Eosinophilic Esophagitis (EoE)
Conditions
Brief summary
The Primary objective is to demonstrate the efficacy of dupilumab treatment compared with placebo in pediatric patients with active eosinophilic esophagitis (EoE) based on histologic improvement meeting validated histologic criteria. The Secondary objectives are: * To demonstrate the efficacy of dupilumab compared to placebo in pediatric patients with active EoE after 16 weeks of treatment as assessed by endoscopic visual measurements of disease activity using the Eosinophilic Esophagitis-Endoscopic Reference Score (EoE-EREFS) and histologic abnormalities as measured by the EoE Histology Scoring System (EoE-HSS) * To evaluate the safety, tolerability, and immunogenicity of dupilumab treatment for up to 16 weeks in pediatric patients with active EoE * To evaluate the effects of dupilumab on transcriptomic signatures associated with EoE and type 2 inflammation * To study the effects of dupilumab on the type 2 inflammation gene expression signature * To evaluate the concentration-time profile of functional dupilumab in serum in this population * To assess efficacy of long-term (up to 160 weeks) dupilumab treatment * To assess the impact of dupilumab treatment on changes in weight and growth during the extended active period and open-label extension period of the study * To assess safety, tolerability, and immunogenicity of long-term (up to 160 weeks) dupilumab treatment * To evaluate the impact of dupilumab treatment on EoE signs and symptoms
Detailed description
This is a 3-part study: * Part A: Double-blind 16-week treatment period * Part B: 36-week extended active treatment period * Part C: Up to108 weeks open-label extension period
Interventions
DRUGDupilumab
Single-use, prefilled syringe
DRUGMatching Placebo
Matching formulation and regimen (depending on the weight tier) as dupilumab without the active substance
Sponsors
Sanofi
Regeneron Pharmaceuticals
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 11 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. A documented diagnosis of eosinophilic esophagitis (EoE) 2. Baseline endoscopic biopsies with a demonstration on central reading of intraepithelial eosinophilic infiltration Key
Exclusion criteria
1. Body weight \<5 kg or ≥60 kg at screening 2. Other causes of esophageal eosinophilia 3. Active Helicobacter pylori 4. History of Crohn's disease, ulcerative colitis, celiac disease, or prior esophageal surgery 5. Any esophageal stricture unable to be passed with a standard, diagnostic, upper endoscope or any critical esophageal stricture that requires dilation at screening 6. Treatment with swallowed topical corticosteroids within 8 weeks prior to baseline standard of care endoscopy 7. History of bleeding disorders or esophageal varices that, in the opinion of the investigator, would put the patient at undue risk for significant complications from an endoscopy procedure 8. Active parasitic infection or suspected parasitic infection 9. Known or suspected immunodeficiency disorder Key Exclusion for Patients Re-Entering the Study (for Entry into Part C, as defined in protocol): 1. Patients who are ≥12 years old, weigh ≥40 kg (or minimum weight for which dupilumab is approved for EoE), and dupilumab is commercially available for the treatment of EoE in their country 2. Patients who, during their previous participation in this clinical trial, developed an SAE and/or AE deemed related to dupilumab, which in the opinion of the investigator or of the medical monitor could indicate that continued treatment with dupilumab may present an unreasonable risk for the patient 3. Patients who did not undergo endoscopy with biopsies at week 16 and/or week 52 or prior to receiving rescue treatment Note: If the endoscopy with biopsies could not occur due to COVID-19 restrictions and rescue treatment was needed to be initiated without delay, these patients will be eligible to participate in Part C 4. Patients who became pregnant during their previous participation in this dupilumab clinical trial 5. Patients who, during their previous participation in this trial, were prematurely withdrawn because of a protocol violation, poor compliance, or inability to complete required study assessments NOTE: Other protocol defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of Less Than or Equal to (≤) 6 Eosinophils/High Power Field (Eos/Hpf) at Week 16 | At Week 16 | Peak esophageal intraepithelial eosinophil count was measured from esophageal biopsies. A total of at least 9 mucosal pinch biopsies were collected from 3 esophageal regions: 3 proximal, 3 mid, and 3 distal. The peak esophageal intraepithelial eosinophil count at each visit was the maximum of the quantities of eosinophils in the most inflamed hpfs across the 3 regions. If the quantity of eosinophils was missing for 1 or 2 esophageal regions, the peak eosinophil count was the maximum of the quantities of eosinophils from the region(s) where eosinophil quantities were available. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Part A: Percent Change From Baseline in Peak Esophageal Intraepithelial Eosinophil Count at Week 16 | Baseline, Week 16 | Peak esophageal intraepithelial eosinophil count was measured from esophageal biopsies. A total of at least 9 mucosal pinch biopsies were collected from 3 esophageal regions: 3 proximal, 3 mid, and 3 distal. The peak esophageal intraepithelial eosinophil count at each visit was the maximum of the quantities of eosinophils in the most inflamed hpfs across the 3 regions. If the quantity of eosinophils was missing for 1 or 2 esophageal regions, the peak eosinophil count was the maximum of the quantities of eosinophils from the region(s) where eosinophil quantities were available. Least squared (LS) mean and standard error (SE) from analysis of covariance (ANCOVA) model with Baseline measurement as covariate and the treatment, baseline weight group strata as fixed factors. |
| Part A: Change From Baseline in Mean Eosinophilic Esophagitis Histology Scoring System (EoE-HSS) Grade Score at Week 16 | Baseline, Week 16 | EoE-HSS is a validated histologic scoring system that measures other histological abnormalities in addition to density of eosinophilic infiltration. Severity (grade) and extent (stage) of abnormalities will be scored using a 4-point scale (0 normal; 3 maximum change). Higher total score indicated greater severity & extent of histological abnormalities. For each of 3 esophageal regions (proximal, mid, and distal), the ratio of the sum of assigned score for each evaluated feature divided by maximum possible score (maximum value is 24) was calculated. The mean grade scores summed over the 3 regions was the final score used in primary analysis, the mean grade score ranged from 0 to 3, with higher score indicating more severe. |
| Part A: Change From Baseline in Mean Eosinophilic Esophagitis Histology Scoring System (EoE-HSS) Stage Score at Week 16 | Baseline, Week 16 | EoE-HSS is a validated histologic scoring system that measures other histological abnormalities in addition to density of eosinophilic infiltration. Severity (grade) and extent (stage) of abnormalities will be scored using a 4-point scale (0 normal; 3 maximum change). Higher total score indicated greater severity & extent of histological abnormalities. For each of 3 esophageal regions (proximal, mid, and distal), the ratio of the sum of assigned score for each evaluated feature divided by maximum possible score (maximum value is 24) was calculated. The mean stage scores summed over the 3 regions was the final score used in primary analysis, the mean stage score ranged from 0 to 3, with higher score indicating more severe. |
| Part A: Normalized Enrichment Score (NES) for the Relative Change From Baseline in the Type 2 Inflammation Signature (T2INF) at Week 16 | Baseline, Week 16 | A Normalized Enrichment Score (NES) is a way to generate a single numerical value to represent a complex gene expression signature. Changes in NES score represented the overall changes in the expression of that molecular phenotype. The NESs calculated for T2INF reflect the expression at Week 16 relative to Baseline of the pre-specified gene set as a way to evaluate normalization of type 2 inflammation with treatment. For each subject, an NES of 0 indicates no change from baseline, a negative score shows a reduction in disease score (more like normal) and positive score shows worsening (more active disease). NES does not have a minimum/maximum score. |
| Part A: Normalized Enrichment Score (NES) for the Relative Change From Baseline in the Eosinophilic Esophagitis (EoE) Diagnostic Panel (EDP) at Week 16 | Baseline, Week 16 | A Normalized Enrichment Score (NES) is a way to generate a single numerical value to represent a complex gene expression signature. Changes in NES score represented the overall changes in the expression of that molecular phenotype. The NESs calculated for the EDP reflect the expression at Week 16 relative to Baseline of a gene set that is differentially expressed between esophageal biopsies from EoE participants compared to healthy controls as a way to evaluate normalization of the molecular pathology. For each subject, an NES of 0 indicates no change from baseline, a negative score shows a reduction in disease score (more like normal) and positive score shows worsening (more active disease). NES does not have minimum/maximum score. |
| Part A: Absolute Change From Baseline in EoE Endoscopic Reference Total Score (EoE-EREFS) at Week 16 | Baseline, Week 16 | The EoE-EREFS is a validated endoscopic scoring system for inflammatory and remodeling features of EoE including edema, rings, exudates, furrows, and stricture. The score was assessed in the proximal and distal esophageal regions with each region scored from 0 to 9 with total scores ranging from 0 to 18. Higher scores indicate worse endoscopic inflammatory and remodeling findings. |
| Part A: Change From Baseline in the Proportion of Days With 1 or More EoE Signs as Measured by Pediatric EoE Sign/Symptom Questionnaire - Caregiver Version (PESQ-C) at Week 16 (for Participants Aged ≥1 to <12 Years) | Baseline, Week 16 | PESQ-C is a novel, observer-reported outcome measure intended to be completed independently by caregivers of all pediatric EoE participants in the study. PESQ-C measures the signs of EoE observed by the caregiver, including stomach pain, heartburn, acid reflux, regurgitation, vomiting, food refusal, and trouble swallowing food. Data from a 14-day period preceding the baseline visit and a 14-day period preceding week 16 will be used to calculate the proportion of days with 1 or more EoE symptoms. |
| Part A: Number of Sign-free Days During the 14-day Period Preceding Week 16 as Measured by the PESQ-C (for Participants Aged ≥1 to <12 Years) | Week 16 | PESQ-C is a novel, observer-reported outcome measure intended to be completed independently by caregivers of all pediatric EoE participants in the study. The PESQ-C measures the signs of EoE observed by the caregiver, including stomach pain, heartburn, acid reflux, regurgitation, vomiting, food refusal, and trouble swallowing food. WOCF approach was used for imputing the missing data due to rescue treatment/AE/lack of efficacy, and the multiple imputations approach was used for the missing data due to other reasons. LS mean SE derived from ANCOVA model. |
| Part A: Change From Baseline in the Proportion of Total Segments Within a Day (Night, Morning, Afternoon, Evening) With 1 or More EoE Signs as Measured by the PESQ-C at Week 16 | Baseline, Week 16 | PESQ-C is a novel, observer-reported outcome measure intended to be completed independently by caregivers of all pediatric EoE participants in the study. The PESQ-C measured the occurrence of signs of EoE and was completed once daily via an electronic diary. Data from a 14-day period preceding the baseline visit and a 14-day period preceding week 16 will be used to calculate the total time segments within a day (night, morning, afternoon, evening) with 1 or more EoE symptoms. |
| Part A: Change From Baseline in the Proportion of Days With 1 or More EoE Signs by Pediatric EoE Sign/Symptom Questionnaire - Participant Version (PESQ-P) (for Participants Aged ≥8 to <12 Years) at Week 16 | Baseline, Week 16 | The PESQ-P was a participant-reported outcome measure intended to be completed independently by participants ≥8 to \<12 years of age. The PESQ-P measured occurrence of signs of EoE and was completed once daily via an electronic diary. Data from a 14-day period preceding the baseline visit and a 14-day period preceding week 16 will be used to calculate the proportion of days with 1 or more EoE symptoms. |
| Part A: Number of Symptom-free Days During the 14-day Period Preceding Week 16 as Measured by the PESQ-P (for Participants Aged ≥8 to <12 Years) | Week 16 | The PESQ-P was a participant-reported outcome measure intended to be completed independently by EoE participants ≥8 to \<12 years of age. The PESQ-P measures the signs of EoE, including stomach pain, heartburn, acid reflux, regurgitation, vomiting, food refusal, and trouble swallowing food. The PESQ-P score was calculated based on the daily responses over a 14-day period (i.e., the 14 days prior to the baseline visit and the week 16 visit). The score ranges from 0 to 1. WOCF approach was used for imputing the missing data due to rescue treatment/AE/lack of efficacy, and the multiple imputations approach was used for the missing data due to other reasons. LS Mean SE from ANCOVA. |
| Part A: Change From Baseline in the Proportion of Total Segments Within a Day (Night, Morning, Afternoon, Evening) With 1 or More EoE Signs as Measured by the PESQ-P (for Participants Aged ≥8 to <12 Years) at Week 16 | Baseline, Week 16 | The PESQ-P was a participant-reported outcome measure intended to be completed independently by EoE participants ≥8 to \<12 years of age. The PESQ-P measured the occurrence of signs of EoE and was completed once daily via an electronic diary. Data from a 14-day period preceding the baseline visit and a 14-day period preceding week 16 will be used to calculate the total time segments within a day (night, morning, afternoon, evening) with 1 or more EoE symptoms. |
| Part B: Absolute Change From Baseline in EoE Endoscopic Reference Total Score (EoE-EREFS) at Week 52 | Baseline, Week 52 | The EoE-EREFS is a validated endoscopic scoring system for inflammatory and remodeling features of EoE including edema, rings, exudates, furrows, and stricture. The score was assessed in the proximal and distal esophageal regions with each region scored from 0 to 9 with total scores possibly ranging from 0 to 18. Higher scores indicate worse endoscopic inflammatory and remodeling findings. |
| Part A: Change From Baseline in Total Score as Measured by the Pediatric Eosinophilic Esophagitis Symptom Score (PEESS) Version 2.0 Caregiver Version (PEESSv2.0-C) at Week 16 | Baseline, Week 16 | The PEESSv2.0-C is a caregiver-reported outcome measure that assesses the frequency and severity of EoE symptoms among pediatric participants. The PEESSv2.0-C consists of 20 items and has a one-month recall period. Each item had a 0-4 scale, which was transformed to 0-100 as follows: 0 = 0, 1 = 25, 2 = 50, 3 = 75, 4 = 100. The mean total PEESSv2.0 score was computed as the sum of all the item scores over the number of items answered. The total PEESSv2.0-C score ranges from 0 to 100 where higher scores indicate greater symptom burden among pediatric EoE participants. Values after first rescue treatment use were set to missing (censoring). WOCF approach was used for imputing the missing data due to rescue treatment/AE/lack of efficacy, and the MI approach was used for the missing data due to other reasons. LS mean SE from ANCOVA model. |
| Part A: Concentration of Functional Dupilumab in Serum at Baseline, Week 4 and 16 | Baseline, Week 4 and 16 | Concentration of functional dupilumab in serum at Baseline, Week 4 and 16 was reported in this outcome measure. |
| Part B: Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of ≤6 Eosinophils/High Power Field at Week 52 | At Week 52 | Peak esophageal intraepithelial eosinophil count was measured from esophageal biopsies. A total of at least 9 mucosal pinch biopsies were collected from 3 esophageal regions: 3 proximal, 3 mid, and 3 distal. The peak esophageal intraepithelial eosinophil count at each visit was the maximum of the quantities of eosinophils in the most inflamed hpfs across the 3 regions. If the quantity of eosinophils was missing for 1 or 2 esophageal regions, the peak eosinophil count was the maximum of the quantities of eosinophils from the region(s) where eosinophil quantities were available. |
| Part B: Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of <15 Eosinophils/High Power Field at Week 52 | At Week 52 | Peak esophageal intraepithelial eosinophil count was measured from esophageal biopsies. A total of at least 9 mucosal pinch biopsies were collected from 3 esophageal regions: 3 proximal, 3 mid, and 3 distal. The peak esophageal intraepithelial eosinophil count at each visit was the maximum of the quantities of eosinophils in the most inflamed hpfs across the 3 regions. If the quantity of eosinophils was missing for 1 or 2 esophageal regions, the peak eosinophil count was the maximum of the quantities of eosinophils from the region(s) where eosinophil quantities were available. |
| Part B: Percent Change From Baseline in Peak Esophageal Intraepithelial Eosinophil Count at Week 52 | Baseline, Week 52 | Peak esophageal intraepithelial eosinophil count was measured from esophageal biopsies. A total of at least 9 mucosal pinch biopsies were collected from 3 esophageal regions: 3 proximal, 3 mid, and 3 distal. The peak esophageal intraepithelial eosinophil count at each visit was the maximum of the quantities of eosinophils in the most inflamed hpfs across the 3 regions. If the quantity of eosinophils was missing for 1 or 2 esophageal regions, the peak eosinophil count was the maximum of the quantities of eosinophils from the region(s) where eosinophil quantities were available. |
| Part B: Change From Baseline in Mean Eosinophilic Esophagitis Histology Scoring System (EoE-HSS) Grade Score at Week 52 | Baseline, Week 52 | EoE-HSS is a validated histologic scoring system that measures other histological abnormalities in addition to density of eosinophilic infiltration. Severity (grade) and extent (stage) of abnormalities will be scored using a 4-point scale (0 normal; 3 maximum change). Higher total score indicated greater severity & extent of histological abnormalities. For each of 3 esophageal regions (proximal, mid, and distal), the ratio of the sum of assigned score for each evaluated feature divided by maximum possible score (maximum value is 24) was calculated. The mean grade scores summed over the 3 regions was the final score used in primary analysis, the mean grade score ranged from 0 to 3, with higher score indicating more severe. |
| Part B: Change From Baseline in Mean Eosinophilic Esophagitis Histology Scoring System (EoE-HSS) Stage Score at Week 52 | Baseline, Week 52 | EoE-HSS is a validated histologic scoring system that measures other histological abnormalities in addition to density of eosinophilic infiltration. Severity (grade) and extent (stage) of abnormalities will be scored using a 4-point scale (0 normal; 3 maximum change). Higher total score indicated greater severity & extent of histological abnormalities. For each of 3 esophageal regions (proximal, mid, and distal), the ratio of the sum of assigned score for each evaluated feature divided by maximum possible score (maximum value is 24) was calculated. The mean stage scores summed over the 3 regions was the final score used in primary analysis, the mean stage score ranged from 0 to 3, with higher score indicating more severe. |
| Part C: NES for the Relative Change in the Type 2 Inflammation Transcriptome Signature From Baseline to Week 160 | Baseline to Week 160 | — |
| Part B: Change From Baseline in the Proportion of Days With 1 or More EoE Signs Measured by Pediatric EoE Sign/Symptom Questionnaire - Caregiver Version (PESQ-C) at Week 52 | Baseline, Week 52 | PESQ-C is a novel, observer-reported outcome measure intended to be completed independently by caregivers of all pediatric EoE participants in the study. |
| Part B: Number of Sign-free Days During the 14-day Period Preceding Week 52 as Measured by the PESQ-C (for Participants Aged ≥1 to <12 Years) | Week 52 | PESQ-C is a novel, observer-reported outcome measure intended to be completed independently by caregivers of all pediatric EoE participants in the study. |
| Part B: Change From Baseline in the Proportion of Total Segments Within a Day (Night, Morning, Afternoon, Evening) With 1 or More EoE Signs as Measured by the PESQ-C at Week 52 | Baseline, Week 52 | PESQ-C is a novel, observer-reported outcome measure intended to be completed independently by caregivers of all pediatric EoE participants in the study. The PESQ-C measured the occurrence of signs of EoE and was completed once daily via an electronic diary. |
| Part B: Change From Baseline in the Proportion of Days With 1 or More EoE Signs by Pediatric EoE Sign/Symptom Questionnaire - Participant Version (PESQ-P) (for Participants Aged ≥8 to <12 Years) at Week 52 | Baseline, Week 52 | The PESQ-P was a participant-reported outcome measure intended to be completed independently by participants ≥8 to \<12 years of age. The PESQ-P measured occurrence of signs of EoE and was completed once daily via an electronic diary. Data from a 14-day period preceding the baseline visit and a 14-day period preceding week 16 will be used to calculate the proportion of days with 1 or more EoE symptoms. |
| Part B: Number of Symptom-free Days During the 14-day Period Preceding Week 52 as Measured by the PESQ-P (for Participants Aged ≥8 to <12 Years) | Week 52 | The PESQ-P was a participant-reported outcome measure intended to be completed independently by participants ≥8 to \<12 years of age. The PESQ-P measures the signs of EoE, including stomach pain, heartburn, acid reflux, regurgitation, vomiting, food refusal, and trouble swallowing food. |
| Part B: Change From Baseline in the Proportion of Total Segments Within a Day (Night, Morning, Afternoon, Evening) With 1 or More EoE Signs as Measured by the PESQ-P (for Participants Aged ≥8 to <12 Years) at Week 52 | Baseline, Week 52 | The PESQ-P was a participant-reported outcome measure intended to be completed independently by EoE participants ≥8 to \<12 years of age. The PESQ-P measured the occurrence of signs of EoE and was completed once daily via an electronic diary. Data from a 14-day period preceding the baseline visit and a 14-day period preceding week 16 will be used to calculate the total time segments within a day (night, morning, afternoon, evening) with 1 or more EoE symptoms. |
| Part B: Normalized Enrichment Score (NES) for the Relative Change From Baseline in the EoE Diagnostic Panel (EDP) at Week 52 | Baseline, Week 52 | A Normalized Enrichment Score (NES) is a way to generate a single numerical value to represent a complex gene expression signature. Changes in NES score represented the overall changes in the expression of that molecular phenotype. The NESs calculated for the EDP reflect the expression at post-baseline relative to Baseline of a gene set that is differentially expressed between esophageal biopsies from EoE participants compared to healthy controls as a way to evaluate normalization of the molecular pathology. For each subject, an NES of 0 indicates no change from baseline, a negative score shows a reduction in disease score (more like normal) and positive score shows worsening (more active disease). NES does not have minimum/maximum score. |
| Part B: Normalized Enrichment Score (NES) for the Relative Change From Baseline in the Type 2 Inflammation Signature (T2INF) at Week 52 | Baseline, Week 52 | A Normalized Enrichment Score (NES) is a way to generate a single numerical value to represent a complex gene expression signature. Changes in NES score represented the overall changes in the expression of that molecular phenotype. The NESs calculated for T2INF reflect the expression at post-baseline relative to Baseline of the pre-specified gene set as a way to evaluate normalization of type 2 inflammation with treatment. For each subject, an NES of 0 indicates no change from baseline, a negative score shows a reduction in disease score (more like normal) and positive score shows worsening (more active disease). NES does not have minimum/maximum score. |
| Part B: Change From Baseline in Body Weight for Age Percentile at Week 52 | Baseline, Week 52 | Body weight for age percentile was calculated based on the growth charts from the Centers for Disease Control and Prevention (CDC) for ages 0 to 20 years (for ages 2 to \<12 years) and World Health Organization (WHO) growth charts for ages 0 to \<2 years (for ages 1 to \<2 years). These charts included a set of smoothed percentiles along with CDC LMS (Lambda-Mu-Sigma) parameters to allow the calculation of percentiles. |
| Part B: Change From Baseline in Body Mass Index (BMI) for Age Z-score for Participants ≥2 Years of Age at Week 52 | Baseline, Week 52 | BMI for age z-score indicates how much higher or lower a participant's BMI for age is relative to a reference growth chart (based on the growth charts from Centers for Disease Control and Prevention \[CDC\] for ages 0 to 20 years \[for ages 2 to \<12 years\]). A z-score of 0 represents the population mean. An increase in the mean change in BMI for age z-score (ie, increase in the standard deviation \[SD\] from the reference growth chart) indicates an increase in BMI for age relative to the reference. |
| Part B: Change From Baseline in Weight for Age Z-score at Week 52 | Baseline, Week 52 | Weight for age z-score indicates how much higher or lower a participant's weight for age is relative to a reference growth chart (based on the growth charts from CDC for ages 0 to 20 years \[for ages 2 to \<12 years\] and World Health Organization (WHO) growth charts for ages 0 to \<2 years \[for ages 1 to \<2 years\]). A z-score of 0 represents the population mean. An increase in the mean change in weight for age z-score (increase in the SD from the reference growth chart) indicates an increase in weight for age relative to the reference. |
| Part B: Change From Baseline in Body Weight From Height Z-score at Week 52 | Baseline, Week 52 | Weight for height z-score indicates how much higher or lower a participant's weight for height is relative to a reference growth chart (based on the growth charts from CDC for ages 0 to 20 years \[for ages 2 to \<12 years\] and WHO growth charts for ages 0 to \<2 years \[for ages 1 to \<2 years\]). A z-score of 0 represents the population mean. An increase in the mean change in weight for height z-score (increase in the SD from the reference growth chart) indicates an increase in weight for height relative to the reference. |
| Part B: Concentration of Functional Dupilumab in Serum at Week 32 and 52 | Week 32 and 52 | Concentration of functional dupilumab in serum at Week 32 and 52 was reported in this outcome measure. |
| Part A: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Adverse Events of Special Interest (AESIs) and TEAEs Leading to Permanent Discontinuation of Study Drug | From Baseline up to Week 16 in Part A | An adverse event (AE) was defined as any untoward medical occurrence in a participant or clinical investigation patient administered with a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. A serious AE was any untoward medical occurrence that at any dose resulted in death, life-threatening, initial or prolonged inpatient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or a medically important event. The term TEAE is defined as AEs starting or worsening after the first intake of the study drug. TEAEs include both Serious TEAEs and non-serious TEAEs. An AESI was defined as one of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and rapid communication by the Investigator to the Sponsor was appropriate. |
| Part B: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Adverse Events of Special Interest (AESIs) and TEAEs Leading to Permanent Discontinuation of Study Drug | From Week 16 up to Week 52 in Part B | An AE was defined as any untoward medical occurrence in a participant or clinical investigation patient administered with a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. A serious AE was any untoward medical occurrence that at any dose resulted in death, life-threatening, initial or prolonged inpatient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or a medically important event. The term TEAE is defined as AEs starting or worsening after the first intake of the study drug. TEAEs include both Serious TEAEs and non-serious TEAEs. An AESI was defined as one of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and rapid communication by the Investigator to the Sponsor was appropriate. |
| Part A: Number of Participants With Positive Treatment-emergent Antidrug Antibodies (ADA) Response | From Baseline up to Week 16 in Part A | Treatment-emergent ADA was defined as a negative result or missing result at baseline with at least one positive post baseline result in the ADA assay. Samples positive in the dupilumab ADA assay were characterized for ADA titers (low, moderate and high). The low treatment-emergent ADA titer as defined as titer level \<1000, moderate as 1000 to 10000 and high as \>10000. |
| Part A: Number of Participants With Positive Treatment-emergent Antidrug Antibodies (ADA) by Maximum Titer Category | From Baseline up to Week 16 in Part A | Treatment-emergent ADA was defined as a negative result or missing result at baseline with at least one positive post baseline result in the ADA assay. Samples positive in the dupilumab ADA assay were characterized for ADA titers (low, moderate and high). The low treatment-emergent ADA titer as defined as titer level \<1000, moderate as 1000 to 10000 and high as \>10000. |
| Part C: Change in Body Weight for Age Percentile From Baseline up to Week 100 | Baseline up to Week 100 | Body weight for age percentile was calculated based on the growth charts from the Centers for Disease Control and Prevention (CDC) for ages 0 to 20 years (for ages 2 to \<12 years) and World Health Organization (WHO) growth charts for ages 0 to \<2 years (for ages 1 to \<2 years). These charts included a set of smoothed percentiles along with CDC LMS (Lambda-Mu-Sigma) parameters to allow the calculation of percentiles. |
| Part B: Number of Participants With Positive Treatment-emergent Antidrug Antibodies (ADA) Response and Titer | From Week 16 up to Week 52 in Part B | Treatment-emergent ADA was defined as a negative result or missing result at baseline with at least one positive post baseline result in the ADA assay. Samples positive in the dupilumab ADA assay were characterized for ADA titers (low, moderate and high). The low treatment-emergent ADA titer as defined as titer level \<1000, moderate as 1000 to 10000 and high as \>10000. No participant exhibited a treatment-emergent ADA response in Part B and titer was not reported. |
| Part C: Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of <15 Eos/Hpf At Week 100 | At Week 100 | — |
| Part C: Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of <15 Eos/Hpf At Week 160 | At Week 160 | — |
| Part C: Percent Change in Peak Esophageal Intraepithelial Eosinophil Count (Eos/Hpf) From Baseline to Week 100 | Baseline to Week 100 | — |
| Part C: Percent Change in Peak Esophageal Intraepithelial Eosinophil Count (Eos/Hpf) From Baseline to Week 160 | Baseline to Week 160 | — |
| Part C: Absolute Change in Mean EoE-HSS From Baseline to Week 100 | Baseline to Week 100 | — |
| Part C: Absolute Change in Mean EoE-HSS From Baseline to Week 160 | Baseline to Week 160 | — |
| Part C: Absolute Change in EoE-EREFS From Baseline to Week 100 | Baseline to Week 100 | — |
| Part C: Absolute Change in EoE-EREFS From Baseline to Week 160 | Baseline to Week 160 | — |
| Part C: Change in Total Score as Measured by the PEESSv2.0- Caregiver Version Questionnaire From Baseline to Week 100 | Baseline to Week 100 | The PEESSv2.0-C is a caregiver-reported outcome measure that assesses the frequency and severity of EoE symptoms among pediatric participants. The PEESSv2.0-C consists of 20 items and has a one-month recall period. Each item had a 0-4 scale, which was transformed to 0-100 as follows: 0 = 0, 1 = 25, 2 = 50, 3 = 75, 4 = 100. The mean total PEESSv2.0 score was computed as the sum of all the item scores over the number of items answered. The total PEESSv2.0-C score ranges from 0 to 100 where higher scores indicate greater symptom burden among pediatric EoE participants. |
| Part C: NES for the Relative Change in the EDP Transcriptome Signature From Baseline to Week 100 | Baseline to Week 100 | A Normalized Enrichment Score (NES) is a way to generate a single numerical value to represent a complex gene expression signature. Changes in NES score represented the overall changes in the expression of that molecular phenotype. The NESs calculated for the EDP reflect the expression at post-baseline relative to Baseline of a gene set that is differentially expressed between esophageal biopsies from EoE participants compared to healthy controls as a way to evaluate normalization of the molecular pathology. For each subject, an NES of 0 indicates no change from baseline, a negative score shows a reduction in disease score (more like normal) and positive score shows worsening (more active disease). NES does not have minimum/maximum score. |
| Part C: NES for the Relative Change in the EDP Transcriptome Signature From Baseline to Week 160 | Baseline to Week 160 | A Normalized Enrichment Score (NES) is a way to generate a single numerical value to represent a complex gene expression signature. Changes in NES score represented the overall changes in the expression of that molecular phenotype. The NESs calculated for the EDP reflect the expression at post-baseline relative to Baseline of a gene set that is differentially expressed between esophageal biopsies from EoE participants compared to healthy controls as a way to evaluate normalization of the molecular pathology. For each subject, an NES of 0 indicates no change from baseline, a negative score shows a reduction in disease score (more like normal) and positive score shows worsening (more active disease). NES does not have minimum/maximum score. |
| Part C: NES for the Relative Change in the Type 2 Inflammation Transcriptome Signature Baseline to Week 100 | Baseline to Week 100 | — |
| Part C: Concentration of Functional Dupilumab in Serum at Week 100 | At Week 100 | — |
| Part C: Change in Body Mass Index for Age Z-score From Baseline up to Week 100 | Baseline up to Week 100 | Difference in the 100-week change from baseline in BMI-for-age Z-score. BMI-for-age Z-scores are based on a reference growth chart (based on the growth charts from Centers for Disease Control and Prevention \[CDC\] for ages 0 to 20 years \[for ages 2 to \<12 years\]. A z-score of 0 represents the population mean. The Z-score indicates the number of standard deviations away from the mean of the reference population. A negative Z-score indicates values lower than the population mean while a positive Z-score indicates values higher than the population mean. |
| Part C: Change in Weight for Age Z-score From Baseline up to Week 100 | Baseline up to Week 100 | Difference in the 100-week change from baseline in weight-for-age Z-score. Weight-for-age Z-scores are based on a reference growth chart (based on the growth charts from Centers for Disease Control and Prevention \[CDC\] for ages 0 to 20 years \[for ages 2 to \<12 years\]. A z-score of 0 represents the population mean. The Z-score indicates the number of standard deviations away from the mean of the reference population. A negative Z-score indicates values lower than the population mean while a positive Z-score indicates values higher than the population mean. |
| Part C: Change in Weight for Age Z-score From Baseline up to Week 160 | Baseline up to Week 160 | Weight for age z-score indicates how much higher or lower a participant's weight for age is relative to a reference growth chart (based on the growth charts from CDC for ages 0 to 20 years \[for ages 2 to \<12 years\] and World Health Organization (WHO) growth charts for ages 0 to \<2 years \[for ages 1 to \<2 years\]). An increase in the mean change in weight for age z-score (increase in the SD from the reference growth chart) indicates an increase in weight for age relative to the reference. |
| Part C: Change in Weight for Height Z-score From Baseline up to Week 100 | Baseline up to Week 100 | Difference in the 100-week change from baseline in Weight for height Z-score. Weight for height Z-scores are based on a reference growth chart (based on the growth charts from Centers for Disease Control and Prevention \[CDC\] for ages 0 to 20 years \[for ages 2 to \<12 years\]. A z-score of 0 represents the population mean. The Z-score indicates the number of standard deviations away from the mean of the reference population. A negative Z-score indicates values lower than the population mean while a positive Z-score indicates values higher than the population mean. |
| Part C: Change in Weight for Height Z-score From Baseline up to Week 160 | Baseline up to Week 160 | Weight for height z-score indicates how much higher or lower a participant's weight for height is relative to a reference growth chart (based on the growth charts from CDC for ages 0 to 20 years \[for ages 2 to \<12 years\] and WHO growth charts for ages 0 to \<2 years \[for ages 1 to \<2 years\]). An increase in the mean change in weight for height z-score (increase in the SD from the reference growth chart) indicates an increase in weight for height relative to the reference. |
| Part C: Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of ≤6 Eos/Hpf (400×) at Week 100 | At Week 100 | — |
| Part A: Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of <15 Eosinophils/High Power Field at Week 16 | At Week 16 | Peak esophageal intraepithelial eosinophil count was measured from esophageal biopsies. A total of at least 9 mucosal pinch biopsies were collected from 3 esophageal regions: 3 proximal, 3 mid, and 3 distal. The peak esophageal intraepithelial eosinophil count at each visit was the maximum of the quantities of eosinophils in the most inflamed hpfs across the 3 regions. If the quantity of eosinophils was missing for 1 or 2 esophageal regions, the peak eosinophil count was the maximum of the quantities of eosinophils from the region(s) where eosinophil quantities were available. |
| Part C: Percentage of Participants (With Food Elimination Diet Regimens at Baseline) That Have a Re-introduction of a Previously Eliminated Food Group From Baseline up to Week 100 | Baseline up to Week 100 | — |
| Part C: Percentage of Participants (With Food Elimination Diet Regimens at Baseline) That Have a Re-introduction of a Previously Eliminated Food Group From Baseline up to Week 160 | Baseline up to Week 160 | — |
| Part C: Number of Participants With TEAEs | Up to Week 152 | — |
| Part C: Number of Participants With Treatment-emergent SAEs | Up to Week 152 | — |
| Part C: Number of Participants With Treatment-emergent AESIs | Up to Week 152 | — |
| Part C: Number of Participants With TEAEs Leading to Permanent Discontinuation of Study Treatment | Up to Week 152 | — |
| Part C: Number of Participants With Treatment-emergent ADA Responses | From Week 52 up to Week 152 | — |
| Part C: Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of ≤6 Eos/Hpf (400×) at Week 160 | At Week 160 | — |
Countries
Canada, United States
Participant flow
Pre-assignment details
This study consisted of 3 parts: Part A (double-blind 16-week treatment period), Part B (36-week extended active treatment period) and Part C (open-label extension period of up to 108 weeks).
Participants by arm
| Arm | Count |
|---|---|
| Part A: Pooled Placebo Participants who received subcutaneous (SC) injection of placebo matched to higher exposure dupilumab or lower exposure dupilumab in Part A. Lower exposure dupilumab regimen were exposures approximating those in adolescents and adults receiving 300 mg dupilumab Q2W). Higher exposure dupilumab regimen were exposures approximating those in adolescents and adults receiving 300 mg dupilumab QW. | 34 |
| Part A: Dupilumab Low Dose Participants received subcutaneous (SC) injection of lower exposure dupilumab in Part A. Lower exposure dupilumab regimen were exposures approximating those in adolescents and adults receiving 300 mg dupilumab Q2W | 31 |
| Part A: Dupilumab High Dose Participants received subcutaneous (SC) injection of higher exposure dupilumab in Part A. Higher exposure dupilumab regimen were exposures approximating those in adolescents and adults receiving 300 mg dupilumab QW | 37 |
| Total | 102 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Part A (16 Weeks) | Adverse Event | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part A (16 Weeks) | Physician Decision | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part A (16 Weeks) | Withdrawal by Subject | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Part B (36 Weeks) | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Part C: (Up to Wk108+12Wk Follow-up) | Other | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 32 |
| Part C: (Up to Wk108+12Wk Follow-up) | Physician Decision | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 3 |
| Part C: (Up to Wk108+12Wk Follow-up) | Protocol Violation | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 |
| Part C: (Up to Wk108+12Wk Follow-up) | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 16 |
Baseline characteristics
| Characteristic | Part A: Pooled Placebo | Part A: Dupilumab Low Dose | Part A: Dupilumab High Dose | Total |
|---|---|---|---|---|
| Age, Continuous | 7.2 years STANDARD_DEVIATION 3.03 | 7.2 years STANDARD_DEVIATION 3.07 | 6.8 years STANDARD_DEVIATION 3.11 | 7.1 years STANDARD_DEVIATION 3.05 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 2 Participants | 2 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 30 Participants | 29 Participants | 33 Participants | 92 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 2 Participants | 3 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race/Ethnicity, Customized Black or African American | 3 Participants | 4 Participants | 4 Participants | 11 Participants |
| Race/Ethnicity, Customized Other | 1 Participants | 4 Participants | 0 Participants | 5 Participants |
| Race/Ethnicity, Customized White | 30 Participants | 22 Participants | 32 Participants | 84 Participants |
| Sex: Female, Male Female | 9 Participants | 6 Participants | 9 Participants | 24 Participants |
| Sex: Female, Male Male | 25 Participants | 25 Participants | 28 Participants | 78 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 | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 34 | 0 / 30 | 0 / 37 | 0 / 14 | 0 / 18 | 0 / 29 | 0 / 37 | 0 / 61 |
| other Total, other adverse events | 28 / 34 | 24 / 30 | 26 / 37 | 14 / 14 | 16 / 18 | 27 / 29 | 31 / 37 | 48 / 61 |
| serious Total, serious adverse events | 0 / 34 | 0 / 30 | 2 / 37 | 1 / 14 | 0 / 18 | 2 / 29 | 2 / 37 | 3 / 61 |
Outcome results
Primary
Part A: Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of Less Than or Equal to (≤) 6 Eosinophils/High Power Field (Eos/Hpf) at Week 16
Peak esophageal intraepithelial eosinophil count was measured from esophageal biopsies. A total of at least 9 mucosal pinch biopsies were collected from 3 esophageal regions: 3 proximal, 3 mid, and 3 distal. The peak esophageal intraepithelial eosinophil count at each visit was the maximum of the quantities of eosinophils in the most inflamed hpfs across the 3 regions. If the quantity of eosinophils was missing for 1 or 2 esophageal regions, the peak eosinophil count was the maximum of the quantities of eosinophils from the region(s) where eosinophil quantities were available.
Time frame: At Week 16
Population: Analysis was performed on Part A FAS which included all randomized participants in Part A.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Pooled Placebo | Part A: Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of Less Than or Equal to (≤) 6 Eosinophils/High Power Field (Eos/Hpf) at Week 16 | 2.9 percentage of participants |
| Part A: Dupilumab High Dose | Part A: Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of Less Than or Equal to (≤) 6 Eosinophils/High Power Field (Eos/Hpf) at Week 16 | 67.6 percentage of participants |
| Part A: Dupilumab Low Dose | Part A: Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of Less Than or Equal to (≤) 6 Eosinophils/High Power Field (Eos/Hpf) at Week 16 | 58.1 percentage of participants |
Comparison: Part A: Dupilumab High Dose versus Part A: Pooled Placebop-value: <0.000195% CI: [7.37, 392.82]Cochran-Mantel-Haenszel
Comparison: Part A: Dupilumab Low Dose versus Part A: Pooled Placebop-value: <0.000195% CI: [5.47, 399.54]Cochran-Mantel-Haenszel
Secondary
Part A: Absolute Change From Baseline in EoE Endoscopic Reference Total Score (EoE-EREFS) at Week 16
The EoE-EREFS is a validated endoscopic scoring system for inflammatory and remodeling features of EoE including edema, rings, exudates, furrows, and stricture. The score was assessed in the proximal and distal esophageal regions with each region scored from 0 to 9 with total scores ranging from 0 to 18. Higher scores indicate worse endoscopic inflammatory and remodeling findings.
Time frame: Baseline, Week 16
Population: Analysis was performed on Part A FAS which included all randomized participants in Part A.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pooled Placebo | Part A: Absolute Change From Baseline in EoE Endoscopic Reference Total Score (EoE-EREFS) at Week 16 | 0.3 score on a scale | Standard Error 0.45 |
| Part A: Dupilumab High Dose | Part A: Absolute Change From Baseline in EoE Endoscopic Reference Total Score (EoE-EREFS) at Week 16 | -3.5 score on a scale | Standard Error 0.42 |
| Part A: Dupilumab Low Dose | Part A: Absolute Change From Baseline in EoE Endoscopic Reference Total Score (EoE-EREFS) at Week 16 | -3.0 score on a scale | Standard Error 0.48 |
Comparison: Part A: Dupilumab High Dose versus Part A: Pooled Placebop-value: <0.000195% CI: [-4.94, -2.63]ANCOVA
Comparison: Part A: Dupilumab Low Dose versus Part A: Pooled Placebop-value: <0.000195% CI: [-4.59, -2.1]ANCOVA
Secondary
Part A: Change From Baseline in Mean Eosinophilic Esophagitis Histology Scoring System (EoE-HSS) Grade Score at Week 16
EoE-HSS is a validated histologic scoring system that measures other histological abnormalities in addition to density of eosinophilic infiltration. Severity (grade) and extent (stage) of abnormalities will be scored using a 4-point scale (0 normal; 3 maximum change). Higher total score indicated greater severity & extent of histological abnormalities. For each of 3 esophageal regions (proximal, mid, and distal), the ratio of the sum of assigned score for each evaluated feature divided by maximum possible score (maximum value is 24) was calculated. The mean grade scores summed over the 3 regions was the final score used in primary analysis, the mean grade score ranged from 0 to 3, with higher score indicating more severe.
Time frame: Baseline, Week 16
Population: Analysis was performed on Part A FAS which included all randomized participants in Part A.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pooled Placebo | Part A: Change From Baseline in Mean Eosinophilic Esophagitis Histology Scoring System (EoE-HSS) Grade Score at Week 16 | 0.023 Score on a scale | Standard Error 0.0498 |
| Part A: Dupilumab High Dose | Part A: Change From Baseline in Mean Eosinophilic Esophagitis Histology Scoring System (EoE-HSS) Grade Score at Week 16 | -0.879 Score on a scale | Standard Error 0.0481 |
| Part A: Dupilumab Low Dose | Part A: Change From Baseline in Mean Eosinophilic Esophagitis Histology Scoring System (EoE-HSS) Grade Score at Week 16 | -0.757 Score on a scale | Standard Error 0.0524 |
Comparison: Part A: Dupilumab High Dose versus Part A: Pooled Placebop-value: <0.000195% CI: [-1.0325, -0.7714]ANCOVA
Comparison: Part A: Dupilumab Low Dose versus Part A: Pooled Placebop-value: <0.000195% CI: [-0.917, -0.644]ANCOVA
Secondary
Part A: Change From Baseline in Mean Eosinophilic Esophagitis Histology Scoring System (EoE-HSS) Stage Score at Week 16
EoE-HSS is a validated histologic scoring system that measures other histological abnormalities in addition to density of eosinophilic infiltration. Severity (grade) and extent (stage) of abnormalities will be scored using a 4-point scale (0 normal; 3 maximum change). Higher total score indicated greater severity & extent of histological abnormalities. For each of 3 esophageal regions (proximal, mid, and distal), the ratio of the sum of assigned score for each evaluated feature divided by maximum possible score (maximum value is 24) was calculated. The mean stage scores summed over the 3 regions was the final score used in primary analysis, the mean stage score ranged from 0 to 3, with higher score indicating more severe.
Time frame: Baseline, Week 16
Population: Analysis was performed on Part A FAS which included all randomized participants in Part A.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pooled Placebo | Part A: Change From Baseline in Mean Eosinophilic Esophagitis Histology Scoring System (EoE-HSS) Stage Score at Week 16 | 0.048 Score on a scale | Standard Error 0.0482 |
| Part A: Dupilumab High Dose | Part A: Change From Baseline in Mean Eosinophilic Esophagitis Histology Scoring System (EoE-HSS) Stage Score at Week 16 | -0.835 Score on a scale | Standard Error 0.0466 |
| Part A: Dupilumab Low Dose | Part A: Change From Baseline in Mean Eosinophilic Esophagitis Histology Scoring System (EoE-HSS) Stage Score at Week 16 | -0.721 Score on a scale | Standard Error 0.0507 |
Comparison: Part A: Dupilumab High Dose versus Part A: Pooled Placebop-value: <0.000195% CI: [-1.0095, -0.7568]ANCOVA
Comparison: Part A: Dupilumab Low Dose versus Part A: Pooled Placebop-value: <0.000195% CI: [-0.9013, -0.6362]ANCOVA
Secondary
Part A: Change From Baseline in the Proportion of Days With 1 or More EoE Signs as Measured by Pediatric EoE Sign/Symptom Questionnaire - Caregiver Version (PESQ-C) at Week 16 (for Participants Aged ≥1 to <12 Years)
PESQ-C is a novel, observer-reported outcome measure intended to be completed independently by caregivers of all pediatric EoE participants in the study. PESQ-C measures the signs of EoE observed by the caregiver, including stomach pain, heartburn, acid reflux, regurgitation, vomiting, food refusal, and trouble swallowing food. Data from a 14-day period preceding the baseline visit and a 14-day period preceding week 16 will be used to calculate the proportion of days with 1 or more EoE symptoms.
Time frame: Baseline, Week 16
Population: Analysis was performed on Part A FAS which included all randomized participants in Part A.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pooled Placebo | Part A: Change From Baseline in the Proportion of Days With 1 or More EoE Signs as Measured by Pediatric EoE Sign/Symptom Questionnaire - Caregiver Version (PESQ-C) at Week 16 (for Participants Aged ≥1 to <12 Years) | -0.17 proportion of days | Standard Error 0.054 |
| Part A: Dupilumab High Dose | Part A: Change From Baseline in the Proportion of Days With 1 or More EoE Signs as Measured by Pediatric EoE Sign/Symptom Questionnaire - Caregiver Version (PESQ-C) at Week 16 (for Participants Aged ≥1 to <12 Years) | -0.28 proportion of days | Standard Error 0.052 |
| Part A: Dupilumab Low Dose | Part A: Change From Baseline in the Proportion of Days With 1 or More EoE Signs as Measured by Pediatric EoE Sign/Symptom Questionnaire - Caregiver Version (PESQ-C) at Week 16 (for Participants Aged ≥1 to <12 Years) | -0.18 proportion of days | Standard Error 0.06 |
Comparison: Part A: Dupilumab High Dose versus Part A: Pooled Placebop-value: 0.152695% CI: [-0.244, 0.038]ANCOVA
Comparison: Part A: Dupilumab Low Dose versus Part A: Pooled Placebop-value: 0.953395% CI: [-0.155, 0.146]ANCOVA
Secondary
Part A: Change From Baseline in the Proportion of Days With 1 or More EoE Signs by Pediatric EoE Sign/Symptom Questionnaire - Participant Version (PESQ-P) (for Participants Aged ≥8 to <12 Years) at Week 16
The PESQ-P was a participant-reported outcome measure intended to be completed independently by participants ≥8 to \<12 years of age. The PESQ-P measured occurrence of signs of EoE and was completed once daily via an electronic diary. Data from a 14-day period preceding the baseline visit and a 14-day period preceding week 16 will be used to calculate the proportion of days with 1 or more EoE symptoms.
Time frame: Baseline, Week 16
Population: Analysis was performed on Part A FAS which included all randomized participants in Part A. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pooled Placebo | Part A: Change From Baseline in the Proportion of Days With 1 or More EoE Signs by Pediatric EoE Sign/Symptom Questionnaire - Participant Version (PESQ-P) (for Participants Aged ≥8 to <12 Years) at Week 16 | -0.26 proportion of days | Standard Error 0.068 |
| Part A: Dupilumab High Dose | Part A: Change From Baseline in the Proportion of Days With 1 or More EoE Signs by Pediatric EoE Sign/Symptom Questionnaire - Participant Version (PESQ-P) (for Participants Aged ≥8 to <12 Years) at Week 16 | -0.13 proportion of days | Standard Error 0.077 |
| Part A: Dupilumab Low Dose | Part A: Change From Baseline in the Proportion of Days With 1 or More EoE Signs by Pediatric EoE Sign/Symptom Questionnaire - Participant Version (PESQ-P) (for Participants Aged ≥8 to <12 Years) at Week 16 | -0.16 proportion of days | Standard Error 0.067 |
Comparison: Part A: Dupilumab High Dose versus Part A: Pooled Placebop-value: 0.208695% CI: [-0.072, 0.33]ANCOVA
Comparison: Part A: Dupilumab Low Dose versus Part A: Pooled Placebop-value: 0.297595% CI: [-0.088, 0.286]ANCOVA
Secondary
Part A: Change From Baseline in the Proportion of Total Segments Within a Day (Night, Morning, Afternoon, Evening) With 1 or More EoE Signs as Measured by the PESQ-C at Week 16
PESQ-C is a novel, observer-reported outcome measure intended to be completed independently by caregivers of all pediatric EoE participants in the study. The PESQ-C measured the occurrence of signs of EoE and was completed once daily via an electronic diary. Data from a 14-day period preceding the baseline visit and a 14-day period preceding week 16 will be used to calculate the total time segments within a day (night, morning, afternoon, evening) with 1 or more EoE symptoms.
Time frame: Baseline, Week 16
Population: Analysis was performed on Part A FAS which included all randomized participants in Part A.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pooled Placebo | Part A: Change From Baseline in the Proportion of Total Segments Within a Day (Night, Morning, Afternoon, Evening) With 1 or More EoE Signs as Measured by the PESQ-C at Week 16 | -0.11 proportion of segments | Standard Error 0.032 |
| Part A: Dupilumab High Dose | Part A: Change From Baseline in the Proportion of Total Segments Within a Day (Night, Morning, Afternoon, Evening) With 1 or More EoE Signs as Measured by the PESQ-C at Week 16 | -0.16 proportion of segments | Standard Error 0.031 |
| Part A: Dupilumab Low Dose | Part A: Change From Baseline in the Proportion of Total Segments Within a Day (Night, Morning, Afternoon, Evening) With 1 or More EoE Signs as Measured by the PESQ-C at Week 16 | -0.09 proportion of segments | Standard Error 0.036 |
Comparison: Part A: Dupilumab High Dose versus Part A: Pooled Placebop-value: 0.206495% CI: [-0.139, 0.03]ANCOVA
Comparison: Part A: Dupilumab Low Dose versus Part A: Pooled Placebop-value: 0.636195% CI: [-0.069, 0.112]ANCOVA
Secondary
Part A: Change From Baseline in the Proportion of Total Segments Within a Day (Night, Morning, Afternoon, Evening) With 1 or More EoE Signs as Measured by the PESQ-P (for Participants Aged ≥8 to <12 Years) at Week 16
The PESQ-P was a participant-reported outcome measure intended to be completed independently by EoE participants ≥8 to \<12 years of age. The PESQ-P measured the occurrence of signs of EoE and was completed once daily via an electronic diary. Data from a 14-day period preceding the baseline visit and a 14-day period preceding week 16 will be used to calculate the total time segments within a day (night, morning, afternoon, evening) with 1 or more EoE symptoms.
Time frame: Baseline, Week 16
Population: Analysis was performed on Part A FAS which included all randomized participants in Part A. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pooled Placebo | Part A: Change From Baseline in the Proportion of Total Segments Within a Day (Night, Morning, Afternoon, Evening) With 1 or More EoE Signs as Measured by the PESQ-P (for Participants Aged ≥8 to <12 Years) at Week 16 | -0.15 proportion of segments | Standard Error 0.04 |
| Part A: Dupilumab High Dose | Part A: Change From Baseline in the Proportion of Total Segments Within a Day (Night, Morning, Afternoon, Evening) With 1 or More EoE Signs as Measured by the PESQ-P (for Participants Aged ≥8 to <12 Years) at Week 16 | -0.08 proportion of segments | Standard Error 0.045 |
| Part A: Dupilumab Low Dose | Part A: Change From Baseline in the Proportion of Total Segments Within a Day (Night, Morning, Afternoon, Evening) With 1 or More EoE Signs as Measured by the PESQ-P (for Participants Aged ≥8 to <12 Years) at Week 16 | -0.08 proportion of segments | Standard Error 0.039 |
Comparison: Part A: Dupilumab High Dose versus Part A: Pooled Placebop-value: 0.23695% CI: [-0.046, 0.186]ANCOVA
Comparison: Part A: Dupilumab Low Dose versus Part A: Pooled Placebop-value: 0.193995% CI: [-0.037, 0.181]ANCOVA
Secondary
Part A: Change From Baseline in Total Score as Measured by the Pediatric Eosinophilic Esophagitis Symptom Score (PEESS) Version 2.0 Caregiver Version (PEESSv2.0-C) at Week 16
The PEESSv2.0-C is a caregiver-reported outcome measure that assesses the frequency and severity of EoE symptoms among pediatric participants. The PEESSv2.0-C consists of 20 items and has a one-month recall period. Each item had a 0-4 scale, which was transformed to 0-100 as follows: 0 = 0, 1 = 25, 2 = 50, 3 = 75, 4 = 100. The mean total PEESSv2.0 score was computed as the sum of all the item scores over the number of items answered. The total PEESSv2.0-C score ranges from 0 to 100 where higher scores indicate greater symptom burden among pediatric EoE participants. Values after first rescue treatment use were set to missing (censoring). WOCF approach was used for imputing the missing data due to rescue treatment/AE/lack of efficacy, and the MI approach was used for the missing data due to other reasons. LS mean SE from ANCOVA model.
Time frame: Baseline, Week 16
Population: Analysis was performed on Part A FAS which included all randomized participants in Part A.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pooled Placebo | Part A: Change From Baseline in Total Score as Measured by the Pediatric Eosinophilic Esophagitis Symptom Score (PEESS) Version 2.0 Caregiver Version (PEESSv2.0-C) at Week 16 | -11.83 score on a scale | Standard Error 2.909 |
| Part A: Dupilumab High Dose | Part A: Change From Baseline in Total Score as Measured by the Pediatric Eosinophilic Esophagitis Symptom Score (PEESS) Version 2.0 Caregiver Version (PEESSv2.0-C) at Week 16 | -19.86 score on a scale | Standard Error 2.577 |
| Part A: Dupilumab Low Dose | Part A: Change From Baseline in Total Score as Measured by the Pediatric Eosinophilic Esophagitis Symptom Score (PEESS) Version 2.0 Caregiver Version (PEESSv2.0-C) at Week 16 | -10.10 score on a scale | Standard Error 2.785 |
Secondary
Part A: Concentration of Functional Dupilumab in Serum at Baseline, Week 4 and 16
Concentration of functional dupilumab in serum at Baseline, Week 4 and 16 was reported in this outcome measure.
Time frame: Baseline, Week 4 and 16
Population: Analysis was performed on pharmacokinetic analysis set (PKAS) that includes all participants who received any study drug and had at least 1 non-missing result following the first dose of study drug. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure and 'number analyzed' = participants with available data for each specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Pooled Placebo | Part A: Concentration of Functional Dupilumab in Serum at Baseline, Week 4 and 16 | Baseline | 0 milligrams per liter (mg/L) | Standard Deviation 0 |
| Part A: Pooled Placebo | Part A: Concentration of Functional Dupilumab in Serum at Baseline, Week 4 and 16 | Week 4 | 75.7 milligrams per liter (mg/L) | Standard Deviation 25.7 |
| Part A: Pooled Placebo | Part A: Concentration of Functional Dupilumab in Serum at Baseline, Week 4 and 16 | Week 16 | 163 milligrams per liter (mg/L) | Standard Deviation 60.8 |
| Part A: Dupilumab High Dose | Part A: Concentration of Functional Dupilumab in Serum at Baseline, Week 4 and 16 | Baseline | 0 milligrams per liter (mg/L) | Standard Deviation 0 |
| Part A: Dupilumab High Dose | Part A: Concentration of Functional Dupilumab in Serum at Baseline, Week 4 and 16 | Week 4 | 40.6 milligrams per liter (mg/L) | Standard Deviation 11.2 |
| Part A: Dupilumab High Dose | Part A: Concentration of Functional Dupilumab in Serum at Baseline, Week 4 and 16 | Week 16 | 86.0 milligrams per liter (mg/L) | Standard Deviation 29.2 |
Secondary
Part A: Normalized Enrichment Score (NES) for the Relative Change From Baseline in the Eosinophilic Esophagitis (EoE) Diagnostic Panel (EDP) at Week 16
A Normalized Enrichment Score (NES) is a way to generate a single numerical value to represent a complex gene expression signature. Changes in NES score represented the overall changes in the expression of that molecular phenotype. The NESs calculated for the EDP reflect the expression at Week 16 relative to Baseline of a gene set that is differentially expressed between esophageal biopsies from EoE participants compared to healthy controls as a way to evaluate normalization of the molecular pathology. For each subject, an NES of 0 indicates no change from baseline, a negative score shows a reduction in disease score (more like normal) and positive score shows worsening (more active disease). NES does not have minimum/maximum score.
Time frame: Baseline, Week 16
Population: Analysis was performed on Part A FAS which included all randomized participants in Part A. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Pooled Placebo | Part A: Normalized Enrichment Score (NES) for the Relative Change From Baseline in the Eosinophilic Esophagitis (EoE) Diagnostic Panel (EDP) at Week 16 | 0.180 Score on a scale |
| Part A: Dupilumab High Dose | Part A: Normalized Enrichment Score (NES) for the Relative Change From Baseline in the Eosinophilic Esophagitis (EoE) Diagnostic Panel (EDP) at Week 16 | -2.630 Score on a scale |
| Part A: Dupilumab Low Dose | Part A: Normalized Enrichment Score (NES) for the Relative Change From Baseline in the Eosinophilic Esophagitis (EoE) Diagnostic Panel (EDP) at Week 16 | -2.710 Score on a scale |
Comparison: Part A: Dupilumab High Dose versus Part A: Pooled Placebop-value: <0.000195% CI: [-3.35, -1.96]Wilcoxon rank-sum test
Comparison: Part A: Dupilumab Low Dose versus Part A: Pooled Placebop-value: <0.000195% CI: [-3.31, -1.62]Wilcoxon rank-sum test
Secondary
Part A: Normalized Enrichment Score (NES) for the Relative Change From Baseline in the Type 2 Inflammation Signature (T2INF) at Week 16
A Normalized Enrichment Score (NES) is a way to generate a single numerical value to represent a complex gene expression signature. Changes in NES score represented the overall changes in the expression of that molecular phenotype. The NESs calculated for T2INF reflect the expression at Week 16 relative to Baseline of the pre-specified gene set as a way to evaluate normalization of type 2 inflammation with treatment. For each subject, an NES of 0 indicates no change from baseline, a negative score shows a reduction in disease score (more like normal) and positive score shows worsening (more active disease). NES does not have a minimum/maximum score.
Time frame: Baseline, Week 16
Population: Analysis was performed on Part A FAS which included all randomized participants in Part A. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Pooled Placebo | Part A: Normalized Enrichment Score (NES) for the Relative Change From Baseline in the Type 2 Inflammation Signature (T2INF) at Week 16 | 0.34 Score on a scale |
| Part A: Dupilumab High Dose | Part A: Normalized Enrichment Score (NES) for the Relative Change From Baseline in the Type 2 Inflammation Signature (T2INF) at Week 16 | -1.895 Score on a scale |
| Part A: Dupilumab Low Dose | Part A: Normalized Enrichment Score (NES) for the Relative Change From Baseline in the Type 2 Inflammation Signature (T2INF) at Week 16 | -1.930 Score on a scale |
Comparison: Part A: Dupilumab High Dose versus Part A: Pooled Placebop-value: <0.000195% CI: [-2.44, -1.95]Wilcoxon rank-sum test
Comparison: Part A: Dupilumab Low Dose versus Part A: Pooled Placebop-value: <0.000195% CI: [-2.45, -1.82]Wilcoxon rank-sum test
Secondary
Part A: Number of Participants With Positive Treatment-emergent Antidrug Antibodies (ADA) by Maximum Titer Category
Treatment-emergent ADA was defined as a negative result or missing result at baseline with at least one positive post baseline result in the ADA assay. Samples positive in the dupilumab ADA assay were characterized for ADA titers (low, moderate and high). The low treatment-emergent ADA titer as defined as titer level \<1000, moderate as 1000 to 10000 and high as \>10000.
Time frame: From Baseline up to Week 16 in Part A
Population: Analysis was performed on AAS which included all participants who received any amount of study drug (active or placebo) and had at least one non-missing anti-drug antibody result following the first dose of study drug or placebo. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure and overall number of participants analyzed = 0 denotes that no participant had positive treatment-emergent ADA response to measure titer level.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: Pooled Placebo | Part A: Number of Participants With Positive Treatment-emergent Antidrug Antibodies (ADA) by Maximum Titer Category | Treatment-emergent ADA Titer: High | 0 Participants |
| Part A: Pooled Placebo | Part A: Number of Participants With Positive Treatment-emergent Antidrug Antibodies (ADA) by Maximum Titer Category | Treatment-emergent ADA Titer: Moderate | 0 Participants |
| Part A: Pooled Placebo | Part A: Number of Participants With Positive Treatment-emergent Antidrug Antibodies (ADA) by Maximum Titer Category | Treatment-emergent ADA Titer: Low | 1 Participants |
| Part A: Dupilumab High Dose | Part A: Number of Participants With Positive Treatment-emergent Antidrug Antibodies (ADA) by Maximum Titer Category | Treatment-emergent ADA Titer: High | 0 Participants |
| Part A: Dupilumab High Dose | Part A: Number of Participants With Positive Treatment-emergent Antidrug Antibodies (ADA) by Maximum Titer Category | Treatment-emergent ADA Titer: Moderate | 0 Participants |
| Part A: Dupilumab High Dose | Part A: Number of Participants With Positive Treatment-emergent Antidrug Antibodies (ADA) by Maximum Titer Category | Treatment-emergent ADA Titer: Low | 1 Participants |
| Part A: Dupilumab Low Dose | Part A: Number of Participants With Positive Treatment-emergent Antidrug Antibodies (ADA) by Maximum Titer Category | Treatment-emergent ADA Titer: High | 0 Participants |
| Part A: Dupilumab Low Dose | Part A: Number of Participants With Positive Treatment-emergent Antidrug Antibodies (ADA) by Maximum Titer Category | Treatment-emergent ADA Titer: Low | 0 Participants |
| Part A: Dupilumab Low Dose | Part A: Number of Participants With Positive Treatment-emergent Antidrug Antibodies (ADA) by Maximum Titer Category | Treatment-emergent ADA Titer: Moderate | 0 Participants |
Secondary
Part A: Number of Participants With Positive Treatment-emergent Antidrug Antibodies (ADA) Response
Treatment-emergent ADA was defined as a negative result or missing result at baseline with at least one positive post baseline result in the ADA assay. Samples positive in the dupilumab ADA assay were characterized for ADA titers (low, moderate and high). The low treatment-emergent ADA titer as defined as titer level \<1000, moderate as 1000 to 10000 and high as \>10000.
Time frame: From Baseline up to Week 16 in Part A
Population: Analysis was performed on ADA analysis set (AAS) which included all participants who received any amount of study drug (active or placebo) and had at least one non-missing anti-drug antibody result following the first dose of study drug or placebo. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Pooled Placebo | Part A: Number of Participants With Positive Treatment-emergent Antidrug Antibodies (ADA) Response | 1 Participants |
| Part A: Dupilumab High Dose | Part A: Number of Participants With Positive Treatment-emergent Antidrug Antibodies (ADA) Response | 1 Participants |
| Part A: Dupilumab Low Dose | Part A: Number of Participants With Positive Treatment-emergent Antidrug Antibodies (ADA) Response | 0 Participants |
Secondary
Part A: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Adverse Events of Special Interest (AESIs) and TEAEs Leading to Permanent Discontinuation of Study Drug
An adverse event (AE) was defined as any untoward medical occurrence in a participant or clinical investigation patient administered with a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. A serious AE was any untoward medical occurrence that at any dose resulted in death, life-threatening, initial or prolonged inpatient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or a medically important event. The term TEAE is defined as AEs starting or worsening after the first intake of the study drug. TEAEs include both Serious TEAEs and non-serious TEAEs. An AESI was defined as one of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and rapid communication by the Investigator to the Sponsor was appropriate.
Time frame: From Baseline up to Week 16 in Part A
Population: Analysis was performed on Part A SAF which included all randomized patients who received any Part A study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: Pooled Placebo | Part A: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Adverse Events of Special Interest (AESIs) and TEAEs Leading to Permanent Discontinuation of Study Drug | Participants with any TEAE leading to permanent discontinuation of study drug | 2 Participants |
| Part A: Pooled Placebo | Part A: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Adverse Events of Special Interest (AESIs) and TEAEs Leading to Permanent Discontinuation of Study Drug | Participants with any TEAE | 31 Participants |
| Part A: Pooled Placebo | Part A: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Adverse Events of Special Interest (AESIs) and TEAEs Leading to Permanent Discontinuation of Study Drug | Participants with any AESI | 1 Participants |
| Part A: Pooled Placebo | Part A: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Adverse Events of Special Interest (AESIs) and TEAEs Leading to Permanent Discontinuation of Study Drug | Participants with any Serious TEAE | 0 Participants |
| Part A: Dupilumab High Dose | Part A: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Adverse Events of Special Interest (AESIs) and TEAEs Leading to Permanent Discontinuation of Study Drug | Participants with any TEAE leading to permanent discontinuation of study drug | 0 Participants |
| Part A: Dupilumab High Dose | Part A: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Adverse Events of Special Interest (AESIs) and TEAEs Leading to Permanent Discontinuation of Study Drug | Participants with any AESI | 2 Participants |
| Part A: Dupilumab High Dose | Part A: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Adverse Events of Special Interest (AESIs) and TEAEs Leading to Permanent Discontinuation of Study Drug | Participants with any Serious TEAE | 2 Participants |
| Part A: Dupilumab High Dose | Part A: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Adverse Events of Special Interest (AESIs) and TEAEs Leading to Permanent Discontinuation of Study Drug | Participants with any TEAE | 27 Participants |
| Part A: Dupilumab Low Dose | Part A: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Adverse Events of Special Interest (AESIs) and TEAEs Leading to Permanent Discontinuation of Study Drug | Participants with any AESI | 1 Participants |
| Part A: Dupilumab Low Dose | Part A: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Adverse Events of Special Interest (AESIs) and TEAEs Leading to Permanent Discontinuation of Study Drug | Participants with any Serious TEAE | 1 Participants |
| Part A: Dupilumab Low Dose | Part A: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Adverse Events of Special Interest (AESIs) and TEAEs Leading to Permanent Discontinuation of Study Drug | Participants with any TEAE leading to permanent discontinuation of study drug | 0 Participants |
| Part A: Dupilumab Low Dose | Part A: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Adverse Events of Special Interest (AESIs) and TEAEs Leading to Permanent Discontinuation of Study Drug | Participants with any TEAE | 26 Participants |
Secondary
Part A: Number of Sign-free Days During the 14-day Period Preceding Week 16 as Measured by the PESQ-C (for Participants Aged ≥1 to <12 Years)
PESQ-C is a novel, observer-reported outcome measure intended to be completed independently by caregivers of all pediatric EoE participants in the study. The PESQ-C measures the signs of EoE observed by the caregiver, including stomach pain, heartburn, acid reflux, regurgitation, vomiting, food refusal, and trouble swallowing food. WOCF approach was used for imputing the missing data due to rescue treatment/AE/lack of efficacy, and the multiple imputations approach was used for the missing data due to other reasons. LS mean SE derived from ANCOVA model.
Time frame: Week 16
Population: Analysis was performed on Part A FAS which included all randomized participants in Part A.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pooled Placebo | Part A: Number of Sign-free Days During the 14-day Period Preceding Week 16 as Measured by the PESQ-C (for Participants Aged ≥1 to <12 Years) | 8.93 sign-free days | Standard Error 0.756 |
| Part A: Dupilumab High Dose | Part A: Number of Sign-free Days During the 14-day Period Preceding Week 16 as Measured by the PESQ-C (for Participants Aged ≥1 to <12 Years) | 10.38 sign-free days | Standard Error 0.735 |
| Part A: Dupilumab Low Dose | Part A: Number of Sign-free Days During the 14-day Period Preceding Week 16 as Measured by the PESQ-C (for Participants Aged ≥1 to <12 Years) | 8.93 sign-free days | Standard Error 0.84 |
Comparison: Part A: Dupilumab High Dose versus Part A: Pooled Placebop-value: 0.150795% CI: [-0.527, 3.422]ANCOVA
Comparison: Part A: Dupilumab Low Dose versus Part A: Pooled Placebop-value: 0.996595% CI: [-2.107, 2.117]ANCOVA
Secondary
Part A: Number of Symptom-free Days During the 14-day Period Preceding Week 16 as Measured by the PESQ-P (for Participants Aged ≥8 to <12 Years)
The PESQ-P was a participant-reported outcome measure intended to be completed independently by EoE participants ≥8 to \<12 years of age. The PESQ-P measures the signs of EoE, including stomach pain, heartburn, acid reflux, regurgitation, vomiting, food refusal, and trouble swallowing food. The PESQ-P score was calculated based on the daily responses over a 14-day period (i.e., the 14 days prior to the baseline visit and the week 16 visit). The score ranges from 0 to 1. WOCF approach was used for imputing the missing data due to rescue treatment/AE/lack of efficacy, and the multiple imputations approach was used for the missing data due to other reasons. LS Mean SE from ANCOVA.
Time frame: Week 16
Population: Analysis was performed on Part A FAS which included all randomized participants in Part A. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pooled Placebo | Part A: Number of Symptom-free Days During the 14-day Period Preceding Week 16 as Measured by the PESQ-P (for Participants Aged ≥8 to <12 Years) | 10.49 sign-free days | Standard Error 0.953 |
| Part A: Dupilumab High Dose | Part A: Number of Symptom-free Days During the 14-day Period Preceding Week 16 as Measured by the PESQ-P (for Participants Aged ≥8 to <12 Years) | 8.69 sign-free days | Standard Error 1.081 |
| Part A: Dupilumab Low Dose | Part A: Number of Symptom-free Days During the 14-day Period Preceding Week 16 as Measured by the PESQ-P (for Participants Aged ≥8 to <12 Years) | 9.13 sign-free days | Standard Error 0.936 |
Comparison: Part A: Dupilumab High Dose versus Part A: Pooled Placebop-value: 0.208595% CI: [-4.615, 1.007]ANCOVA
Comparison: Part A: Dupilumab Low Dose versus Part A: Pooled Placebop-value: 0.309895% CI: [-3.972, 1.26]ANCOVA
Secondary
Part A: Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of <15 Eosinophils/High Power Field at Week 16
Peak esophageal intraepithelial eosinophil count was measured from esophageal biopsies. A total of at least 9 mucosal pinch biopsies were collected from 3 esophageal regions: 3 proximal, 3 mid, and 3 distal. The peak esophageal intraepithelial eosinophil count at each visit was the maximum of the quantities of eosinophils in the most inflamed hpfs across the 3 regions. If the quantity of eosinophils was missing for 1 or 2 esophageal regions, the peak eosinophil count was the maximum of the quantities of eosinophils from the region(s) where eosinophil quantities were available.
Time frame: At Week 16
Population: Analysis was performed on Part A FAS which included all randomized participants in Part A.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Pooled Placebo | Part A: Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of <15 Eosinophils/High Power Field at Week 16 | 2.9 percentage of participants |
| Part A: Dupilumab High Dose | Part A: Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of <15 Eosinophils/High Power Field at Week 16 | 83.8 percentage of participants |
| Part A: Dupilumab Low Dose | Part A: Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of <15 Eosinophils/High Power Field at Week 16 | 67.7 percentage of participants |
Comparison: Part A: Dupilumab High Dose versus Part A: Pooled Placebop-value: <0.000195% CI: [18.84, 1682.4]Cochran-Mantel-Haenszel
Comparison: Part A: Dupilumab Low Dose versus Part A: Pooled Placebop-value: <0.000195% CI: [7.45, 410.23]Cochran-Mantel-Haenszel
Secondary
Part A: Percent Change From Baseline in Peak Esophageal Intraepithelial Eosinophil Count at Week 16
Peak esophageal intraepithelial eosinophil count was measured from esophageal biopsies. A total of at least 9 mucosal pinch biopsies were collected from 3 esophageal regions: 3 proximal, 3 mid, and 3 distal. The peak esophageal intraepithelial eosinophil count at each visit was the maximum of the quantities of eosinophils in the most inflamed hpfs across the 3 regions. If the quantity of eosinophils was missing for 1 or 2 esophageal regions, the peak eosinophil count was the maximum of the quantities of eosinophils from the region(s) where eosinophil quantities were available. Least squared (LS) mean and standard error (SE) from analysis of covariance (ANCOVA) model with Baseline measurement as covariate and the treatment, baseline weight group strata as fixed factors.
Time frame: Baseline, Week 16
Population: Analysis was performed on Part A FAS which included all randomized participants in Part A.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pooled Placebo | Part A: Percent Change From Baseline in Peak Esophageal Intraepithelial Eosinophil Count at Week 16 | 20.98 percent change | Standard Error 12.23 |
| Part A: Dupilumab High Dose | Part A: Percent Change From Baseline in Peak Esophageal Intraepithelial Eosinophil Count at Week 16 | -86.09 percent change | Standard Error 11.84 |
| Part A: Dupilumab Low Dose | Part A: Percent Change From Baseline in Peak Esophageal Intraepithelial Eosinophil Count at Week 16 | -77.93 percent change | Standard Error 12.89 |
Comparison: Part A: Dupilumab High Dose versus Part A: Pooled Placebop-value: <0.000195% CI: [-139.249, -74.9]ANCOVA
Comparison: Part A: Dupilumab Low Dose versus Part A: Pooled Placebop-value: <0.000195% CI: [-132.463, -65.37]ANCOVA
Secondary
Part B: Absolute Change From Baseline in EoE Endoscopic Reference Total Score (EoE-EREFS) at Week 52
The EoE-EREFS is a validated endoscopic scoring system for inflammatory and remodeling features of EoE including edema, rings, exudates, furrows, and stricture. The score was assessed in the proximal and distal esophageal regions with each region scored from 0 to 9 with total scores possibly ranging from 0 to 18. Higher scores indicate worse endoscopic inflammatory and remodeling findings.
Time frame: Baseline, Week 52
Population: Analysis was performed on Part B SAF which included all participants who received at least 1 dose of Part B study drug. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pooled Placebo | Part B: Absolute Change From Baseline in EoE Endoscopic Reference Total Score (EoE-EREFS) at Week 52 | -5.82 score on a scale | Standard Deviation 1.722 |
| Part A: Dupilumab High Dose | Part B: Absolute Change From Baseline in EoE Endoscopic Reference Total Score (EoE-EREFS) at Week 52 | -3.64 score on a scale | Standard Deviation 3.342 |
| Part A: Dupilumab Low Dose | Part B: Absolute Change From Baseline in EoE Endoscopic Reference Total Score (EoE-EREFS) at Week 52 | -4.50 score on a scale | Standard Deviation 3.203 |
| Part B: Dupilumab High Dose to Dupilumab High Dose | Part B: Absolute Change From Baseline in EoE Endoscopic Reference Total Score (EoE-EREFS) at Week 52 | -4.77 score on a scale | Standard Deviation 3.081 |
Secondary
Part B: Change From Baseline in Body Mass Index (BMI) for Age Z-score for Participants ≥2 Years of Age at Week 52
BMI for age z-score indicates how much higher or lower a participant's BMI for age is relative to a reference growth chart (based on the growth charts from Centers for Disease Control and Prevention \[CDC\] for ages 0 to 20 years \[for ages 2 to \<12 years\]). A z-score of 0 represents the population mean. An increase in the mean change in BMI for age z-score (ie, increase in the standard deviation \[SD\] from the reference growth chart) indicates an increase in BMI for age relative to the reference.
Time frame: Baseline, Week 52
Population: Analysis was performed on Part B SAF which included all participants who received at least 1 dose of Part B study drug. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pooled Placebo | Part B: Change From Baseline in Body Mass Index (BMI) for Age Z-score for Participants ≥2 Years of Age at Week 52 | -0.0206 z-score | Standard Deviation 0.54625 |
| Part A: Dupilumab High Dose | Part B: Change From Baseline in Body Mass Index (BMI) for Age Z-score for Participants ≥2 Years of Age at Week 52 | 0.0687 z-score | Standard Deviation 0.47605 |
| Part A: Dupilumab Low Dose | Part B: Change From Baseline in Body Mass Index (BMI) for Age Z-score for Participants ≥2 Years of Age at Week 52 | -0.0549 z-score | Standard Deviation 0.88582 |
| Part B: Dupilumab High Dose to Dupilumab High Dose | Part B: Change From Baseline in Body Mass Index (BMI) for Age Z-score for Participants ≥2 Years of Age at Week 52 | 0.0987 z-score | Standard Deviation 0.72329 |
Secondary
Part B: Change From Baseline in Body Weight for Age Percentile at Week 52
Body weight for age percentile was calculated based on the growth charts from the Centers for Disease Control and Prevention (CDC) for ages 0 to 20 years (for ages 2 to \<12 years) and World Health Organization (WHO) growth charts for ages 0 to \<2 years (for ages 1 to \<2 years). These charts included a set of smoothed percentiles along with CDC LMS (Lambda-Mu-Sigma) parameters to allow the calculation of percentiles.
Time frame: Baseline, Week 52
Population: Analysis was performed on Part B SAF which included all participants who received at least 1 dose of Part B study drug. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pooled Placebo | Part B: Change From Baseline in Body Weight for Age Percentile at Week 52 | -0.02 Percentile | Standard Deviation 13.893 |
| Part A: Dupilumab High Dose | Part B: Change From Baseline in Body Weight for Age Percentile at Week 52 | 5.48 Percentile | Standard Deviation 12.644 |
| Part A: Dupilumab Low Dose | Part B: Change From Baseline in Body Weight for Age Percentile at Week 52 | 4.75 Percentile | Standard Deviation 11.968 |
| Part B: Dupilumab High Dose to Dupilumab High Dose | Part B: Change From Baseline in Body Weight for Age Percentile at Week 52 | 5.96 Percentile | Standard Deviation 11.519 |
Secondary
Part B: Change From Baseline in Body Weight From Height Z-score at Week 52
Weight for height z-score indicates how much higher or lower a participant's weight for height is relative to a reference growth chart (based on the growth charts from CDC for ages 0 to 20 years \[for ages 2 to \<12 years\] and WHO growth charts for ages 0 to \<2 years \[for ages 1 to \<2 years\]). A z-score of 0 represents the population mean. An increase in the mean change in weight for height z-score (increase in the SD from the reference growth chart) indicates an increase in weight for height relative to the reference.
Time frame: Baseline, Week 52
Population: Analysis was performed on Part B SAF which included all participants who received at least 1 dose of Part B study drug. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pooled Placebo | Part B: Change From Baseline in Body Weight From Height Z-score at Week 52 | 0.0962 z-score | Standard Deviation 0.48902 |
| Part A: Dupilumab High Dose | Part B: Change From Baseline in Body Weight From Height Z-score at Week 52 | -0.0100 z-score | Standard Deviation 0.51706 |
| Part A: Dupilumab Low Dose | Part B: Change From Baseline in Body Weight From Height Z-score at Week 52 | -0.2700 z-score | Standard Deviation 1.04895 |
| Part B: Dupilumab High Dose to Dupilumab High Dose | Part B: Change From Baseline in Body Weight From Height Z-score at Week 52 | -0.0151 z-score | Standard Deviation 0.67968 |
Secondary
Part B: Change From Baseline in Mean Eosinophilic Esophagitis Histology Scoring System (EoE-HSS) Grade Score at Week 52
EoE-HSS is a validated histologic scoring system that measures other histological abnormalities in addition to density of eosinophilic infiltration. Severity (grade) and extent (stage) of abnormalities will be scored using a 4-point scale (0 normal; 3 maximum change). Higher total score indicated greater severity & extent of histological abnormalities. For each of 3 esophageal regions (proximal, mid, and distal), the ratio of the sum of assigned score for each evaluated feature divided by maximum possible score (maximum value is 24) was calculated. The mean grade scores summed over the 3 regions was the final score used in primary analysis, the mean grade score ranged from 0 to 3, with higher score indicating more severe.
Time frame: Baseline, Week 52
Population: Analysis was performed on Part B SAF which included all participants who received at least 1 dose of Part B study drug. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pooled Placebo | Part B: Change From Baseline in Mean Eosinophilic Esophagitis Histology Scoring System (EoE-HSS) Grade Score at Week 52 | -0.804 Score on a scale | Standard Deviation 0.3099 |
| Part A: Dupilumab High Dose | Part B: Change From Baseline in Mean Eosinophilic Esophagitis Histology Scoring System (EoE-HSS) Grade Score at Week 52 | -0.885 Score on a scale | Standard Deviation 0.2962 |
| Part A: Dupilumab Low Dose | Part B: Change From Baseline in Mean Eosinophilic Esophagitis Histology Scoring System (EoE-HSS) Grade Score at Week 52 | -0.773 Score on a scale | Standard Deviation 0.3374 |
| Part B: Dupilumab High Dose to Dupilumab High Dose | Part B: Change From Baseline in Mean Eosinophilic Esophagitis Histology Scoring System (EoE-HSS) Grade Score at Week 52 | -0.967 Score on a scale | Standard Deviation 0.392 |
Secondary
Part B: Change From Baseline in Mean Eosinophilic Esophagitis Histology Scoring System (EoE-HSS) Stage Score at Week 52
EoE-HSS is a validated histologic scoring system that measures other histological abnormalities in addition to density of eosinophilic infiltration. Severity (grade) and extent (stage) of abnormalities will be scored using a 4-point scale (0 normal; 3 maximum change). Higher total score indicated greater severity & extent of histological abnormalities. For each of 3 esophageal regions (proximal, mid, and distal), the ratio of the sum of assigned score for each evaluated feature divided by maximum possible score (maximum value is 24) was calculated. The mean stage scores summed over the 3 regions was the final score used in primary analysis, the mean stage score ranged from 0 to 3, with higher score indicating more severe.
Time frame: Baseline, Week 52
Population: Analysis was performed on Part B SAF which included all participants who received at least 1 dose of Part B study drug. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pooled Placebo | Part B: Change From Baseline in Mean Eosinophilic Esophagitis Histology Scoring System (EoE-HSS) Stage Score at Week 52 | -0.767 Score on a scale | Standard Deviation 0.3114 |
| Part A: Dupilumab High Dose | Part B: Change From Baseline in Mean Eosinophilic Esophagitis Histology Scoring System (EoE-HSS) Stage Score at Week 52 | -0.855 Score on a scale | Standard Deviation 0.3485 |
| Part A: Dupilumab Low Dose | Part B: Change From Baseline in Mean Eosinophilic Esophagitis Histology Scoring System (EoE-HSS) Stage Score at Week 52 | -0.784 Score on a scale | Standard Deviation 0.3183 |
| Part B: Dupilumab High Dose to Dupilumab High Dose | Part B: Change From Baseline in Mean Eosinophilic Esophagitis Histology Scoring System (EoE-HSS) Stage Score at Week 52 | -0.892 Score on a scale | Standard Deviation 0.3181 |
Secondary
Part B: Change From Baseline in the Proportion of Days With 1 or More EoE Signs by Pediatric EoE Sign/Symptom Questionnaire - Participant Version (PESQ-P) (for Participants Aged ≥8 to <12 Years) at Week 52
The PESQ-P was a participant-reported outcome measure intended to be completed independently by participants ≥8 to \<12 years of age. The PESQ-P measured occurrence of signs of EoE and was completed once daily via an electronic diary. Data from a 14-day period preceding the baseline visit and a 14-day period preceding week 16 will be used to calculate the proportion of days with 1 or more EoE symptoms.
Time frame: Baseline, Week 52
Population: Analysis was performed on Part B SAF which included all participants who received at least 1 dose of Part B study drug. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pooled Placebo | Part B: Change From Baseline in the Proportion of Days With 1 or More EoE Signs by Pediatric EoE Sign/Symptom Questionnaire - Participant Version (PESQ-P) (for Participants Aged ≥8 to <12 Years) at Week 52 | -0.33 proportion of days | Standard Deviation 0.322 |
| Part A: Dupilumab High Dose | Part B: Change From Baseline in the Proportion of Days With 1 or More EoE Signs by Pediatric EoE Sign/Symptom Questionnaire - Participant Version (PESQ-P) (for Participants Aged ≥8 to <12 Years) at Week 52 | -0.43 proportion of days | Standard Deviation 0.369 |
| Part A: Dupilumab Low Dose | Part B: Change From Baseline in the Proportion of Days With 1 or More EoE Signs by Pediatric EoE Sign/Symptom Questionnaire - Participant Version (PESQ-P) (for Participants Aged ≥8 to <12 Years) at Week 52 | -0.42 proportion of days | Standard Deviation 0.4 |
| Part B: Dupilumab High Dose to Dupilumab High Dose | Part B: Change From Baseline in the Proportion of Days With 1 or More EoE Signs by Pediatric EoE Sign/Symptom Questionnaire - Participant Version (PESQ-P) (for Participants Aged ≥8 to <12 Years) at Week 52 | -0.26 proportion of days | Standard Deviation 0.396 |
Secondary
Part B: Change From Baseline in the Proportion of Days With 1 or More EoE Signs Measured by Pediatric EoE Sign/Symptom Questionnaire - Caregiver Version (PESQ-C) at Week 52
PESQ-C is a novel, observer-reported outcome measure intended to be completed independently by caregivers of all pediatric EoE participants in the study.
Time frame: Baseline, Week 52
Population: Analysis was performed on Part B SAF which included all participants who received at least 1 dose of Part B study drug. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pooled Placebo | Part B: Change From Baseline in the Proportion of Days With 1 or More EoE Signs Measured by Pediatric EoE Sign/Symptom Questionnaire - Caregiver Version (PESQ-C) at Week 52 | -0.20 proportion of days | Standard Deviation 0.373 |
| Part A: Dupilumab High Dose | Part B: Change From Baseline in the Proportion of Days With 1 or More EoE Signs Measured by Pediatric EoE Sign/Symptom Questionnaire - Caregiver Version (PESQ-C) at Week 52 | -0.47 proportion of days | Standard Deviation 0.395 |
| Part A: Dupilumab Low Dose | Part B: Change From Baseline in the Proportion of Days With 1 or More EoE Signs Measured by Pediatric EoE Sign/Symptom Questionnaire - Caregiver Version (PESQ-C) at Week 52 | -0.49 proportion of days | Standard Deviation 0.339 |
| Part B: Dupilumab High Dose to Dupilumab High Dose | Part B: Change From Baseline in the Proportion of Days With 1 or More EoE Signs Measured by Pediatric EoE Sign/Symptom Questionnaire - Caregiver Version (PESQ-C) at Week 52 | -0.30 proportion of days | Standard Deviation 0.299 |
Secondary
Part B: Change From Baseline in the Proportion of Total Segments Within a Day (Night, Morning, Afternoon, Evening) With 1 or More EoE Signs as Measured by the PESQ-C at Week 52
PESQ-C is a novel, observer-reported outcome measure intended to be completed independently by caregivers of all pediatric EoE participants in the study. The PESQ-C measured the occurrence of signs of EoE and was completed once daily via an electronic diary.
Time frame: Baseline, Week 52
Population: Analysis was performed on Part B SAF which included all participants who received at least 1 dose of Part B study drug. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pooled Placebo | Part B: Change From Baseline in the Proportion of Total Segments Within a Day (Night, Morning, Afternoon, Evening) With 1 or More EoE Signs as Measured by the PESQ-C at Week 52 | -0.03 proportion of segments | Standard Deviation 0.249 |
| Part A: Dupilumab High Dose | Part B: Change From Baseline in the Proportion of Total Segments Within a Day (Night, Morning, Afternoon, Evening) With 1 or More EoE Signs as Measured by the PESQ-C at Week 52 | -0.24 proportion of segments | Standard Deviation 0.221 |
| Part A: Dupilumab Low Dose | Part B: Change From Baseline in the Proportion of Total Segments Within a Day (Night, Morning, Afternoon, Evening) With 1 or More EoE Signs as Measured by the PESQ-C at Week 52 | -0.26 proportion of segments | Standard Deviation 0.25 |
| Part B: Dupilumab High Dose to Dupilumab High Dose | Part B: Change From Baseline in the Proportion of Total Segments Within a Day (Night, Morning, Afternoon, Evening) With 1 or More EoE Signs as Measured by the PESQ-C at Week 52 | -0.17 proportion of segments | Standard Deviation 0.187 |
Secondary
Part B: Change From Baseline in the Proportion of Total Segments Within a Day (Night, Morning, Afternoon, Evening) With 1 or More EoE Signs as Measured by the PESQ-P (for Participants Aged ≥8 to <12 Years) at Week 52
The PESQ-P was a participant-reported outcome measure intended to be completed independently by EoE participants ≥8 to \<12 years of age. The PESQ-P measured the occurrence of signs of EoE and was completed once daily via an electronic diary. Data from a 14-day period preceding the baseline visit and a 14-day period preceding week 16 will be used to calculate the total time segments within a day (night, morning, afternoon, evening) with 1 or more EoE symptoms.
Time frame: Baseline, Week 52
Population: Analysis was performed on Part B SAF which included all participants who received at least 1 dose of Part B study drug. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pooled Placebo | Part B: Change From Baseline in the Proportion of Total Segments Within a Day (Night, Morning, Afternoon, Evening) With 1 or More EoE Signs as Measured by the PESQ-P (for Participants Aged ≥8 to <12 Years) at Week 52 | -0.17 proportion of segments | Standard Deviation 0.164 |
| Part A: Dupilumab High Dose | Part B: Change From Baseline in the Proportion of Total Segments Within a Day (Night, Morning, Afternoon, Evening) With 1 or More EoE Signs as Measured by the PESQ-P (for Participants Aged ≥8 to <12 Years) at Week 52 | -0.26 proportion of segments | Standard Deviation 0.269 |
| Part A: Dupilumab Low Dose | Part B: Change From Baseline in the Proportion of Total Segments Within a Day (Night, Morning, Afternoon, Evening) With 1 or More EoE Signs as Measured by the PESQ-P (for Participants Aged ≥8 to <12 Years) at Week 52 | -0.21 proportion of segments | Standard Deviation 0.293 |
| Part B: Dupilumab High Dose to Dupilumab High Dose | Part B: Change From Baseline in the Proportion of Total Segments Within a Day (Night, Morning, Afternoon, Evening) With 1 or More EoE Signs as Measured by the PESQ-P (for Participants Aged ≥8 to <12 Years) at Week 52 | -0.16 proportion of segments | Standard Deviation 0.284 |
Secondary
Part B: Change From Baseline in Weight for Age Z-score at Week 52
Weight for age z-score indicates how much higher or lower a participant's weight for age is relative to a reference growth chart (based on the growth charts from CDC for ages 0 to 20 years \[for ages 2 to \<12 years\] and World Health Organization (WHO) growth charts for ages 0 to \<2 years \[for ages 1 to \<2 years\]). A z-score of 0 represents the population mean. An increase in the mean change in weight for age z-score (increase in the SD from the reference growth chart) indicates an increase in weight for age relative to the reference.
Time frame: Baseline, Week 52
Population: Analysis was performed on Part B SAF which included all participants who received at least 1 dose of Part B study drug. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pooled Placebo | Part B: Change From Baseline in Weight for Age Z-score at Week 52 | 0.0640 z-score | Standard Deviation 0.46264 |
| Part A: Dupilumab High Dose | Part B: Change From Baseline in Weight for Age Z-score at Week 52 | 0.2016 z-score | Standard Deviation 0.39446 |
| Part A: Dupilumab Low Dose | Part B: Change From Baseline in Weight for Age Z-score at Week 52 | 0.1445 z-score | Standard Deviation 0.4031 |
| Part B: Dupilumab High Dose to Dupilumab High Dose | Part B: Change From Baseline in Weight for Age Z-score at Week 52 | 0.2049 z-score | Standard Deviation 0.40305 |
Secondary
Part B: Concentration of Functional Dupilumab in Serum at Week 32 and 52
Concentration of functional dupilumab in serum at Week 32 and 52 was reported in this outcome measure.
Time frame: Week 32 and 52
Population: Analysis was performed on PKAS. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure and 'number analyzed' = participants with available data for each specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Pooled Placebo | Part B: Concentration of Functional Dupilumab in Serum at Week 32 and 52 | Week 32 | 105 mg/L | Standard Deviation 49.8 |
| Part A: Pooled Placebo | Part B: Concentration of Functional Dupilumab in Serum at Week 32 and 52 | Week 52 | 101 mg/L | Standard Deviation 44.3 |
| Part A: Dupilumab High Dose | Part B: Concentration of Functional Dupilumab in Serum at Week 32 and 52 | Week 52 | 149 mg/L | Standard Deviation 59.1 |
| Part A: Dupilumab High Dose | Part B: Concentration of Functional Dupilumab in Serum at Week 32 and 52 | Week 32 | 142 mg/L | Standard Deviation 48.5 |
| Part A: Dupilumab Low Dose | Part B: Concentration of Functional Dupilumab in Serum at Week 32 and 52 | Week 32 | 99.0 mg/L | Standard Deviation 42.8 |
| Part A: Dupilumab Low Dose | Part B: Concentration of Functional Dupilumab in Serum at Week 32 and 52 | Week 52 | 83.0 mg/L | Standard Deviation 33.2 |
| Part B: Dupilumab High Dose to Dupilumab High Dose | Part B: Concentration of Functional Dupilumab in Serum at Week 32 and 52 | Week 32 | 186 mg/L | Standard Deviation 59.5 |
| Part B: Dupilumab High Dose to Dupilumab High Dose | Part B: Concentration of Functional Dupilumab in Serum at Week 32 and 52 | Week 52 | 179 mg/L | Standard Deviation 75.3 |
Secondary
Part B: Normalized Enrichment Score (NES) for the Relative Change From Baseline in the EoE Diagnostic Panel (EDP) at Week 52
A Normalized Enrichment Score (NES) is a way to generate a single numerical value to represent a complex gene expression signature. Changes in NES score represented the overall changes in the expression of that molecular phenotype. The NESs calculated for the EDP reflect the expression at post-baseline relative to Baseline of a gene set that is differentially expressed between esophageal biopsies from EoE participants compared to healthy controls as a way to evaluate normalization of the molecular pathology. For each subject, an NES of 0 indicates no change from baseline, a negative score shows a reduction in disease score (more like normal) and positive score shows worsening (more active disease). NES does not have minimum/maximum score.
Time frame: Baseline, Week 52
Population: Analysis was performed on Part B SAF which included all participants who received at least 1 dose of Part B study drug. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Pooled Placebo | Part B: Normalized Enrichment Score (NES) for the Relative Change From Baseline in the EoE Diagnostic Panel (EDP) at Week 52 | -2.715 Score on a scale |
| Part A: Dupilumab High Dose | Part B: Normalized Enrichment Score (NES) for the Relative Change From Baseline in the EoE Diagnostic Panel (EDP) at Week 52 | -2.615 Score on a scale |
| Part A: Dupilumab Low Dose | Part B: Normalized Enrichment Score (NES) for the Relative Change From Baseline in the EoE Diagnostic Panel (EDP) at Week 52 | -2.625 Score on a scale |
| Part B: Dupilumab High Dose to Dupilumab High Dose | Part B: Normalized Enrichment Score (NES) for the Relative Change From Baseline in the EoE Diagnostic Panel (EDP) at Week 52 | -2.670 Score on a scale |
Secondary
Part B: Normalized Enrichment Score (NES) for the Relative Change From Baseline in the Type 2 Inflammation Signature (T2INF) at Week 52
A Normalized Enrichment Score (NES) is a way to generate a single numerical value to represent a complex gene expression signature. Changes in NES score represented the overall changes in the expression of that molecular phenotype. The NESs calculated for T2INF reflect the expression at post-baseline relative to Baseline of the pre-specified gene set as a way to evaluate normalization of type 2 inflammation with treatment. For each subject, an NES of 0 indicates no change from baseline, a negative score shows a reduction in disease score (more like normal) and positive score shows worsening (more active disease). NES does not have minimum/maximum score.
Time frame: Baseline, Week 52
Population: Analysis was performed on Part B SAF which included all participants who received at least 1 dose of Part B study drug. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Pooled Placebo | Part B: Normalized Enrichment Score (NES) for the Relative Change From Baseline in the Type 2 Inflammation Signature (T2INF) at Week 52 | -1.960 Score on a scale |
| Part A: Dupilumab High Dose | Part B: Normalized Enrichment Score (NES) for the Relative Change From Baseline in the Type 2 Inflammation Signature (T2INF) at Week 52 | -1.965 Score on a scale |
| Part A: Dupilumab Low Dose | Part B: Normalized Enrichment Score (NES) for the Relative Change From Baseline in the Type 2 Inflammation Signature (T2INF) at Week 52 | -1.920 Score on a scale |
| Part B: Dupilumab High Dose to Dupilumab High Dose | Part B: Normalized Enrichment Score (NES) for the Relative Change From Baseline in the Type 2 Inflammation Signature (T2INF) at Week 52 | -1.920 Score on a scale |
Secondary
Part B: Number of Participants With Positive Treatment-emergent Antidrug Antibodies (ADA) Response and Titer
Treatment-emergent ADA was defined as a negative result or missing result at baseline with at least one positive post baseline result in the ADA assay. Samples positive in the dupilumab ADA assay were characterized for ADA titers (low, moderate and high). The low treatment-emergent ADA titer as defined as titer level \<1000, moderate as 1000 to 10000 and high as \>10000. No participant exhibited a treatment-emergent ADA response in Part B and titer was not reported.
Time frame: From Week 16 up to Week 52 in Part B
Population: Analysis was performed on AAS which included all participants who received any amount of study drug and had at least one non-missing anti-drug antibody result following the first dose.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Pooled Placebo | Part B: Number of Participants With Positive Treatment-emergent Antidrug Antibodies (ADA) Response and Titer | 0 Participants |
| Part A: Dupilumab High Dose | Part B: Number of Participants With Positive Treatment-emergent Antidrug Antibodies (ADA) Response and Titer | 0 Participants |
| Part A: Dupilumab Low Dose | Part B: Number of Participants With Positive Treatment-emergent Antidrug Antibodies (ADA) Response and Titer | 0 Participants |
| Part B: Dupilumab High Dose to Dupilumab High Dose | Part B: Number of Participants With Positive Treatment-emergent Antidrug Antibodies (ADA) Response and Titer | 0 Participants |
Secondary
Part B: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Adverse Events of Special Interest (AESIs) and TEAEs Leading to Permanent Discontinuation of Study Drug
An AE was defined as any untoward medical occurrence in a participant or clinical investigation patient administered with a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. A serious AE was any untoward medical occurrence that at any dose resulted in death, life-threatening, initial or prolonged inpatient hospitalization, persistent or significant disability/incapacity, congenital anomaly/birth defect, or a medically important event. The term TEAE is defined as AEs starting or worsening after the first intake of the study drug. TEAEs include both Serious TEAEs and non-serious TEAEs. An AESI was defined as one of scientific and medical concern specific to the Sponsor's product or program, for which ongoing monitoring and rapid communication by the Investigator to the Sponsor was appropriate.
Time frame: From Week 16 up to Week 52 in Part B
Population: Analysis was performed on Part B SAF which included all participants who received at least 1 dose of Part B study drug.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part A: Pooled Placebo | Part B: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Adverse Events of Special Interest (AESIs) and TEAEs Leading to Permanent Discontinuation of Study Drug | Participants with any TEAE | 14 Participants |
| Part A: Pooled Placebo | Part B: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Adverse Events of Special Interest (AESIs) and TEAEs Leading to Permanent Discontinuation of Study Drug | Participants with any Serious TEAE | 1 Participants |
| Part A: Pooled Placebo | Part B: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Adverse Events of Special Interest (AESIs) and TEAEs Leading to Permanent Discontinuation of Study Drug | Participants with any TEAE leading to permanent discontinuation of study drug | 0 Participants |
| Part A: Pooled Placebo | Part B: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Adverse Events of Special Interest (AESIs) and TEAEs Leading to Permanent Discontinuation of Study Drug | Participants with any AESI | 0 Participants |
| Part A: Dupilumab High Dose | Part B: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Adverse Events of Special Interest (AESIs) and TEAEs Leading to Permanent Discontinuation of Study Drug | Participants with any TEAE leading to permanent discontinuation of study drug | 0 Participants |
| Part A: Dupilumab High Dose | Part B: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Adverse Events of Special Interest (AESIs) and TEAEs Leading to Permanent Discontinuation of Study Drug | Participants with any TEAE | 15 Participants |
| Part A: Dupilumab High Dose | Part B: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Adverse Events of Special Interest (AESIs) and TEAEs Leading to Permanent Discontinuation of Study Drug | Participants with any Serious TEAE | 0 Participants |
| Part A: Dupilumab High Dose | Part B: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Adverse Events of Special Interest (AESIs) and TEAEs Leading to Permanent Discontinuation of Study Drug | Participants with any AESI | 1 Participants |
| Part A: Dupilumab Low Dose | Part B: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Adverse Events of Special Interest (AESIs) and TEAEs Leading to Permanent Discontinuation of Study Drug | Participants with any AESI | 3 Participants |
| Part A: Dupilumab Low Dose | Part B: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Adverse Events of Special Interest (AESIs) and TEAEs Leading to Permanent Discontinuation of Study Drug | Participants with any TEAE leading to permanent discontinuation of study drug | 0 Participants |
| Part A: Dupilumab Low Dose | Part B: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Adverse Events of Special Interest (AESIs) and TEAEs Leading to Permanent Discontinuation of Study Drug | Participants with any Serious TEAE | 3 Participants |
| Part A: Dupilumab Low Dose | Part B: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Adverse Events of Special Interest (AESIs) and TEAEs Leading to Permanent Discontinuation of Study Drug | Participants with any TEAE | 28 Participants |
| Part B: Dupilumab High Dose to Dupilumab High Dose | Part B: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Adverse Events of Special Interest (AESIs) and TEAEs Leading to Permanent Discontinuation of Study Drug | Participants with any AESI | 4 Participants |
| Part B: Dupilumab High Dose to Dupilumab High Dose | Part B: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Adverse Events of Special Interest (AESIs) and TEAEs Leading to Permanent Discontinuation of Study Drug | Participants with any Serious TEAE | 2 Participants |
| Part B: Dupilumab High Dose to Dupilumab High Dose | Part B: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Adverse Events of Special Interest (AESIs) and TEAEs Leading to Permanent Discontinuation of Study Drug | Participants with any TEAE leading to permanent discontinuation of study drug | 1 Participants |
| Part B: Dupilumab High Dose to Dupilumab High Dose | Part B: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs, Adverse Events of Special Interest (AESIs) and TEAEs Leading to Permanent Discontinuation of Study Drug | Participants with any TEAE | 34 Participants |
Secondary
Part B: Number of Sign-free Days During the 14-day Period Preceding Week 52 as Measured by the PESQ-C (for Participants Aged ≥1 to <12 Years)
PESQ-C is a novel, observer-reported outcome measure intended to be completed independently by caregivers of all pediatric EoE participants in the study.
Time frame: Week 52
Population: Analysis was performed on Part B SAF which included all participants who received at least 1 dose of Part B study drug. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pooled Placebo | Part B: Number of Sign-free Days During the 14-day Period Preceding Week 52 as Measured by the PESQ-C (for Participants Aged ≥1 to <12 Years) | 11.58 sign-free days | Standard Deviation 3.968 |
| Part A: Dupilumab High Dose | Part B: Number of Sign-free Days During the 14-day Period Preceding Week 52 as Measured by the PESQ-C (for Participants Aged ≥1 to <12 Years) | 12.10 sign-free days | Standard Deviation 4.652 |
| Part A: Dupilumab Low Dose | Part B: Number of Sign-free Days During the 14-day Period Preceding Week 52 as Measured by the PESQ-C (for Participants Aged ≥1 to <12 Years) | 11.35 sign-free days | Standard Deviation 3.947 |
| Part B: Dupilumab High Dose to Dupilumab High Dose | Part B: Number of Sign-free Days During the 14-day Period Preceding Week 52 as Measured by the PESQ-C (for Participants Aged ≥1 to <12 Years) | 12.13 sign-free days | Standard Deviation 4.053 |
Secondary
Part B: Number of Symptom-free Days During the 14-day Period Preceding Week 52 as Measured by the PESQ-P (for Participants Aged ≥8 to <12 Years)
The PESQ-P was a participant-reported outcome measure intended to be completed independently by participants ≥8 to \<12 years of age. The PESQ-P measures the signs of EoE, including stomach pain, heartburn, acid reflux, regurgitation, vomiting, food refusal, and trouble swallowing food.
Time frame: Week 52
Population: Analysis was performed on Part B SAF which included all participants who received at least 1 dose of Part B study drug. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pooled Placebo | Part B: Number of Symptom-free Days During the 14-day Period Preceding Week 52 as Measured by the PESQ-P (for Participants Aged ≥8 to <12 Years) | 9.33 sign-free days | Standard Deviation 8.083 |
| Part A: Dupilumab High Dose | Part B: Number of Symptom-free Days During the 14-day Period Preceding Week 52 as Measured by the PESQ-P (for Participants Aged ≥8 to <12 Years) | 11.67 sign-free days | Standard Deviation 5.715 |
| Part A: Dupilumab Low Dose | Part B: Number of Symptom-free Days During the 14-day Period Preceding Week 52 as Measured by the PESQ-P (for Participants Aged ≥8 to <12 Years) | 10.64 sign-free days | Standard Deviation 4.943 |
| Part B: Dupilumab High Dose to Dupilumab High Dose | Part B: Number of Symptom-free Days During the 14-day Period Preceding Week 52 as Measured by the PESQ-P (for Participants Aged ≥8 to <12 Years) | 13.63 sign-free days | Standard Deviation 0.874 |
Secondary
Part B: Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of <15 Eosinophils/High Power Field at Week 52
Peak esophageal intraepithelial eosinophil count was measured from esophageal biopsies. A total of at least 9 mucosal pinch biopsies were collected from 3 esophageal regions: 3 proximal, 3 mid, and 3 distal. The peak esophageal intraepithelial eosinophil count at each visit was the maximum of the quantities of eosinophils in the most inflamed hpfs across the 3 regions. If the quantity of eosinophils was missing for 1 or 2 esophageal regions, the peak eosinophil count was the maximum of the quantities of eosinophils from the region(s) where eosinophil quantities were available.
Time frame: At Week 52
Population: Analysis was performed on Part B SAF which included all participants who received at least 1 dose of Part B study drug. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Pooled Placebo | Part B: Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of <15 Eosinophils/High Power Field at Week 52 | 92.9 percentage of participants |
| Part A: Dupilumab High Dose | Part B: Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of <15 Eosinophils/High Power Field at Week 52 | 64.7 percentage of participants |
| Part A: Dupilumab Low Dose | Part B: Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of <15 Eosinophils/High Power Field at Week 52 | 69.0 percentage of participants |
| Part B: Dupilumab High Dose to Dupilumab High Dose | Part B: Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of <15 Eosinophils/High Power Field at Week 52 | 85.7 percentage of participants |
Secondary
Part B: Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of ≤6 Eosinophils/High Power Field at Week 52
Peak esophageal intraepithelial eosinophil count was measured from esophageal biopsies. A total of at least 9 mucosal pinch biopsies were collected from 3 esophageal regions: 3 proximal, 3 mid, and 3 distal. The peak esophageal intraepithelial eosinophil count at each visit was the maximum of the quantities of eosinophils in the most inflamed hpfs across the 3 regions. If the quantity of eosinophils was missing for 1 or 2 esophageal regions, the peak eosinophil count was the maximum of the quantities of eosinophils from the region(s) where eosinophil quantities were available.
Time frame: At Week 52
Population: Analysis was performed on Part B safety analysis set (SAF) which included all participants who received at least 1 dose of Part B study drug. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Pooled Placebo | Part B: Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of ≤6 Eosinophils/High Power Field at Week 52 | 92.9 percentage of participants |
| Part A: Dupilumab High Dose | Part B: Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of ≤6 Eosinophils/High Power Field at Week 52 | 52.9 percentage of participants |
| Part A: Dupilumab Low Dose | Part B: Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of ≤6 Eosinophils/High Power Field at Week 52 | 65.5 percentage of participants |
| Part B: Dupilumab High Dose to Dupilumab High Dose | Part B: Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of ≤6 Eosinophils/High Power Field at Week 52 | 62.9 percentage of participants |
Secondary
Part B: Percent Change From Baseline in Peak Esophageal Intraepithelial Eosinophil Count at Week 52
Peak esophageal intraepithelial eosinophil count was measured from esophageal biopsies. A total of at least 9 mucosal pinch biopsies were collected from 3 esophageal regions: 3 proximal, 3 mid, and 3 distal. The peak esophageal intraepithelial eosinophil count at each visit was the maximum of the quantities of eosinophils in the most inflamed hpfs across the 3 regions. If the quantity of eosinophils was missing for 1 or 2 esophageal regions, the peak eosinophil count was the maximum of the quantities of eosinophils from the region(s) where eosinophil quantities were available.
Time frame: Baseline, Week 52
Population: Analysis was performed on Part B SAF which included all participants who received at least 1 dose of Part B study drug. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pooled Placebo | Part B: Percent Change From Baseline in Peak Esophageal Intraepithelial Eosinophil Count at Week 52 | -92.72 percent change | Standard Deviation 19.229 |
| Part A: Dupilumab High Dose | Part B: Percent Change From Baseline in Peak Esophageal Intraepithelial Eosinophil Count at Week 52 | -76.83 percent change | Standard Deviation 41.228 |
| Part A: Dupilumab Low Dose | Part B: Percent Change From Baseline in Peak Esophageal Intraepithelial Eosinophil Count at Week 52 | -85.41 percent change | Standard Deviation 22.851 |
| Part B: Dupilumab High Dose to Dupilumab High Dose | Part B: Percent Change From Baseline in Peak Esophageal Intraepithelial Eosinophil Count at Week 52 | -90.97 percent change | Standard Deviation 14.482 |
Secondary
Part C: Absolute Change in EoE-EREFS From Baseline to Week 100
Time frame: Baseline to Week 100
Population: Here 'n' = number of evaluable participants at the specified timepoint
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pooled Placebo | Part C: Absolute Change in EoE-EREFS From Baseline to Week 100 | -5.34 Score on a scale | Standard Deviation 2.535 |
Secondary
Part C: Absolute Change in EoE-EREFS From Baseline to Week 160
Time frame: Baseline to Week 160
Population: No data was collected for this endpoint. No participants reached end of part C treatment period (week 160).
Secondary
Part C: Absolute Change in Mean EoE-HSS From Baseline to Week 100
Time frame: Baseline to Week 100
Population: Here 'n' = number of evaluable participants at the specified timepoint
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part A: Pooled Placebo | Part C: Absolute Change in Mean EoE-HSS From Baseline to Week 100 | EoE-HSS Grade Score | -0.851 Score on a scale | Standard Deviation 0.3909 |
| Part A: Pooled Placebo | Part C: Absolute Change in Mean EoE-HSS From Baseline to Week 100 | EoE-HSS Stage Score | -0.850 Score on a scale | Standard Deviation 0.3648 |
Secondary
Part C: Absolute Change in Mean EoE-HSS From Baseline to Week 160
Time frame: Baseline to Week 160
Population: No data was collected for this endpoint. No participants reached end of part C treatment period (week 160).
Secondary
Part C: Change in Body Mass Index for Age Z-score From Baseline up to Week 100
Difference in the 100-week change from baseline in BMI-for-age Z-score. BMI-for-age Z-scores are based on a reference growth chart (based on the growth charts from Centers for Disease Control and Prevention \[CDC\] for ages 0 to 20 years \[for ages 2 to \<12 years\]. A z-score of 0 represents the population mean. The Z-score indicates the number of standard deviations away from the mean of the reference population. A negative Z-score indicates values lower than the population mean while a positive Z-score indicates values higher than the population mean.
Time frame: Baseline up to Week 100
Population: Here 'n' = number of evaluable participants at the specified timepoint
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pooled Placebo | Part C: Change in Body Mass Index for Age Z-score From Baseline up to Week 100 | 0.2009 z-score | Standard Deviation 0.67389 |
Secondary
Part C: Change in Body Weight for Age Percentile From Baseline up to Week 100
Body weight for age percentile was calculated based on the growth charts from the Centers for Disease Control and Prevention (CDC) for ages 0 to 20 years (for ages 2 to \<12 years) and World Health Organization (WHO) growth charts for ages 0 to \<2 years (for ages 1 to \<2 years). These charts included a set of smoothed percentiles along with CDC LMS (Lambda-Mu-Sigma) parameters to allow the calculation of percentiles.
Time frame: Baseline up to Week 100
Population: Here 'n' = number of evaluable participants at the specified timepoint
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pooled Placebo | Part C: Change in Body Weight for Age Percentile From Baseline up to Week 100 | 10.63 Percentile | Standard Deviation 18.227 |
Secondary
Part C: Change in Total Score as Measured by the PEESSv2.0- Caregiver Version Questionnaire From Baseline to Week 100
The PEESSv2.0-C is a caregiver-reported outcome measure that assesses the frequency and severity of EoE symptoms among pediatric participants. The PEESSv2.0-C consists of 20 items and has a one-month recall period. Each item had a 0-4 scale, which was transformed to 0-100 as follows: 0 = 0, 1 = 25, 2 = 50, 3 = 75, 4 = 100. The mean total PEESSv2.0 score was computed as the sum of all the item scores over the number of items answered. The total PEESSv2.0-C score ranges from 0 to 100 where higher scores indicate greater symptom burden among pediatric EoE participants.
Time frame: Baseline to Week 100
Population: Here 'n' = number of evaluable participants at the specified timepoint
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pooled Placebo | Part C: Change in Total Score as Measured by the PEESSv2.0- Caregiver Version Questionnaire From Baseline to Week 100 | -25.03 Score on a scale | Standard Deviation 21.867 |
Secondary
Part C: Change in Weight for Age Z-score From Baseline up to Week 100
Difference in the 100-week change from baseline in weight-for-age Z-score. Weight-for-age Z-scores are based on a reference growth chart (based on the growth charts from Centers for Disease Control and Prevention \[CDC\] for ages 0 to 20 years \[for ages 2 to \<12 years\]. A z-score of 0 represents the population mean. The Z-score indicates the number of standard deviations away from the mean of the reference population. A negative Z-score indicates values lower than the population mean while a positive Z-score indicates values higher than the population mean.
Time frame: Baseline up to Week 100
Population: Here 'n' = number of evaluable participants at the specified timepoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pooled Placebo | Part C: Change in Weight for Age Z-score From Baseline up to Week 100 | 0.3376 z-score | Standard Deviation 0.59272 |
Secondary
Part C: Change in Weight for Age Z-score From Baseline up to Week 160
Weight for age z-score indicates how much higher or lower a participant's weight for age is relative to a reference growth chart (based on the growth charts from CDC for ages 0 to 20 years \[for ages 2 to \<12 years\] and World Health Organization (WHO) growth charts for ages 0 to \<2 years \[for ages 1 to \<2 years\]). An increase in the mean change in weight for age z-score (increase in the SD from the reference growth chart) indicates an increase in weight for age relative to the reference.
Time frame: Baseline up to Week 160
Population: No data was collected for this endpoint. No participants reached end of part C treatment period (week 160).
Secondary
Part C: Change in Weight for Height Z-score From Baseline up to Week 100
Difference in the 100-week change from baseline in Weight for height Z-score. Weight for height Z-scores are based on a reference growth chart (based on the growth charts from Centers for Disease Control and Prevention \[CDC\] for ages 0 to 20 years \[for ages 2 to \<12 years\]. A z-score of 0 represents the population mean. The Z-score indicates the number of standard deviations away from the mean of the reference population. A negative Z-score indicates values lower than the population mean while a positive Z-score indicates values higher than the population mean.
Time frame: Baseline up to Week 100
Population: Here 'n' = number of evaluable participants at the specified timepoint
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pooled Placebo | Part C: Change in Weight for Height Z-score From Baseline up to Week 100 | 0.3301 z-score | Standard Deviation 0.84791 |
Secondary
Part C: Change in Weight for Height Z-score From Baseline up to Week 160
Weight for height z-score indicates how much higher or lower a participant's weight for height is relative to a reference growth chart (based on the growth charts from CDC for ages 0 to 20 years \[for ages 2 to \<12 years\] and WHO growth charts for ages 0 to \<2 years \[for ages 1 to \<2 years\]). An increase in the mean change in weight for height z-score (increase in the SD from the reference growth chart) indicates an increase in weight for height relative to the reference.
Time frame: Baseline up to Week 160
Population: No data was collected for this endpoint. No participants reached end of part C treatment period (week 160).
Secondary
Part C: Concentration of Functional Dupilumab in Serum at Week 100
Time frame: At Week 100
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pooled Placebo | Part C: Concentration of Functional Dupilumab in Serum at Week 100 | 180 mg/L | Standard Deviation 96.9 |
Secondary
Part C: NES for the Relative Change in the EDP Transcriptome Signature From Baseline to Week 100
A Normalized Enrichment Score (NES) is a way to generate a single numerical value to represent a complex gene expression signature. Changes in NES score represented the overall changes in the expression of that molecular phenotype. The NESs calculated for the EDP reflect the expression at post-baseline relative to Baseline of a gene set that is differentially expressed between esophageal biopsies from EoE participants compared to healthy controls as a way to evaluate normalization of the molecular pathology. For each subject, an NES of 0 indicates no change from baseline, a negative score shows a reduction in disease score (more like normal) and positive score shows worsening (more active disease). NES does not have minimum/maximum score.
Time frame: Baseline to Week 100
Population: Here 'n' = number of evaluable participants at the specified timepoint
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Pooled Placebo | Part C: NES for the Relative Change in the EDP Transcriptome Signature From Baseline to Week 100 | -2.720 Score on a scale |
Secondary
Part C: NES for the Relative Change in the EDP Transcriptome Signature From Baseline to Week 160
A Normalized Enrichment Score (NES) is a way to generate a single numerical value to represent a complex gene expression signature. Changes in NES score represented the overall changes in the expression of that molecular phenotype. The NESs calculated for the EDP reflect the expression at post-baseline relative to Baseline of a gene set that is differentially expressed between esophageal biopsies from EoE participants compared to healthy controls as a way to evaluate normalization of the molecular pathology. For each subject, an NES of 0 indicates no change from baseline, a negative score shows a reduction in disease score (more like normal) and positive score shows worsening (more active disease). NES does not have minimum/maximum score.
Time frame: Baseline to Week 160
Population: No data was collected for this endpoint. No participants reached end of part C treatment period (week 160).
Secondary
Part C: NES for the Relative Change in the Type 2 Inflammation Transcriptome Signature Baseline to Week 100
Time frame: Baseline to Week 100
Population: Here 'n' = number of evaluable participants at the specified timepoint
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Part A: Pooled Placebo | Part C: NES for the Relative Change in the Type 2 Inflammation Transcriptome Signature Baseline to Week 100 | -1.970 Score on a scale |
Secondary
Part C: NES for the Relative Change in the Type 2 Inflammation Transcriptome Signature From Baseline to Week 160
Time frame: Baseline to Week 160
Population: No data was collected for this endpoint. No participants reached end of part C treatment period (week 160).
Secondary
Part C: Number of Participants With TEAEs
Time frame: Up to Week 152
Population: No participants completed 160 weeks, longest duration was 152 weeks.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Pooled Placebo | Part C: Number of Participants With TEAEs | 53 Participants |
Secondary
Part C: Number of Participants With TEAEs Leading to Permanent Discontinuation of Study Treatment
Time frame: Up to Week 152
Population: No participants completed 160 weeks, longest duration was 152 weeks.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Pooled Placebo | Part C: Number of Participants With TEAEs Leading to Permanent Discontinuation of Study Treatment | 0 Participants |
Secondary
Part C: Number of Participants With Treatment-emergent ADA Responses
Time frame: From Week 52 up to Week 152
Population: Anti-Drug Antibody Analysis Set (AAS): The Part C AAS included all participants who received any amount of study drug in Part C and had at least 1 non-missing ADA result following the first dose of study drug. Analysis was based on treatment received.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Pooled Placebo | Part C: Number of Participants With Treatment-emergent ADA Responses | 0 Participants |
Secondary
Part C: Number of Participants With Treatment-emergent AESIs
Time frame: Up to Week 152
Population: No participants completed 160 weeks, longest duration was 152 weeks.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Pooled Placebo | Part C: Number of Participants With Treatment-emergent AESIs | 6 Participants |
Secondary
Part C: Number of Participants With Treatment-emergent SAEs
Time frame: Up to Week 152
Population: No participants completed 160 weeks, longest duration was 152 weeks.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part A: Pooled Placebo | Part C: Number of Participants With Treatment-emergent SAEs | 3 Participants |
Secondary
Part C: Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of <15 Eos/Hpf At Week 100
Time frame: At Week 100
Population: Here 'n' = number of evaluable participants at the specified timepoint
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Pooled Placebo | Part C: Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of <15 Eos/Hpf At Week 100 | 92.7 Percentage of participants |
Secondary
Part C: Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of <15 Eos/Hpf At Week 160
Time frame: At Week 160
Population: No data was collected for this endpoint. No participants reached end of part C treatment period (week 160).
Secondary
Part C: Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of ≤6 Eos/Hpf (400×) at Week 100
Time frame: At Week 100
Population: Here 'n' = number of evaluable participants at the specified timepoint
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Pooled Placebo | Part C: Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of ≤6 Eos/Hpf (400×) at Week 100 | 70.7 Percentage of participants |
Secondary
Part C: Percentage of Participants Achieving Peak Esophageal Intraepithelial Eosinophil Count of ≤6 Eos/Hpf (400×) at Week 160
Time frame: At Week 160
Population: No data was collected for this endpoint. No participants reached end of part C treatment period (week 160).
Secondary
Part C: Percentage of Participants (With Food Elimination Diet Regimens at Baseline) That Have a Re-introduction of a Previously Eliminated Food Group From Baseline up to Week 100
Time frame: Baseline up to Week 100
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Part A: Pooled Placebo | Part C: Percentage of Participants (With Food Elimination Diet Regimens at Baseline) That Have a Re-introduction of a Previously Eliminated Food Group From Baseline up to Week 100 | 14.8 Percentage of participants |
Secondary
Part C: Percentage of Participants (With Food Elimination Diet Regimens at Baseline) That Have a Re-introduction of a Previously Eliminated Food Group From Baseline up to Week 160
Time frame: Baseline up to Week 160
Population: No data was collected for this endpoint. No participants reached end of part C treatment period (week 160).
Secondary
Part C: Percent Change in Peak Esophageal Intraepithelial Eosinophil Count (Eos/Hpf) From Baseline to Week 100
Time frame: Baseline to Week 100
Population: Here 'n' = number of evaluable participants at the specified timepoint
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Part A: Pooled Placebo | Part C: Percent Change in Peak Esophageal Intraepithelial Eosinophil Count (Eos/Hpf) From Baseline to Week 100 | -91.50 Percentage of change | Standard Deviation 13.348 |
Secondary
Part C: Percent Change in Peak Esophageal Intraepithelial Eosinophil Count (Eos/Hpf) From Baseline to Week 160
Time frame: Baseline to Week 160
Population: No data was collected for this endpoint. No participants reached end of part C treatment period (week 160).