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Trial record 2 of 2 for:    viaskin milk

Milk Patch for Eosinophilic Esophagitis (SMILEE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02579876
Recruitment Status : Completed
First Posted : October 20, 2015
Results First Posted : July 10, 2019
Last Update Posted : July 10, 2019
Sponsor:
Collaborator:
DBV Technologies
Information provided by (Responsible Party):
Antonella Cianferoni, Children's Hospital of Philadelphia

Tracking Information
First Submitted Date  ICMJE October 14, 2015
First Posted Date  ICMJE October 20, 2015
Results First Submitted Date  ICMJE March 27, 2019
Results First Posted Date  ICMJE July 10, 2019
Last Update Posted Date July 10, 2019
Study Start Date  ICMJE October 2015
Actual Primary Completion Date December 20, 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 20, 2019)
  • Change in Maximum Esophageal Eosinophil Count From Baseline to End of Double-blind Treatment. (Intent to Treat Population) [ Time Frame: 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) [ Time Frame: 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.
Original Primary Outcome Measures  ICMJE
 (submitted: October 16, 2015)
Change in maximum esophageal eosinophil count from baseline to end of treatment. [ Time Frame: From baseline to Month 12. ]
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).
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 20, 2019)
  • Eosinophilic Esophagitis Symptom Score (Intent to Treat Population) [ Time Frame: Total Symptom Score at End of DB Phase, Month 11 ]
    Symptoms of Eosinophilic Esophagitis range from abdominal pain, gastroesophageal reflux, vomiting, and difficult swallowing. Investigator assessment of the subject's symptoms was completed on a 4-point Likert scale for 3 separate symptoms (vomiting, abdominal pain and dysphagia). Investigator assessment of the subject's symptoms was completed on a 4-point Likert scale for 3 separate symptoms (vomiting, abdominal pain and dysphagia). (0-none, 1-mild, 2-moderate, 3-severe, ). Total score is reported with a range of 0 to 9. A lower score is better.
  • Esophageal Endoscopy Score (ITT) [ Time Frame: At end of DB phase, at 11 months ]
    Upper endoscopies with biopsies (2 each of proximal and distal, plus any inflamed areas) will be completed before and after each treatment period. Each endoscopy will be scored using a validated standardized measure which examines 4 major esophageal features (rings, furrows, exudates and edema) and the presence of minor features of narrow caliber esophagus, feline esophagus, stricture and crepe paper esophagus. Each feature is graded: 0-none, 1 mild, 2-moderate, 3-severe. The scores are summed including both minor and major criteria. Total score is presented and lower score is better. The range is from 0-12
  • Eosinophils Per HPF at End of Double Bind Protocol (Per Protocol) Patients [ Time Frame: End of DB Phase, at 11 months ]
    Maximum Eosinophils/HPF after milk reintroduction at the end of double bind phase
  • Pediatric Eosinophilic Esophagitis Symptom Score (ITT) [ Time Frame: Month 11, end of Double Blind Phase ]
    Measure of Pediatric Eosinophilic Esophagitis symptom Score (PEESS) at the end of DB phase for the Intent to Treat Population The PEESS® is a 20 question survey asking patient symptom intensity and frequency on a 5 point scale (0 to 4) for each question for the preceding month. Therefore, the total score can range from 0 to 80. The total score is reported and lower score is better
  • Endoscopy Score (Per Protocol Patients) [ Time Frame: Month 11 (end of double blind phase) ]
    Upper endoscopies with biopsies (2 each of proximal and distal, plus any inflamed areas) will be completed before and after each treatment period. Each endoscopy will be scored using a validated standardized measure which examines 4 major esophageal features (rings, furrows, exudates and edema) and the presence of minor features of narrow caliber esophagus, feline esophagus, stricture and crepe paper esophagus. Each feature is graded: 0-none, 1 mild, 2-moderate, 3-severe. The scores including both major and minor criteria are summed. Total score is presented and lower score is better. The range is from 0-12
  • Pediatric Eosinophil Esophagitis Symptom Score (PP Population) [ Time Frame: Month 11, End of Double Blind Placebo Control ]
    Pediatric Eosinophilic Esophagitis Symptom Score at end of DB phase using the validated Pediatric Eosinophilic Esophagitis Symptom Score (PEESS).The PEESS® is a 20 question survey asking patient symptom intensity and frequency on a 5 point scale (0 to 4) for each question for the preceding month. Therefore, the total score can range from 0 to 80. The total score is reported and lower score is better.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 16, 2015)
  • Change in Eosinophilic Esophagitis symptom score between baseline and end of treatment. [ Time Frame: From baseline to Month 12 ]
    Symptoms of Eosinophilic Esophagitis range from abdominal pain, gastroesophageal reflux, vomiting, and difficult swallowing. The symptoms will range from none to very severe as in Spergel54. The symptoms will be in 3 categories and individual symptoms and total symptoms scores will be collected on a range of 0-4 (0-none, 1-mild, 2-moderate, 3-severe and 4-very severe).
  • Change in Esophageal Endoscopy Score between baseline and end of treatment. [ Time Frame: From baseline to Month 12 ]
    Upper endoscopies with biopsies (2 each of proximal and distal, plus any inflamed areas) will be completed before and after treatment. Each endoscopy will be scored using a validated standardized measure which examines 4 major esophageal features (rings, furrows, exudates and edema) and the presence of minor features of narrow caliber esophagus, feline esophagus, stricture and crepe paper esophagus. Each feature is graded: 0-none, 1 mild, 2-moderate, 3-severe.
  • Change in the Eosinophilic Esophagitis Quality of Life (QOL) Score between baseline and end of treatment. [ Time Frame: From baseline to Month 12 ]
    Quality of life is a measurement of a subject's overall well-being. QOL will be measured by the validated age specific PedsQL Eosinophilic Esophagitis tool. The 33-item questionnaire includes for self-rating of symptoms (chest/throat/stomach pain and nausea/vomiting, trouble swallowing), Treatment, Worry (about treatment and disease), Communication with others, Food and Eating (allergies and limitations), Food Feelings (emotions associated with food allergies). The format is a Likert response scale, with higher scores indicating better HRQOL and lower EoE symptoms and problems.
  • Time to development symptoms after milk reintroduction (month 9) until the end of treatment. [ Time Frame: From Month 9 to Month 12 ]
    Milk will be reintroduced to all subjects 9 months after the second endoscopy in a similar amount and duration as done during the screening period while the subject is on a proton pump inhibitor. A daily symptom diary will be completed by subjects to record dietary information, symptoms and medications or treatment taken for symptoms.
  • Change in T cell count between baseline and end of treatment. [ Time Frame: Baseline to month 12 ]
  • Change in IgE levels specific to milk between baseline and end of treatment. [ Time Frame: Baseline to month 12 ]
  • Change in IgG4 levels specific to milk between baseline and end of treatment. [ Time Frame: Baseline to month 12 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Milk Patch for Eosinophilic Esophagitis
Official Title  ICMJE A Double, Blind Placebo-controlled, Randomized Trial to Study Efficacy and Safety of the Viaskin Milk for Treating Milk Induced Eosinophilic Esophagitis in Children
Brief Summary 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.
Detailed Description

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Eosinophilic Esophagitis
  • Milk Allergy
Intervention  ICMJE
  • Drug: Viaskin Milk 500 mcg
    Biological: Viaskin Milk 500 mcg Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing 500 mcg cow's milk proteins.
    Other Names:
    • Milk Patch
    • Viaskin Epicutaneous ImmunoTherapy (EPIT)
  • Drug: Viaskin Placebo
    Biological: Viaskin Placebo Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing a matching placebo formulation.
    Other Names:
    • Placebo Patch
    • Placebo Epicutaneous ImmunoTherapy (EPIT)
Study Arms  ICMJE
  • Active Comparator: Viaskin Milk 500 mcg
    Viaskin patch containing milk protein. The patch is applied to the skin
    Intervention: Drug: Viaskin Milk 500 mcg
  • Placebo Comparator: Viaskin Placebo
    Viaksin patch without any milk protein.
    Intervention: Drug: Viaskin Placebo
Publications * Spergel JM, Elci OU, Muir AB, Liacouras CA, Wilkins BJ, Burke D, Lewis MO, Brown-Whitehorn T, Cianferoni A. Efficacy of Epicutaneous Immunotherapy in Children With Milk-Induced Eosinophilic Esophagitis. Clin Gastroenterol Hepatol. 2020 Feb;18(2):328-336.e7. doi: 10.1016/j.cgh.2019.05.014. Epub 2019 May 14.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 16, 2015)
20
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE November 20, 2018
Actual Primary Completion Date December 20, 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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:

    1. Uncontrolled persistent asthma by National Asthma Education and Prevention Program Asthma guidelines (2007).
    2. at least two systemic corticosteroid courses for asthma in the past year or one oral corticosteroid course for asthma in the past three months;
    3. 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 1.
  • 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 1.
  • 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 1.
  • Subjects on any experimental drugs or treatments.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 4 Years to 17 Years   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02579876
Other Study ID Numbers  ICMJE 13-010148
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Antonella Cianferoni, Children's Hospital of Philadelphia
Study Sponsor  ICMJE Children's Hospital of Philadelphia
Collaborators  ICMJE DBV Technologies
Investigators  ICMJE
Principal Investigator: Antonella Cianferoni, MD, PhD Children's Hospital of Philadelphia
PRS Account Children's Hospital of Philadelphia
Verification Date June 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP