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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

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Eosinophilic Esophagitis
Milk Allergy
Interventions Drug: Viaskin Milk 500 mcg
Drug: Viaskin Placebo
Enrollment 20
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Viaskin Milk 500 mcg Viaskin Placebo
Hide Arm/Group Description

Viaskin patch containing milk protein. The patch is applied to the skin

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.

Viaksin patch without any milk protein.

Viaskin Placebo: Biological: Viaskin Placebo Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing a matching placebo formulation.

Period Title: Overall Study
Started 15 5
Completed 14 5
Not Completed 1 0
Arm/Group Title Viaskin Milk 500 mcg Viaskin Placebo Total
Hide Arm/Group Description

Viaskin patch containing milk protein. The patch is applied to the skin

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.

Viaksin patch without any milk protein.

Viaskin Placebo: Biological: Viaskin Placebo Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing a matching placebo formulation.

Total of all reporting groups
Overall Number of Baseline Participants 15 5 20
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants 5 participants 20 participants
<=18 years
15
 100.0%
5
 100.0%
20
 100.0%
Between 18 and 65 years
0
   0.0%
0
   0.0%
0
   0.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 15 participants 5 participants 20 participants
10.46  (2.99) 12.71  (2.03) 10.69  (3.64)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants 5 participants 20 participants
Female
5
  33.3%
0
   0.0%
5
  25.0%
Male
10
  66.7%
5
 100.0%
15
  75.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 15 participants 5 participants 20 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
White
15
 100.0%
5
 100.0%
20
 100.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 15 participants 5 participants 20 participants
15 5 20
Eosinophils (Eos) per high power field (HPF) on Milk  
Mean (Standard Deviation)
Unit of measure:  Eos/hpf
Number Analyzed 15 participants 5 participants 20 participants
72.4  (29.52) 60.93  (49.39) 64  (44.5)
1.Primary Outcome
Title Change in Maximum Esophageal Eosinophil Count From Baseline to End of Double-blind Treatment. (Intent to Treat Population)
Hide Description

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.

Time Frame From baseline to month 11 (end of double blind phase)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Viaskin Milk 500 mcg Viaskin Placebo
Hide Arm/Group Description:

Viaskin patch containing milk protein. The patch is applied to the skin

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.

Viaksin patch without any milk protein.

Viaskin Placebo: Biological: Viaskin Placebo Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing a matching placebo formulation.

Overall Number of Participants Analyzed 14 5
Mean (Standard Deviation)
Unit of Measure: Eosinophils (Eos)/high power field (HPF)
-10.8  (37.73) -24.2  (63)
2.Primary Outcome
Title Change in Eosinophils/High Power Field at End of Double-blind (DB) (Per Protocol Patients)
Hide Description

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.

Time Frame Month 11(end of double blind phase)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Viaskin Milk 500 mcg Viaskin Placebo
Hide Arm/Group Description:

Viaskin patch containing milk protein. The patch is applied to the skin

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.

Viaksin patch without any milk protein.

Viaskin Placebo: Biological: Viaskin Placebo Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing a matching placebo formulation.

Overall Number of Participants Analyzed 7 2
Mean (Standard Deviation)
Unit of Measure: Eosinophils (Eos)/high power field
-26.86  (22.53) 42.5  (31.82)
3.Secondary Outcome
Title Eosinophilic Esophagitis Symptom Score (Intent to Treat Population)
Hide Description

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.

Time Frame Total Symptom Score at End of DB Phase, Month 11
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Viaskin Milk 500 mcg Viaskin Placebo
Hide Arm/Group Description:

Viaskin patch containing milk protein. The patch is applied to the skin

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.

Viaksin patch without any milk protein.

Viaskin Placebo: Biological: Viaskin Placebo Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing a matching placebo formulation.

Overall Number of Participants Analyzed 14 5
Mean (Standard Deviation)
Unit of Measure: units on a scale
1.07  (1.49) 1.40  (1.14)
4.Secondary Outcome
Title Esophageal Endoscopy Score (ITT)
Hide Description

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

Time Frame At end of DB phase, at 11 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Viaskin Milk 500 mcg Viaskin Placebo
Hide Arm/Group Description:

Viaskin patch containing milk protein. The patch is applied to the skin

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.

Viaksin patch without any milk protein.

Viaskin Placebo: Biological: Viaskin Placebo Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing a matching placebo formulation.

Overall Number of Participants Analyzed 14 5
Mean (Standard Deviation)
Unit of Measure: score on a scale
1.93  (1.58) 1.60  (1.67)
5.Secondary Outcome
Title Eosinophils Per HPF at End of Double Bind Protocol (Per Protocol) Patients
Hide Description Maximum Eosinophils/HPF after milk reintroduction at the end of double bind phase
Time Frame End of DB Phase, at 11 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Viaskin Milk 500 mcg Viaskin Placebo
Hide Arm/Group Description:

Viaskin patch containing milk protein. The patch is applied to the skin

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.

Viaksin patch without any milk protein.

Viaskin Placebo: Biological: Viaskin Placebo Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing a matching placebo formulation.

Overall Number of Participants Analyzed 7 2
Mean (Standard Deviation)
Unit of Measure: Eos/hpf
25.57  (31.19) 95  (63.64)
6.Secondary Outcome
Title Pediatric Eosinophilic Esophagitis Symptom Score (ITT)
Hide Description 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
Time Frame Month 11, end of Double Blind Phase
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Viaskin Milk 500 mcg Viaskin Placebo
Hide Arm/Group Description:

Viaskin patch containing milk protein. The patch is applied to the skin

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.

Viaksin patch without any milk protein.

Viaskin Placebo: Biological: Viaskin Placebo Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing a matching placebo formulation.

Overall Number of Participants Analyzed 14 5
Mean (Standard Deviation)
Unit of Measure: units on a scale
11.15  (11.07) 13.2  (7.33)
7.Secondary Outcome
Title Endoscopy Score (Per Protocol Patients)
Hide Description

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

Time Frame Month 11 (end of double blind phase)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Viaskin Milk 500 mcg Viaskin Placebo
Hide Arm/Group Description:

Viaskin patch containing milk protein. The patch is applied to the skin

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.

Viaksin patch without any milk protein.

Viaskin Placebo: Biological: Viaskin Placebo Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing a matching placebo formulation.

Overall Number of Participants Analyzed 7 2
Mean (Standard Deviation)
Unit of Measure: score on a scale
1.43  (1.51) 3  (1.41)
8.Secondary Outcome
Title Pediatric Eosinophil Esophagitis Symptom Score (PP Population)
Hide Description 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.
Time Frame Month 11, End of Double Blind Placebo Control
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Viaskin Milk 500 mcg Viaskin Placebo
Hide Arm/Group Description:

Viaskin patch containing milk protein. The patch is applied to the skin

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.

Viaksin patch without any milk protein.

Viaskin Placebo: Biological: Viaskin Placebo Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing a matching placebo formulation.

Overall Number of Participants Analyzed 7 2
Mean (Standard Deviation)
Unit of Measure: score on a scale
12.2  (8.57) 17  (1.41)
Time Frame The length of time is 1 year from the start of the study to end of double blind phase
Adverse Event Reporting Description All adverse events (AEs) were collected from the start of the study. . All Treatment emergent AEs are reported
 
Arm/Group Title Viaskin Milk 500 mcg Viaskin Placebo
Hide Arm/Group Description

Viaskin patch containing milk protein. The patch is applied to the skin

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.

Viaksin patch without any milk protein.

Viaskin Placebo: Biological: Viaskin Placebo Subjects epicutaneously administered daily (up to 24 hours application per day) with a patch containing a matching placebo formulation.

All-Cause Mortality
Viaskin Milk 500 mcg Viaskin Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/15 (0.00%)      0/5 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Viaskin Milk 500 mcg Viaskin Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/15 (0.00%)      1/5 (20.00%)    
Respiratory, thoracic and mediastinal disorders     
Vocal Cord Dysfunction  1  0/15 (0.00%)  1/5 (20.00%)  1
1
Term from vocabulary, MedDRA (12.0)
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Viaskin Milk 500 mcg Viaskin Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   15/15 (100.00%)      5/5 (100.00%)    
Ear and labyrinth disorders     
Ear infections  1  1/15 (6.67%)  1 0/5 (0.00%)  0
Gastrointestinal disorders     
General GI Symptoms  1  10/15 (66.67%)  10 2/5 (40.00%)  2
General disorders     
Administration Site Conditions  1  12/15 (80.00%)  12 5/5 (100.00%)  5
Infections and infestations     
Infections  1  8/15 (53.33%)  8 3/5 (60.00%)  3
Musculoskeletal and connective tissue disorders     
Muscloskeletal  1  2/15 (13.33%)  2 1/5 (20.00%)  1
Respiratory, thoracic and mediastinal disorders     
Upper Respiratory Infections * 1  7/15 (46.67%)  7 5/5 (100.00%)  5
Skin and subcutaneous tissue disorders     
Skin  1  1/15 (6.67%)  1 0/5 (0.00%)  0
1
Term from vocabulary, MedDRA (12.0)
Indicates events were collected by systematic assessment
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Jonathan Spergel
Organization: The Children's Hospital of Philadelphia
Phone: 215 590 1000
Responsible Party: Antonella Cianferoni, Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier: NCT02579876     History of Changes
Other Study ID Numbers: 13-010148
First Submitted: October 14, 2015
First Posted: October 20, 2015
Results First Submitted: March 27, 2019
Results First Posted: July 10, 2019
Last Update Posted: July 10, 2019