Phase 2, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Effects of EP262 in Subjects With Chronic Spontaneous Urticaria

The UAS is a chronic spontaneous urticaria (CSU)-specific, 24-hour self-evaluation, patient-reported outcome measure based on the assessment of key CSU symptoms: intensity of itch (assessed as the Itch Severity Score \[ISS\]) and number of wheals (assessed as the Hive Severity Score \[HSS\]). The UAS scales for both itch and wheal assessment are recorded as a score from 0 to 3, with 0 representing no itch/hives to 3 representing intense itch/hives. ISS and HSS scores are summed over 7 consecutive days to create the ISS7 and HSS7 scores, which range from 0 to 21. Higher scores indicate greater disease severity. The UAS score is the sum of the ISS and HSS scores. Daily UAS scores are summed over 7 consecutive days to create the UAS7 score, which ranges from 0 to 42. Higher scores indicate greater disease severity. The 7 daily UAS/ISS/HSS scores prior to or on the nominal Visit 4 (Week 6) date (including the nominal Week 6 visit date UAS/ISS/HSS score) were summed.

Time frame: Baseline; Week 6

Population: Full Analysis Set: all randomized participants who took ≥1 dose of randomized study drug. Participants were analyzed according to randomized treatment assignment. Only participants with available data were analyzed. Mixed model for repeated measures (MMRM) included fixed effects for treatment group, week, treatment group by week interaction, prior omalizumab use, and the Baseline score as a covariate. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

The HSS is part of the UAS, a CSU-specific, 24-hour self-evaluation, patient-reported outcome measure based on the assessment of key CSU symptoms: intensity of itch (assessed as the ISS) and number of wheals (assessed as the HSS). The UAS scale for wheal assessment is recorded as a score from 0 to 3, with 0 representing no hives to 3 representing intense hives. HSS scores are summed over 7 consecutive days to create the HSS7 score, which ranges from 0 to 21. Higher scores indicate greater disease severity. The 7 daily HSS scores prior to or on the nominal Visit 4 (Week 6) date (including the nominal Week 6 visit date HSS score) were summed. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

Time frame: Baseline; Week 6

Population: Full Analysis Set. Only participants with available data were analyzed.

The ISS is part of the UAS, a CSU-specific, 24-hour self-evaluation, patient-reported outcome measure based on the assessment of key CSU symptoms: intensity of itch (assessed as the ISS) and number of wheals (assessed as the HSS). The UAS scale for itch is recorded as a score from 0 to 3, with 0 representing no itch to 3 representing intense itch. ISS scores are summed over 7 consecutive days to create the ISS7 score, which ranges from 0 to 21. Higher scores indicate greater disease severity. The 7 daily ISS scores prior to or on the nominal Visit 4 (Week 6) date (including the nominal Week 6 visit date ISS score) were summed. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.

Time frame: Baseline; Week 6

Population: Full Analysis Set. Only participants with available data were analyzed.

Clinically meaningful changes were determined by the investigator.

Time frame: up to 81 days

Population: Safety Analysis Set

Clinically meaningful changes were determined by the investigator.

Time frame: up to 81 days

Population: Safety Analysis Set

Clinically meaningful changes were determined by the investigator.

Time frame: up to 81 days

Population: Safety Analysis Set

An AE was any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE could therefore have been any unfavorable or unintended sign (including a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product. Medical conditions present at baseline that worsened in severity or frequency after exposure to study drug were considered TEAEs. TEAEs were graded for severity (i.e., intensity) using Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. Grade 1: mild; asymptomatic or mild symptoms; intervention not indicated. Grade 2: moderate; minimal, local or noninvasive intervention indicated. Grade 3: severe or medically significant, but not immediately life-threatening. Grade 4: life-threatening consequences; urgent intervention indicated. Grade 5: death related to TEAE.

Time frame: up to 81 days

Population: Safety Analysis Set

An adverse event (AE) was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have a causal relationship with this treatment. An AE could therefore have been any unfavorable or unintended sign (including a clinically significant abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal (investigational) product. Medical conditions present at baseline that worsened in severity or frequency after exposure to study drug were considered TEAEs. A TEAE was any condition that was not present prior to treatment with the study drug but appeared following treatment, was present at treatment initiation but worsened during treatment, or was present at treatment initiation but resolved and then reappeared while the individual was on treatment (regardless of the intensity of the AE when the treatment was initiated).

Time frame: up to 81 days

Population: Safety Analysis Set: all participants who were randomized and took at least 1 dose of randomized study drug. Safety analyses were based upon treatment actually received.