A Study to Evaluate the Efficacy and Safety of CC-93538 in Adult and Adolescent Participants With Eosinophilic Esophagitis

Blood samples were collected to assess esophageal eosinophil count.

Blood samples were collected to assess esophageal eosinophil count.

Blood samples were collected to assess esophageal eosinophil count.

Dysphagia Days (DD) was assessed using a modified daily symptom diary (mDSD). The DD was evaluated over the prior 14-day period using the mDSD, which includes 6 primary questions. These questions assess solid food consumption that day (Q1), experience with trouble swallowing (Q2), food going down slowly (Q3), food getting stuck in the throat or chest (Q4), actions taken by participants to obtain relief (Q5), and any pain associated with swallowing (Q6). The number of DD was normalized by calculating the number of diary days with a "yes" to any or all of Q2, Q3, and Q4 in the 14-day period prior to a visit, dividing by the number of measurable diary days in the 14-day period, and then multiplying by the length of the period (14). A measurable diary day for DD is defined as a diary day for which Questions 2 to 4 are answered. Mean DD ranges from 0 to 14 for the 14-day period.

The EREFS, measures features of EoE including esophageal edema, fixed rings, exudates, furrows, and strictures. The instrument grades edema as none (0) or present (1) or severe; furrows as absent (0), present (1); rings as none (0), mild (1), moderate (2) and severe (3); exudates as none (0), mild (1) or severe (2); and strictures as absent (0) or present (1). Two sub-component scores will be calculated by adding up the grade from respective features across the 3 esophagus levels (proximal, mid, and distal). Inflammation composite score (ranging 0 to 12) includes edema, furrows and exudates while remodeling composite score (0 to 12) consist of stricture and fixed rings. The EREFS total score is the sum of the inflammation and remodeling composite scores. The EREFS total score ranges from 0 to 24. High score signifies severe condition.

The EREFS, measures features of EoE including esophageal edema, fixed rings, exudates, furrows, and strictures. The instrument grades edema as none (0) or present (1) or severe; furrows as absent (0), present (1); rings as none (0), mild (1), moderate (2) and severe (3); exudates as none (0), mild (1) or severe (2); and strictures as absent (0) or present (1). Two sub-component scores will be calculated by adding up the grade from respective features across the 3 esophagus levels (proximal, mid, and distal). Inflammation composite score (ranging 0 to 12) includes edema, furrows and exudates while remodeling composite score (0 to 12) consist of stricture and fixed rings. The EREFS total score is the sum of the inflammation and remodeling composite scores. The EREFS total score ranges from 0 to 24. High score signifies severe condition.

EoEHSS evaluates the grade (severity) of multiple pathologic features in esophageal biopsies. It has 8 features eosinophil inflammation, basal zone hyperplasia, eosinophil abscess, eosinophil surface layering, dilated intercellular spaces, surface epithelial alteration, dyskeratotic epithelial cells, and lamina propria fibrosis. In 3 separate esophagus levels (proximal, mid, and distal), each feature is scored independently for grade using a 4-point Likert scale (0 [absent] to 3 [severe]). The mean adjusted grade score is calculated by averaging the adjusted scores for the 3 levels (proximal, mid, and distal). The mean adjusted scores range from 0 to 100. High score signifies severe condition.

EoEHSS evaluates the grade (severity) of multiple pathologic features in esophageal biopsies. It has 8 features eosinophil inflammation, basal zone hyperplasia, eosinophil abscess, eosinophil surface layering, dilated intercellular spaces, surface epithelial alteration, dyskeratotic epithelial cells, and lamina propria fibrosis. In 3 separate esophagus levels (proximal, mid, and distal), each feature is scored independently for grade using a 4-point Likert scale (0 [absent] to 3 [severe]). The mean adjusted grade score is calculated by averaging the adjusted scores for the 3 levels (proximal, mid, and distal). The mean adjusted scores range from 0 to 100. High score signifies severe condition.

EoEHSS evaluates the stage (extent) of multiple pathologic features in esophageal biopsies. It has 8 features eosinophil inflammation (determined by peak EoS count(PEC)) and presence of basal zone hyperplasia, eosinophil abscess, eosinophil surface layering, dilated intercellular spaces, surface epithelial alteration, dyskeratotic epithelial cells, and lamina propria fibrosis in epithelium . In 3 separate esophagus levels (proximal, mid, and distal), each feature is scored independently for stage using a 4-point Likert scale (0 [absent], 1[PEC ≥15/hpf in <33% of hpfs or (any grade >0) <33% of epithelium for other features], 2 [PEC ≥15/hpf in 33-66% of hpfs or (any grade >0) in 33-66% of epithelium to 3 [PEC ≥15/hpf in >66% of hpfs or (any grade >0) in > 66% of epithelium]). The mean adjusted stage score is calculated by averaging the adjusted scores for the 3 levels (proximal, mid, and distal). The mean adjusted scores range from 0 to 100. High score signifies severe condition.

EoEHSS evaluates the stage (extent) of multiple pathologic features in esophageal biopsies. It has 8 features eosinophil inflammation (determined by peak EoS count(PEC)) and presence of basal zone hyperplasia, eosinophil abscess, eosinophil surface layering, dilated intercellular spaces, surface epithelial alteration, dyskeratotic epithelial cells, and lamina propria fibrosis in epithelium . In 3 separate esophagus levels (proximal, mid, and distal), each feature is scored independently for stage using a 4-point Likert scale (0 [absent], 1[PEC ≥15/hpf in <33% of hpfs or (any grade >0) <33% of epithelium for other features], 2 [PEC ≥15/hpf in 33-66% of hpfs or (any grade >0) in 33-66% of epithelium to 3 [PEC ≥15/hpf in >66% of hpfs or (any grade >0) in > 66% of epithelium]). The mean adjusted stage score is calculated by averaging the adjusted scores for the 3 levels (proximal, mid, and distal). The mean adjusted scores range from 0 to 100. High score signifies severe condition.

The mDSD composite score is evaluated over the prior 14-day period using the mDSD, which includes 6 primary questions. These questions assess solid food consumption that day (Q1), experience with trouble swallowing (Q2), food going down slowly (Q3), food getting stuck in the throat or chest (Q4), actions taken by participants to obtain relief (Q5), and any pain associated with swallowing (Q6). The daily symptom score (mDSD) is calculated by summing the responses to Q2, Q3, and Q4 (where "Yes" to any/all items equals 1, and "No" to all items equals 0), adding Q5 over the 14-day period prior to a visit, dividing by the number of measurable diary days over the 14-day period, and then multiplying by the length of the period (14). The daily symptom score ranges from 0 to 5, and the mDSD composite score ranges from 0 to 70 for the 14-day period. A higher composite diary score indicates more frequent and/or severe dysphagia symptoms.

The mDSD composite score is evaluated over the prior 14-day period using the mDSD, which includes 6 primary questions. These questions assess solid food consumption that day (Q1), experience with trouble swallowing (Q2), food going down slowly (Q3), food getting stuck in the throat or chest (Q4), actions taken by participants to obtain relief (Q5), and any pain associated with swallowing (Q6). The daily symptom score (mDSD) is calculated by summing the responses to Q2, Q3, and Q4 (where "Yes" to any/all items equals 1, and "No" to all items equals 0), adding Q5 over the 14-day period prior to a visit, dividing by the number of measurable diary days over the 14-day period, and then multiplying by the length of the period (14). The daily symptom score ranges from 0 to 5, and the mDSD composite score ranges from 0 to 70 for the 14-day period. A higher composite diary score indicates more frequent and/or severe dysphagia symptoms.

Dysphagia Days (DD) was assessed using a modified daily symptom diary (mDSD). The DD was evaluated over the prior 14-day period using the mDSD, which includes 6 primary questions. These questions assess solid food consumption that day (Q1), experience with trouble swallowing (Q2), food going down slowly (Q3), food getting stuck in the throat or chest (Q4), actions taken by participants to obtain relief (Q5), and any pain associated with swallowing (Q6). The number of DD was normalized by calculating the number of diary days with a "yes" to any or all of Q2, Q3, and Q4 in the 14-day period prior to a visit, dividing by the number of measurable diary days in the 14-day period, and then multiplying by the length of the period (14). A measurable diary day for DD is defined as a diary day for which Questions 2 to 4 are answered. DD ranges from 0 to 14 for the 14-day period.

Dysphagia Days (DD) was assessed using a modified daily symptom diary (mDSD). The DD was evaluated over the prior 14-day period using the mDSD, which includes 6 primary questions. These questions assess solid food consumption that day (Q1), experience with trouble swallowing (Q2), food going down slowly (Q3), food getting stuck in the throat or chest (Q4), actions taken by participants to obtain relief (Q5), and any pain associated with swallowing (Q6). The number of DD was normalized by calculating the number of diary days with a "yes" to any or all of Q2, Q3, and Q4 in the 14-day period prior to a visit, dividing by the number of measurable diary days in the 14-day period, and then multiplying by the length of the period (14). A measurable diary day for DD is defined as a diary day for which Questions 2 to 4 are answered. DD ranges from 0 to 14 for the 14-day period.

Dysphagia Days (DD) was assessed using a modified daily symptom diary (mDSD). The DD was evaluated over the prior 14-day period using the mDSD, which includes 6 primary questions. These questions assess solid food consumption that day (Q1), experience with trouble swallowing (Q2), food going down slowly (Q3), food getting stuck in the throat or chest (Q4), actions taken by participants to obtain relief (Q5), and any pain associated with swallowing (Q6). The number of DD was normalized by calculating the number of diary days with a "yes" to any or all of Q2, Q3, and Q4 in the 14-day period prior to a visit, dividing by the number of measurable diary days in the 14-day period, and then multiplying by the length of the period (14). A measurable diary day for DD is defined as a diary day for which Questions 2 to 4 are answered. Mean DD ranges from 0 to 14 for the 14-day period.

The mDSD composite score is evaluated over the prior 14-day period using the mDSD, which includes 6 primary questions. These questions assess solid food consumption that day (Q1), experience with trouble swallowing (Q2), food going down slowly (Q3), food getting stuck in the throat or chest (Q4), actions taken by participants to obtain relief (Q5), and any pain associated with swallowing (Q6). The daily symptom score (mDSD) is calculated by summing the responses to Q2, Q3, and Q4 (where "Yes" to any/all items equals 1, and "No" to all items equals 0), adding Q5 over the 14-day period prior to a visit, dividing by the number of measurable diary days over the 14-day period, and then multiplying by the length of the period (14). The daily symptom score ranges from 0 to 5, and the mDSD composite score ranges from 0 to 70 for the 14-day period. A higher composite diary score indicates more frequent and/or severe dysphagia symptoms.

First incidence of corresponding EoE flare event for any participant was considered in the analysis. Median and 95% CI are from Kaplan-Meier estimates. Participants without an event of EoE flare or discontinued the study by the end of maintenance phase were censored, if they are a dropout, they are censored at study discontinuation date, otherwise they are censored at either last dose date or last visit, whichever was longer.

First use of rescue therapy including EoE standard of care pharmacotherapy, dietary modification (e.g., food elimination diet), and/or dilation procedure. was considered in the analysis. Median and 95% CI are from Kaplan-Meier estimates. Participants without an event or discontinued the study by the end of maintenance phase were censored, if they are a dropout, they are censored at study discontinuation date, otherwise they are censored at either last dose date or last visit, whichever was longer.

Use of rescue therapy including EoE standard of care pharmacotherapy, dietary modification (e.g., food elimination diet), and/or dilation procedure was considered in the analysis.

First incidence of corresponding EoE flare event for any participant was considered in the analysis.

An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a clinical investigation participant administered study treatment and that does not necessarily have a causal relationship with this treatment. A Serious Adverse Event (SAE) is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization.

Blood samples were collected to assess clinical laboratory parameters. The row title contains parameter and category title contains shift. The category 'Normal to High' signifies the readings for the parameter were 'Normal' at baseline and it changed to 'High' post baseline.

Vital signs like feart rate (beats per minute) and systolic blood pressure (mmHg) and diastolic blood pressure (mmHg) was measured to assess the abnormalities.

Height was measured at specified timepoints to assess the change from baseline.

Height was measured at specified timepoints to assess the change from baseline.

Weight was measured at specified timepoints to assess the change from baseline.

Weight was measured at specified timepoints to assess the change from baseline.

Data was collected for height and weight to assess body mass index.

Data was collected for height and weight to assess body mass index.

ADA status were categorized as Baseline ADA Positive: Pre-existing Immunoreactivity (baseline positive and 1) post baseline negative or 2) titer < 4-fold baseline titer). NAb+/baseline ADA+: At least one ADA positive sample with positive NAb in participant with pre-existing immunoreactivity. ADA Positive Status: 1) at least one positive response post first dose given negative or missing baseline; or 2) at least one post-baseline with titer greater than or equal to 4-fold of baseline titer given positive baseline. NAb+/ADA+: At least one ADA positive sample with positive NAb in ADA positive participant.

Blood samples were collected to assess trough concentration of CC-93538. The Evaluable PK population is defined as all participants in the PK population who have at least one evaluable trough concentration.