Atopic Dermatitis
Conditions
Brief summary
Primary objective: To demonstrate that tralokinumab in combination with topical corticosteroids (TCS) is superior to placebo in combination with TCS in treating severe AD in subjects who are not adequately controlled with or have contraindications to oral cyclosporine A (CSA). Secondary objectives: To evaluate the efficacy of tralokinumab in combination with TCS on severity and extent of AD, itch, and health-related quality of life compared to placebo in combination with TCS. To evaluate the safety of tralokinumab in combination with TCS when treating severe AD in subjects who are not adequately controlled with or have contraindications to oral CSA compared to placebo in combination with TCS.
Interventions
DRUGTralokinumab
Tralokinumab is a human recombinant monoclonal antibody of the IgG4 subclass that specifically binds to human IL-13 and blocks interaction with the IL-13 receptors. It is presented as a liquid formulation for subcutaneous (SC) administration.
OTHERPlacebo
Placebo contains the same excipients in the same concentration only lacking tralokinumab.
Sponsors
LEO Pharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Age 18 and above * Diagnosis of AD as defined by the Hanifin and Rajka (1980) criteria for AD * History of AD for 1 year or more * Subjects with a history within 1 year prior to screening of inadequate response to treatment with topical medications or subjects for whom topical treatments are otherwise medically inadvisable * AD involvement of 10% (or more) body surface area at screening and baseline (visit 3) according to component A of SCORAD * Documented history of either no previous CSA exposure and not currently a candidate for CSA treatment OR previous exposure to CSA in which case CSA treatment should not be continued or restarted * Subjects must have applied a stable dose of emollient twice daily (or more, as needed) for at least 14 days before randomisation Key
Exclusion criteria
* Subjects for whom TCSs are medically inadvisable in the opinion of the investigator * Use of tanning beds or phototherapy (NBUVB, UVB, UVA1, PUVA), within 6 weeks prior to randomisation * Treatment with immunomodulatory medications or bleach baths within 4 weeks prior to randomisation * Treatment with topical phosphodiesterase-4 (PDE-4) inhibitor within 2 weeks prior to randomisation * Receipt of any marketed or investigational biologic agent (e.g. cell-depleting agents or dupilumab) within 6 months prior to randomisation or until cell counts return to normal, whichever is longer * History of any active skin infection within 1 week prior to randomisation * History of a clinically significant infection (systemic infection or serious skin infection requiring parenteral treatment) within 4 weeks prior to randomisation * A helminth parasitic infection within 6 months prior to the date informed consent is obtained that has not been treated with, or has failed to respond to, standard of care therapy * Tuberculosis requiring treatment within the 12 months prior to screening. Evaluation will be according to local guidelines as per local standard of care * History of any known primary immunodeficiency disorder including a positive HIV test at screening, or the subject taking antiretroviral medications
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| At Least 75% Reduction in Eczema Area and Severity Index (EASI75) From Week 0 to Week 16 | Week 0 to Week 16 | EASI (Eczema Area and Severity Index) is a validated measure used in clinical practice and clinical trials to assess the severity and extent of AD. The EASI is a composite index with scores ranging from 0 to 72, with higher values indicating more severe and/or more extensive condition. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Scoring Atopic Dermatitis (SCORAD) From Week 0 to Week 16 | Week 0 to Week 16 | SCORAD is a validated tool to evaluate the extent and severity of AD lesions, along with subjective symptoms. The maximum total score is 103, with higher values indicating more severe disease. |
| Change in Dermatology Life Quality Index (DLQI) Score From Week 0 to Week 16 | Week 0 to Week 16 | DLQI is a validated questionnaire with content specific to those with dermatology conditions. It consists of 10 items addressing the subject's perception of the impact of their skin disease on different aspects of their health-related quality of life (HRQoL) over the last week such as dermatology-related symptoms and feelings, daily activities, leisure, work or school, personal relationships, and the treatment. Each item is scored on a 4-point Likert scale (0 = not at all ∕not relevant; 1 = a little; 2 = a lot; 3 = very much). The total score is the sum of the 10 items (0 to 30); a high score is indicative of a poor HRQoL. |
| Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Week 16 | Week 16 | IGA is an instrument used in clinical trials to rate the severity of the subject's global AD and is based on a 5-point scale ranging from 0 (clear) to 4 (severe). |
| At Least 75% Reduction in Eczema Area and Severity Index (EASI75) From Week 0 to Week 26 | Week 0 to Week 26 | EASI (Eczema Area and Severity Index) is a validated measure used in clinical practice and clinical trials to assess the severity and extent of AD. The EASI is a composite index with scores ranging from 0 to 72, with higher values indicating more severe and/or more extensive condition. |
| Reduction of Worst Daily Pruritus Numeric Rating Scale (NRS) (Weekly Average) of at Least 4 From Week 0 to Week 26 | Week 0 to Week 26 | Subjects will assess their worst itch severity over the past 24 hours using an 11-point numeric rating scale ('Worst Daily Pruritus NRS') with 0 indicating 'no itch' and 10 indicating 'worst itch imaginable'. |
| Reduction of Worst Daily Pruritus Numeric Rating Scale (NRS) (Weekly Average) of at Least 4 From Week 0 to Week 16 | Week 0 to Week 16 | Subjects will assess their worst itch severity over the past 24 hours using an 11-point NRS ('Worst Daily Pruritus NRS') with 0 indicating 'no itch' and 10 indicating 'worst itch imaginable'. |
| Change in Dermatology Life Quality Index (DLQI) Score From Week 0 to Week 26 | Week 0 to Week 26 | DLQI is a validated questionnaire with content specific to those with dermatology conditions. It consists of 10 items addressing the subject's perception of the impact of their skin disease on different aspects of their health-related quality of life (HRQoL) over the last week such as dermatology-related symptoms and feelings, daily activities, leisure, work or school, personal relationships, and the treatment. Each item is scored on a 4-point Likert scale (0 = not at all ∕not relevant; 1 = a little; 2 = a lot; 3 = very much). The total score is the sum of the 10 items (0 to 30); a high score is indicative of a poor HRQoL. |
| Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Week 26 | Week 26 | IGA is an instrument used in clinical trials to rate the severity of the subject's global AD and is based on a 5-point scale ranging from 0 (clear) to 4 (severe). |
| Frequency of Anti-drug Antibodies (ADA) From Week 0 to Week 40 | Week 0 to Week 40 | Presence of ADA from Week 0 to Week 40 was measured. Data were reported in the following categories: positive (presence of ADA at baseline and/or presence of ADA at at least 1 post-baseline assessment), perishing (presence of ADA at baseline and absence of ADA at all post-baseline assessments), negative (absence of ADA at all assessments), no post-baseline ADA assessment. |
| Number of Adverse Events From Week 0 to Week 40 | Week 0 to Week 40 | All adverse events are presented below under Adverse Events |
| Change in Scoring Atopic Dermatitis (SCORAD) From Week 0 to Week 26 | Week 0 to Week 26 | SCORAD is a validated tool to evaluate the extent and severity of AD lesions, along with subjective symptoms. The maximum total score is 103, with higher values indicating more severe disease. |
Countries
Belgium, Czechia, France, Germany, Poland, Spain, United Kingdom
Participant flow
Pre-assignment details
After the participant gave informed consent, they went through a 2- to 6-week screening period. Eligibility was assessed at the (first) screening visit and on Day 0 (hereinafter baseline) prior to randomisation.
Participants by arm
| Arm | Count |
|---|---|
| Tralokinumab + TCS Participants in the treatment period (Week 0 to Week 26) treated with tralokinumab every second week (Q2W) and topical corticosteroid (TCS) as needed.
Participants received a loading dose of 600 mg tralokinumab at baseline followed by a dose of 300 mg tralokinumab Q2W from Week 2. The last dose of IMP was administered at Week 24. | 140 |
| Placebo + TCS Participants in the treatment period (Week 0 to Week 26) treated with placebo every second week (Q2W) and topical corticosteroid (TCS) as needed.
Participants were administered placebo at baseline followed by administration of placebo every second week from Week 2. The last dose of IMP was administered at Week 24. | 137 |
| Total | 277 |
Baseline characteristics
| Characteristic | Total | Placebo + TCS | Tralokinumab + TCS |
|---|---|---|---|
| Age at onset of atopic dermatitis | 3.0 Years | 3.0 Years | 2.5 Years |
| Age, Continuous | 34.0 Years | 34.0 Years | 33.0 Years |
| Age, Customized 18-64 | 265 Participants | 131 Participants | 134 Participants |
| Age, Customized 65-84 | 12 Participants | 6 Participants | 6 Participants |
| Body surface area with atopic dermatitis | 52.0 Percentage affected | 52.0 Percentage affected | 52.0 Percentage affected |
| Dermatology Life Quality Index (DLQI) | 16.00 Units on a scale | 16.00 Units on a scale | 16.00 Units on a scale |
| Duration of atopic dermatitis | 26.0 Years | 25.0 Years | 26.0 Years |
| Eczema Area and Severity Index (EASI) | 28.80 Units on a scale | 29.10 Units on a scale | 28.60 Units on a scale |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants | 4 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 267 Participants | 133 Participants | 134 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Investigator's Global Assessment (IGA) Moderate Disease | 138 Participants | 70 Participants | 68 Participants |
| Investigator's Global Assessment (IGA) Severe Disease | 137 Participants | 67 Participants | 70 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 272 Participants | 135 Participants | 137 Participants |
| Region of Enrollment Belgium | 52 Participants | 27 Participants | 25 Participants |
| Region of Enrollment Czechia | 26 Participants | 12 Participants | 14 Participants |
| Region of Enrollment France | 19 Participants | 7 Participants | 12 Participants |
| Region of Enrollment Germany | 40 Participants | 18 Participants | 22 Participants |
| Region of Enrollment Poland | 77 Participants | 43 Participants | 34 Participants |
| Region of Enrollment Spain | 49 Participants | 21 Participants | 28 Participants |
| Region of Enrollment United Kingdom | 14 Participants | 9 Participants | 5 Participants |
| Scoring Atopic Dermatitis (SCORAD) | 69.10 Units on a scale | 68.90 Units on a scale | 69.20 Units on a scale |
| Sex: Female, Male Female | 112 Participants | 54 Participants | 58 Participants |
| Sex: Female, Male Male | 165 Participants | 83 Participants | 82 Participants |
| Worst Daily Pruritus numeric rating scale (NRS) (weekly average) | 7.43 Units on a scale | 7.50 Units on a scale | 7.43 Units on a scale |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 138 | 0 / 137 | 0 / 75 | 0 / 83 |
| other Total, other adverse events | 107 / 138 | 108 / 137 | 4 / 75 | 6 / 83 |
| serious Total, serious adverse events | 1 / 138 | 5 / 137 | 0 / 75 | 1 / 83 |
Outcome results
Primary
At Least 75% Reduction in Eczema Area and Severity Index (EASI75) From Week 0 to Week 16
EASI (Eczema Area and Severity Index) is a validated measure used in clinical practice and clinical trials to assess the severity and extent of AD. The EASI is a composite index with scores ranging from 0 to 72, with higher values indicating more severe and/or more extensive condition.
Time frame: Week 0 to Week 16
Population: Full analysis set (FAS). Of the 277 participants randomised to initial treatment, 275 were treated. Therefore, the FAS consisted of 275 participants (138 participants in the tralokinumab+TCS group + 137 participants in the placebo+TCS group).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tralokinumab+TCS | At Least 75% Reduction in Eczema Area and Severity Index (EASI75) From Week 0 to Week 16 | 64.2 Percentage of responders |
| Placebo+TCS | At Least 75% Reduction in Eczema Area and Severity Index (EASI75) From Week 0 to Week 16 | 50.5 Percentage of responders |
Comparison: Subjects who received rescue treatment or permanently discontinued IMP, without prior subject-onset of the COVID-19 pandemic (SOC19), were considered non-responders after the relevant event occurred. Any data from subjects who had SOC19 as their first prior intercurrent event (ICE) were multiple imputed (MI) assuming missing at random (MAR) following start of SOC19. Data missing prior to any ICE were handled as non-response, except data missing due to the pandemic, which was MI assuming MAR.p-value: 0.01895% CI: [2.5, 25.7]Mantel Haenszel
Secondary
At Least 75% Reduction in Eczema Area and Severity Index (EASI75) From Week 0 to Week 26
EASI (Eczema Area and Severity Index) is a validated measure used in clinical practice and clinical trials to assess the severity and extent of AD. The EASI is a composite index with scores ranging from 0 to 72, with higher values indicating more severe and/or more extensive condition.
Time frame: Week 0 to Week 26
Population: Full analysis set (FAS).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tralokinumab+TCS | At Least 75% Reduction in Eczema Area and Severity Index (EASI75) From Week 0 to Week 26 | 68.8 Percentage of responders |
| Placebo+TCS | At Least 75% Reduction in Eczema Area and Severity Index (EASI75) From Week 0 to Week 26 | 55.3 Percentage of responders |
Comparison: Subjects who received rescue treatment or permanently discontinued IMP, without prior subject-onset of the COVID-19 pandemic (SOC19), were considered non-responders after the relevant event occurred. Any data from subjects who had SOC19 as their first prior intercurrent event (ICE) were multiple imputed (MI) assuming missing at random (MAR) following start of SOC19. Data missing prior to any ICE were handled as non-response, except data missing due to the pandemic, which was MI assuming MAR.p-value: 0.01495% CI: [2.9, 25.3]Mantel Haenszel
Secondary
Change in Dermatology Life Quality Index (DLQI) Score From Week 0 to Week 16
DLQI is a validated questionnaire with content specific to those with dermatology conditions. It consists of 10 items addressing the subject's perception of the impact of their skin disease on different aspects of their health-related quality of life (HRQoL) over the last week such as dermatology-related symptoms and feelings, daily activities, leisure, work or school, personal relationships, and the treatment. Each item is scored on a 4-point Likert scale (0 = not at all ∕not relevant; 1 = a little; 2 = a lot; 3 = very much). The total score is the sum of the 10 items (0 to 30); a high score is indicative of a poor HRQoL.
Time frame: Week 0 to Week 16
Population: Full Set Analysis (FAS).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tralokinumab+TCS | Change in Dermatology Life Quality Index (DLQI) Score From Week 0 to Week 16 | -11.2 Units on a scale | Standard Error 0.4 |
| Placebo+TCS | Change in Dermatology Life Quality Index (DLQI) Score From Week 0 to Week 16 | -9.6 Units on a scale | Standard Error 0.4 |
Comparison: Data collected after permanent discontinuation of IMP, after initiation of rescue treatment, or after subject-onset of the COVID-19 pandemic will not be included in the analysis.p-value: 0.00995% CI: [-2.6, -0.4]Repeated measurements model
Secondary
Change in Dermatology Life Quality Index (DLQI) Score From Week 0 to Week 26
DLQI is a validated questionnaire with content specific to those with dermatology conditions. It consists of 10 items addressing the subject's perception of the impact of their skin disease on different aspects of their health-related quality of life (HRQoL) over the last week such as dermatology-related symptoms and feelings, daily activities, leisure, work or school, personal relationships, and the treatment. Each item is scored on a 4-point Likert scale (0 = not at all ∕not relevant; 1 = a little; 2 = a lot; 3 = very much). The total score is the sum of the 10 items (0 to 30); a high score is indicative of a poor HRQoL.
Time frame: Week 0 to Week 26
Population: Full Set Analysis (FAS).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tralokinumab+TCS | Change in Dermatology Life Quality Index (DLQI) Score From Week 0 to Week 26 | -11.5 Units on a scale | Standard Error 0.4 |
| Placebo+TCS | Change in Dermatology Life Quality Index (DLQI) Score From Week 0 to Week 26 | -9.9 Units on a scale | Standard Error 0.4 |
Comparison: Data collected after permanent discontinuation of IMP, after initiation of rescue treatment, or after subject-onset of the COVID-19 pandemic will not be included in the analysis.p-value: 0.00595% CI: [-2.7, -0.5]Repeated measurements model
Secondary
Change in Scoring Atopic Dermatitis (SCORAD) From Week 0 to Week 16
SCORAD is a validated tool to evaluate the extent and severity of AD lesions, along with subjective symptoms. The maximum total score is 103, with higher values indicating more severe disease.
Time frame: Week 0 to Week 16
Population: Full analysis set (FAS).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tralokinumab+TCS | Change in Scoring Atopic Dermatitis (SCORAD) From Week 0 to Week 16 | -42.7 Units on a scale | Standard Error 1.6 |
| Placebo+TCS | Change in Scoring Atopic Dermatitis (SCORAD) From Week 0 to Week 16 | -34.1 Units on a scale | Standard Error 1.6 |
Comparison: Data collected after permanent discontinuation of IMP, after initiation of rescue treatment, or after subject-onset of the COVID-19 pandemic will not be included in the analysis.p-value: <0.00195% CI: [-13, -4.2]Repeated measurements model
Secondary
Change in Scoring Atopic Dermatitis (SCORAD) From Week 0 to Week 26
SCORAD is a validated tool to evaluate the extent and severity of AD lesions, along with subjective symptoms. The maximum total score is 103, with higher values indicating more severe disease.
Time frame: Week 0 to Week 26
Population: Full analysis set (FAS).
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Tralokinumab+TCS | Change in Scoring Atopic Dermatitis (SCORAD) From Week 0 to Week 26 | -46.3 Units on a scale | Standard Error 1.5 |
| Placebo+TCS | Change in Scoring Atopic Dermatitis (SCORAD) From Week 0 to Week 26 | -37.3 Units on a scale | Standard Error 1.6 |
Comparison: Data collected after permanent discontinuation of IMP, after initiation of rescue treatment, or after subject-onset of the COVID-19 pandemic will not be included in the analysis.p-value: <0.00195% CI: [-13.2, -4.6]Repeated measurements model
Secondary
Frequency of Anti-drug Antibodies (ADA) From Week 0 to Week 40
Presence of ADA from Week 0 to Week 40 was measured. Data were reported in the following categories: positive (presence of ADA at baseline and/or presence of ADA at at least 1 post-baseline assessment), perishing (presence of ADA at baseline and absence of ADA at all post-baseline assessments), negative (absence of ADA at all assessments), no post-baseline ADA assessment.
Time frame: Week 0 to Week 40
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Tralokinumab+TCS | Frequency of Anti-drug Antibodies (ADA) From Week 0 to Week 40 | Positive | 2 Participants |
| Tralokinumab+TCS | Frequency of Anti-drug Antibodies (ADA) From Week 0 to Week 40 | Negative | 134 Participants |
| Tralokinumab+TCS | Frequency of Anti-drug Antibodies (ADA) From Week 0 to Week 40 | Perishing | 1 Participants |
| Tralokinumab+TCS | Frequency of Anti-drug Antibodies (ADA) From Week 0 to Week 40 | No post-baseline ADA assessment | 1 Participants |
| Placebo+TCS | Frequency of Anti-drug Antibodies (ADA) From Week 0 to Week 40 | No post-baseline ADA assessment | 0 Participants |
| Placebo+TCS | Frequency of Anti-drug Antibodies (ADA) From Week 0 to Week 40 | Positive | 3 Participants |
| Placebo+TCS | Frequency of Anti-drug Antibodies (ADA) From Week 0 to Week 40 | Perishing | 1 Participants |
| Placebo+TCS | Frequency of Anti-drug Antibodies (ADA) From Week 0 to Week 40 | Negative | 133 Participants |
Secondary
Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Week 16
IGA is an instrument used in clinical trials to rate the severity of the subject's global AD and is based on a 5-point scale ranging from 0 (clear) to 4 (severe).
Time frame: Week 16
Population: Full analysis set (FAS).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tralokinumab+TCS | Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Week 16 | 40.9 Percentage of responders |
| Placebo+TCS | Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Week 16 | 26.0 Percentage of responders |
Comparison: Subjects who received rescue treatment or permanently discontinued IMP, without prior subject-onset of the COVID-19 pandemic (SOC19), were considered non-responders after the relevant event occurred. Any data from subjects who had SOC19 as their first prior intercurrent event (ICE) were multiple imputed (MI) assuming missing at random (MAR) following start of SOC19. Data missing prior to any ICE were handled as non-response, except data missing due to the pandemic, which was MI assuming MAR.p-value: 0.00595% CI: [4.8, 26.3]Mantel Haenszel
Secondary
Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Week 26
IGA is an instrument used in clinical trials to rate the severity of the subject's global AD and is based on a 5-point scale ranging from 0 (clear) to 4 (severe).
Time frame: Week 26
Population: Full analysis set (FAS).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tralokinumab+TCS | Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Week 26 | 47.0 Percentage of responders |
| Placebo+TCS | Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Week 26 | 33.4 Percentage of responders |
Comparison: Subjects who received rescue treatment or permanently discontinued IMP, without prior subject-onset of the COVID-19 pandemic (SOC19), were considered non-responders after the relevant event occurred. Any data from subjects who had SOC19 as their first prior intercurrent event (ICE) were multiple imputed (MI) assuming missing at random (MAR) following start of SOC19. Data missing prior to any ICE were handled as non-response, except data missing due to the pandemic, which was MI assuming MAR.p-value: 0.01495% CI: [2.9, 25.6]Mantel Haenszel
Secondary
Number of Adverse Events From Week 0 to Week 40
All adverse events are presented below under Adverse Events
Time frame: Week 0 to Week 40
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tralokinumab+TCS | Number of Adverse Events From Week 0 to Week 40 | 389 number of adverse events |
| Placebo+TCS | Number of Adverse Events From Week 0 to Week 40 | 435 number of adverse events |
Secondary
Reduction of Worst Daily Pruritus Numeric Rating Scale (NRS) (Weekly Average) of at Least 4 From Week 0 to Week 16
Subjects will assess their worst itch severity over the past 24 hours using an 11-point NRS ('Worst Daily Pruritus NRS') with 0 indicating 'no itch' and 10 indicating 'worst itch imaginable'.
Time frame: Week 0 to Week 16
Population: Participants in the full analysis set with a Worst Daily Pruritus NRS (weekly average) of at least 4 at baseline (Week 0).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tralokinumab+TCS | Reduction of Worst Daily Pruritus Numeric Rating Scale (NRS) (Weekly Average) of at Least 4 From Week 0 to Week 16 | 45.5 Percentage of responders |
| Placebo+TCS | Reduction of Worst Daily Pruritus Numeric Rating Scale (NRS) (Weekly Average) of at Least 4 From Week 0 to Week 16 | 35.6 Percentage of responders |
Comparison: Subjects who received rescue treatment or permanently discontinued IMP, without prior subject-onset of the COVID-19 pandemic (SOC19), were considered non-responders after the relevant event occurred. Any data from subjects who had SOC19 as their first prior intercurrent event (ICE) were multiple imputed (MI) assuming missing at random (MAR) following start of SOC19. Data missing prior to any ICE were handled as non-response, except data missing due to the pandemic, which was MI assuming MAR.p-value: 0.10695% CI: [-2, 21.4]Mantel Haenszel
Secondary
Reduction of Worst Daily Pruritus Numeric Rating Scale (NRS) (Weekly Average) of at Least 4 From Week 0 to Week 26
Subjects will assess their worst itch severity over the past 24 hours using an 11-point numeric rating scale ('Worst Daily Pruritus NRS') with 0 indicating 'no itch' and 10 indicating 'worst itch imaginable'.
Time frame: Week 0 to Week 26
Population: Participants in the full analysis set with a Worst Daily Pruritus NRS (weekly average) of at least 4 at baseline (Week 0).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Tralokinumab+TCS | Reduction of Worst Daily Pruritus Numeric Rating Scale (NRS) (Weekly Average) of at Least 4 From Week 0 to Week 26 | 47.2 Percentage of responders |
| Placebo+TCS | Reduction of Worst Daily Pruritus Numeric Rating Scale (NRS) (Weekly Average) of at Least 4 From Week 0 to Week 26 | 39.7 Percentage of responders |
Comparison: Subjects who received rescue treatment or permanently discontinued IMP, without prior subject-onset of the COVID-19 pandemic (SOC19), were considered non-responders after the relevant event occurred. Any data from subjects who had SOC19 as their first prior intercurrent event (ICE) were multiple imputed (MI) assuming missing at random (MAR) following start of SOC19. Data missing prior to any ICE were handled as non-response, except data missing due to the pandemic, which was MI assuming MAR.p-value: 0.22895% CI: [-4.6, 19.2]Mantel Haenszel