A Double, Blind Placebo-controlled, Randomized Trial to Study Efficacy and Safety of the Viaskin Milk for Treating Milk Induced Eosinophilic Esophagitis in Children
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Change in Maximum Esophageal Eosinophil Count From Baseline to End of Double-blind Treatment. (Intent to Treat Population)
研究概览
简要总结
This is a single-site, double-blind, placebo-controlled, randomized trial to study efficacy and safety of the Viaskin® Milk Patch for children with milk induced Eosinophilic Esophagitis (EoE). 20 subjects will be randomized 3:1 to Viaskin® Milk or placebo patch.
详细描述
This is a double-blind, placebo-controlled, randomized trial to study the efficacy and safety of Viaskin® Milk, an allergen extract of milk administered epicutaneously using the Viaskin® epicutaneous delivery system (EPIT) in subjects from 4 to 17 years old with a milk induced Eosinophilic Esophagitis. Subjects will be randomized in a 3:1 ratio into two different treatment groups, to receive EPIT with Viaskin® Milk (500 µg of milk proteins) or placebo.
Subjects who complete the double-blind treatment period (approximately 11 months), will automatically rollover into an open label treatment period (additional 11 months). All subjects will receive the 500 µg (micrograms) Viaskin Milk patch.
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
- 4 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Well-documented medical history of Eosinophilic Esophagitis after ingestion of milk and currently following a strict milk-free diet.
- •Upper endoscopy and biopsy at initial clinical evaluation during Visit 2 showing greater than 15 eosinophils/high power field (HPF) isolated to the esophagus meeting the consensus diagnosis of Eosinophilic Esophagitis, after milk was re-introduced into the subject's diet (30 ml/day for 1 week to 2 months), while the subject was on proton pump inhibitor.
- •Upper endoscopy and biopsy at second clinical evaluation during Visit 3 showing less than 5 eosinophils per HPF isolated to the esophagus after a minimum of 6 weeks under milk-free diet, and while the subject is on proton pump inhibitor.
- •Negative pregnancy test for female subjects of childbearing potential. Females of childbearing potential must use effective method of contraception to prevent pregnancy and agree to continue to practice an acceptable method of contraception for the duration of participation in the study. Sexual abstinence will be accepted as an effective method of contraception for girls below 18 years of age.
- •Subjects and/or parents/guardians willing to comply with all study requirements during their participation in the study.
- •Signed informed consent from parent(s)/guardian(s) of children < 18 years + children's assent.
- •Subjects agree to maintain a constant diet during the trial, with the exception of milk.
- •Subjects will maintain constant medications for asthma and allergic rhinitis during the trial.
排除标准
- •Subjects with a history of severe anaphylaxis to milk with the following symptoms: hypotension, hypoxia, neurological compromise (collapse, loss of consciousness or incontinence), Quincke Edema or requiring intubation.
- •Active IgE- mediated milk allergy.
- •Pregnancy or lactation.
- •Subjects with other eosinophilic gastrointestinal disorders.
- •Subjects on swallowed corticosteroids or anti-leukotrienes for Eosinophilic Esophagitis.
- •Subjects with symptomatic allergy to pollens whose symptoms during the corresponding pollen season might interfere with the recording of symptoms during the upper endoscopy/biopsy, if the upper endoscopy/biopsy is conducted during the pollen season. The Investigator will have to ensure that the period for conducting the upper endoscopy for such a subject will be outside of the pollen season.
- •Subjects treated with systemic long-acting corticosteroids (depot corticosteroids) within 12 weeks prior to Visit 1 and/or systemic short-acting corticosteroid within 4 weeks prior to Visit 1 or any systemic corticosteroid at screening.
- •Subjects with asthma conditions defined as follows:
- •Uncontrolled persistent asthma by National Asthma Education and Prevention Program Asthma guidelines (2007).
- •at least two systemic corticosteroid courses for asthma in the past year or one oral corticosteroid course for asthma in the past three months;
- •prior intubation for asthma in the past two years.
- •Subjects on β-blocking agents, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, calcium channel blockers or tricyclic antidepressant therapy.
- •Subjects undergoing any type of immunotherapy to any food within one year prior to Visit
- •Subjects presently on aeroallergen immunotherapy and unwilling or unable to discontinue.
- •Subjects currently treated with anti-tumor necrosis factor drugs or anti-Immunoglobulin E (IgE) drugs or any biologic immunomodulatory therapy within one year prior to Visit
- •Allergy or known hypersensitivity to placebo excipients either of the Viaskin® or Tegaderm®.
- •Subjects suffering from generalized dermatologic diseases with no intact skin zones to apply the Viaskin®, or urticarial and mast cell disorders such as chronic idiopathic urticaria.
- •Subjects (or parents of subjects) with obvious excessive anxiety and unlikely to cope with the conditions of an upper endoscopy and biopsy.
- •Past or current disease(s), which in the opinion the sponsor-investigator, may affect the subject's participation in this study including but not limited to active autoimmune disorders, immunodeficiency, malignancy, uncontrolled diseases (hypertension, psychiatric (especially anxiety), cardiac), or other disorders (e.g., liver, gastrointestinal, kidney, cardiovascular, pulmonary disease, or blood disorders).
- •Any history of drug or alcohol abuse in the past five years.
- •Subjects unable to follow the protocol and the protocol requirements.
- •Participation in another clinical intervention study in the three months prior to Study Visit
- •Subjects on any experimental drugs or treatments.
研究组 & 干预措施
Viaskin Milk 500 mcg
Viaskin patch containing milk protein. The patch is applied to the skin
干预措施: Viaskin Milk 500 mcg (Drug)
Viaskin Placebo
Viaksin patch without any milk protein.
干预措施: Viaskin Placebo (Drug)
结局指标
主要结局
Change in Maximum Esophageal Eosinophil Count From Baseline to End of Double-blind Treatment. (Intent to Treat Population)
时间窗: From baseline to month 11 (end of double blind phase)
Esophageal biopsy samples will be obtained prior to randomization and after completion of treatment. Intraepithelial eosinophils will be counted in all high powered fields (HPFs) using light microscopy. A HPF will be counted only if at least half of the field is occupied by tissue. The maximum eosinophil count per HPF will be reported for each esophageal biopsy site (at each of 2 levels). The maximum eosinophil count for each patient will be calculated from either level. For the final outcome, mean from each individual patients maximum eosinophil count/hpf along with standard deviation will be calculated.
Change in Eosinophils/High Power Field at End of Double-blind (DB) (Per Protocol Patients)
时间窗: Month 11(end of double blind phase)
Esophageal biopsy samples will be obtained prior to randomization and after completion of treatment. Intraepithelial eosinophils will be counted in all high powered fields (HPFs) using light microscopy. A HPF will be counted only if at least half of the field is occupied by tissue. The maximum eosinophil count per HPF will be reported for each esophageal biopsy site (at each of 2 levels). The maximum eosinophil count for each patient will be calculated from either level. For the final outcome, mean from each individual patients maximum eosinophil count/hpf along with standard deviation will be calculated.
次要结局
- Esophageal Endoscopy Score (ITT)(At end of DB phase, at 11 months)
- Eosinophils Per HPF at End of Double Bind Protocol (Per Protocol) Patients(End of DB Phase, at 11 months)
- Pediatric Eosinophil Esophagitis Symptom Score (PP Population)(Month 11, End of Double Blind Placebo Control)
- Eosinophilic Esophagitis Symptom Score (Intent to Treat Population)(Total Symptom Score at End of DB Phase, Month 11)
- Pediatric Eosinophilic Esophagitis Symptom Score (ITT)(Month 11, end of Double Blind Phase)
- Endoscopy Score (Per Protocol Patients)(Month 11 (end of double blind phase))
研究者
Antonella Cianferoni
Assistant Professor
Children's Hospital of Philadelphia