Chronic Spontaneous Urticaria
Conditions
Brief summary
Primary Objective: This study aimed to demonstrate the efficacy of dupilumab in study participants with CSU who remained symptomatic despite the use of H1 antihistamine (Study A and C: omalizumab naïve; Study B: omalizumab intolerant or incomplete responders) Secondary Objectives: This study aimed to demonstrate the efficacy of dupilumab on urticaria activity composite endpoint and itch or hives, separately, at various timepoints This study aimed to demonstrate the efficacy of dupilumab on angioedema This study aimed to demonstrate the efficacy of dupilumab on urticaria control This study aimed to demonstrate improvement in health-related quality of life and overall disease status and severity This study aimed to evaluate the ability of dupilumab in reducing the proportion of participants who require treatment with oral corticosteroids (OCS) This study aimed to evaluate safety outcome measures This study aimed to evaluate immunogenicity of dupilumab
Detailed description
The duration of study for each participant included 2-4 weeks of screening period, 24 weeks of treatment period and 12 weeks of post treatment period.
Interventions
Pharmaceutical form:Injection solution Route of administration: Subcutaneous
DRUGPlacebo
Pharmaceutical form:Injection solution Route of administration: Subcutaneous
Pharmaceutical form:Tablet Route of administration: oral administration
Sponsors
Regeneron Pharmaceuticals
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
6 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Study A and C: Participant were ≥6 years to 80 years of age at the time of signing the informed consent. * Study B: Participant were ≥12 years (or the minimum legal age for adolescents in the country of the investigational site) to 80 years of age at the time of signing the informed consent * Participants who had a diagnosis of CSU refractory to H1 antihistamines (H1-AH) at the time of randomization defined by * Diagnosis of CSU\>6 months prior to screening visit * Presence of itch and hives for \>6 consecutive weeks at any time prior to screening visit despite the use of H1-AH during that time period * Used a study defined H1-antihistamine for CSU treatment * During the 7 days before randomization: UAS7≥16 ISS7≥ 8 * Study A and C: omalizumab naïve, Study B; intolerant or incomplete responder to omalizumab * Participants were willing and able to complete a daily symptom e-Diary for the duration of the study
Exclusion criteria
Participants were excluded from any of the studies if any of the following criteria apply: * Weight was less than 30 kg in adults and adolescents and 15 kg in children aged 6 to\<12years * Clearly defined underlying etiology for chronic urticarias other than CSU * Presented of skin morbidities other than CSU that may interfere with the assessment of the study outcomes * Active atopic dermatitis * Severe concomitant illness(es) that, in the investigator's judgment, would have adversely affected the participant's participation in the study * Active tuberculosis or non-tuberculous mycobacterial infection, or a history of incompletely treated tuberculosis unless documented adequately treated. * Diagnosed active endoparasitic infections; suspected or high risk of endoparasitic infection * Active chronic or acute infection requiring treatment with systemic antibiotics, antivirals, antiprotozoals, or antifungals within 2 weeks before the screening visit and during the screening period * Known or suspected immunodeficiency * Active malignancy or history of malignancy within 5 years before the baseline visit, except completely treated in situ carcinoma of the cervix, completely treated and resolved non-metastatic squamous or basal cell carcinoma of the skin * History of systemic hypersensitivity or anaphylaxis to omalizumab or any biologic therapy, including any excipients * Participation in prior dupilumab clinical study, or have been treated with commercially available dupilumab. The above information is not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Weekly Itch Severity Score at Week 24 | Baseline (Day 1) and Week 24 | ISS was recorded in e-diary. The ISS represents severity of itch on a scale ranging from 0 (none) to 3 (intense). The ISS7 score was the sum of daily ISS scores recorded by a participant at the same time each day over 7 days with an overall scale of 0 (no impact) to 21 (severe impact). Higher scores indicated greater intensity of itch. Least squares (LS) mean is presented. Baseline was defined as the sum of daily scores obtained for 7 days prior to randomization. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Weekly Hives Severity Score at Week 24 | Baseline (Day 1) and Week 24 | Daily HSS was recorded in e-diary. The HSS7 score is the sum of daily HSS ranging from 0 (none) to 3 (more than 50 hives) recorded by a participant at the same time of each day over 7 days with an overall scale of 0 (no hives) to 21 (severe hives). Higher scores indicate greater intensity of hives. LS mean is presented. Baseline was defined as the sum of the daily scores for the 7 days prior to the day of randomization. |
| Percentage of Responders for Weekly Itch Severity Score Minimally Important Difference (MID) at Week 24 | Week 24 | The ISS represents severity of itch on a scale ranging from 0 (none) to 3 (intense). The ISS7 score was the sum of daily ISS scores recorded by a participant at the same time each day over 7 days with an overall scale of 0 (no impact) to 21 (severe impact). Higher scores indicated greater intensity of itch. An ISS7 MID response was defined as \>=5 points decrease from baseline after study intervention. |
| Percentage of Participants With Weekly Urticaria Activity Score <=6 at Week 24 | Week 24 | UAS is a validated composite PRO measure for assessing CSU activity. The once daily UAS is the sum of the daily HSS and daily ISS recorded in e-diary. Daily HSS assesses number of wheals and range from 0 (none) to 3 (more than 50 hives) whereas daily ISS assesses itch intensity and range from 0 (none) to 3 (intense). The daily UAS scores range from 0 to 6 point/day. Once daily UAS scores are summed over 7-day period to create the UAS7 with an overall scale of 0 (no urticaria) to 42 (severe urticaria). Higher scores indicate greater severity of urticaria symptoms. In evaluating urticaria control using UAS7, an UAS7 score of \<=6 indicated a well-controlled urticaria. |
| Percentage of Participants With Weekly Urticaria Activity Score =0 at Week 24 | Week 24 | UAS is a validated composite PRO measure for assessing CSU activity. The once daily UAS is the sum of the daily HSS and daily ISS recorded in e-diary. Daily HSS assesses number of wheals and range from 0 (none) to 3 (more than 50 hives) whereas daily ISS assesses itch intensity and range from 0 (none) to 3 (intense). The daily UAS scores range from 0 to 6 point/day. Once daily UAS scores are summed over 7-day period to create the UAS7 with an overall scale of 0 (no urticaria) to 42 (severe urticaria). Higher scores indicate greater severity of urticaria symptoms. In evaluating urticaria control using UAS7, an UAS7 score of 0 indicated an absence of both itch and hives and a complete resolution of CSU symptoms. |
| Change From Baseline in Urticaria Control Test (UCT) at Week 24 | Baseline (Day 1) and Week 24 | The UCT assessed urticaria control based on 4 items (severity of pruritus and wheals urticaria symptoms; frequency of treatment being not sufficient; quality-of-life \[QoL\] impairment; overall urticarial control). Each item was rated on a 5-point Likert-type scale from 0 (no control) to 4 (maximum control). The overall UCT score was the sum of all 4 individual item scores with a range of 0 (no disease control) to 16 (complete disease control). Higher scores indicated greater disease control. LS mean is presented. Baseline was defined as the last available value up to randomization date and prior to the first dose of study intervention. |
| Change From Baseline in Weekly Itch Severity Score at Week 12 | Baseline (Day 1) and Week 12 | ISS was recorded in e-diary. The ISS represents severity of itch on a scale ranging from 0 (none) to 3 (intense). The ISS7 score was the sum of daily ISS scores recorded by a participant at the same time each day over 7 days with an overall scale of 0 (no impact) to 21 (severe impact). Higher scores indicated greater intensity of itch. LS mean is presented. Baseline was defined as the sum of daily scores obtained for 7 days prior to randomization. |
| Change From Baseline in Weekly Urticaria Activity Score at Week 12 | Baseline (Day 1) and Week 12 | UAS is a validated composite PRO measure for assessing CSU activity. The once daily UAS is the sum of the daily HSS and daily ISS recorded in e-diary. Daily HSS assesses number of wheals and range from 0 (none) to 3 (more than 50 hives) whereas daily ISS assesses itch intensity and range from 0 (none) to 3 (intense). The daily UAS scores range from 0 to 6 point/day. Once daily UAS scores are summed over 7-day period to create the UAS7 with an overall scale of 0 (no urticaria) to 42 (severe urticaria). Higher scores indicate greater severity of urticaria symptoms. LS mean is presented. Baseline was defined as the sum of the daily scores for the 7 days prior to the day of randomization. |
| Percentage of Participants With Weekly Urticaria Activity Score <=6 and =0 at Week 12 | Week 12 | UAS is a validated composite PRO measure for assessing CSU activity. The once daily UAS is the sum of the daily HSS and daily ISS recorded in e-diary. Daily HSS assesses number of wheals and range from 0 (none) to 3 (more than 50 hives) whereas daily ISS assesses itch intensity and range from 0 (none) to 3 (intense). The daily UAS scores range from 0 to 6 point/day. Once daily UAS scores are summed over 7-day period to create the UAS7 with an overall scale of 0 (no urticaria) to 42 (severe urticaria). Higher scores indicate greater severity of urticaria symptoms. In evaluating urticaria control using UAS7, an UAS7 score of \<=6 indicated a well-controlled urticaria and an UAS7 score of 0 indicated an absence of both itch and hives and a complete resolution of CSU symptoms. |
| Percentage of Responders for Weekly Itch Severity Score Minimally Important Difference at Week 12 | Week 12 | The ISS represents severity of itch on a scale ranging from 0 (none) to 3 (intense). The ISS7 score was the sum of daily ISS scores recorded by a participant at the same time each day over 7 days with an overall scale of 0 (no impact) to 21 (severe impact). Higher scores indicated greater intensity of itch. An ISS7 MID response was defined as \>=5 points decrease from baseline after study intervention. |
| Change From Baseline in Weekly Hives Severity Score at Week 12 | Baseline (Day 1) and Week 12 | Daily HSS was recorded in e-diary. The HSS7 score is the sum of daily HSS ranging from 0 (none) to 3 (more than 50 hives) recorded by a participant at the same time of each day over 7 days with an overall scale of 0 (no hives) to 21 (severe hives). Higher scores indicate greater intensity of hives. LS mean is presented. Baseline was defined as the sum of the daily scores for the 7 days prior to the day of randomization. |
| Change From Baseline in Urticaria Control Test at Week 12 | Baseline (Day 1) and Week 12 | The UCT assessed urticaria control based on 4 items (severity of pruritus and wheals urticaria symptoms; frequency of treatment being not sufficient; quality-of-life \[QoL\] impairment; overall urticarial control). Each item was rated on a 5-point Likert-type scale from 0 (no control) to 4 (maximum control). The overall UCT score was the sum of all 4 individual item scores with a range of 0 (no disease control) to 16 (complete disease control). Higher scores indicated greater disease control. LS mean is presented. Baseline was defined as the last available value up to randomization date and prior to the first dose of study intervention. |
| Change From Baseline in Weekly Urticaria Activity Score at Week 24 | Baseline (Day 1) and Week 24 | UAS is a validated composite patient-reported outcome (PRO) measure for assessing chronic spontaneous urticaria (CSU) activity. The once daily UAS is the sum of the daily hives severity score (HSS) and daily ISS recorded in e-diary. Daily HSS assesses number of wheals and range from 0 (none) to 3 (more than 50 hives) whereas daily ISS assesses itch intensity and range from 0 (none) to 3 (intense). The daily UAS scores range from 0 to 6 point/day. Once daily UAS scores are summed over 7-day period to create the UAS7 with an overall scale of 0 (no urticaria) to 42 (severe urticaria). Higher scores indicate greater severity of urticaria symptoms. LS mean is presented. Baseline was defined as the sum of the daily scores for the 7 days prior to the day of randomization. |
| Time to First Weekly Itch Severity Score Minimally Important Difference Response During the 24-Week Treatment Period | Baseline (Day 1) up to Week 24 | The ISS represents severity of itch on a scale ranging from 0 (none) to 3 (intense). The ISS7 score was the sum of daily ISS scores recorded by a participant at the same time each day over 7 days with an overall scale of 0 (no impact) to 21 (severe impact). Higher scores indicated greater intensity of itch. The MID for ISS7 was a change of 5.0 points. Time to first ISS7 MID response (ISS7 \>=5) was defined as time to reduction from baseline of 5 points or more. Kaplan-Meier estimate is presented. Baseline was defined as the sum of daily scores obtained for 7 days prior to randomization. |
| Change From Baseline in Angioedema Activity Score Over 7 Days (AAS7) at Weeks 12 and 24 | Baseline (Day 1) and Weeks 12 and 24 | The AAS is a diary in which participants document on a daily basis the presence or absence of angioedema during the past 24 hours. If angioedema is present, participants answer 5 additional questions about the time of the day the swelling episode occurred and the severity and impact on daily functioning and appearance this swelling episode has had. Each AAS item is scored between 0 (minimum) and 3 (maximum). The daily AASs range from 0 (no episode) to 15 (severe) points. The AAS7 score is the sum of daily AAS scores reported by a participant at the same time of each day over 7 days, with a range of 0 (no angioedema episodes) to 105 (highest angioedema severity). Higher scores indicate greater angioedema activity. Mean is presented. Baseline was defined as the sum of the daily scores for the 7 days prior to the day of randomization. |
| Percentage of Well-controlled Participants (Urticaria Control Test >=12) at Weeks 12 and 24 | Weeks 12 and 24 | The UCT assessed urticaria control based on 4 items (severity of pruritus and wheals urticaria symptoms; frequency of treatment being not sufficient; QoL impairment; overall urticarial control). Each item was rated on a 5-point Likert-type scale from 0 (no control) to 4 (maximum control). The overall UCT score was the sum of all 4 individual item scores with a range of 0 (no disease control) to 16 (complete disease control). Higher scores indicated greater disease control. An UCT score of \>=12 (out of maximum 16) indicated a well-controlled urticaria disease status. |
| Change From Baseline in Health-related Quality-of-life (HRQoL) as Measured by Dermatology Life Quality Index (DLQI) in Participants >=16 Years Old at Weeks 12 and 24 | Baseline (Day 1) and Weeks 12 and 24 | The DLQI is an assessment assessing the impact of skin disease on participants' HRQoL over the previous week and contains 10 questions related to symptoms, leisure activities, work/school or holiday time, personal relationships including intimate, the side effects of treatment, and emotional reactions to having a skin disease. The questions (except question 7) were scored on a 4-point Likert scale: 0 (not at all), 1 (a little), 2 (a lot), 3 (very much). Question 7 about work/studying asked whether work/study had been prevented and then (if No) to what degree the skin condition has been a problem at work/study; the item was again rated on a 3-point Likert scale: 0 (not at all) to 3 (a lot). Total DLQI was calculated by summing the score of each question and ranged from 0 (no impact) to 30 (severe impact). Higher scores indicated poor HRQoL. Mean is presented. Baseline was defined as the last available value up to randomization date and prior to the first dose of study intervention. |
| Change From Baseline in Health-related Quality-of-life as Measured by Children's Dermatology Life Quality Index (CDLQI) in Participants >=6 to <16 Years Old at Weeks 12 and 24 | Baseline (Day 1) and Weeks 12 and 24 | The CDLQI is a validated questionnaire designed to measure the impact of skin disease on children's HRQoL. Participants provide responses to 10 questions (symptoms feelings associated with disease, the impact of the disease on leisure, school or holidays, personal relationships, sleep, and side effects of treatment for the skin disease). The instrument has a recall period of 7 days. 9 of the 10 questions are scored on a 4-point Likert scale ranging from 0 (not at all/question unanswered) to 3 (very much). Question 7 has an additional possible response (prevented school) which is assigned a score of 3 (0 \[not at all\] to 3 \[definitely\]). The total CDLQI score is the sum of the score of each question ranging 0 (no impact) to 30 (severe impact). The higher the score, the greater the impact is on the child's HRQoL. Mean is presented. Baseline was defined as the last available value up to randomization date and prior to the first dose of study intervention. |
| Patient Global Impression of Change (PGIC) of Chronic Spontaneous Urticaria at Weeks 12 and 24 | Weeks 12 and 24 | The PGIC is a 1-item questionnaire that asks the participant to provide the overall self-assessment of change in their CSU on a 7-point scale compared to just before participant started taking the study intervention. Response choices are: 0 (very much better), 1 (moderately better), 2 (a little better), 3 (no change), 4 (a little worse), 5 (moderately worse), 6 (very much worse). Higher score indicate worsening. |
| Change From Baseline in Patient Global Impression of Severity (PGIS) of Chronic Spontaneous Urticaria at Weeks 12 and 24 | Baseline (Day 1) and Weeks 12 and 24 | The PGIS is a 1-item questionnaire that asks participants to provide the overall self-assessment of their disease severity on a 4-point scale for the past week. Response choices are: 1 (none), 2 (mild), 3 (moderate), 4 (severe). Higher score indicate more severity. Baseline was defined as the last available value up to randomization date and prior to the first dose of study intervention. |
| Time to First Oral Corticosteroid (OCS) Use for Chronic Spontaneous Urticaria During the 24-week Treatment Period | Baseline (Day 1) up to Week 24 | Participants receiving OCS as rescue medications for CSU were recorded by the Investigator in e-case report form (eCRF) during the 24-week treatment period. Kaplan-Meier estimate for time to first OCS use is presented. |
| Percentage of Participants Receiving Oral Corticosteroid for Chronic Spontaneous Urticaria During the 24-week Treatment Period | Baseline (Day 1) up to Week 24 | Percentage of participants receiving OCS as rescue medications for CSU were recorded by the Investigator in eCRF during the 24-week treatment period. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | From first dose of study intervention (Day 1) up to end of follow-up, approximately 36 weeks each for Study A, B and C | An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. SAE was any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, was a congenital anomaly/birth defect or was an important medical event. TEAEs were defined as AEs that developed, worsened or became serious during the TE period. |
| Number of Participants With Treatment-emergent Anti-drug Antibodies (ADA) Against Dupilumab | Up to Week 24 | Blood samples were collected at specified timepoints and ADA samples were assayed using validated methods. Treatment-emergent ADA response was defined as a positive response in the ADA assay post first dose when baseline results were negative or missing. Number of participants with treatment-emergent ADA response is presented. |
| Change From Baseline in Weekly Itch Severity Score at Weeks 4, 8, 16 and 20 | Baseline (Day 1) and Weeks 4, 8, 16 and 20 | ISS was recorded in e-diary. The ISS represents severity of itch on a scale ranging from 0 (none) to 3 (intense). The ISS7 score was the sum of daily ISS scores recorded by a participant at the same time each day over 7 days with an overall scale of 0 (no impact) to 21 (severe impact). Higher scores indicated greater intensity of itch. Mean is presented. Baseline was defined as the sum of daily scores obtained for 7 days prior to randomization. |
Countries
Argentina, Canada, China, France, Germany, Hungary, Japan, Russia, Spain, United Kingdom, United States
Participant flow
Recruitment details
This study comprised of 3 randomized studies of similar design: 2 studies were conducted in participants who were omalizumab naïve (Study A \[55 centers in 9 countries\] and Study C \[50 centers in 9 countries\]) and 1 study was conducted in participants who were omalizumab intolerant or incomplete responders (Study B \[61 centers in 11 countries\]).
Pre-assignment details
A total of 138 participants in Study A, 108 participants in Study B and 151 participants in Study C were randomized in a 1:1 ratio to receive either weight-tiered dupilumab or matching placebo in respective studies. As pre-specified in the protocol and statistical analysis plan (SAP), the results are presented by study and treatment group/intervention.
Participants by arm
| Arm | Count |
|---|---|
| Study A: Placebo Participants who were omalizumab naïve received placebo matched to dupilumab as SC injection including loading dose from Day 1 up to 24 weeks. | 68 |
| Study A: Dupilumab Participants who were omalizumab naïve received dupilumab for 24 weeks as follows:
* 300 mg SC injection q2w for adults and those adolescents who weighed \>=60 kg at screening starting from Week 2 following a loading dose of 600 mg (2×300 mg injections) on Day 1,
* 200 mg SC injection q2w for adolescents who weighed \<60 kg and children (\>=6 to \<12 years of age) who weighed \>=30 kg at screening starting from Week 2 following a loading dose of 400 mg (2×200 mg injections) on Day 1 and
* 300 mg SC injection q4w for children (\>=6 to \<12 years of age) who weighed \<30 kg and \>=15 kg at screening starting from Week 4 following a loading dose of 600 mg (2×300 mg injections) on Day 1. | 70 |
| Study B: Placebo Participants who were intolerant or incomplete responders to omalizumab received placebo matched to dupilumab as SC injection including loading dose from Day 1 up to 24 weeks. | 54 |
| Study B: Dupilumab Participants who were intolerant or incomplete responders to omalizumab received dupilumab for 24 weeks as follows:
* 300 mg SC injection q2w for adults and those adolescents weighing \>=60 kg at screening starting from Week 2 following a loading dose of 600 mg (2×300 mg injections) on Day 1 or
* 200 mg SC injection q2w for adolescents weighing \<60 kg at screening starting from Week 2 following a loading dose of 400 mg (2×200 mg injections) on Day 1. | 54 |
| Study C: Placebo Participants who were omalizumab naïve received placebo matched to dupilumab as SC injection including loading dose from Day 1 up to 24 weeks. | 77 |
| Study C: Dupilumab Participants who were omalizumab naïve received dupilumab for 24 weeks as follows:
* 300 mg SC injection q2w for adults and those adolescents who weighed \>=60 kg at screening starting from Week 2 following a loading dose of 600 mg (2×300 mg injections) on Day 1,
* 200 mg SC injection q2w for adolescents who weighed \<60 kg and children (\>=6 to \<12 years of age) who weighed \>=30 kg at screening starting from Week 2 following a loading dose of 400 mg (2×200 mg injections) on Day 1 and
* 300 mg SC injection q4w for children (\>=6 to \<12 years of age) who weighed \<30 kg and \>=15 kg at screening starting from Week 4 following a loading dose of 600 mg (2×300 mg injections) on Day 1. | 74 |
| Total | 397 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 2 | 0 | 0 | 0 | 0 |
| Overall Study | Not related to Coronavirus Disease-2019 (COVID-19) | 2 | 1 | 1 | 3 | 2 | 2 |
| Overall Study | Poor compliance to protocol | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 8 | 4 | 5 | 2 | 8 | 6 |
Baseline characteristics
| Characteristic | Study A: Placebo | Total | Study C: Dupilumab | Study C: Placebo | Study B: Dupilumab | Study B: Placebo | Study A: Dupilumab |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 41.9 years STANDARD_DEVIATION 14.8 | 44.4 years STANDARD_DEVIATION 16.3 | 45.6 years STANDARD_DEVIATION 17.1 | 44.0 years STANDARD_DEVIATION 16.7 | 48.6 years STANDARD_DEVIATION 15.6 | 46.8 years STANDARD_DEVIATION 16.3 | 40.7 years STANDARD_DEVIATION 16.2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 16 Participants | 114 Participants | 33 Participants | 29 Participants | 6 Participants | 11 Participants | 19 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 10 Participants | 0 Participants | 2 Participants | 3 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 5 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 16 Participants | 7 Participants | 6 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 48 Participants | 249 Participants | 32 Participants | 38 Participants | 43 Participants | 41 Participants | 47 Participants |
| Sex: Female, Male Female | 50 Participants | 275 Participants | 47 Participants | 59 Participants | 37 Participants | 41 Participants | 41 Participants |
| Sex: Female, Male Male | 18 Participants | 122 Participants | 27 Participants | 18 Participants | 17 Participants | 13 Participants | 29 Participants |
| Weekly Itch-Severity (ISS7) Score | 15.7 score on a scale STANDARD_DEVIATION 4.1 | 15.7 score on a scale STANDARD_DEVIATION 3.9 | 15.3 score on a scale STANDARD_DEVIATION 3.6 | 15.0 score on a scale STANDARD_DEVIATION 3.9 | 15.9 score on a scale STANDARD_DEVIATION 4 | 16.2 score on a scale STANDARD_DEVIATION 3.8 | 16.1 score on a scale STANDARD_DEVIATION 4 |
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 |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 68 | 0 / 70 | 0 / 54 | 0 / 54 | 0 / 77 | 0 / 74 |
| other Total, other adverse events | 19 / 68 | 12 / 70 | 15 / 54 | 17 / 54 | 15 / 77 | 20 / 74 |
| serious Total, serious adverse events | 5 / 68 | 2 / 70 | 2 / 54 | 3 / 54 | 1 / 77 | 5 / 74 |
Outcome results
Primary
Change From Baseline in Weekly Itch Severity Score at Week 24
ISS was recorded in e-diary. The ISS represents severity of itch on a scale ranging from 0 (none) to 3 (intense). The ISS7 score was the sum of daily ISS scores recorded by a participant at the same time each day over 7 days with an overall scale of 0 (no impact) to 21 (severe impact). Higher scores indicated greater intensity of itch. Least squares (LS) mean is presented. Baseline was defined as the sum of daily scores obtained for 7 days prior to randomization.
Time frame: Baseline (Day 1) and Week 24
Population: The intent-to-treat (ITT) population included all randomized participants analyzed according to the intervention group allocated by randomization.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Study A: Placebo | Change From Baseline in Weekly Itch Severity Score at Week 24 | -6.01 score on a scale | Standard Error 0.94 |
| Study A: Dupilumab | Change From Baseline in Weekly Itch Severity Score at Week 24 | -10.24 score on a scale | Standard Error 0.91 |
| Study B: Placebo | Change From Baseline in Weekly Itch Severity Score at Week 24 | -4.81 score on a scale | Standard Error 1.08 |
| Study B: Dupilumab | Change From Baseline in Weekly Itch Severity Score at Week 24 | -7.68 score on a scale | Standard Error 1.1 |
| Study C: Placebo | Change From Baseline in Weekly Itch Severity Score at Week 24 | -6.10 score on a scale | Standard Error 1.4 |
| Study C: Dupilumab | Change From Baseline in Weekly Itch Severity Score at Week 24 | -8.64 score on a scale | Standard Error 1.41 |
Comparison: Analyzed by fitting an analysis of covariance (ANCOVA) model with the corresponding baseline value, intervention group, presence of angioedema at baseline, and regions as covariates.p-value: 0.000595% CI: [-6.63, -1.84]ANCOVA
Comparison: Analyzed by fitting an ANCOVA model with the corresponding baseline value, intervention group, presence of angioedema at baseline, and regions as covariates.p-value: 0.044995% CI: [-5.68, -0.07]ANCOVA
Comparison: Analyzed by fitting an ANCOVA model with the corresponding baseline value, intervention group, presence of angioedema at baseline, and regions as covariates.p-value: 0.018495% CI: [-4.65, -0.43]ANCOVA
Secondary
Change From Baseline in Angioedema Activity Score Over 7 Days (AAS7) at Weeks 12 and 24
The AAS is a diary in which participants document on a daily basis the presence or absence of angioedema during the past 24 hours. If angioedema is present, participants answer 5 additional questions about the time of the day the swelling episode occurred and the severity and impact on daily functioning and appearance this swelling episode has had. Each AAS item is scored between 0 (minimum) and 3 (maximum). The daily AASs range from 0 (no episode) to 15 (severe) points. The AAS7 score is the sum of daily AAS scores reported by a participant at the same time of each day over 7 days, with a range of 0 (no angioedema episodes) to 105 (highest angioedema severity). Higher scores indicate greater angioedema activity. Mean is presented. Baseline was defined as the sum of the daily scores for the 7 days prior to the day of randomization.
Time frame: Baseline (Day 1) and Weeks 12 and 24
Population: The ITT population included all randomized participants analyzed according to the intervention group allocated by randomization. Only those participants with angioedema at baseline and with data collected at specified timepoints are reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Study A: Placebo | Change From Baseline in Angioedema Activity Score Over 7 Days (AAS7) at Weeks 12 and 24 | Week 12 | -23.46 score on a scale | Standard Deviation 21.76 |
| Study A: Placebo | Change From Baseline in Angioedema Activity Score Over 7 Days (AAS7) at Weeks 12 and 24 | Week 24 | -23.56 score on a scale | Standard Deviation 23.04 |
| Study A: Dupilumab | Change From Baseline in Angioedema Activity Score Over 7 Days (AAS7) at Weeks 12 and 24 | Week 12 | -19.14 score on a scale | Standard Deviation 18.89 |
| Study A: Dupilumab | Change From Baseline in Angioedema Activity Score Over 7 Days (AAS7) at Weeks 12 and 24 | Week 24 | -18.76 score on a scale | Standard Deviation 22.85 |
| Study B: Placebo | Change From Baseline in Angioedema Activity Score Over 7 Days (AAS7) at Weeks 12 and 24 | Week 12 | -16.74 score on a scale | Standard Deviation 21.74 |
| Study B: Placebo | Change From Baseline in Angioedema Activity Score Over 7 Days (AAS7) at Weeks 12 and 24 | Week 24 | -15.83 score on a scale | Standard Deviation 25.73 |
| Study B: Dupilumab | Change From Baseline in Angioedema Activity Score Over 7 Days (AAS7) at Weeks 12 and 24 | Week 12 | -19.41 score on a scale | Standard Deviation 34.44 |
| Study B: Dupilumab | Change From Baseline in Angioedema Activity Score Over 7 Days (AAS7) at Weeks 12 and 24 | Week 24 | -13.95 score on a scale | Standard Deviation 37.22 |
| Study C: Placebo | Change From Baseline in Angioedema Activity Score Over 7 Days (AAS7) at Weeks 12 and 24 | Week 12 | -32.14 score on a scale | Standard Deviation 32.15 |
| Study C: Placebo | Change From Baseline in Angioedema Activity Score Over 7 Days (AAS7) at Weeks 12 and 24 | Week 24 | -31.00 score on a scale | Standard Deviation 36.38 |
| Study C: Dupilumab | Change From Baseline in Angioedema Activity Score Over 7 Days (AAS7) at Weeks 12 and 24 | Week 12 | -34.33 score on a scale | Standard Deviation 36.19 |
| Study C: Dupilumab | Change From Baseline in Angioedema Activity Score Over 7 Days (AAS7) at Weeks 12 and 24 | Week 24 | -36.28 score on a scale | Standard Deviation 27.61 |
Secondary
Change From Baseline in Health-related Quality-of-life as Measured by Children's Dermatology Life Quality Index (CDLQI) in Participants >=6 to <16 Years Old at Weeks 12 and 24
The CDLQI is a validated questionnaire designed to measure the impact of skin disease on children's HRQoL. Participants provide responses to 10 questions (symptoms feelings associated with disease, the impact of the disease on leisure, school or holidays, personal relationships, sleep, and side effects of treatment for the skin disease). The instrument has a recall period of 7 days. 9 of the 10 questions are scored on a 4-point Likert scale ranging from 0 (not at all/question unanswered) to 3 (very much). Question 7 has an additional possible response (prevented school) which is assigned a score of 3 (0 \[not at all\] to 3 \[definitely\]). The total CDLQI score is the sum of the score of each question ranging 0 (no impact) to 30 (severe impact). The higher the score, the greater the impact is on the child's HRQoL. Mean is presented. Baseline was defined as the last available value up to randomization date and prior to the first dose of study intervention.
Time frame: Baseline (Day 1) and Weeks 12 and 24
Population: The ITT population included all randomized participants analyzed according to the intervention group allocated by randomization. Only those participants \>=6 and \<16 years with data collected at specified timepoints are reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Study A: Placebo | Change From Baseline in Health-related Quality-of-life as Measured by Children's Dermatology Life Quality Index (CDLQI) in Participants >=6 to <16 Years Old at Weeks 12 and 24 | Week 12 | -5.00 score on a scale | — |
| Study A: Dupilumab | Change From Baseline in Health-related Quality-of-life as Measured by Children's Dermatology Life Quality Index (CDLQI) in Participants >=6 to <16 Years Old at Weeks 12 and 24 | Week 24 | -12.50 score on a scale | Standard Deviation 12.02 |
| Study A: Dupilumab | Change From Baseline in Health-related Quality-of-life as Measured by Children's Dermatology Life Quality Index (CDLQI) in Participants >=6 to <16 Years Old at Weeks 12 and 24 | Week 12 | -8.00 score on a scale | Standard Deviation 5.66 |
| Study B: Dupilumab | Change From Baseline in Health-related Quality-of-life as Measured by Children's Dermatology Life Quality Index (CDLQI) in Participants >=6 to <16 Years Old at Weeks 12 and 24 | Week 24 | -7 score on a scale | — |
| Study B: Dupilumab | Change From Baseline in Health-related Quality-of-life as Measured by Children's Dermatology Life Quality Index (CDLQI) in Participants >=6 to <16 Years Old at Weeks 12 and 24 | Week 12 | -7 score on a scale | — |
| Study C: Placebo | Change From Baseline in Health-related Quality-of-life as Measured by Children's Dermatology Life Quality Index (CDLQI) in Participants >=6 to <16 Years Old at Weeks 12 and 24 | Week 12 | -4.60 score on a scale | Standard Deviation 10.04 |
| Study C: Placebo | Change From Baseline in Health-related Quality-of-life as Measured by Children's Dermatology Life Quality Index (CDLQI) in Participants >=6 to <16 Years Old at Weeks 12 and 24 | Week 24 | -5.60 score on a scale | Standard Deviation 7.83 |
| Study C: Dupilumab | Change From Baseline in Health-related Quality-of-life as Measured by Children's Dermatology Life Quality Index (CDLQI) in Participants >=6 to <16 Years Old at Weeks 12 and 24 | Week 24 | -4.50 score on a scale | Standard Deviation 7.78 |
| Study C: Dupilumab | Change From Baseline in Health-related Quality-of-life as Measured by Children's Dermatology Life Quality Index (CDLQI) in Participants >=6 to <16 Years Old at Weeks 12 and 24 | Week 12 | -9.00 score on a scale | Standard Deviation 2.83 |
Secondary
Change From Baseline in Health-related Quality-of-life (HRQoL) as Measured by Dermatology Life Quality Index (DLQI) in Participants >=16 Years Old at Weeks 12 and 24
The DLQI is an assessment assessing the impact of skin disease on participants' HRQoL over the previous week and contains 10 questions related to symptoms, leisure activities, work/school or holiday time, personal relationships including intimate, the side effects of treatment, and emotional reactions to having a skin disease. The questions (except question 7) were scored on a 4-point Likert scale: 0 (not at all), 1 (a little), 2 (a lot), 3 (very much). Question 7 about work/studying asked whether work/study had been prevented and then (if No) to what degree the skin condition has been a problem at work/study; the item was again rated on a 3-point Likert scale: 0 (not at all) to 3 (a lot). Total DLQI was calculated by summing the score of each question and ranged from 0 (no impact) to 30 (severe impact). Higher scores indicated poor HRQoL. Mean is presented. Baseline was defined as the last available value up to randomization date and prior to the first dose of study intervention.
Time frame: Baseline (Day 1) and Weeks 12 and 24
Population: The ITT population included all randomized participants analyzed according to the intervention group allocated by randomization. Only those participants \>=16 years with data collected at specified timepoints are reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Study A: Placebo | Change From Baseline in Health-related Quality-of-life (HRQoL) as Measured by Dermatology Life Quality Index (DLQI) in Participants >=16 Years Old at Weeks 12 and 24 | Week 24 | -7.56 score on a scale | Standard Deviation 8.13 |
| Study A: Placebo | Change From Baseline in Health-related Quality-of-life (HRQoL) as Measured by Dermatology Life Quality Index (DLQI) in Participants >=16 Years Old at Weeks 12 and 24 | Week 12 | -7.55 score on a scale | Standard Deviation 7.47 |
| Study A: Dupilumab | Change From Baseline in Health-related Quality-of-life (HRQoL) as Measured by Dermatology Life Quality Index (DLQI) in Participants >=16 Years Old at Weeks 12 and 24 | Week 24 | -9.50 score on a scale | Standard Deviation 5.92 |
| Study A: Dupilumab | Change From Baseline in Health-related Quality-of-life (HRQoL) as Measured by Dermatology Life Quality Index (DLQI) in Participants >=16 Years Old at Weeks 12 and 24 | Week 12 | -8.55 score on a scale | Standard Deviation 6.27 |
| Study B: Placebo | Change From Baseline in Health-related Quality-of-life (HRQoL) as Measured by Dermatology Life Quality Index (DLQI) in Participants >=16 Years Old at Weeks 12 and 24 | Week 12 | -4.53 score on a scale | Standard Deviation 6.28 |
| Study B: Placebo | Change From Baseline in Health-related Quality-of-life (HRQoL) as Measured by Dermatology Life Quality Index (DLQI) in Participants >=16 Years Old at Weeks 12 and 24 | Week 24 | -4.96 score on a scale | Standard Deviation 6.87 |
| Study B: Dupilumab | Change From Baseline in Health-related Quality-of-life (HRQoL) as Measured by Dermatology Life Quality Index (DLQI) in Participants >=16 Years Old at Weeks 12 and 24 | Week 12 | -6.77 score on a scale | Standard Deviation 6.92 |
| Study B: Dupilumab | Change From Baseline in Health-related Quality-of-life (HRQoL) as Measured by Dermatology Life Quality Index (DLQI) in Participants >=16 Years Old at Weeks 12 and 24 | Week 24 | -6.91 score on a scale | Standard Deviation 7.51 |
| Study C: Placebo | Change From Baseline in Health-related Quality-of-life (HRQoL) as Measured by Dermatology Life Quality Index (DLQI) in Participants >=16 Years Old at Weeks 12 and 24 | Week 12 | -5.01 score on a scale | Standard Deviation 6.25 |
| Study C: Placebo | Change From Baseline in Health-related Quality-of-life (HRQoL) as Measured by Dermatology Life Quality Index (DLQI) in Participants >=16 Years Old at Weeks 12 and 24 | Week 24 | -6.81 score on a scale | Standard Deviation 6.54 |
| Study C: Dupilumab | Change From Baseline in Health-related Quality-of-life (HRQoL) as Measured by Dermatology Life Quality Index (DLQI) in Participants >=16 Years Old at Weeks 12 and 24 | Week 24 | -8.09 score on a scale | Standard Deviation 7.66 |
| Study C: Dupilumab | Change From Baseline in Health-related Quality-of-life (HRQoL) as Measured by Dermatology Life Quality Index (DLQI) in Participants >=16 Years Old at Weeks 12 and 24 | Week 12 | -6.61 score on a scale | Standard Deviation 7.04 |
Secondary
Change From Baseline in Patient Global Impression of Severity (PGIS) of Chronic Spontaneous Urticaria at Weeks 12 and 24
The PGIS is a 1-item questionnaire that asks participants to provide the overall self-assessment of their disease severity on a 4-point scale for the past week. Response choices are: 1 (none), 2 (mild), 3 (moderate), 4 (severe). Higher score indicate more severity. Baseline was defined as the last available value up to randomization date and prior to the first dose of study intervention.
Time frame: Baseline (Day 1) and Weeks 12 and 24
Population: The ITT population included all randomized participants analyzed according to the intervention group allocated by randomization. Only those participants with data collected at specified timepoints are reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Study A: Placebo | Change From Baseline in Patient Global Impression of Severity (PGIS) of Chronic Spontaneous Urticaria at Weeks 12 and 24 | Week 12 | -0.89 score on a scale | Standard Deviation 0.98 |
| Study A: Placebo | Change From Baseline in Patient Global Impression of Severity (PGIS) of Chronic Spontaneous Urticaria at Weeks 12 and 24 | Week 24 | -0.97 score on a scale | Standard Deviation 1.18 |
| Study A: Dupilumab | Change From Baseline in Patient Global Impression of Severity (PGIS) of Chronic Spontaneous Urticaria at Weeks 12 and 24 | Week 12 | -1.23 score on a scale | Standard Deviation 0.93 |
| Study A: Dupilumab | Change From Baseline in Patient Global Impression of Severity (PGIS) of Chronic Spontaneous Urticaria at Weeks 12 and 24 | Week 24 | -1.44 score on a scale | Standard Deviation 0.92 |
| Study B: Placebo | Change From Baseline in Patient Global Impression of Severity (PGIS) of Chronic Spontaneous Urticaria at Weeks 12 and 24 | Week 12 | -0.46 score on a scale | Standard Deviation 0.93 |
| Study B: Placebo | Change From Baseline in Patient Global Impression of Severity (PGIS) of Chronic Spontaneous Urticaria at Weeks 12 and 24 | Week 24 | -0.54 score on a scale | Standard Deviation 1.16 |
| Study B: Dupilumab | Change From Baseline in Patient Global Impression of Severity (PGIS) of Chronic Spontaneous Urticaria at Weeks 12 and 24 | Week 12 | -1.15 score on a scale | Standard Deviation 1.04 |
| Study B: Dupilumab | Change From Baseline in Patient Global Impression of Severity (PGIS) of Chronic Spontaneous Urticaria at Weeks 12 and 24 | Week 24 | -0.96 score on a scale | Standard Deviation 1.05 |
| Study C: Placebo | Change From Baseline in Patient Global Impression of Severity (PGIS) of Chronic Spontaneous Urticaria at Weeks 12 and 24 | Week 12 | -0.82 score on a scale | Standard Deviation 0.98 |
| Study C: Placebo | Change From Baseline in Patient Global Impression of Severity (PGIS) of Chronic Spontaneous Urticaria at Weeks 12 and 24 | Week 24 | -1.03 score on a scale | Standard Deviation 1.09 |
| Study C: Dupilumab | Change From Baseline in Patient Global Impression of Severity (PGIS) of Chronic Spontaneous Urticaria at Weeks 12 and 24 | Week 12 | -0.95 score on a scale | Standard Deviation 0.97 |
| Study C: Dupilumab | Change From Baseline in Patient Global Impression of Severity (PGIS) of Chronic Spontaneous Urticaria at Weeks 12 and 24 | Week 24 | -1.33 score on a scale | Standard Deviation 1.05 |
Secondary
Change From Baseline in Urticaria Control Test at Week 12
The UCT assessed urticaria control based on 4 items (severity of pruritus and wheals urticaria symptoms; frequency of treatment being not sufficient; quality-of-life \[QoL\] impairment; overall urticarial control). Each item was rated on a 5-point Likert-type scale from 0 (no control) to 4 (maximum control). The overall UCT score was the sum of all 4 individual item scores with a range of 0 (no disease control) to 16 (complete disease control). Higher scores indicated greater disease control. LS mean is presented. Baseline was defined as the last available value up to randomization date and prior to the first dose of study intervention.
Time frame: Baseline (Day 1) and Week 12
Population: The ITT population included all randomized participants analyzed according to the intervention group allocated by randomization.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Study A: Placebo | Change From Baseline in Urticaria Control Test at Week 12 | 4.62 score on a scale | Standard Error 0.57 |
| Study A: Dupilumab | Change From Baseline in Urticaria Control Test at Week 12 | 6.48 score on a scale | Standard Error 0.57 |
| Study B: Placebo | Change From Baseline in Urticaria Control Test at Week 12 | 3.11 score on a scale | Standard Error 0.65 |
| Study B: Dupilumab | Change From Baseline in Urticaria Control Test at Week 12 | 5.48 score on a scale | Standard Error 0.67 |
| Study C: Placebo | Change From Baseline in Urticaria Control Test at Week 12 | 3.26 score on a scale | Standard Error 0.88 |
| Study C: Dupilumab | Change From Baseline in Urticaria Control Test at Week 12 | 4.61 score on a scale | Standard Error 0.89 |
Secondary
Change From Baseline in Urticaria Control Test (UCT) at Week 24
The UCT assessed urticaria control based on 4 items (severity of pruritus and wheals urticaria symptoms; frequency of treatment being not sufficient; quality-of-life \[QoL\] impairment; overall urticarial control). Each item was rated on a 5-point Likert-type scale from 0 (no control) to 4 (maximum control). The overall UCT score was the sum of all 4 individual item scores with a range of 0 (no disease control) to 16 (complete disease control). Higher scores indicated greater disease control. LS mean is presented. Baseline was defined as the last available value up to randomization date and prior to the first dose of study intervention.
Time frame: Baseline (Day 1) and Week 24
Population: The ITT population included all randomized participants analyzed according to the intervention group allocated by randomization.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Study A: Placebo | Change From Baseline in Urticaria Control Test (UCT) at Week 24 | 4.88 score on a scale | Standard Error 0.61 |
| Study A: Dupilumab | Change From Baseline in Urticaria Control Test (UCT) at Week 24 | 7.71 score on a scale | Standard Error 0.59 |
| Study B: Placebo | Change From Baseline in Urticaria Control Test (UCT) at Week 24 | 3.38 score on a scale | Standard Error 0.74 |
| Study B: Dupilumab | Change From Baseline in Urticaria Control Test (UCT) at Week 24 | 5.33 score on a scale | Standard Error 0.77 |
| Study C: Placebo | Change From Baseline in Urticaria Control Test (UCT) at Week 24 | 4.16 score on a scale | Standard Error 0.94 |
| Study C: Dupilumab | Change From Baseline in Urticaria Control Test (UCT) at Week 24 | 5.09 score on a scale | Standard Error 0.95 |
Comparison: Analyzed by fitting an ANCOVA model with the corresponding baseline value, intervention group, presence of angioedema at baseline, and regions as covariates.p-value: 0.19495% CI: [-0.48, 2.34]ANCOVA
Secondary
Change From Baseline in Weekly Hives Severity Score at Week 12
Daily HSS was recorded in e-diary. The HSS7 score is the sum of daily HSS ranging from 0 (none) to 3 (more than 50 hives) recorded by a participant at the same time of each day over 7 days with an overall scale of 0 (no hives) to 21 (severe hives). Higher scores indicate greater intensity of hives. LS mean is presented. Baseline was defined as the sum of the daily scores for the 7 days prior to the day of randomization.
Time frame: Baseline (Day 1) and Week 12
Population: The ITT population included all randomized participants analyzed according to the intervention group allocated by randomization.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Study A: Placebo | Change From Baseline in Weekly Hives Severity Score at Week 12 | -5.69 score on a scale | Standard Error 0.83 |
| Study A: Dupilumab | Change From Baseline in Weekly Hives Severity Score at Week 12 | -8.39 score on a scale | Standard Error 0.83 |
| Study B: Placebo | Change From Baseline in Weekly Hives Severity Score at Week 12 | -3.71 score on a scale | Standard Error 1.01 |
| Study B: Dupilumab | Change From Baseline in Weekly Hives Severity Score at Week 12 | -5.97 score on a scale | Standard Error 1.02 |
| Study C: Placebo | Change From Baseline in Weekly Hives Severity Score at Week 12 | -4.22 score on a scale | Standard Error 1.28 |
| Study C: Dupilumab | Change From Baseline in Weekly Hives Severity Score at Week 12 | -5.75 score on a scale | Standard Error 1.28 |
Secondary
Change From Baseline in Weekly Hives Severity Score at Week 24
Daily HSS was recorded in e-diary. The HSS7 score is the sum of daily HSS ranging from 0 (none) to 3 (more than 50 hives) recorded by a participant at the same time of each day over 7 days with an overall scale of 0 (no hives) to 21 (severe hives). Higher scores indicate greater intensity of hives. LS mean is presented. Baseline was defined as the sum of the daily scores for the 7 days prior to the day of randomization.
Time frame: Baseline (Day 1) and Week 24
Population: The ITT population included all randomized participants analyzed according to the intervention group allocated by randomization.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Study A: Placebo | Change From Baseline in Weekly Hives Severity Score at Week 24 | -5.90 score on a scale | Standard Error 0.93 |
| Study A: Dupilumab | Change From Baseline in Weekly Hives Severity Score at Week 24 | -10.28 score on a scale | Standard Error 0.91 |
| Study B: Placebo | Change From Baseline in Weekly Hives Severity Score at Week 24 | -3.63 score on a scale | Standard Error 1.11 |
| Study B: Dupilumab | Change From Baseline in Weekly Hives Severity Score at Week 24 | -6.64 score on a scale | Standard Error 1.11 |
| Study C: Placebo | Change From Baseline in Weekly Hives Severity Score at Week 24 | -5.11 score on a scale | Standard Error 1.31 |
| Study C: Dupilumab | Change From Baseline in Weekly Hives Severity Score at Week 24 | -7.27 score on a scale | Standard Error 1.32 |
Comparison: Analyzed by fitting an ANCOVA model with the corresponding baseline value, intervention group, presence of angioedema at baseline, and regions as covariates.p-value: 0.000395% CI: [-6.78, -1.98]ANCOVA
Comparison: Analyzed by fitting an ANCOVA model with the corresponding baseline value, intervention group, presence of angioedema at baseline, and regions as covariates.p-value: 0.031695% CI: [-4.15, -0.19]ANCOVA
Secondary
Change From Baseline in Weekly Itch Severity Score at Week 12
ISS was recorded in e-diary. The ISS represents severity of itch on a scale ranging from 0 (none) to 3 (intense). The ISS7 score was the sum of daily ISS scores recorded by a participant at the same time each day over 7 days with an overall scale of 0 (no impact) to 21 (severe impact). Higher scores indicated greater intensity of itch. LS mean is presented. Baseline was defined as the sum of daily scores obtained for 7 days prior to randomization.
Time frame: Baseline (Day 1) and Week 12
Population: The ITT population included all randomized participants analyzed according to the intervention group allocated by randomization.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Study A: Placebo | Change From Baseline in Weekly Itch Severity Score at Week 12 | -6.01 score on a scale | Standard Error 0.85 |
| Study A: Dupilumab | Change From Baseline in Weekly Itch Severity Score at Week 12 | -8.37 score on a scale | Standard Error 0.84 |
| Study B: Placebo | Change From Baseline in Weekly Itch Severity Score at Week 12 | -4.52 score on a scale | Standard Error 0.95 |
| Study B: Dupilumab | Change From Baseline in Weekly Itch Severity Score at Week 12 | -7.37 score on a scale | Standard Error 0.97 |
| Study C: Placebo | Change From Baseline in Weekly Itch Severity Score at Week 12 | -5.31 score on a scale | Standard Error 1.32 |
| Study C: Dupilumab | Change From Baseline in Weekly Itch Severity Score at Week 12 | -7.15 score on a scale | Standard Error 1.32 |
Comparison: Analyzed by fitting an ANCOVA model with the corresponding baseline value, intervention group, presence of angioedema at baseline, and regions as covariates.p-value: 0.037795% CI: [-4.6, -0.13]ANCOVA
Secondary
Change From Baseline in Weekly Itch Severity Score at Weeks 4, 8, 16 and 20
ISS was recorded in e-diary. The ISS represents severity of itch on a scale ranging from 0 (none) to 3 (intense). The ISS7 score was the sum of daily ISS scores recorded by a participant at the same time each day over 7 days with an overall scale of 0 (no impact) to 21 (severe impact). Higher scores indicated greater intensity of itch. Mean is presented. Baseline was defined as the sum of daily scores obtained for 7 days prior to randomization.
Time frame: Baseline (Day 1) and Weeks 4, 8, 16 and 20
Population: The ITT population included all randomized participants analyzed according to the intervention group allocated by randomization. Only those participants with data collected at specified timepoints are reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Study A: Placebo | Change From Baseline in Weekly Itch Severity Score at Weeks 4, 8, 16 and 20 | Week 4 | -3.30 score on a scale | Standard Deviation 6.54 |
| Study A: Placebo | Change From Baseline in Weekly Itch Severity Score at Weeks 4, 8, 16 and 20 | Week 8 | -4.98 score on a scale | Standard Deviation 7.49 |
| Study A: Placebo | Change From Baseline in Weekly Itch Severity Score at Weeks 4, 8, 16 and 20 | Week 16 | -5.61 score on a scale | Standard Deviation 7.45 |
| Study A: Placebo | Change From Baseline in Weekly Itch Severity Score at Weeks 4, 8, 16 and 20 | Week 20 | -6.40 score on a scale | Standard Deviation 7.82 |
| Study A: Dupilumab | Change From Baseline in Weekly Itch Severity Score at Weeks 4, 8, 16 and 20 | Week 20 | -10.04 score on a scale | Standard Deviation 7.22 |
| Study A: Dupilumab | Change From Baseline in Weekly Itch Severity Score at Weeks 4, 8, 16 and 20 | Week 4 | -4.96 score on a scale | Standard Deviation 5.49 |
| Study A: Dupilumab | Change From Baseline in Weekly Itch Severity Score at Weeks 4, 8, 16 and 20 | Week 8 | -6.99 score on a scale | Standard Deviation 6.78 |
| Study A: Dupilumab | Change From Baseline in Weekly Itch Severity Score at Weeks 4, 8, 16 and 20 | Week 16 | -9.43 score on a scale | Standard Deviation 6.86 |
| Study B: Placebo | Change From Baseline in Weekly Itch Severity Score at Weeks 4, 8, 16 and 20 | Week 20 | -5.35 score on a scale | Standard Deviation 7.17 |
| Study B: Placebo | Change From Baseline in Weekly Itch Severity Score at Weeks 4, 8, 16 and 20 | Week 4 | -4.12 score on a scale | Standard Deviation 6.28 |
| Study B: Placebo | Change From Baseline in Weekly Itch Severity Score at Weeks 4, 8, 16 and 20 | Week 8 | -4.27 score on a scale | Standard Deviation 5.92 |
| Study B: Placebo | Change From Baseline in Weekly Itch Severity Score at Weeks 4, 8, 16 and 20 | Week 16 | -4.52 score on a scale | Standard Deviation 6.68 |
| Study B: Dupilumab | Change From Baseline in Weekly Itch Severity Score at Weeks 4, 8, 16 and 20 | Week 4 | -5.51 score on a scale | Standard Deviation 5.64 |
| Study B: Dupilumab | Change From Baseline in Weekly Itch Severity Score at Weeks 4, 8, 16 and 20 | Week 8 | -7.25 score on a scale | Standard Deviation 6.29 |
| Study B: Dupilumab | Change From Baseline in Weekly Itch Severity Score at Weeks 4, 8, 16 and 20 | Week 20 | -7.54 score on a scale | Standard Deviation 7.94 |
| Study B: Dupilumab | Change From Baseline in Weekly Itch Severity Score at Weeks 4, 8, 16 and 20 | Week 16 | -8.05 score on a scale | Standard Deviation 7.43 |
| Study C: Placebo | Change From Baseline in Weekly Itch Severity Score at Weeks 4, 8, 16 and 20 | Week 16 | -6.22 score on a scale | Standard Deviation 5.78 |
| Study C: Placebo | Change From Baseline in Weekly Itch Severity Score at Weeks 4, 8, 16 and 20 | Week 20 | -6.64 score on a scale | Standard Deviation 6.43 |
| Study C: Placebo | Change From Baseline in Weekly Itch Severity Score at Weeks 4, 8, 16 and 20 | Week 4 | -3.78 score on a scale | Standard Deviation 4.73 |
| Study C: Placebo | Change From Baseline in Weekly Itch Severity Score at Weeks 4, 8, 16 and 20 | Week 8 | -4.92 score on a scale | Standard Deviation 5.67 |
| Study C: Dupilumab | Change From Baseline in Weekly Itch Severity Score at Weeks 4, 8, 16 and 20 | Week 20 | -9.27 score on a scale | Standard Deviation 6.58 |
| Study C: Dupilumab | Change From Baseline in Weekly Itch Severity Score at Weeks 4, 8, 16 and 20 | Week 4 | -5.26 score on a scale | Standard Deviation 5.16 |
| Study C: Dupilumab | Change From Baseline in Weekly Itch Severity Score at Weeks 4, 8, 16 and 20 | Week 8 | -7.83 score on a scale | Standard Deviation 6.02 |
| Study C: Dupilumab | Change From Baseline in Weekly Itch Severity Score at Weeks 4, 8, 16 and 20 | Week 16 | -8.24 score on a scale | Standard Deviation 7.37 |
Secondary
Change From Baseline in Weekly Urticaria Activity Score at Week 12
UAS is a validated composite PRO measure for assessing CSU activity. The once daily UAS is the sum of the daily HSS and daily ISS recorded in e-diary. Daily HSS assesses number of wheals and range from 0 (none) to 3 (more than 50 hives) whereas daily ISS assesses itch intensity and range from 0 (none) to 3 (intense). The daily UAS scores range from 0 to 6 point/day. Once daily UAS scores are summed over 7-day period to create the UAS7 with an overall scale of 0 (no urticaria) to 42 (severe urticaria). Higher scores indicate greater severity of urticaria symptoms. LS mean is presented. Baseline was defined as the sum of the daily scores for the 7 days prior to the day of randomization.
Time frame: Baseline (Day 1) and Week 12
Population: The ITT population included all randomized participants analyzed according to the intervention group allocated by randomization.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Study A: Placebo | Change From Baseline in Weekly Urticaria Activity Score at Week 12 | -11.79 score on a scale | Standard Error 1.64 |
| Study A: Dupilumab | Change From Baseline in Weekly Urticaria Activity Score at Week 12 | -16.81 score on a scale | Standard Error 1.62 |
| Study B: Placebo | Change From Baseline in Weekly Urticaria Activity Score at Week 12 | -8.22 score on a scale | Standard Error 1.91 |
| Study B: Dupilumab | Change From Baseline in Weekly Urticaria Activity Score at Week 12 | -13.33 score on a scale | Standard Error 1.94 |
| Study C: Placebo | Change From Baseline in Weekly Urticaria Activity Score at Week 12 | -9.51 score on a scale | Standard Error 2.54 |
| Study C: Dupilumab | Change From Baseline in Weekly Urticaria Activity Score at Week 12 | -12.87 score on a scale | Standard Error 2.54 |
Comparison: Analyzed by fitting an ANCOVA model with the corresponding baseline value, intervention group, presence of angioedema at baseline, and regions as covariates.p-value: 0.022395% CI: [-9.32, -0.72]ANCOVA
Secondary
Change From Baseline in Weekly Urticaria Activity Score at Week 24
UAS is a validated composite patient-reported outcome (PRO) measure for assessing chronic spontaneous urticaria (CSU) activity. The once daily UAS is the sum of the daily hives severity score (HSS) and daily ISS recorded in e-diary. Daily HSS assesses number of wheals and range from 0 (none) to 3 (more than 50 hives) whereas daily ISS assesses itch intensity and range from 0 (none) to 3 (intense). The daily UAS scores range from 0 to 6 point/day. Once daily UAS scores are summed over 7-day period to create the UAS7 with an overall scale of 0 (no urticaria) to 42 (severe urticaria). Higher scores indicate greater severity of urticaria symptoms. LS mean is presented. Baseline was defined as the sum of the daily scores for the 7 days prior to the day of randomization.
Time frame: Baseline (Day 1) and Week 24
Population: The ITT population included all randomized participants analyzed according to the intervention group allocated by randomization.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Study A: Placebo | Change From Baseline in Weekly Urticaria Activity Score at Week 24 | -12.00 score on a scale | Standard Error 1.81 |
| Study A: Dupilumab | Change From Baseline in Weekly Urticaria Activity Score at Week 24 | -20.53 score on a scale | Standard Error 1.76 |
| Study B: Placebo | Change From Baseline in Weekly Urticaria Activity Score at Week 24 | -8.54 score on a scale | Standard Error 2.14 |
| Study B: Dupilumab | Change From Baseline in Weekly Urticaria Activity Score at Week 24 | -14.37 score on a scale | Standard Error 2.16 |
| Study C: Placebo | Change From Baseline in Weekly Urticaria Activity Score at Week 24 | -11.21 score on a scale | Standard Error 2.65 |
| Study C: Dupilumab | Change From Baseline in Weekly Urticaria Activity Score at Week 24 | -15.86 score on a scale | Standard Error 2.66 |
Comparison: Analyzed by fitting an ANCOVA model with the corresponding baseline value, intervention group, presence of angioedema at baseline, and regions as covariates.p-value: 0.000395% CI: [-13.16, -3.9]ANCOVA
Comparison: Analyzed by fitting an ANCOVA model with the corresponding baseline value, intervention group, presence of angioedema at baseline, and regions as covariates.p-value: 0.022695% CI: [-8.65, -0.65]ANCOVA
Secondary
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
An AE was any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. SAE was any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability/incapacity, was a congenital anomaly/birth defect or was an important medical event. TEAEs were defined as AEs that developed, worsened or became serious during the TE period.
Time frame: From first dose of study intervention (Day 1) up to end of follow-up, approximately 36 weeks each for Study A, B and C
Population: The safety population included all participants randomly assigned to study intervention and who took at least 1 dose of study intervention. As pre-specified in the protocol and SAP, the results are presented by study and treatment group/intervention.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Study A: Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | TEAEs | 40 Participants |
| Study A: Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | TESAEs | 5 Participants |
| Study A: Dupilumab | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | TEAEs | 38 Participants |
| Study A: Dupilumab | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | TESAEs | 2 Participants |
| Study B: Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | TEAEs | 29 Participants |
| Study B: Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | TESAEs | 2 Participants |
| Study B: Dupilumab | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | TEAEs | 33 Participants |
| Study B: Dupilumab | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | TESAEs | 3 Participants |
| Study C: Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | TEAEs | 41 Participants |
| Study C: Placebo | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | TESAEs | 1 Participants |
| Study C: Dupilumab | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | TESAEs | 5 Participants |
| Study C: Dupilumab | Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | TEAEs | 40 Participants |
Secondary
Number of Participants With Treatment-emergent Anti-drug Antibodies (ADA) Against Dupilumab
Blood samples were collected at specified timepoints and ADA samples were assayed using validated methods. Treatment-emergent ADA response was defined as a positive response in the ADA assay post first dose when baseline results were negative or missing. Number of participants with treatment-emergent ADA response is presented.
Time frame: Up to Week 24
Population: The ADA population included all participants in the safety population who had at least 1 non-missing ADA result after first dose of the study intervention.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Study A: Placebo | Number of Participants With Treatment-emergent Anti-drug Antibodies (ADA) Against Dupilumab | 1 Participants |
| Study A: Dupilumab | Number of Participants With Treatment-emergent Anti-drug Antibodies (ADA) Against Dupilumab | 9 Participants |
| Study B: Placebo | Number of Participants With Treatment-emergent Anti-drug Antibodies (ADA) Against Dupilumab | 2 Participants |
| Study B: Dupilumab | Number of Participants With Treatment-emergent Anti-drug Antibodies (ADA) Against Dupilumab | 10 Participants |
| Study C: Placebo | Number of Participants With Treatment-emergent Anti-drug Antibodies (ADA) Against Dupilumab | 0 Participants |
| Study C: Dupilumab | Number of Participants With Treatment-emergent Anti-drug Antibodies (ADA) Against Dupilumab | 1 Participants |
Secondary
Patient Global Impression of Change (PGIC) of Chronic Spontaneous Urticaria at Weeks 12 and 24
The PGIC is a 1-item questionnaire that asks the participant to provide the overall self-assessment of change in their CSU on a 7-point scale compared to just before participant started taking the study intervention. Response choices are: 0 (very much better), 1 (moderately better), 2 (a little better), 3 (no change), 4 (a little worse), 5 (moderately worse), 6 (very much worse). Higher score indicate worsening.
Time frame: Weeks 12 and 24
Population: The ITT population included all randomized participants analyzed according to the intervention group allocated by randomization. Only those participants with data collected at Weeks 12 and 24 are reported.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Study A: Placebo | Patient Global Impression of Change (PGIC) of Chronic Spontaneous Urticaria at Weeks 12 and 24 | Week 12 | 1.68 score on a scale | Standard Deviation 1.43 |
| Study A: Placebo | Patient Global Impression of Change (PGIC) of Chronic Spontaneous Urticaria at Weeks 12 and 24 | Week 24 | 1.70 score on a scale | Standard Deviation 1.5 |
| Study A: Dupilumab | Patient Global Impression of Change (PGIC) of Chronic Spontaneous Urticaria at Weeks 12 and 24 | Week 12 | 1.10 score on a scale | Standard Deviation 1.24 |
| Study A: Dupilumab | Patient Global Impression of Change (PGIC) of Chronic Spontaneous Urticaria at Weeks 12 and 24 | Week 24 | 1.04 score on a scale | Standard Deviation 1.51 |
| Study B: Placebo | Patient Global Impression of Change (PGIC) of Chronic Spontaneous Urticaria at Weeks 12 and 24 | Week 12 | 2.06 score on a scale | Standard Deviation 1.29 |
| Study B: Placebo | Patient Global Impression of Change (PGIC) of Chronic Spontaneous Urticaria at Weeks 12 and 24 | Week 24 | 1.90 score on a scale | Standard Deviation 1.64 |
| Study B: Dupilumab | Patient Global Impression of Change (PGIC) of Chronic Spontaneous Urticaria at Weeks 12 and 24 | Week 12 | 1.62 score on a scale | Standard Deviation 1.46 |
| Study B: Dupilumab | Patient Global Impression of Change (PGIC) of Chronic Spontaneous Urticaria at Weeks 12 and 24 | Week 24 | 1.44 score on a scale | Standard Deviation 1.55 |
| Study C: Placebo | Patient Global Impression of Change (PGIC) of Chronic Spontaneous Urticaria at Weeks 12 and 24 | Week 12 | 1.59 score on a scale | Standard Deviation 1.23 |
| Study C: Placebo | Patient Global Impression of Change (PGIC) of Chronic Spontaneous Urticaria at Weeks 12 and 24 | Week 24 | 1.18 score on a scale | Standard Deviation 1.36 |
| Study C: Dupilumab | Patient Global Impression of Change (PGIC) of Chronic Spontaneous Urticaria at Weeks 12 and 24 | Week 12 | 1.27 score on a scale | Standard Deviation 1.44 |
| Study C: Dupilumab | Patient Global Impression of Change (PGIC) of Chronic Spontaneous Urticaria at Weeks 12 and 24 | Week 24 | 1.01 score on a scale | Standard Deviation 1.48 |
Secondary
Percentage of Participants Receiving Oral Corticosteroid for Chronic Spontaneous Urticaria During the 24-week Treatment Period
Percentage of participants receiving OCS as rescue medications for CSU were recorded by the Investigator in eCRF during the 24-week treatment period.
Time frame: Baseline (Day 1) up to Week 24
Population: The ITT population included all randomized participants analyzed according to the intervention group allocated by randomization.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Study A: Placebo | Percentage of Participants Receiving Oral Corticosteroid for Chronic Spontaneous Urticaria During the 24-week Treatment Period | 10.3 percentage of participants |
| Study A: Dupilumab | Percentage of Participants Receiving Oral Corticosteroid for Chronic Spontaneous Urticaria During the 24-week Treatment Period | 8.6 percentage of participants |
| Study B: Placebo | Percentage of Participants Receiving Oral Corticosteroid for Chronic Spontaneous Urticaria During the 24-week Treatment Period | 14.8 percentage of participants |
| Study B: Dupilumab | Percentage of Participants Receiving Oral Corticosteroid for Chronic Spontaneous Urticaria During the 24-week Treatment Period | 11.1 percentage of participants |
| Study C: Placebo | Percentage of Participants Receiving Oral Corticosteroid for Chronic Spontaneous Urticaria During the 24-week Treatment Period | 6.5 percentage of participants |
| Study C: Dupilumab | Percentage of Participants Receiving Oral Corticosteroid for Chronic Spontaneous Urticaria During the 24-week Treatment Period | 1.4 percentage of participants |
Secondary
Percentage of Participants With Weekly Urticaria Activity Score =0 at Week 24
UAS is a validated composite PRO measure for assessing CSU activity. The once daily UAS is the sum of the daily HSS and daily ISS recorded in e-diary. Daily HSS assesses number of wheals and range from 0 (none) to 3 (more than 50 hives) whereas daily ISS assesses itch intensity and range from 0 (none) to 3 (intense). The daily UAS scores range from 0 to 6 point/day. Once daily UAS scores are summed over 7-day period to create the UAS7 with an overall scale of 0 (no urticaria) to 42 (severe urticaria). Higher scores indicate greater severity of urticaria symptoms. In evaluating urticaria control using UAS7, an UAS7 score of 0 indicated an absence of both itch and hives and a complete resolution of CSU symptoms.
Time frame: Week 24
Population: The ITT population included all randomized participants analyzed according to the intervention group allocated by randomization.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Study A: Placebo | Percentage of Participants With Weekly Urticaria Activity Score =0 at Week 24 | 13.2 percentage of participants |
| Study A: Dupilumab | Percentage of Participants With Weekly Urticaria Activity Score =0 at Week 24 | 31.4 percentage of participants |
| Study B: Placebo | Percentage of Participants With Weekly Urticaria Activity Score =0 at Week 24 | 9.3 percentage of participants |
| Study B: Dupilumab | Percentage of Participants With Weekly Urticaria Activity Score =0 at Week 24 | 13.0 percentage of participants |
| Study C: Placebo | Percentage of Participants With Weekly Urticaria Activity Score =0 at Week 24 | 18.2 percentage of participants |
| Study C: Dupilumab | Percentage of Participants With Weekly Urticaria Activity Score =0 at Week 24 | 29.7 percentage of participants |
Comparison: CMH test was performed on the association between the responder status and intervention group, adjusted by baseline disease severity (UAS7 \<28, \>=28), presence of angioedema at baseline, and region.p-value: 0.019995% CI: [1.173, 7.209]Cochran-Mantel-Haenszel
Comparison: CMH test was performed on the association between the responder status and intervention group, adjusted by baseline disease severity (UAS7 \<28, \>=28), presence of angioedema at baseline, and region.p-value: 0.018795% CI: [1.127, 6.359]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Weekly Urticaria Activity Score <=6 and =0 at Week 12
UAS is a validated composite PRO measure for assessing CSU activity. The once daily UAS is the sum of the daily HSS and daily ISS recorded in e-diary. Daily HSS assesses number of wheals and range from 0 (none) to 3 (more than 50 hives) whereas daily ISS assesses itch intensity and range from 0 (none) to 3 (intense). The daily UAS scores range from 0 to 6 point/day. Once daily UAS scores are summed over 7-day period to create the UAS7 with an overall scale of 0 (no urticaria) to 42 (severe urticaria). Higher scores indicate greater severity of urticaria symptoms. In evaluating urticaria control using UAS7, an UAS7 score of \<=6 indicated a well-controlled urticaria and an UAS7 score of 0 indicated an absence of both itch and hives and a complete resolution of CSU symptoms.
Time frame: Week 12
Population: The ITT population included all randomized participants analyzed according to the intervention group allocated by randomization.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Study A: Placebo | Percentage of Participants With Weekly Urticaria Activity Score <=6 and =0 at Week 12 | UAS7 <=6 | 17.6 percentage of participants |
| Study A: Placebo | Percentage of Participants With Weekly Urticaria Activity Score <=6 and =0 at Week 12 | UAS7=0 | 8.8 percentage of participants |
| Study A: Dupilumab | Percentage of Participants With Weekly Urticaria Activity Score <=6 and =0 at Week 12 | UAS7 <=6 | 34.3 percentage of participants |
| Study A: Dupilumab | Percentage of Participants With Weekly Urticaria Activity Score <=6 and =0 at Week 12 | UAS7=0 | 15.7 percentage of participants |
| Study B: Placebo | Percentage of Participants With Weekly Urticaria Activity Score <=6 and =0 at Week 12 | UAS7 <=6 | 9.3 percentage of participants |
| Study B: Placebo | Percentage of Participants With Weekly Urticaria Activity Score <=6 and =0 at Week 12 | UAS7=0 | 1.9 percentage of participants |
| Study B: Dupilumab | Percentage of Participants With Weekly Urticaria Activity Score <=6 and =0 at Week 12 | UAS7 <=6 | 24.1 percentage of participants |
| Study B: Dupilumab | Percentage of Participants With Weekly Urticaria Activity Score <=6 and =0 at Week 12 | UAS7=0 | 13.0 percentage of participants |
| Study C: Placebo | Percentage of Participants With Weekly Urticaria Activity Score <=6 and =0 at Week 12 | UAS7 <=6 | 16.9 percentage of participants |
| Study C: Placebo | Percentage of Participants With Weekly Urticaria Activity Score <=6 and =0 at Week 12 | UAS7=0 | 11.7 percentage of participants |
| Study C: Dupilumab | Percentage of Participants With Weekly Urticaria Activity Score <=6 and =0 at Week 12 | UAS7 <=6 | 31.1 percentage of participants |
| Study C: Dupilumab | Percentage of Participants With Weekly Urticaria Activity Score <=6 and =0 at Week 12 | UAS7=0 | 17.6 percentage of participants |
Comparison: CMH test was performed on the association between the responder status and intervention group, adjusted by baseline disease severity (UAS7 \<28, \>=28), presence of angioedema at baseline, and region.p-value: 0.021595% CI: [1.154, 6.061]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With Weekly Urticaria Activity Score <=6 at Week 24
UAS is a validated composite PRO measure for assessing CSU activity. The once daily UAS is the sum of the daily HSS and daily ISS recorded in e-diary. Daily HSS assesses number of wheals and range from 0 (none) to 3 (more than 50 hives) whereas daily ISS assesses itch intensity and range from 0 (none) to 3 (intense). The daily UAS scores range from 0 to 6 point/day. Once daily UAS scores are summed over 7-day period to create the UAS7 with an overall scale of 0 (no urticaria) to 42 (severe urticaria). Higher scores indicate greater severity of urticaria symptoms. In evaluating urticaria control using UAS7, an UAS7 score of \<=6 indicated a well-controlled urticaria.
Time frame: Week 24
Population: The ITT population included all randomized participants analyzed according to the intervention group allocated by randomization.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Study A: Placebo | Percentage of Participants With Weekly Urticaria Activity Score <=6 at Week 24 | 23.5 percentage of participants |
| Study A: Dupilumab | Percentage of Participants With Weekly Urticaria Activity Score <=6 at Week 24 | 45.7 percentage of participants |
| Study B: Placebo | Percentage of Participants With Weekly Urticaria Activity Score <=6 at Week 24 | 18.5 percentage of participants |
| Study B: Dupilumab | Percentage of Participants With Weekly Urticaria Activity Score <=6 at Week 24 | 24.1 percentage of participants |
| Study C: Placebo | Percentage of Participants With Weekly Urticaria Activity Score <=6 at Week 24 | 23.4 percentage of participants |
| Study C: Dupilumab | Percentage of Participants With Weekly Urticaria Activity Score <=6 at Week 24 | 40.5 percentage of participants |
Comparison: CMH test was performed on the association between the responder status and intervention group, adjusted by baseline disease severity (UAS7 \<28, \>=28), presence of angioedema at baseline, and region.p-value: 0.007595% CI: [1.301, 6.234]Cochran-Mantel-Haenszel
Comparison: CMH test was performed on the association between the responder status and intervention group, adjusted by baseline disease severity (UAS7 \<28, \>=28), presence of angioedema at baseline, and region.p-value: 0.004595% CI: [1.371, 7.176]Cochran-Mantel-Haenszel
Secondary
Percentage of Responders for Weekly Itch Severity Score Minimally Important Difference at Week 12
The ISS represents severity of itch on a scale ranging from 0 (none) to 3 (intense). The ISS7 score was the sum of daily ISS scores recorded by a participant at the same time each day over 7 days with an overall scale of 0 (no impact) to 21 (severe impact). Higher scores indicated greater intensity of itch. An ISS7 MID response was defined as \>=5 points decrease from baseline after study intervention.
Time frame: Week 12
Population: The ITT population included all randomized participants analyzed according to the intervention group allocated by randomization.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Study A: Placebo | Percentage of Responders for Weekly Itch Severity Score Minimally Important Difference at Week 12 | 52.9 percentage of participants |
| Study A: Dupilumab | Percentage of Responders for Weekly Itch Severity Score Minimally Important Difference at Week 12 | 70.0 percentage of participants |
| Study B: Placebo | Percentage of Responders for Weekly Itch Severity Score Minimally Important Difference at Week 12 | 46.3 percentage of participants |
| Study B: Dupilumab | Percentage of Responders for Weekly Itch Severity Score Minimally Important Difference at Week 12 | 64.8 percentage of participants |
| Study C: Placebo | Percentage of Responders for Weekly Itch Severity Score Minimally Important Difference at Week 12 | 51.9 percentage of participants |
| Study C: Dupilumab | Percentage of Responders for Weekly Itch Severity Score Minimally Important Difference at Week 12 | 58.1 percentage of participants |
Comparison: CMH test was performed on the association between the responder status and intervention group, adjusted by baseline disease severity (UAS7 \<28, \>=28), presence of angioedema at baseline, and region.p-value: 0.097195% CI: [0.893, 3.923]Cochran-Mantel-Haenszel
Secondary
Percentage of Responders for Weekly Itch Severity Score Minimally Important Difference (MID) at Week 24
The ISS represents severity of itch on a scale ranging from 0 (none) to 3 (intense). The ISS7 score was the sum of daily ISS scores recorded by a participant at the same time each day over 7 days with an overall scale of 0 (no impact) to 21 (severe impact). Higher scores indicated greater intensity of itch. An ISS7 MID response was defined as \>=5 points decrease from baseline after study intervention.
Time frame: Week 24
Population: The ITT population included all randomized participants analyzed according to the intervention group allocated by randomization.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Study A: Placebo | Percentage of Responders for Weekly Itch Severity Score Minimally Important Difference (MID) at Week 24 | 42.6 percentage of participants |
| Study A: Dupilumab | Percentage of Responders for Weekly Itch Severity Score Minimally Important Difference (MID) at Week 24 | 72.9 percentage of participants |
| Study B: Placebo | Percentage of Responders for Weekly Itch Severity Score Minimally Important Difference (MID) at Week 24 | 38.9 percentage of participants |
| Study B: Dupilumab | Percentage of Responders for Weekly Itch Severity Score Minimally Important Difference (MID) at Week 24 | 59.3 percentage of participants |
| Study C: Placebo | Percentage of Responders for Weekly Itch Severity Score Minimally Important Difference (MID) at Week 24 | 51.9 percentage of participants |
| Study C: Dupilumab | Percentage of Responders for Weekly Itch Severity Score Minimally Important Difference (MID) at Week 24 | 70.3 percentage of participants |
Comparison: Cochran-Mantel-Haenszel (CMH) test was performed on association between responder status and intervention group, adjusted by baseline disease severity (UAS7\<28,\>=28), presence of angioedema at baseline and region.p-value: 0.001495% CI: [1.596, 7.299]Cochran-Mantel-Haenszel
Comparison: CMH test was performed on the association between the responder status and intervention group, adjusted by baseline disease severity (UAS7 \<28, \>=28), presence of angioedema at baseline, and region.p-value: 0.010995% CI: [1.231, 5.107]Cochran-Mantel-Haenszel
Secondary
Percentage of Well-controlled Participants (Urticaria Control Test >=12) at Weeks 12 and 24
The UCT assessed urticaria control based on 4 items (severity of pruritus and wheals urticaria symptoms; frequency of treatment being not sufficient; QoL impairment; overall urticarial control). Each item was rated on a 5-point Likert-type scale from 0 (no control) to 4 (maximum control). The overall UCT score was the sum of all 4 individual item scores with a range of 0 (no disease control) to 16 (complete disease control). Higher scores indicated greater disease control. An UCT score of \>=12 (out of maximum 16) indicated a well-controlled urticaria disease status.
Time frame: Weeks 12 and 24
Population: The ITT population included all randomized participants analyzed according to the intervention group allocated by randomization.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Study A: Placebo | Percentage of Well-controlled Participants (Urticaria Control Test >=12) at Weeks 12 and 24 | Week 12 | 27.9 percentage of participants |
| Study A: Placebo | Percentage of Well-controlled Participants (Urticaria Control Test >=12) at Weeks 12 and 24 | Week 24 | 30.9 percentage of participants |
| Study A: Dupilumab | Percentage of Well-controlled Participants (Urticaria Control Test >=12) at Weeks 12 and 24 | Week 12 | 44.3 percentage of participants |
| Study A: Dupilumab | Percentage of Well-controlled Participants (Urticaria Control Test >=12) at Weeks 12 and 24 | Week 24 | 48.6 percentage of participants |
| Study B: Placebo | Percentage of Well-controlled Participants (Urticaria Control Test >=12) at Weeks 12 and 24 | Week 12 | 18.5 percentage of participants |
| Study B: Placebo | Percentage of Well-controlled Participants (Urticaria Control Test >=12) at Weeks 12 and 24 | Week 24 | 20.4 percentage of participants |
| Study B: Dupilumab | Percentage of Well-controlled Participants (Urticaria Control Test >=12) at Weeks 12 and 24 | Week 24 | 44.4 percentage of participants |
| Study B: Dupilumab | Percentage of Well-controlled Participants (Urticaria Control Test >=12) at Weeks 12 and 24 | Week 12 | 51.9 percentage of participants |
| Study C: Placebo | Percentage of Well-controlled Participants (Urticaria Control Test >=12) at Weeks 12 and 24 | Week 12 | 22.1 percentage of participants |
| Study C: Placebo | Percentage of Well-controlled Participants (Urticaria Control Test >=12) at Weeks 12 and 24 | Week 24 | 39.0 percentage of participants |
| Study C: Dupilumab | Percentage of Well-controlled Participants (Urticaria Control Test >=12) at Weeks 12 and 24 | Week 12 | 37.8 percentage of participants |
| Study C: Dupilumab | Percentage of Well-controlled Participants (Urticaria Control Test >=12) at Weeks 12 and 24 | Week 24 | 50.0 percentage of participants |
Secondary
Time to First Oral Corticosteroid (OCS) Use for Chronic Spontaneous Urticaria During the 24-week Treatment Period
Participants receiving OCS as rescue medications for CSU were recorded by the Investigator in e-case report form (eCRF) during the 24-week treatment period. Kaplan-Meier estimate for time to first OCS use is presented.
Time frame: Baseline (Day 1) up to Week 24
Population: The ITT population included all randomized participants analyzed according to the intervention group allocated by randomization.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Study A: Placebo | Time to First Oral Corticosteroid (OCS) Use for Chronic Spontaneous Urticaria During the 24-week Treatment Period | 0.110 weeks |
| Study A: Dupilumab | Time to First Oral Corticosteroid (OCS) Use for Chronic Spontaneous Urticaria During the 24-week Treatment Period | 0.087 weeks |
| Study B: Placebo | Time to First Oral Corticosteroid (OCS) Use for Chronic Spontaneous Urticaria During the 24-week Treatment Period | 0.158 weeks |
| Study B: Dupilumab | Time to First Oral Corticosteroid (OCS) Use for Chronic Spontaneous Urticaria During the 24-week Treatment Period | 0.116 weeks |
| Study C: Placebo | Time to First Oral Corticosteroid (OCS) Use for Chronic Spontaneous Urticaria During the 24-week Treatment Period | 0.067 weeks |
| Study C: Dupilumab | Time to First Oral Corticosteroid (OCS) Use for Chronic Spontaneous Urticaria During the 24-week Treatment Period | 0.014 weeks |
Secondary
Time to First Weekly Itch Severity Score Minimally Important Difference Response During the 24-Week Treatment Period
The ISS represents severity of itch on a scale ranging from 0 (none) to 3 (intense). The ISS7 score was the sum of daily ISS scores recorded by a participant at the same time each day over 7 days with an overall scale of 0 (no impact) to 21 (severe impact). Higher scores indicated greater intensity of itch. The MID for ISS7 was a change of 5.0 points. Time to first ISS7 MID response (ISS7 \>=5) was defined as time to reduction from baseline of 5 points or more. Kaplan-Meier estimate is presented. Baseline was defined as the sum of daily scores obtained for 7 days prior to randomization.
Time frame: Baseline (Day 1) up to Week 24
Population: The ITT population included all randomized participants analyzed according to the intervention group allocated by randomization.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Study A: Placebo | Time to First Weekly Itch Severity Score Minimally Important Difference Response During the 24-Week Treatment Period | 4.0 weeks |
| Study A: Dupilumab | Time to First Weekly Itch Severity Score Minimally Important Difference Response During the 24-Week Treatment Period | 3.0 weeks |
| Study B: Placebo | Time to First Weekly Itch Severity Score Minimally Important Difference Response During the 24-Week Treatment Period | 4.0 weeks |
| Study B: Dupilumab | Time to First Weekly Itch Severity Score Minimally Important Difference Response During the 24-Week Treatment Period | 3.0 weeks |
| Study C: Placebo | Time to First Weekly Itch Severity Score Minimally Important Difference Response During the 24-Week Treatment Period | 5.0 weeks |
| Study C: Dupilumab | Time to First Weekly Itch Severity Score Minimally Important Difference Response During the 24-Week Treatment Period | 3.5 weeks |