To Compare Efficacy and Safety of CT-P39 and EU-approved Xolair in Patients With Chronic Spontaneous Urticaria

The ISS was recorded twice daily (morning and evening) in the patient eDiary, on scale of 0 (none) to 3 (severe) points. The daily ISS is the average of the morning and evening scores and the ISS7 is the sum of the daily ISS over 7 days. The ISS7 can range from 0 to 21. The higher scores mean a worse outcome. The relative potency was not calculated due to the assumption of parallel-line assay not being met. A parallel-line assay assumes that dose-efficacy response relationships are linear and parallel on log-dose scale which requires the equal slope in the regression model used to estimate relative potency. However, the slopes of the two treatment groups were estimated to be different, indicating a violation of the parallelism assumption. As a result, the relative potency was not computed.

Time frame: Week 12

Population: Analysis was performed based on mITT Set which had different definition with RAN set for disposition table.~This table presents the actual number of patients who had a result and were included in the analysis.~The mITT Set was defined as all randomly assigned patients who received at least 1 full dose of either of the study drugs during Treatment Period I.

The primary efficacy evaluation was comparison of mean change from baseline in ISS7 of 300 mg of CT-P39 (Arm 1) and 300 mg of Xolair (Arm 2) at Week 12, calculated as ISS7 at Week 12 minus the baseline ISS7. The ISS was recorded twice daily (morning and evening) in the patient eDiary, on scale of 0 (none) to 3 (severe) points. The daily ISS is the average of the morning and evening scores and the ISS7 is the sum of the daily ISS over 7 days. The ISS7 can range from 0 to 21. The higher scores mean a worse outcome. The analysis was conducted by analysis of covariance (ANCOVA). The ANCOVA model included the treatment group as a fixed effect and baseline ISS7, body weight on Day 1 and country as covariates.

Time frame: Week 12

Population: Analysis was performed based on mITT Set which had different definition with RAN set for disposition table.~This table presents the actual number of patients who had a result and were included in the analysis.~The mITT Set was defined as all randomly assigned patients who received at least 1 full dose of either of the study drugs during Treatment Period I.

The change from baseline in the number of tablets/week of rescue therapy used at Week 12 is presented. The number of tablets for each week of rescue therapy will be defined as the sum of daily use of rescue therapy over the study days which make up a given study week. The higher value means a worse outcome. If a subject switched rescue therapy medication and started a different medication or the prescribed dose of the rescue therapy medication changed during the study, the subject was excluded from the summary.

Time frame: Week 12

Population: Analysis was performed based on mITT Set which had different definition with RAN set for disposition table.~This table presents the actual number of patients who had a result and were included in the analysis.~The mITT Set was defined as all randomly assigned patients who received at least 1 full dose of either of the study drugs during Treatment Period I.

The change from baseline in the number of tablets/week of rescue therapy used at Week 24 is presented. The number of tablets for each week of rescue therapy will be defined as the sum of daily use of rescue therapy over the study days which make up a given study week. The higher value means a worse outcome. If a subject switched rescue therapy medication and started a different medication or the prescribed dose of the rescue therapy medication changed during the study, the subject was excluded from the summary.

Time frame: Week 24

Population: Analysis was performed based on mITT-TP2 Subset which had different definition with RAN set for disposition table.~This table presents the actual number of patients who had a result and were included in the analysis.~The mITT-TP2 Subset was defined as all patients in the mITT Set who underwent the second randomization and received at least 1 full dose of either of the study drugs during Treatment Period II.

The change from baseline in mean overall CU-Q2oL score at Week 12 is presented. The CU-Q2oL is a 23-item CSU specific health-related QoL questionnaire across 6 domains: pruritus, swelling, impact on life activities, sleep problems, limits, and looks. Patients rated their CSU symptoms and the impact of their CSU on various aspects of their lives. Each question was scored from 1 (not at all) to 5 (extremely), and overall raw score, on a scale of 23 to 115, was calculated by summing the individual raw domain scores. The higher result means a worse outcome. Overall raw scores of CU-Q2oL were converted to 0 to 100 point scores according to the following formula:\[(sum of items - minimum) / (maximum - minimum)\] × 100, where minimum=23 (1 score for all 23 items), maximum=115 (5 score for all 23 items).

Time frame: Week 12

Population: Analysis was performed based on mITT Set which had different definition with RAN set for disposition table.~This table presents the actual number of patients who had a result and were included in the analysis.~The mITT Set was defined as all randomly assigned patients who received at least 1 full dose of either of the study drugs during Treatment Period I.

The change from baseline in mean overall CU-Q2oL score at Week 24 is presented. The CU-Q2oL is a 23-item CSU specific health-related QoL questionnaire across 6 domains: pruritus, swelling, impact on life activities, sleep problems, limits, and looks. Patients rated their CSU symptoms and the impact of their CSU on various aspects of their lives. Each question was scored from 1 (not at all) to 5 (extremely), and overall raw score, on a scale of 23 to 115, was calculated by summing the individual raw domain scores. The higher result means a worse outcome. Overall raw scores of CU-Q2oL were converted to 0 to 100 point scores according to the following formula: \[(sum of items - minimum) / (maximum - minimum)\] × 100, where minimum=23 (1 score for all 23 items), maximum=115 (5 score for all 23 items)

Time frame: Week 24

Population: Analysis was performed based on mITT-TP2 Subset which had different definition with RAN set for disposition table.~This table presents the actual number of patients who had a result and were included in the analysis.~The mITT-TP2 Subset was defined as all patients in the mITT Set who underwent the second randomization and received at least 1 full dose of either of the study drugs during Treatment Period II.

The change from baseline in mean overall DLQI score at Week 12 is presented. The DLQI is a 10-item dermatology-specific health-related questionnaire across 6 domains: symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. Patients rated their dermatology symptoms as well as the impact of their skin condition on various aspect of their lives. Each question is scored from 0 to 3. Overall DLQI ranges on a scale of 0 to 30. The higher result means a worse outcome.

Time frame: Week 12

Population: Analysis was performed based on mITT Set which had different definition with RAN set for disposition table.~This table presents the actual number of patients who had a result and were included in the analysis.~The mITT Set was defined as all randomly assigned patients who received at least 1 full dose of either of the study drugs during Treatment Period I.

The change from baseline in mean overall DLQI score at Week 24 is presented. The DLQI is a 10-item dermatology-specific health-related questionnaire across 6 domains: symptoms and feelings, daily activities, leisure, work and school, personal relationships, and treatment. Patients rated their dermatology symptoms as well as the impact of their skin condition on various aspect of their lives. Each question is scored from 0 to 3. Overall DLQI ranges on a scale of 0 to 30. The higher result means a worse outcome.

Time frame: Week 24

Population: Analysis was performed based on mITT-TP2 Subset which had different definition with RAN set for disposition table.~This table presents the actual number of patients who had a result and were included in the analysis.~The mITT-TP2 Subset was defined as all patients in the mITT Set who underwent the second randomization and received at least 1 full dose of either of the study drugs during Treatment Period II.

The change from baseline in HSS7 at Week 12 was calculated as HSS7 at Week 12 minus the baseline HSS7. The HSS was counted twice daily (morning and evening) in the patient eDiary, on a scale of 0 (none) to 3 (intense) points. The daily HSS is the average of the morning and evening scores, and the HSS7 is the sum of the daily HSS over 7 days. HSS7 can range from 0 to 21. The higher scores mean a worse outcome.

Time frame: Week 12

Population: Analysis was performed based on mITT Set which had different definition with RAN set for disposition table.~This table presents the actual number of patients who had a result and were included in the analysis.~The mITT Set was defined as all randomly assigned patients who received at least 1 full dose of either of the study drugs during Treatment Period I.

The change from baseline in HSS7 at Week 24 was calculated as HSS7 at Week 24 minus the baseline HSS7. The HSS was counted twice daily (morning and evening) in the patient eDiary, on a scale of 0 (none) to 3 (intense) points. The daily HSS is the average of the morning and evening scores, and the HSS7 is the sum of the daily HSS over 7 days. HSS7 can range from 0 to 21. The higher scores mean a worse outcome.

Time frame: Week 24

Population: Analysis was performed based on mITT-TP2 Subset which had different definition with RAN set for disposition table.~This table presents the actual number of patients who had a result and were included in the analysis.~The mITT-TP2 Subset was defined as all patients in the mITT Set who underwent the second randomization and received at least 1 full dose of either of the study drugs during Treatment Period II.

The change from baseline in ISS7 at Week 12 was calculated as ISS7 at Week 12 minus the baseline ISS7. The ISS was recorded twice daily (morning and evening) in the patient eDiary, on scale of 0 (none) to 3 (severe) points. The daily ISS is the average of the morning and evening scores and the ISS7 is the sum of the daily ISS over 7 days. The ISS7 can range from 0 to 21. The higher scores mean a worse outcome. The relative potency based on the CFB of ISS7 at Week 12 was not calculated due to assumption of parallel-line assay not being met.

Time frame: Week 12

Population: Analysis was performed based on mITT Set which had different definition with RAN set for disposition table.~This table presents the actual number of patients who had a result and were included in the analysis.~The mITT Set was defined as all randomly assigned patients who received at least 1 full dose of either of the study drugs during Treatment Period I.

The change from baseline in ISS7 at Week 24 was calculated as ISS7 at Week 24 minus the baseline ISS7. The ISS was recorded twice daily (morning and evening) in the patient eDiary, on scale of 0 (none) to 3 (severe) points. The daily ISS is the average of the morning and evening scores and the ISS7 is the sum of the daily ISS over 7 days. The ISS7 can range from 0 to 21. The higher scores mean a worse outcome.

Time frame: Week 24

Population: Analysis was performed based on mITT-TP2 Subset which had different definition with RAN set for disposition table.~This table presents the actual number of patients who had a result and were included in the analysis.~The mITT-TP2 Subset was defined as all patients in the mITT Set who underwent the second randomization and received at least 1 full dose of either of the study drugs during Treatment Period II.

The change from baseline in UAS7 at Week 12 was calculated as UAS7 at Week 12 minus the baseline UAS7. The UAS was calculated as the sum of the ISS and the HSS by diary-based documentation. The sum of the scores represented disease severity on a scale from 0 (minimum) to 6 (maximum). The daily UAS is the average of the morning and evening scores and the UAS7 is the sum of the daily UAS over 7 days. UAS7 can range from 0 to 42. The higher scores mean a worse outcome.

Time frame: Week 12

Population: Analysis was performed based on mITT Set which had different definition with RAN set for disposition table.~This table presents the actual number of patients who had a result and were included in the analysis.~The mITT Set was defined as all randomly assigned patients who received at least 1 full dose of either of the study drugs during Treatment Period I.

The change from baseline in UAS7 at Week 24 was calculated as UAS7 at Week 24 minus the baseline UAS7. The UAS was calculated as the sum of the ISS and the HSS by diary-based documentation. The sum of the scores represented disease severity on a scale from 0 (minimum) to 6 (maximum). The daily UAS is the average of the morning and evening scores and the UAS7 is the sum of the daily UAS over 7 days. UAS7 can range from 0 to 42. The higher scores mean a worse outcome.

Time frame: Week 24

Population: Analysis was performed based on mITT-TP2 Subset which had different definition with RAN set for disposition table.~This table presents the actual number of patients who had a result and were included in the analysis.~The mITT-TP2 Subset was defined as all patients in the mITT Set who underwent the second randomization and received at least 1 full dose of either of the study drugs during Treatment Period II.

Anti-drug Antibody test involved both screening and confirmatory assays to confirm true positive results. Samples that are positive in the screening assay underwent further testing in the confirmatory assay to determine if patients are true positive. Samples that are positive in the ADA confirmatory assay were analyzed further to conduct a NAb assessment.

Time frame: Week 12

Population: Analysis was performed based on Safety Set which had different definition with RAN set for disposition table.~This table presents the actual number of patients who had a result and were included in the analysis.~The Safety Set was defined as all randomly assigned patients who received at least 1 dose (full or partial) of either of the study drugs.

Anti-drug Antibody test involved both screening and confirmatory assays to confirm true positive results. Samples that are positive in the screening assay underwent further testing in the confirmatory assay to determine if patients are true positive. Samples that are positive in the ADA confirmatory assay were analyzed further to conduct a NAb assessment.

Time frame: Week 24

Population: Analysis was performed based on Safety-TP2 Subset which had different definition with RAN set for disposition table.~This table presents the actual number of patients who had a result and were included in the analysis.~The Safety-TP2 Subset was defined as all patients in Safety Set who received at least 1 dose (full or partial) of either of the study drugs during Treatment Period II.

The proportion of angioedema-free days from Week 4 to Week 12 is defined as the number of days for which the patient indicated a 'No' response to the angioedema question in the patient eDiary divided by the total number of days with a non-missing diary entry starting on Week 4 visit date and ending the day prior to Week 12 visit date. Patients who had missing responses for \> 40% of the daily diary entries between Week 4 visit date and Week 12 visit date were not included in this analysis. The higher result means a better outcome.

Time frame: Week 4 to 12

Population: Analysis was performed based on mITT Set which had different definition with RAN set for disposition table.~This table presents the actual number of patients who had a result and were included in the analysis.~The mITT Set was defined as all randomly assigned patients who received at least 1 full dose of either of the study drugs during Treatment Period I.

Number of patients who achieved MID response at Week 12 were presented. MID response is a change from baseline in ISS7 of ≤ -5. If a patient had missing weekly scores for the given week the patient was classified as a non-responder. The higher percentage means a better outcome.

Time frame: Week 12

Population: Analysis was performed based on mITT Set which had different definition with RAN set for disposition table.~The mITT Set was defined as all randomly assigned patients who received at least 1 full dose of either of the study drugs during Treatment Period I.

Percentage of patients with Weekly Urticaria Activity Score (UAS7) of ≤ 6 points and complete responders (UAS7 = 0) at Week 12 is presented. If a patient had missing weekly scores for the given week the patient was classified as a non-responder. UAS7 can range from 0 to 42. The higher result means a better outcome.

Time frame: Week 12

Population: Analysis was performed based on mITT Set which had different definition with RAN set for disposition table.~The mITT Set was defined as all randomly assigned patients who received at least 1 full dose of either of the study drugs during Treatment Period I.

The number of patients with Weekly Urticaria Activity Score (UAS7) of ≤ 6 points and complete responders (UAS7 = 0) at Week 24 is presented. If a patient had missing weekly scores for the given week the patient was classified as a non-responder. UAS7 can range from 0 to 42. The higher result means a better outcome.

Time frame: Week 24

Population: Analysis was performed based on mITT-TP2 Subset which had different definition with RAN set for disposition table.~The mITT-TP2 Subset was defined as all patients in the mITT Set who underwent the second randomization and received at least 1 full dose of either of the study drugs during Treatment Period II.

Time to MID response was the time (in weeks) from Day 1 to the study week when reduction of 5 points or more from baseline for ISS7 was first achieved up to Week 12. If a patient failed to achieve an MID response up to Week 12 or terminated the study prior to Week 12 without achieving MID response, the patient was censored at the date (in weeks) of the last non-missing ISS7 evaluation. Time to MID was estimated by Kaplan-Meier method. The lower result means a better outcome.

Time frame: Up to Week 12

Population: Analysis was performed based on mITT Set which had different definition with RAN set for disposition table.~The mITT Set was defined as all randomly assigned patients who received at least 1 full dose of either of the study drugs during Treatment Period I.

All concentration below lower limit of quantification (BLQ) values were treated as zero (0) for PK parameter summary. Below lower limit of quantification (BLQ) is treated as zero (0).

Time frame: Week 12

Population: Analysis was performed based on PK Set which had different definition with RAN set for disposition table.~This table presents the actual number of patients who had a result and were included in the analysis.~The PK Set was defined as all patients who received at least 1 full dose of either of the study drugs during Treatment Period I and had at least 1 post-treatment PK result prior to dosing at Week 12.

All concentration below lower limit of quantification (BLQ) values were treated as zero (0) for PK parameter summary. Below lower limit of quantification (BLQ) is treated as zero (0).

Time frame: Week 24

Population: Analysis was performed based on PK-TP2 Subset which had different definition with RAN set for disposition table.~This table presents the actual number of patients who had a result and were included in the analysis.~The PK-TP2 Subset was defined as all patients in PK Set who received at least 1 full dose of either of the study drugs during Treatment Period II and had at least 1 post-treatment PK result after Week 12