A Randomized, Placebo-controlled Phase IIa Clinical Trial to Evaluate the Efficacy and Safety of Subcutaneous Dupilumab in Localized Scleroderma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 45
- 试验地点
- 4
- 主要终点
- LoSCAT target lesion
研究概览
简要总结
The DupiMorph study evaluates the efficacy of Dupilumab in localized scleroderma patients. Dupilumab is approved in the US and EU for the treatment of moderate/severe atopic dermatitis and since 2018 in the US for severe asthma therapy.
详细描述
Localized scleroderma (LS) comprises a heterogenous group of sclerotic skin disorders. The incidence of LS is reported to be approximately 27 cases/ 1x106 and is hence approximately 2-3-fold higher compared to systemic scleroderma. Although in most cases not lethal the disease can significantly impact quality of life. Depending on the location of fibrosis, the disorder can cause bone deformities, alopecia, skin atrophy or lesions with severe hypo-/hyperpigmentation.
The disease is pathomechanistically poorly understood and no effective therapy is currently approved. The most promising treatments up to date include methotrexate ± pulsed corticosteroids or phototherapy with PUVA or UVA1. Yet, the number of treated patients in these studies is low. The response rates are low and inconsistent with approximately 50% of patients treated with UVA1 experience a recurrence within three years. There are no studies on efficacy of topical corticosteroids in LS. Small pilot studies and few case reports describe regression of lesions after topical calcineurin inhibitors. In addition, current therapies can only be applied for a short time during the acute phase due to the side effect profile after long-term use (e.g. skin atrophy in response to topical steroids, skin cancer in response to long term UV therapy, multiple side effects by long- term use of methotrexate and/or corticosteroids). Hence, this study evaluates, in comparison with placebo, the efficacy of Dupilumab administered subcutaneously every 14 days in patients with Morphea (plaque type) or generalized localized scleroderma (affecting at least three anatomic sites).
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)
盲法说明
Permuted blocks of varying length with allocation ratio (verum:placebo = 2:1); double-blind, i.e. patients and investigators are masked
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
- •Subject is a male or female ≥18 years of age on the day the study informed consent is signed
- •Out-patient status
- •Caucasian
- •Morphea (plaque type) or Generalized localized scleroderma (affecting at least three anatomic sites)
- •At least one lesions with lilac ring (active phase of the disease);
- •Activity of LS within the last 12 month (as defined by progression of size or new developing plaque)
- •For women of childbearing potential: negative pregnancy test at Visit 1
- •For women of childbearing potential: Use of effective method of contraception from 4 weeks prior to enrolment, throughout study treatment until 12 weeks after the last IMP dose.
- •Written informed consent signed
排除标准
- •Systemic immunosuppressive therapy or UV therapy less than 3 months before enrollment.
- •Participation in another trial of IMPs or devices parallel to, or less than 6 months before or previous participation in this trial
- •Pregnancy or breastfeeding mother
- •Diagnosis of other significant chronic inflammatory or autoimmune disorders. Patients with the following autoimmune disorders are excluded from the study: Multiple sclerosis, primary biliary cirrhosis, type I diabetes mellitus. Patients with the following autoimmune disorders are regarded as eligible: Lichen sclerosus, vitiligo, alopecia arthritis, thyroid diseases (e.g. Hashimoto disease). Patients with any autoimmune disorder not listed above should only be included after consultation with the principal coordinating investigator.
- •Topical immunosuppressive therapy less than 1 month before enrollment
- •Concurrent phototherapy
- •Known infection with helminths (helminthosis)
- •Any condition or laboratory abnormality that, in the judgment of the investigator, would put the subject at unacceptable risk for participation in the study or may interfere with the assessments included in the study. E.g. uncontrolled psychiatric illness or history of clinical relevant drug abuse.
- •Known hypersensitivity to any components of the IMP
- •Treatment with a live (attenuated) vaccine within 3 months prior to enrollment
- •History of malignancy (except patients with completely treated in situ carcinoma of the cervix, completely treated and resolved non-metastatic squamous or basal cell carcinoma of the skin)
- •Known diagnosis of active tuberculosis or non-tuberculous mycobacterial infection or latent untreated tuberculosis unless it is well documented by a specialist that the patient has been adequately treated
- •Known diagnosis of HIV, HBV or HCV infection
- •Regular use (more than 2 visits per week) of a tanning booth/parlor
- •Known diagnosis of asthma
研究组 & 干预措施
Dupilumab
30 patients; Dupilumab s.c. injection; 2 ready-to-use syringes (600 mg) initial (V1), 1 ready-to-use syringe (300 mg) every 14 days (V2- V13) Dupilumab s.c. injection in healthy skin, 24 weeks
干预措施: Dupilumab 300Mg Solution for Injection (Drug)
Placebo
15 patients; placebo s.c. injection; 2 ready-to-use syringes initial (V1), 1 ready-to-use syringe every 14 days (V2-V13) placebo s.c. injection in healthy skin, 24 weeks
干预措施: Placebo (Other)
结局指标
主要结局
LoSCAT target lesion
时间窗: Baseline to End of Treatment Visit, 24 weeks
Treatment response is assessed using the LoSCAT (Localized Scleroderma Cutaneous Assessment Tool). Target lesion will be assessed at Baseline and End of Treatment. Score reduction by 50% after 24 weeks (End of Treatment Visit V14) compared to Baseline Visit (V1) is defined as treatment response.
次要结局
- Body weight(Baseline to Follow-Up Visit, 48 weeks)
- LoSDI all lesions(Baseline to Follow-Up Visit, 48 weeks)
- Body temperature(Baseline to Follow-Up Visit, 48 weeks)
- Anti-nuclear antibodies (ANAs) levels(Baseline to Follow-Up Visit, 48 weeks)
- mLoSSI all lesions(Baseline to Follow-Up Visit, 48 weeks)
- RT-qPCR(Baseline to End of Treatment Visit, 24 weeks)
- Adverse events (AEs)(Baseline to Follow-Up Visit, 48 weeks)
- DLQI(Baseline to Follow-Up Visit, 48 weeks)
- Blood pressure(Baseline to Follow-Up Visit, 48 weeks)
- Pulse rate(Baseline to Follow-Up Visit, 48 weeks)
- Haematocrit (HcT)(Baseline to Follow-Up Visit, 48 weeks)
- Haemoglobin(Baseline to Follow-Up Visit, 48 weeks)
- Blood cell count(Baseline to Follow-Up Visit, 48 weeks)
- Clinical Chemistry(Baseline to Follow-Up Visit, 48 weeks)
- Number of lesions(Baseline to Follow-Up Visit, 48 weeks)
- RNAseq(Baseline to End of Treatment Visit, 24 weeks)
- Physical examination(Baseline to Follow-Up Visit, 48 weeks)
- Serum cytokine levels(Baseline to Follow-Up Visit, 48 weeks)
- Blood Enzymes(Baseline to Follow-Up Visit, 48 weeks)
研究者
Sabine Eming
Principal Coordinating Investigator
University of Cologne