Peanut Allergy
Conditions
Keywords
EPIT, Epicutaneous, Immunotherapy, Viaskin
Brief summary
The study aims to assess the safety and efficacy of Viaskin Peanut to induce desensitization to peanut in peanut-allergic children 1 to 3 years of age after a 12-month treatment by EPicutaneous ImmunoTherapy (EPIT).
Detailed description
The study comprised of two parts: * In part A, subjects were randomized to receive either Viaskin Peanut 250 mcg, or Viaskin Peanut 100 mcg or the placebo in a 2:1 ratio, for 12 months. After 3 months of treatment, a data safety monitoring board had to determine the active dose to be applyed during the part B * In Part B, subjects were randomized to receive either Viaskin Peanut 250 mcg or the placebo in a 2:1 ratio, for 12 months
Interventions
BIOLOGICALPart A Viaskin Peanut 250 mcg
Viaskin Peanut 250 mcg, once daily
BIOLOGICALPart A Viaskin Peanut 100 mcg
Viaskin Peanut 100 mcg, once daily
BIOLOGICALPart A Placebo
Placebo patch, once daily
BIOLOGICALPart B Viaskin Peanut 250 mcg
Viaskin Peanut 250 mcg, once daily
BIOLOGICALPart B Placebo
Placebo patch, once daily
Sponsors
DBV Technologies
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
1 Years to 3 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Male or female from 1-3 years of age; * Physician-diagnosed peanut allergy; * Peanut-specific IgE level \> 0.7 kU/L; * Positive peanut SPT with a largest wheal diameter ≥ 6 mm; * Positive DBPCFC at ≤ 300 mg peanut protein; Key
Exclusion criteria
* Uncontrolled asthma; * History of severe anaphylaxis to peanut; * Prior immunotherapy to any food or other immunotherapy; * Generalized severe dermatologic disease;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Treatment Responders at Month 12 | Month 12 | A participant was defined as a treatment responder if the initial eliciting dose (ED) was \> 10 milligram (mg) peanut protein and the ED was ≥1000 mg peanut protein at the post-treatment double-blind placebo-controlled food challenge (DBPCFC) at Month 12 OR the initial ED at baseline was ≤10 mg peanut protein and the ED was ≥300 mg peanut protein at the post-treatment DBPCFC at Month 12. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Reactive Dose (CRD) of Peanut Protein at Month 12 Using Analysis of Covariance (ANCOVA) Model | Month 12 | The peanut protein CRD was defined as the sum of all peanut protein doses taken by the participant during the DBPCFC, calculated as follows: If the ED reported by the investigator in the electronic case report form (eCRF) is missing, then the CRD is missing; If the ED reported by the investigator in the eCRF was not missing then the CRD was calculated as the sum of all doses given, including also the partial doses. The CRD in each treatment group at Month 12 was compared using ANCOVA model. |
| Change From Baseline in CRD of Peanut Protein to Month 12 | Baseline (Day 1) and Month 12 | The peanut protein CRD was defined as the sum of all peanut protein doses taken by the participant during the DBPCFC, calculated as follows: If the ED reported by the investigator in the eCRF is missing, then the CRD is missing; If the ED reported by the investigator in the eCRF was not missing then the CRD was calculated as the sum of all doses given, including also the partial doses. |
| ED of Peanut Protein at Month 12 Using ANCOVA Model | Month 12 | The peanut protein ED was the individual dose of peanut protein administered to participants during the food challenge procedure, which triggered objective allergic reactions, leading to stopping the challenge. The ED in each treatment group at Month 12 was compared using ANCOVA model. |
| Change From Baseline in ED of Peanut Protein to Month 12 | Baseline (Day 1) and Month 12 | The peanut protein ED was the individual dose of peanut protein administered to participants during the food challenge procedure, which triggered objective allergic reactions, leading to stopping the challenge. |
| Percentage of Participants With Severity of Objective Symptoms at Baseline and Month 12 During Double-Blind Placebo-Controlled Food Challenge | Baseline (Day 1) and Month 12 | The objective symptoms collected during the DBPCFC included skin (erythematous rash, pruritus, urticaria/angioedema, rash), upper respiratory (sneezing/itching, nasal congestion, rhinorrhea, laryngeal), lower respiratory (wheezing), gastrointestinal (diarrhea, vomiting, cardiovascular), and eyes (conjunctivitis, any other objective symptoms), with the exception of erythematous rash (recorded as Yes/No), each symptom was graded as: 0= absent,1= mild, 2= moderate or 3= severe. For erythematous rash, the percent area involved was collected. Percentages were calculated based on the number of participants in each time point. Subjective abdominal pain (when graded 2 or 3) was also considered for this analysis. |
Countries
Australia, Canada, France, Germany, Ireland, Netherlands, United Kingdom, United States
Participant flow
Recruitment details
This Phase III was conducted in participants aged 1 to 3 years with peanut-allergy at 51 centers in Australia, Canada, Europe, and the United States of America. The entire duration of study was approximately 62 weeks (6-week: screening period; 12-month treatment period; and 4-week follow-up period).
Pre-assignment details
In Part A, a total of 51 participants were randomized either in the placebo arm or in the 2 active arms (Viaskin Peanut (DBV712) 100 mcg or 250 mcg) in a 1:2:2 ratio. In Part B, a total of 362 participants were randomized in a 2:1 ratio to receive Viaskin Peanut (DBV712) 250 mcg or placebo.
Participants by arm
| Arm | Count |
|---|---|
| Part B Viaskin Peanut 250 mcg Participants applied 1 new Viaskin Peanut 250 mcg patch on intact skin for 24 hours daily for up to 12 months. Each patch contained 250 mcg peanut protein extract for epicutaneous administration. The application duration was progressively increased to a duration of 24 ±4 hours daily over a 4-week period (2 hours during the first week, 4 hours during the second week, 8 hours during the third week, 12 hours during the fourth week onwards, and 24 ± 4 hours every day fifth week onwards). | 244 |
| Part B Placebo Participants applied 1 new placebo patch on intact skin for 24 hours daily for up to 12 months. The application duration was progressively increased to a duration of 24 ±4 hours daily over a 4-week period (2 hours during the first week, 4 hours during the second week, 8 hours during the third week, 12 hours during the fourth week onwards, and 24 ± 4 hours every day fifth week onwards). | 118 |
| Part A Viaskin Peanut 250 mcg Participants applied 1 new Viaskin Peanut 250 mcg patch on intact skin for 24 hours daily for up to 12 months. Each patch contained 250 mcg peanut protein extract for epicutaneous administration. The application duration was progressively increased to a duration of 24 ±4 hours daily over a 4-week period (2 hours during the first week, 4 hours during the second week, 8 hours during the third week, 12 hours during the fourth week onwards, and 24 ± 4 hours every day fifth week onwards). | 21 |
| Part A Viaskin Peanut 100 mcg Participants applied 1 new Viaskin Peanut 100 mcg patch on intact skin for 24 hours daily for up to 12 months. Each patch contained 100 mcg peanut protein extract for epicutaneous administration. The application duration was progressively increased to a duration of 24 ±4 hours daily over a 4-week period (2 hours during the first week, 4 hours during the second week, 8 hours during the third week, 12 hours during the fourth week onwards, and 24 ± 4 hours every day fifth week onwards). | 20 |
| Part A Placebo Participants applied 1 new placebo patch on intact skin for 24 hours daily for up to 12 months. The application duration was progressively increased to a duration of 24 ±4 hours daily over a 4-week period (2 hours during the first week, 4 hours during the second week, 8 hours during the third week, 12 hours during the fourth week onwards, and 24 ± 4 hours every day fifth week onwards). | 10 |
| Total | 413 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 8 | 0 | 1 | 0 | 0 |
| Overall Study | Lost to Follow-up | 2 | 1 | 0 | 0 | 0 |
| Overall Study | Non-compliance with study drug | 2 | 0 | 0 | 0 | 0 |
| Overall Study | Participant did not want to complete oral food challenge | 5 | 2 | 1 | 3 | 1 |
| Overall Study | Participant withdrawal by Parent or Caregiver | 18 | 13 | 2 | 1 | 0 |
| Overall Study | Physician Decision | 1 | 2 | 0 | 0 | 0 |
| Overall Study | Protocol Violation | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Part B Viaskin Peanut 250 mcg | Part B Placebo | Part A Viaskin Peanut 250 mcg | Part A Viaskin Peanut 100 mcg | Part A Placebo | Total |
|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 244 Participants | 118 Participants | 21 Participants | 20 Participants | 10 Participants | 413 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 41 Participants | 24 Participants | 1 Participants | 2 Participants | 1 Participants | 69 Participants |
| Race/Ethnicity, Customized Black or African American | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Not collected | 8 Participants | 6 Participants | 0 Participants | 0 Participants | 0 Participants | 14 Participants |
| Race/Ethnicity, Customized Other | 35 Participants | 17 Participants | 5 Participants | 1 Participants | 2 Participants | 60 Participants |
| Race/Ethnicity, Customized White | 159 Participants | 70 Participants | 15 Participants | 17 Participants | 7 Participants | 268 Participants |
| Sex: Female, Male Female | 79 Participants | 34 Participants | 8 Participants | 5 Participants | 4 Participants | 130 Participants |
| Sex: Female, Male Male | 165 Participants | 84 Participants | 13 Participants | 15 Participants | 6 Participants | 283 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 244 | 0 / 118 | 0 / 21 | 0 / 20 | 0 / 10 |
| other Total, other adverse events | 244 / 244 | 117 / 118 | 21 / 21 | 20 / 20 | 10 / 10 |
| serious Total, serious adverse events | 21 / 244 | 3 / 118 | 0 / 21 | 0 / 20 | 0 / 10 |
Outcome results
Primary
Percentage of Treatment Responders at Month 12
A participant was defined as a treatment responder if the initial eliciting dose (ED) was \> 10 milligram (mg) peanut protein and the ED was ≥1000 mg peanut protein at the post-treatment double-blind placebo-controlled food challenge (DBPCFC) at Month 12 OR the initial ED at baseline was ≤10 mg peanut protein and the ED was ≥300 mg peanut protein at the post-treatment DBPCFC at Month 12.
Time frame: Month 12
Population: The FAS comprised of all participants who were randomized in the study.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part B Viaskin Peanut 250 mcg | Percentage of Treatment Responders at Month 12 | 67.0 Percentage of participants |
| Part B Placebo | Percentage of Treatment Responders at Month 12 | 33.5 Percentage of participants |
| Part A Viaskin Peanut 250 mcg | Percentage of Treatment Responders at Month 12 | 52.4 Percentage of participants |
| Part A Viaskin Peanut 100 mcg | Percentage of Treatment Responders at Month 12 | 70.0 Percentage of participants |
| Part A Placebo | Percentage of Treatment Responders at Month 12 | 60.0 Percentage of participants |
Comparison: Analysis of the difference in response rates between DBV712 250 μg group and Placebo group and 2-sided Farrington-Manning 95% confidence interval (CI). P-value was obtained from a 2-sided 5% test to evaluate the null hypothesis of no difference in response rates between treatment groups using the Wald method. Clinical relevance was evaluated based on the lower bound of the Farrignton-Manning 95% CI of the difference in response rates ≥15%.p-value: <0.00195% CI: [22.36, 44.49]Wald test
Secondary
Change From Baseline in CRD of Peanut Protein to Month 12
The peanut protein CRD was defined as the sum of all peanut protein doses taken by the participant during the DBPCFC, calculated as follows: If the ED reported by the investigator in the eCRF is missing, then the CRD is missing; If the ED reported by the investigator in the eCRF was not missing then the CRD was calculated as the sum of all doses given, including also the partial doses.
Time frame: Baseline (Day 1) and Month 12
Population: The FAS comprised of all participants who were randomized in the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part B Viaskin Peanut 250 mcg | Change From Baseline in CRD of Peanut Protein to Month 12 | 1300.0 mg |
| Part B Placebo | Change From Baseline in CRD of Peanut Protein to Month 12 | 0.0 mg |
| Part A Viaskin Peanut 250 mcg | Change From Baseline in CRD of Peanut Protein to Month 12 | 540.0 mg |
| Part A Viaskin Peanut 100 mcg | Change From Baseline in CRD of Peanut Protein to Month 12 | 1250.0 mg |
| Part A Placebo | Change From Baseline in CRD of Peanut Protein to Month 12 | 1000.0 mg |
Secondary
Change From Baseline in ED of Peanut Protein to Month 12
The peanut protein ED was the individual dose of peanut protein administered to participants during the food challenge procedure, which triggered objective allergic reactions, leading to stopping the challenge.
Time frame: Baseline (Day 1) and Month 12
Population: The FAS comprised of all participants who were randomized in the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part B Viaskin Peanut 250 mcg | Change From Baseline in ED of Peanut Protein to Month 12 | 900.0 mg |
| Part B Placebo | Change From Baseline in ED of Peanut Protein to Month 12 | 0.0 mg |
| Part A Viaskin Peanut 250 mcg | Change From Baseline in ED of Peanut Protein to Month 12 | 700.0 mg |
| Part A Viaskin Peanut 100 mcg | Change From Baseline in ED of Peanut Protein to Month 12 | 700.0 mg |
| Part A Placebo | Change From Baseline in ED of Peanut Protein to Month 12 | 700.0 mg |
Secondary
Cumulative Reactive Dose (CRD) of Peanut Protein at Month 12 Using Analysis of Covariance (ANCOVA) Model
The peanut protein CRD was defined as the sum of all peanut protein doses taken by the participant during the DBPCFC, calculated as follows: If the ED reported by the investigator in the electronic case report form (eCRF) is missing, then the CRD is missing; If the ED reported by the investigator in the eCRF was not missing then the CRD was calculated as the sum of all doses given, including also the partial doses. The CRD in each treatment group at Month 12 was compared using ANCOVA model.
Time frame: Month 12
Population: The FAS comprised of all participants who were randomized in the study.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Part B Viaskin Peanut 250 mcg | Cumulative Reactive Dose (CRD) of Peanut Protein at Month 12 Using Analysis of Covariance (ANCOVA) Model | 1010.31 milligram (mg) |
| Part B Placebo | Cumulative Reactive Dose (CRD) of Peanut Protein at Month 12 Using Analysis of Covariance (ANCOVA) Model | 322.57 milligram (mg) |
| Part A Viaskin Peanut 250 mcg | Cumulative Reactive Dose (CRD) of Peanut Protein at Month 12 Using Analysis of Covariance (ANCOVA) Model | 788.74 milligram (mg) |
| Part A Viaskin Peanut 100 mcg | Cumulative Reactive Dose (CRD) of Peanut Protein at Month 12 Using Analysis of Covariance (ANCOVA) Model | 1155.90 milligram (mg) |
| Part A Placebo | Cumulative Reactive Dose (CRD) of Peanut Protein at Month 12 Using Analysis of Covariance (ANCOVA) Model | 1153.47 milligram (mg) |
Secondary
ED of Peanut Protein at Month 12 Using ANCOVA Model
The peanut protein ED was the individual dose of peanut protein administered to participants during the food challenge procedure, which triggered objective allergic reactions, leading to stopping the challenge. The ED in each treatment group at Month 12 was compared using ANCOVA model.
Time frame: Month 12
Population: The FAS comprised of all participants who were randomized in the study.
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) |
|---|---|---|
| Part B Viaskin Peanut 250 mcg | ED of Peanut Protein at Month 12 Using ANCOVA Model | 659.36 mg |
| Part B Placebo | ED of Peanut Protein at Month 12 Using ANCOVA Model | 223.12 mg |
| Part A Viaskin Peanut 250 mcg | ED of Peanut Protein at Month 12 Using ANCOVA Model | 526.31 mg |
| Part A Viaskin Peanut 100 mcg | ED of Peanut Protein at Month 12 Using ANCOVA Model | 730.38 mg |
| Part A Placebo | ED of Peanut Protein at Month 12 Using ANCOVA Model | 760.60 mg |
Secondary
Percentage of Participants With Severity of Objective Symptoms at Baseline and Month 12 During Double-Blind Placebo-Controlled Food Challenge
The objective symptoms collected during the DBPCFC included skin (erythematous rash, pruritus, urticaria/angioedema, rash), upper respiratory (sneezing/itching, nasal congestion, rhinorrhea, laryngeal), lower respiratory (wheezing), gastrointestinal (diarrhea, vomiting, cardiovascular), and eyes (conjunctivitis, any other objective symptoms), with the exception of erythematous rash (recorded as Yes/No), each symptom was graded as: 0= absent,1= mild, 2= moderate or 3= severe. For erythematous rash, the percent area involved was collected. Percentages were calculated based on the number of participants in each time point. Subjective abdominal pain (when graded 2 or 3) was also considered for this analysis.
Time frame: Baseline (Day 1) and Month 12
Population: The FAS comprised of all participants who were randomized in the study. This outcome was measured on Part B subjects only. Therefore subjects from Part A are reported as zero in the outcome measure data table.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part B Viaskin Peanut 250 mcg | Percentage of Participants With Severity of Objective Symptoms at Baseline and Month 12 During Double-Blind Placebo-Controlled Food Challenge | Baseline: Mild | 7.0 Percentage of participants |
| Part B Viaskin Peanut 250 mcg | Percentage of Participants With Severity of Objective Symptoms at Baseline and Month 12 During Double-Blind Placebo-Controlled Food Challenge | Baseline: Severe | 24.6 Percentage of participants |
| Part B Viaskin Peanut 250 mcg | Percentage of Participants With Severity of Objective Symptoms at Baseline and Month 12 During Double-Blind Placebo-Controlled Food Challenge | Baseline: Absent | 0 Percentage of participants |
| Part B Viaskin Peanut 250 mcg | Percentage of Participants With Severity of Objective Symptoms at Baseline and Month 12 During Double-Blind Placebo-Controlled Food Challenge | Month 12: Absent | 16.0 Percentage of participants |
| Part B Viaskin Peanut 250 mcg | Percentage of Participants With Severity of Objective Symptoms at Baseline and Month 12 During Double-Blind Placebo-Controlled Food Challenge | Month 12: Severe | 12.5 Percentage of participants |
| Part B Viaskin Peanut 250 mcg | Percentage of Participants With Severity of Objective Symptoms at Baseline and Month 12 During Double-Blind Placebo-Controlled Food Challenge | Month 12: Mild | 20.5 Percentage of participants |
| Part B Viaskin Peanut 250 mcg | Percentage of Participants With Severity of Objective Symptoms at Baseline and Month 12 During Double-Blind Placebo-Controlled Food Challenge | Baseline: Moderate | 68.4 Percentage of participants |
| Part B Viaskin Peanut 250 mcg | Percentage of Participants With Severity of Objective Symptoms at Baseline and Month 12 During Double-Blind Placebo-Controlled Food Challenge | Month 12: Moderate | 51.0 Percentage of participants |
| Part B Placebo | Percentage of Participants With Severity of Objective Symptoms at Baseline and Month 12 During Double-Blind Placebo-Controlled Food Challenge | Baseline: Moderate | 67.8 Percentage of participants |
| Part B Placebo | Percentage of Participants With Severity of Objective Symptoms at Baseline and Month 12 During Double-Blind Placebo-Controlled Food Challenge | Month 12: Moderate | 51.0 Percentage of participants |
| Part B Placebo | Percentage of Participants With Severity of Objective Symptoms at Baseline and Month 12 During Double-Blind Placebo-Controlled Food Challenge | Month 12: Severe | 28.6 Percentage of participants |
| Part B Placebo | Percentage of Participants With Severity of Objective Symptoms at Baseline and Month 12 During Double-Blind Placebo-Controlled Food Challenge | Baseline: Mild | 7.6 Percentage of participants |
| Part B Placebo | Percentage of Participants With Severity of Objective Symptoms at Baseline and Month 12 During Double-Blind Placebo-Controlled Food Challenge | Baseline: Absent | 0 Percentage of participants |
| Part B Placebo | Percentage of Participants With Severity of Objective Symptoms at Baseline and Month 12 During Double-Blind Placebo-Controlled Food Challenge | Baseline: Severe | 24.6 Percentage of participants |
| Part B Placebo | Percentage of Participants With Severity of Objective Symptoms at Baseline and Month 12 During Double-Blind Placebo-Controlled Food Challenge | Month 12: Absent | 6.1 Percentage of participants |
| Part B Placebo | Percentage of Participants With Severity of Objective Symptoms at Baseline and Month 12 During Double-Blind Placebo-Controlled Food Challenge | Month 12: Mild | 14.3 Percentage of participants |