilast to Demonstrate Efficacy in Subjects With Nummular Eczema
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 31
- 试验地点
- 1
- 主要终点
- PGA
研究概览
简要总结
This is an investigator-initiated, single-center, prospective, randomized, double-blind, interventional phase IIb study. Forty patients with clinically and histologically confirmed nummular eczema will be enrolled according to inclusion and exclusion criteria. Patients will be included after written informed consent is obtained. Prior to randomization, average application rate of class II topical steroids per day will be measured for 4 weeks. Subsequently, patients will be randomized in a 1:1 ratio into one arm to receive Apremilast 30 mg BID (following titration phase) for 16 weeks or a second arm receiving identically matching placebo for 16 weeks. From beginning of week 17, all patients will start an open-label treatment with Apremilast 30 mg BID until week 32. Concomitant use of topical steroids (class II) is allowed during the study. During the treatment period both placebo and Apremilast will be applied p.o. from week 0 until week 32.
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
- Quadruple (Participant, Care Provider, 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
- •Clinically confirmed diagnosis of nummular eczema
- •Biopsy-proven, meaning histology consistent with eczema (including PAS-staining)
- •PGA ≥ 3 on a 5 point scale
- •History of continuous use of topical steroids for the last 8 weeks
- •Age 18-85 years of age, body weight ≥ 40 kg and ≤ 160 kg
- •Signed informed consent from patient
排除标准
- •Permanent severe diseases, especially those affecting the immune system
- •Pregnancy or breast feeding
- •History or presence of epilepsy, significant neurological disorders, depression, suicidal ideation and behaviour, cerebrovascular attacks or ischemia
- •History or presence of myocardial infarction or cardiac arrhythmia which requires drug therapy
- •Evidence of severe renal dysfunction defined as:
- •eGFR < 30 ml/min/1,73 m2 (calculated using the MDRD formula) at screening (Visit 1)
- •Evidence of significant hepatic disease defined as:
- •At screening (Visit 1):
- •Alkaline phosphatase >3x upper limit of normal (ULN) or alkaline phosphatase >2,5x ULN and total bilirubin > 2xULN or
- •Aspartate transaminase (AST, SGOT]) and alanine transaminase (ALT, SGPT]) > 2.5x upper limit of normal (ULN)
- •History of lymphoproliferative disorders
- •Patients who are considered potentially unreliable or where it is envisaged the patient may not consistently attend scheduled study visits
- •Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant unless they use effective contraception during the study and for 4 weeks after study completion or discontinuation. The chosen form of birth control must be effective by the time the patient receives her first dose of study drug.
- •Inability or unwillingness to undergo repeated venipuncture (e.g., because of poor tolerability or lack of access to veins)
- •Inability or unwillingness to undergo repeated punch biopsies
- •History of allergy to any component of the study medication
- •Current use of strong cytochrome P450 enzyme inducers (eg, rifampicin, phenobarbital, carbamazepine, phenytoin and St John's wort)
- •Patients with rare hereditary problems of galactose intolerance, lapp lactase deficiency or glucose-galactose malabsorption
- •Evidence of acute contact dermatitis at screening
- •Evidence of underweight, defined as BMI < 18,5 kg/m2
- •Evidence of Zink deficiency defined as Zink level < 20 µg/dL in serum
研究组 & 干预措施
Apremilast
Patients randomized to this arm will start Apremilast with a titration phase of 5 days, followed by 30 mg Apremilast tablets twice daily (BID) by mouth (PO) for a total of 32 weeks (including titration phase).
干预措施: Apremilast (Drug)
Placebo + Apremilast
Patients randomized to this arm will receive identically matching placebo (including the titration phase) by mouth for first 16 weeks. Placebo participants will be switched to receive Apremilast 30 mg BID from beginning of Week 17 for another 16 weeks. In this arm Apremilast will be started without titration.
干预措施: Apremilast (Drug)
Placebo + Apremilast
Patients randomized to this arm will receive identically matching placebo (including the titration phase) by mouth for first 16 weeks. Placebo participants will be switched to receive Apremilast 30 mg BID from beginning of Week 17 for another 16 weeks. In this arm Apremilast will be started without titration.
干预措施: Placebo Oral Tablet (Drug)
结局指标
主要结局
PGA
时间窗: week 16
Number of Patients Achieving an Improvement (Decrease) in PGA (Physician Global Assessment) by two or more points at week 16 as compared to week 0 or achieving an absolute PGA of 0 or 1 at Week 16
次要结局
- Safety: Safety of Apremilast will be Assessed by Evaluating Adverse Events (AEs) - Type, frequency, severity, and relationship of the AEs to apremilast(week 36)
- EASI(week 16 and 32)
- Use of topical steroids(week 16 and 32)
- Histology(week 16)
- PGA score Arm 2(week 32)
- Transepidermal Waterloss (TEWL)(week 16 and 32)
- DLQI(week 16 and 32)
- Pruritus Visual Analog Scale (VAS)(week 16 and 32)
- TSQM(week 16 and 32)