A Phase 2, Multicentre, Single Arm, Pilot Study to Assess the Efficacy and the Safety of 150 mg Twice a Day Oral DF2156A in Patients With Active Bullous Pemphigoid.
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 4
- 试验地点
- 4
- 主要终点
- Total number of blisters from baseline
研究概览
简要总结
The objective of this clinical trial was to evaluate whether DF2156A has a potential in improving the clinical outcome in patients with active blistering bullous pemphigoid (BP) to warrant its further development. The safety of DF2156A in the specific clinical setting was also evaluated.
详细描述
The study was a phase 2, multicentre, single arm, pilot study. It has been designed to determine if DF2156A has sufficient activity to warrant its further development.
A total of twelve (12) BP patients were planned to be involved. They were planned to receive DF2156A orally at the dose of 150 mg twice a day for a maximum of 14 days.
Recruitment was intended to be competitive among the study sites, until the planned number of patients is enrolled. Competitive recruitment has been chosen to increase the speed of recruitment and to account for any unexpected occurrence at a site that negatively impact enrolment rate.
The single arm design has been chosen as an appropriate tool for this pilot phase 2 study, considering that BP is a rare disease where a placebo control is not acceptable. Moreover, as there is no spontaneous acute recovery from the active blistering condition, any improvement in patient outcome can be attributed to a positive effect of the Investigational Product.
Each patient was intended to be involved in the study for a screening period, for 14 days of treatment, for all required measurements up to hospital discharge (planned on day 8+1 of treatment) and for one assessment occasion on day 15+1, either during hospital stay or after hospital discharge (out-patient visit). An optional post-treatment visit might be scheduled at day 30+3.
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
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 and female patients aged >50 years.
- •Patients with newly diagnosed or relapsing bullous pemphigoid based on clinical diagnosis to be confirmed by direct immunofluorescence and indirect immunofluorescence on salt-spit skin (or BP180 and/or BP230 ELISA). Confirmation by laboratory tests will be obtained ideally before or anyway within one week after enrolment.
- •For the purpose of this study, clinical relapses are defined as re-appearance of clinical symptoms after the patient had attained remission lasting for more than 3 months without immunosuppressive treatment. In patients with relapsing BP, clinical diagnosis will be confirmed by indirect immunofluorescence or BP180 and/or BP230 ELISA only.
- •Patients with mild to moderate active blistering disease (total number of blisters between 1 and 30) whether associated or not with urticarial/eczematous lesions.
- •Patients with modified ABSIS score ≤50
- •Patients free from any systemic treatments that may affect the course of the disease with the following off-period prior to enrolment:
- •3 weeks: steroids, dapsone, tetracyclines, nicotinamide,
- •3 months: azathioprine, mycofenolate mofetil, cyclophosphamide, methotrexate, intravenous immunoglobulins, immunoadsorption, TNF antagonists
- •12 months: rituximab, leflunomide
- •Patients free from any topical treatments other than topical antibiotics and antiseptics in the 4 days prior to enrolment.
- •Patients able to comply with the protocol procedures for the duration of the study, including scheduled follow-up visits and examinations.
- •Patients able to provide informed consent.
排除标准
- •Patients with a Karnofsky rating score <40%.
- •Patients with mucosal involvement.
- •Patients with moderate to severe renal impairment as per calculated creatinine clearance (CLcr) < 50 mL/min according to the Cockcroft-Gault formula (Cockcroft-Gault , 1976).
- •Patients with hepatic dysfunction defined by increased ALT/AST > 3 x upper limit of normal (ULN) and increased total bilirubin > 3 mg/dL [>51.3 μmol/L].
- •Patients with hypoalbuminemia defined as serum albumin < 3 g/dL.
- •Patients with a baseline (day 0/1, pre-dose) QTcF > 470 msec.
- •Patients who had a myocardial infarction in the 6 months prior to enrolment.
- •Patients on treatment with phenytoin, warfarin, sulphonylurea hypoglycemics (e.g. tolbutamide, glipizide, glibenclamide/glyburide, glimepiride, nateglinide) and high dose of amitriptyline (> 50 mg/day).
- •Patients with known hypersensitivity to non-steroidal antiinflammatory drugs.
- •Patients using any investigational agent within 12 months prior to enrolment.
- •Pregnant or breast feeding women. Unwillingness to use effective contraceptive measures up to 2 months after the end of study drug administration (females and males).
- •Additional Exclusion Criteria for Germany only:
- •Patients with hypokalemia defined as serum potassium < 3.5 mmol/L.
- •Patients with clinically relevant bradycardia (heart rate < 50 beats/min)
- •Patients with a complete left bundle branch block.
- •Patients with a history of uncontrolled or labile hypertension
- •Patients with a history of congestive heart failure.
- •Patients with a history of cardiomyopathy.
- •Patients with unstable angina pectoris.
- •Patients with a personal or family history of congenital or documented acquired QT interval prolongation.
- •Patients with a significant atrial or ventricular arrhythmia or symptomatic arrhythmia in the past.
研究组 & 干预措施
DF2156A 150 mg
150 mg capsule twice a day (every 12 h) for a maximum of 14 days
干预措施: DF2156A (Drug)
结局指标
主要结局
Total number of blisters from baseline
时间窗: day 0/1 (pre-dose), 8 and 15
Total number of blisters from baseline
Modified ABSIS score change from baseline
时间窗: day 0/1 (pre-dose), 8 and 15
ABSIS score will be measured according to the pemphigus scoring sheet \[Rosenbach, 2009\] adjusted to the clinical manifestation in BP patients, as per specifications in protocol.
Physician Global Assessment (PGA) score measured on a 0-10 scale [Rosenbach, 2009]. Percent change from baseline
时间窗: day 0/1 (pre-dose), 8 and 15
PGA score will be measured according to the following scale: 0 1 2 3 4 5 6 7 8 9 10 Perfect Worst health skin condition imaginable The following guidelines will help standardize PGA: 0: no lesions 2: almost cleared, no functional impairment 4: few lesions / low functional impairment 6: moderate 8: severe / extensive 10: life-threatening
Pruritus measured on a 10 cm visual analogue scale. Absolute value change from baseline
时间窗: day 0/1 (pre-dose), 8 and 15
Pruritus will be measured according to the following scale: 0 10 No pruritus Worst pruritus I can imagine
Eosinophil blood count. Percent change from baseline
时间窗: screening and day 15
Eosinophil blood count. Percent change from baseline
Percentage of patients with treatment failure (drug discontinuation due to disease worsening)
时间窗: day 8
treatment failure (drug discontinuation due to disease worsening)
Percentage of patients completely free from blisters
时间窗: day 15
Percentage of patients completely free from blisters
Number of patients who are still free from blisters without requiring any systemic or topical rescue treatment - Optional
时间窗: Day 30
Number of patients who are still free from blisters without requiring any systemic or topical rescue treatment - Optional
QTcF. Change from baseline
时间窗: Italy: day 0/1 (pre-dose), day 1, 5, 8 and 15___Ger:day 0/1 (pre-dose), day 1, 3, 5, 8 and 15
QTcF. Change from baseline
Incidence of Adverse Events and Serious Adverse Events
时间窗: throughout the study up to day 15 or 30
Incidence of Adverse Events and Serious Adverse Events
Blisters percent change from baseline
时间窗: day 0/1 (pre-dose), 8 and 15
Blisters percent change from baseline
Modified ABSIS score percent change from baseline
时间窗: day 0/1 (pre-dose), 8 and 15
ABSIS score will be measured according to the pemphigus scoring sheet \[Rosenbach, 2009\] adjusted to the clinical manifestation in BP patients, as per specifications in protocol.
Physician Global Assessment (PGA) score measured on a 0-10 scale [Rosenbach, 2009]. Absolute value change from baseline
时间窗: day 0/1 (pre-dose), 8 and 15
PGA score will be measured according to the following scale: 0 1 2 3 4 5 6 7 8 9 10 Perfect Worst health skin condition imaginable The following guidelines will help standardize PGA: 0: no lesions 2: almost cleared, no functional impairment 4: few lesions / low functional impairment 6: moderate 8: severe / extensive 10: life-threatening
Number of patients with treatment failure (drug discontinuation due to disease worsening)
时间窗: day 8
Number of patients with treatment failure (drug discontinuation due to diseas
Pruritus measured on a 10 cm visual analogue scale. Percent change from baseline
时间窗: day 0/1 (pre-dose), 8 and 15
Pruritus will be measured according to the following scale: 0 10 No pruritus Worst pruritus I can imagine
Number of patients completely free from blisters
时间窗: day 15
Number of patients completely free from blisters
QTcF. Absolute value
时间窗: Italy: day 0/1 (pre-dose), day 1, 5, 8 and 15___Ger:day 0/1 (pre-dose), day 1, 3, 5, 8 and 15
QTcF. Absolute value
Eosinophil blood count. Absolute number change from baseline
时间窗: screening and day 15
Eosinophil blood count. Absolute number change from baseline
次要结局
- Plasma levels of DF2156A and its major metabolites (DF2227 and DF2108) at steady state conditions(day 5 and 8)