Atopic Dermatitis
Conditions
Brief summary
Primary objective: To evaluate the efficacy of subcutaneous (SC) administration of tralokinumab compared with placebo in treating adolescent subjects (age 12 to \<18 years) with moderate-to-severe AD. Secondary objectives: To evaluate the efficacy of tralokinumab on severity and extent of AD, itch, and health-related quality of life compared with placebo. To investigate the safety, immunogenicity, and tolerability of SC administration of tralokinumab compared with placebo when used to treat adolescent subjects (age 12 to \<18 years) with moderate-to-severe AD.
Interventions
DRUGTralokinumab
Tralokinumab is a human recombinant monoclonal antibody of the immunoglobulin G4 (IgG4) subclass that specifically binds to human interleukin (IL) 13 and blocks interaction with the IL-13 receptors.
DRUGPlacebos
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)
Masking description
Neither the subject nor any of the investigator or LEO staff who are involved in the treatment or clinical evaluation and monitoring of the subjects will be aware of the treatment received. The packaging and labelling of the investigational medicinal products (IMPs) will contain no evidence of their identity. Since tralokinumab and placebo are visually distinct and not matched for viscosity, IMP will be handled and administered by a qualified, unblinded healthcare professional at the site who will not be involved in the management of trial subjects and who will not perform any of the assessments.
Eligibility
Sex/Gender
ALL
Age
12 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Age 12 to 17. * Diagnosis of AD as defined by the Hanifin and Rajka (1980) criteria for AD. * History of AD for ≥1 year. * History of topical corticosteroid (TCS; Europe: Class 3 or higher; US: Class 4 or lower) and/or topical calcineurin inhibitor (TCI) treatment failure or subjects for whom these topical AD treatments are medically inadvisable. * AD involvement of ≥10% body surface area at screening and baseline. * Stable dose of emollient twice daily (or more, as needed) for at least 14 days before randomisation.
Exclusion criteria
* Active dermatologic conditions that may confound the diagnosis of AD. * Use of tanning beds or phototherapy within 6 weeks prior to randomisation. * Treatment with systemic immunosuppressive/immunomodulating drugs and/or systemic corticosteroid within 4 weeks prior to randomisation. * Treatment with TCS, TCI, or topical phosphodiesterase 4 (PDE-4) inhibitor within 2 weeks prior to randomisation. * Receipt of any marketed biological therapy (i.e. immunoglobulin, anti immunoglobulin E) including dupilumab or investigational biologic agents. * Active skin infection within 1 week prior to randomisation. * Clinically significant infection within 4 weeks prior to randomisation. * A helminth parasitic infection within 6 months prior to the date informed consent is obtained. * Tuberculosis requiring treatment within the 12 months prior to screening. * Known primary immunodeficiency disorder.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Subjects With Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Week 16 | At Week 16 | The 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). |
| Subjects With at Least 75% Reduction in Eczema Area and Severity Index (EASI75) at Week 16 | At Week 16 | The EASI 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 Children's Dermatology Life Quality Index (CDLQI) Score From Baseline to Week 16 | From Week 0 to Week 16 | The CDLQI 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 various aspects of their quality of life over the last week such as dermatology-related symptoms and feelings, leisure, school or holidays, personal relationships, sleep, and the treatment. Each item is scored on a 4-point Likert scale (0 = 'not at all'; 1 = 'only a little'; 2 = 'quite a lot'; 3 = 'very much'). Item 7 (on school time) has one additional response category 'prevented school', which is also scored '3'. The total score of the CDLQI is the sum of the 10 items (0 to 30); a high score is indicative of a poor quality of life. |
| Number of Adverse Events | From Week 0 to Week 16 | Number of AEs during the Initial treatment period is presented. For a summary of AEs and SAEs by MedDRA system organ class (SOC) and preferred term (PT) during the initial treatment period, maintenance treatment period, open-label treatment period, and safety follow-up period, see the Adverse Events Overview section. |
| Presence of Anti-drug Antibodies | From Week 0 to Week 16 | Anti-tralokinumab antibody levels were analysed using a validated bioanalytical method. |
| Subjects With at Least 50% Reduction in Eczema Area and Severity Index (EASI50) at Week 16. | At Week 16 | The EASI 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. |
| Subjects With at Least 90% Reduction in Eczema Area and Severity Index (EASI90) at Week 16. | At Week 16 | The EASI 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. |
| Change in Eczema Area and Severity Index (EASI) Score From Baseline to Week 16 | From Week 0 to Week 16 | The EASI 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. |
| Subjects With at Least 75% Reduction in Scoring Atopic Dermatitis (SCORAD75) at Week 16 | At Week 16 | The SCORAD is a validated tool to evaluate the extent and severity of atopic dermatitis lesions, along with subjective symptoms. The score ranges from 0 to 103, with a higher values indicating a more extensive and/or severe condition. |
| Subjects With Reduction of Adolescent Worst Pruritus Numeric Rating Scale (NRS) (Weekly Average) of at Least 4 From Baseline to Week 16 | At Week 16 | The Adolescent Worst Pruritus NRS is used by subjects to assess their worst itch over the past 24 hours using an 11-point NRS with 0 indicating 'no itch' and 10 indicating 'worst itch possible'. |
| Change in Adolescent Worst Pruritus Numeric Rating Scale (NRS) (Weekly Average) From Baseline to Week 16 | From Week 0 to Week 16 | The Adolescent Worst Pruritus NRS is used by subjects to assess their worst itch over the past 24 hours using an 11-point NRS with 0 indicating 'no itch' and 10 indicating 'worst itch possible'. |
| Participants With Reduction of Adolescent Worst Pruritus Numeric Rating Scale (NRS) (Weekly Average) of at Least 3 From Baseline to Week 16 | At Week 16 | The Adolescent Worst Pruritus NRS is used by subjects to assess their worst itch over the past 24 hours using an 11-point NRS with 0 indicating 'no itch' and 10 indicating 'worst itch possible'. |
| Change in Patient Oriented Eczema Measure (POEM) From Baseline to Week 16 | From Week 0 to Week 16 | The POEM is a validated questionnaire used to assess disease symptoms in atopic eczema patients in both clinical practice and clinical trials. The tool consists of 7 items each addressing a specific symptom (itching, sleep, bleeding, weeping, cracking, flaking, and dryness). Subjects will score how often they have experienced each symptom over the previous week on a 5-point categorical response scale (0 = 'no days'; 1 = '1 to 2 days'; 2 = '3 to 4 days'; 3 = '5 to 6' days; 4 = 'every day'). The total score is the sum of the 7 items (range 0 to 28) and reflects disease-related morbidity; a high score is indicative of a worse disease severity. |
| Tralokinumab Serum Trough Concentration at Week 16 | At Week 16 | Serum samples for determination of tralokinumab concentrations were analysed by a laboratory using a validated bioanalytical method. |
| Subjects With Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Week 52 Among Subjects With IGA Score of 0 or 1 at Week 16 After Initial Randomisation to Tralokinumab and Without Use of Rescue From Week 2 to Week 16 | At Week 52 | The 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). |
| Subjects With at Least 75% Reduction in Eczema Area and Severity Index (EASI75) at Week 52 Among Subjects With at Least 75% Reduction in EASI at Week 16 After Initial Randomisation to Tralokinumab and Without Use of Rescue From Week 2 to Week 16 | At Week 52 | The EASI 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. |
| Tralokinumab Serum Trough Concentration at Week 66 | At Week 66 | Serum samples for determination of tralokinumab concentrations were analysed by a laboratory using a validated bioanalytical method. |
| Subjects With at Least 50% Reduction in Scoring Atopic Dermatitis (SCORAD50) at Week 16 | At Week 16 | The SCORAD is a validated tool to evaluate the extent and severity of atopic dermatitis lesions, along with subjective symptoms. The score ranges from 0 to 103, with a higher values indicating a more extensive and/or severe condition. |
| Change in Scoring Atopic Dermatitis (SCORAD) From Baseline to Week 16 | From Week 0 to Week 16 | The 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
Australia, Belgium, Canada, France, Germany, Japan, Netherlands, Poland, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Initial Treatment Period - Tralokinumab 300 mg Q2W Week 0 to Week 16:
Tralokinumab 300 mg Q2W Tralokinumab: 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 administration.
At Day 0, each subject received 4 subcutaneous injections (each 1.0 mL) of 150 mg tralokinumab to receive a total loading dose of 600 mg tralokinumab. At subsequent visits (Q2W) each subject received 2 subcutaneous injections (each 1.0 mL) of 150 mg tralokinumab to receive a total dose of 300 mg tralokinumab. | 101 |
| Initial Treatment Period - Tralokinumab 150 mg Q2W Week 0 to Week 16:
Tralokinumab 150 mg Q2W. Tralokinumab: 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 administration.
At Day 0, each subject received 2 subcutaneous injections (each 1.0 mL) of 150 mg tralokinumab and 2 subcutaneous injections (each 1.0 mL) of placebo to receive a total loading dose of 300 mg tralokinumab. At subsequent visits (Q2W) each subject received 1 subcutaneous injection (1.0 mL) of 150 mg tralokinumab and 1 subcutaneous injection (1.0 mL) of placebo to receive a total dose of 150 mg tralokinumab. | 100 |
| Initial Treatment Period - Placebo Week 0 to Week 16:
Placebo Q2W Placebo: Placebo contains the same excipients, in the same concentration, only lacking tralokinumab.
At Day 0, each subject received 4 subcutaneous injections (each 1.0 mL) of placebo. At subsequent visits (Q2W) each subject received 2 subcutaneous injections (each 1.0 mL) of placebo. | 100 |
| Total | 301 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 |
|---|---|---|---|---|---|---|---|---|---|---|
| Initial Treatment Period | Not dosed | 1 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Initial Treatment Period | Randomised at site with quality/GCP issues identified, subject withdrawn from the trial | 3 | 1 | 5 | 0 | 0 | 0 | 0 | 0 | 0 |
| Initial Treatment Period | Subject discontinued IMP before Week 16 | 3 | 5 | 8 | 0 | 0 | 0 | 0 | 0 | 0 |
| Maintenance Treatment Period | Randomised at site with quality/GCP issues identified, subject withdrawn from the trial | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Maintenance Treatment Period | Subject discontinued IMP between Week 16 and Week 52 | 0 | 0 | 0 | 1 | 1 | 0 | 1 | 0 | 0 |
| Maintenance Treatment Period | Subject transferred to open-label treatment | 0 | 0 | 0 | 6 | 5 | 4 | 5 | 2 | 0 |
| Open-label Treatment Period | Completed treatment (received the last planned dose of IMP) and withdrew from the trial at Week 50 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Open-label Treatment Period | Randomised at site with quality/GCP issues identified, subject withdrawn from the trial | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 8 |
| Open-label Treatment Period | Subject discontinued IMP between Week 16 and Week 52 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 19 |
Baseline characteristics
| Characteristic | Total | Initial Treatment Period - Tralokinumab 300 mg Q2W | Initial Treatment Period - Tralokinumab 150 mg Q2W | Initial Treatment Period - Placebo |
|---|---|---|---|---|
| Adolescent Worst Pruritus NRS (weekly average) | 7.58 units on a scale STANDARD_DEVIATION 1.58 | 7.79 units on a scale STANDARD_DEVIATION 1.53 | 7.49 units on a scale STANDARD_DEVIATION 1.58 | 7.45 units on a scale STANDARD_DEVIATION 1.62 |
| Age, Continuous | 14.6 years STANDARD_DEVIATION 1.7 | 14.6 years STANDARD_DEVIATION 1.8 | 14.8 years STANDARD_DEVIATION 1.7 | 14.4 years STANDARD_DEVIATION 1.6 |
| Age of onset of atopic dermatitis (AD) | 2.4 years STANDARD_DEVIATION 3.4 | 2.5 years STANDARD_DEVIATION 3.5 | 2.1 years STANDARD_DEVIATION 3.3 | 2.4 years STANDARD_DEVIATION 3.5 |
| Body surface area affected by atopic dermatitis (AD) | 50.9 percentage affected STANDARD_DEVIATION 23 | 49.8 percentage affected STANDARD_DEVIATION 23 | 52.0 percentage affected STANDARD_DEVIATION 22.5 | 50.9 percentage affected STANDARD_DEVIATION 23.5 |
| Children's Dermatology Life Quality Index | 13.10 units on a scale STANDARD_DEVIATION 6.48 | 13.29 units on a scale STANDARD_DEVIATION 7.18 | 12.86 units on a scale STANDARD_DEVIATION 6.27 | 13.14 units on a scale STANDARD_DEVIATION 5.99 |
| Duration of atopic dermatitis (AD) | 12.3 years STANDARD_DEVIATION 3.6 | 12.1 years STANDARD_DEVIATION 3.7 | 12.7 years STANDARD_DEVIATION 3.7 | 12.0 years STANDARD_DEVIATION 3.4 |
| Eczema Area and Severity Index | 31.68 units on a scale STANDARD_DEVIATION 13.6 | 31.90 units on a scale STANDARD_DEVIATION 13.74 | 31.89 units on a scale STANDARD_DEVIATION 12.97 | 31.25 units on a scale STANDARD_DEVIATION 14.19 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 32 Participants | 12 Participants | 10 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 269 Participants | 89 Participants | 90 Participants | 90 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Investigator's Global Assessment Almost Clear | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Investigator's Global Assessment Clear | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Investigator's Global Assessment Mild | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Investigator's Global Assessment Missing | 3 Participants | 1 Participants | 1 Participants | 1 Participants |
| Investigator's Global Assessment Moderate | 161 Participants | 52 Participants | 55 Participants | 54 Participants |
| Investigator's Global Assessment Severe | 137 Participants | 48 Participants | 44 Participants | 45 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 3 Participants | 0 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 72 Participants | 21 Participants | 28 Participants | 23 Participants |
| Race/Ethnicity, Customized Black or African American | 34 Participants | 14 Participants | 8 Participants | 12 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 4 Participants | 2 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Other | 15 Participants | 5 Participants | 6 Participants | 4 Participants |
| Race/Ethnicity, Customized White | 173 Participants | 59 Participants | 56 Participants | 58 Participants |
| Region of Enrollment Australia | 14 participants | 5 participants | 5 participants | 4 participants |
| Region of Enrollment Belgium | 8 participants | 2 participants | 3 participants | 3 participants |
| Region of Enrollment Canada | 52 participants | 21 participants | 19 participants | 12 participants |
| Region of Enrollment France | 8 participants | 2 participants | 2 participants | 4 participants |
| Region of Enrollment Germany | 11 participants | 5 participants | 4 participants | 2 participants |
| Region of Enrollment Japan | 32 participants | 11 participants | 10 participants | 11 participants |
| Region of Enrollment Netherlands | 13 participants | 4 participants | 4 participants | 5 participants |
| Region of Enrollment Poland | 54 participants | 19 participants | 20 participants | 15 participants |
| Region of Enrollment United Kingdom | 4 participants | 1 participants | 0 participants | 3 participants |
| Region of Enrollment United States | 105 participants | 31 participants | 33 participants | 41 participants |
| Scoring Atopic Dermatitis | 67.84 units on a scale STANDARD_DEVIATION 14.23 | 68.41 units on a scale STANDARD_DEVIATION 13.51 | 67.42 units on a scale STANDARD_DEVIATION 14.51 | 67.70 units on a scale STANDARD_DEVIATION 14.77 |
| Sex: Female, Male Female | 146 Participants | 52 Participants | 48 Participants | 46 Participants |
| Sex: Female, Male Male | 155 Participants | 49 Participants | 52 Participants | 54 Participants |
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 | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 97 | 0 / 98 | 0 / 94 | 0 / 11 | 0 / 13 | 0 / 12 | 0 / 14 | 0 / 6 | 0 / 234 | 0 / 234 |
| other Total, other adverse events | 44 / 97 | 47 / 98 | 36 / 94 | 7 / 11 | 6 / 13 | 7 / 12 | 8 / 14 | 4 / 6 | 100 / 234 | 16 / 234 |
| serious Total, serious adverse events | 1 / 97 | 3 / 98 | 5 / 94 | 0 / 11 | 0 / 13 | 0 / 12 | 0 / 14 | 0 / 6 | 7 / 234 | 3 / 234 |
Outcome results
Primary
Subjects With at Least 75% Reduction in Eczema Area and Severity Index (EASI75) at Week 16
The EASI 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: At Week 16
Population: The full analysis set (FAS: All subjects randomised to initial treatment who were exposed to IMP and not randomised at the investigational sites where substantial quality/GCP issues were identified) was used for the primary analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Initial Treatment Period - Tralokinumab 300 mg Q2W | Subjects With at Least 75% Reduction in Eczema Area and Severity Index (EASI75) at Week 16 | 27 Participants |
| Initial Treatment Period - Tralokinumab 150 mg Q2W | Subjects With at Least 75% Reduction in Eczema Area and Severity Index (EASI75) at Week 16 | 28 Participants |
| Initial Treatment Period - Placebo | Subjects With at Least 75% Reduction in Eczema Area and Severity Index (EASI75) at Week 16 | 6 Participants |
Comparison: Subjects who achieved at least 75% reduction in EASI at Week 16 were considered responders. Subjects with missing data or subjects who received rescue medication from Week 2 to Week 16 were considered non-responders. Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity. The null hypothesis of no difference in response rate between tralokinumab 300 mg Q2W and placebo was tested against the 2-sided alternative that there is a difference.p-value: <0.00195% CI: [12, 32]Cochran-Mantel-Haenszel
Comparison: Subjects who achieved at least 75% reduction in EASI at Week 16 were considered responders. Subjects with missing data or subjects who received rescue medication from Week 2 to Week 16 were considered non-responders. Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity. The null hypothesis of no difference in response rate between tralokinumab 150 mg Q2W and placebo was tested against the 2-sided alternative that there is a difference.p-value: <0.00195% CI: [12.4, 32.6]Cochran-Mantel-Haenszel
Primary
Subjects With Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Week 16
The 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: At Week 16
Population: The full analysis set (FAS: All subjects randomised to initial treatment who were exposed to IMP and not randomised at the investigational sites where substantial quality/GCP issues were identified) was used for the primary analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Initial Treatment Period - Tralokinumab 300 mg Q2W | Subjects With Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Week 16 | 17 Participants |
| Initial Treatment Period - Tralokinumab 150 mg Q2W | Subjects With Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Week 16 | 21 Participants |
| Initial Treatment Period - Placebo | Subjects With Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Week 16 | 4 Participants |
Comparison: Subjects with IGA score of 0 (clear) or 1 (almost clear) at Week 16 were considered responders. Subjects with missing data or subjects who received rescue medication from Week 2 to Week 16 were considered non-responders. Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity. The null hypothesis of no difference in response rate between tralokinumab 300 mg Q2W and placebo was tested against the 2-sided alternative that there is a difference.p-value: 0.00295% CI: [5.3, 22.3]Cochran-Mantel-Haenszel
Comparison: Subjects with IGA score of 0 (clear) or 1 (almost clear) at Week 16 were considered responders. Subjects with missing data or subjects who received rescue medication from Week 2 to Week 16 were considered non-responders. Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity. The null hypothesis of no difference in response rate between tralokinumab 150 mg Q2W and placebo was tested against the 2-sided alternative that there is a difference.p-value: <0.00195% CI: [8.4, 26.6]Cochran-Mantel-Haenszel
Secondary
Change in Adolescent Worst Pruritus Numeric Rating Scale (NRS) (Weekly Average) From Baseline to Week 16
The Adolescent Worst Pruritus NRS is used by subjects to assess their worst itch over the past 24 hours using an 11-point NRS with 0 indicating 'no itch' and 10 indicating 'worst itch possible'.
Time frame: From Week 0 to Week 16
Population: Subjects in the full analysis set with non-missing baseline Adolescent Worst Pruritus NRS score. The full analysis set (FAS) comprised all subjects randomised to initial treatment who were exposed to IMP and not randomised at the investigational sites where substantial quality/GCP issues were identified.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Initial Treatment Period - Tralokinumab 300 mg Q2W | Change in Adolescent Worst Pruritus Numeric Rating Scale (NRS) (Weekly Average) From Baseline to Week 16 | -3.0 units on a scale | Standard Error 0.3 |
| Initial Treatment Period - Tralokinumab 150 mg Q2W | Change in Adolescent Worst Pruritus Numeric Rating Scale (NRS) (Weekly Average) From Baseline to Week 16 | -2.7 units on a scale | Standard Error 0.3 |
| Initial Treatment Period - Placebo | Change in Adolescent Worst Pruritus Numeric Rating Scale (NRS) (Weekly Average) From Baseline to Week 16 | -1.5 units on a scale | Standard Error 0.3 |
Comparison: Repeated measurements model on post-baseline data. In case of no post-baseline assessments before initiation of rescue medication, the Week 2 change was imputed as 0. Data collected after permanent discontinuation of IMP or after use of rescue treatment from Week 2 to Week 16 were not included in the analysis.p-value: <0.00195% CI: [-2.4, -0.6]Repeated measurements model
Comparison: Repeated measurements model on post-baseline data. In case of no post-baseline assessments before initiation of rescue medication, the Week 2 change was imputed as 0. Data collected after permanent discontinuation of IMP or after use of rescue treatment from Week 2 to Week 16 were not included in the analysis.p-value: 0.00795% CI: [-2.1, -0.3]Repeated measurements model
Secondary
Change in Children's Dermatology Life Quality Index (CDLQI) Score From Baseline to Week 16
The CDLQI 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 various aspects of their quality of life over the last week such as dermatology-related symptoms and feelings, leisure, school or holidays, personal relationships, sleep, and the treatment. Each item is scored on a 4-point Likert scale (0 = 'not at all'; 1 = 'only a little'; 2 = 'quite a lot'; 3 = 'very much'). Item 7 (on school time) has one additional response category 'prevented school', which is also scored '3'. The total score of the CDLQI is the sum of the 10 items (0 to 30); a high score is indicative of a poor quality of life.
Time frame: From Week 0 to Week 16
Population: Subjects in the full analysis set with non-missing baseline CDLQI score. The full analysis set (FAS) comprised all subjects randomised to initial treatment who were exposed to IMP and not randomised at the investigational sites where substantial quality/GCP issues were identified.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Initial Treatment Period - Tralokinumab 300 mg Q2W | Change in Children's Dermatology Life Quality Index (CDLQI) Score From Baseline to Week 16 | -6.7 units on a scale | Standard Error 0.6 |
| Initial Treatment Period - Tralokinumab 150 mg Q2W | Change in Children's Dermatology Life Quality Index (CDLQI) Score From Baseline to Week 16 | -6.1 units on a scale | Standard Error 0.6 |
| Initial Treatment Period - Placebo | Change in Children's Dermatology Life Quality Index (CDLQI) Score From Baseline to Week 16 | -4.1 units on a scale | Standard Error 0.7 |
Comparison: Repeated measurements model on post-baseline data. In case of no post-baseline assessments before initiation of rescue medication, the Week 2 change was imputed as 0. Data collected after permanent discontinuation of IMP or after use of rescue treatment from Week 2 to Week 16 were not included in the analysis.p-value: 0.00795% CI: [-4.5, -0.7]Repeated measurements model
Comparison: Repeated measurements model on post-baseline data. In case of no post-baseline assessments before initiation of rescue medication, the Week 2 change was imputed as 0. Data collected after permanent discontinuation of IMP or after use of rescue treatment from Week 2 to Week 16 were not included in the analysis.p-value: 0.0495% CI: [-3.9, -0.1]Repeated measurements model
Secondary
Change in Eczema Area and Severity Index (EASI) Score From Baseline to Week 16
The EASI 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: From Week 0 to Week 16
Population: The full analysis set (FAS: All subjects randomised to initial treatment who were exposed to IMP and not randomised at the investigational sites where substantial quality/GCP issues were identified) was used for the primary analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Initial Treatment Period - Tralokinumab 300 mg Q2W | Change in Eczema Area and Severity Index (EASI) Score From Baseline to Week 16 | -18.1 units on a scale | Standard Error 1.3 |
| Initial Treatment Period - Tralokinumab 150 mg Q2W | Change in Eczema Area and Severity Index (EASI) Score From Baseline to Week 16 | -18.1 units on a scale | Standard Error 1.4 |
| Initial Treatment Period - Placebo | Change in Eczema Area and Severity Index (EASI) Score From Baseline to Week 16 | -8.7 units on a scale | Standard Error 1.6 |
Comparison: Repeated measurements model on post-baseline data. In case of no post-baseline assessments before initiation of rescue medication, the Week 2 change was imputed as 0. Data collected after permanent discontinuation of IMP or after use of rescue treatment from Week 2 to Week 16 were not included in the analysis.p-value: <0.00195% CI: [-13.5, -5.3]Repeated measurements model
Comparison: Repeated measurements model on post-baseline data. In case of no post-baseline assessments before initiation of rescue medication, the Week 2 change was imputed as 0. Data collected after permanent discontinuation of IMP or after use of rescue treatment from Week 2 to Week 16 were not included in the analysis.p-value: <0.00195% CI: [-13.6, -5.3]Repeated measurements model
Secondary
Change in Patient Oriented Eczema Measure (POEM) From Baseline to Week 16
The POEM is a validated questionnaire used to assess disease symptoms in atopic eczema patients in both clinical practice and clinical trials. The tool consists of 7 items each addressing a specific symptom (itching, sleep, bleeding, weeping, cracking, flaking, and dryness). Subjects will score how often they have experienced each symptom over the previous week on a 5-point categorical response scale (0 = 'no days'; 1 = '1 to 2 days'; 2 = '3 to 4 days'; 3 = '5 to 6' days; 4 = 'every day'). The total score is the sum of the 7 items (range 0 to 28) and reflects disease-related morbidity; a high score is indicative of a worse disease severity.
Time frame: From Week 0 to Week 16
Population: Subjects in the full analysis set with non-missing baseline POEM score. The full analysis set (FAS) comprised all subjects randomised to initial treatment who were exposed to IMP and not randomised at the investigational sites where substantial quality/GCP issues were identified.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Initial Treatment Period - Tralokinumab 300 mg Q2W | Change in Patient Oriented Eczema Measure (POEM) From Baseline to Week 16 | -8.4 units on a scale | Standard Error 0.8 |
| Initial Treatment Period - Tralokinumab 150 mg Q2W | Change in Patient Oriented Eczema Measure (POEM) From Baseline to Week 16 | -7.8 units on a scale | Standard Error 0.8 |
| Initial Treatment Period - Placebo | Change in Patient Oriented Eczema Measure (POEM) From Baseline to Week 16 | -2.4 units on a scale | Standard Error 1 |
Comparison: Repeated measurements model on post-baseline data. In case of no post-baseline assessments before initiation of rescue medication, the Week 2 change was imputed as 0. Data collected after permanent discontinuation of IMP or after use of rescue treatment from Week 2 to Week 16 were not included in the analysis.p-value: <0.00195% CI: [-8.4, -3.6]Repeated measurements model
Comparison: Repeated measurements model on post-baseline data. In case of no post-baseline assessments before initiation of rescue medication, the Week 2 change was imputed as 0. Data collected after permanent discontinuation of IMP or after use of rescue treatment from Week 2 to Week 16 were not included in the analysis.p-value: <0.00195% CI: [-7.9, -3]Repeated measurements model
Secondary
Change in Scoring Atopic Dermatitis (SCORAD) From Baseline to Week 16
The 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: From Week 0 to Week 16
Population: The full analysis set (FAS: All subjects randomised to initial treatment who were exposed to IMP and not randomised at the investigational sites where substantial quality/GCP issues were identified) was used for the primary analysis.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Initial Treatment Period - Tralokinumab 300 mg Q2W | Change in Scoring Atopic Dermatitis (SCORAD) From Baseline to Week 16 | -29.1 units on a scale | Standard Error 2.4 |
| Initial Treatment Period - Tralokinumab 150 mg Q2W | Change in Scoring Atopic Dermatitis (SCORAD) From Baseline to Week 16 | -27.5 units on a scale | Standard Error 2.4 |
| Initial Treatment Period - Placebo | Change in Scoring Atopic Dermatitis (SCORAD) From Baseline to Week 16 | -9.5 units on a scale | Standard Error 3 |
Comparison: Repeated measurements model on post-baseline data. In case of no post-baseline assessments before initiation of rescue medication, the Week 2 change was imputed as 0. Data collected after permanent discontinuation of IMP or after use of rescue treatment from Week 2 to Week 16 were not included in the analysis.p-value: <0.00195% CI: [-27.1, -12.2]Repeated measurements model
Comparison: Repeated measurements model on post-baseline data. In case of no post-baseline assessments before initiation of rescue medication, the Week 2 change was imputed as 0. Data collected after permanent discontinuation of IMP or after use of rescue treatment from Week 2 to Week 16 were not included in the analysis.p-value: <0.00195% CI: [-25.6, -10.4]Repeated measurements model
Secondary
Number of Adverse Events
Number of AEs during the Initial treatment period is presented. For a summary of AEs and SAEs by MedDRA system organ class (SOC) and preferred term (PT) during the initial treatment period, maintenance treatment period, open-label treatment period, and safety follow-up period, see the Adverse Events Overview section.
Time frame: From Week 0 to Week 16
Population: The analysis was performed on the safety analysis set. The safety analysis set comprised all subjects randomised to initial treatment and exposed to IMP, except for subjects randomised at the investigational sites where substantial quality/GCP issues were identified . The safety analysis set was identical to the full analysis set.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Initial Treatment Period - Tralokinumab 300 mg Q2W | Number of Adverse Events | 130 number of adverse events |
| Initial Treatment Period - Tralokinumab 150 mg Q2W | Number of Adverse Events | 175 number of adverse events |
| Initial Treatment Period - Placebo | Number of Adverse Events | 134 number of adverse events |
Secondary
Participants With Reduction of Adolescent Worst Pruritus Numeric Rating Scale (NRS) (Weekly Average) of at Least 3 From Baseline to Week 16
The Adolescent Worst Pruritus NRS is used by subjects to assess their worst itch over the past 24 hours using an 11-point NRS with 0 indicating 'no itch' and 10 indicating 'worst itch possible'.
Time frame: At Week 16
Population: Subjects in the full analysis set with baseline Adolescent Worst Pruritus weekly average ≥3. The full analysis set (FAS) comprised all subjects randomised to initial treatment who were exposed to IMP and not randomised at the investigational sites where substantial quality/GCP issues were identified.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Initial Treatment Period - Tralokinumab 300 mg Q2W | Participants With Reduction of Adolescent Worst Pruritus Numeric Rating Scale (NRS) (Weekly Average) of at Least 3 From Baseline to Week 16 | 28 Participants |
| Initial Treatment Period - Tralokinumab 150 mg Q2W | Participants With Reduction of Adolescent Worst Pruritus Numeric Rating Scale (NRS) (Weekly Average) of at Least 3 From Baseline to Week 16 | 29 Participants |
| Initial Treatment Period - Placebo | Participants With Reduction of Adolescent Worst Pruritus Numeric Rating Scale (NRS) (Weekly Average) of at Least 3 From Baseline to Week 16 | 8 Participants |
Comparison: Subjects with at least 3-point reduction in Adolescent Worst Pruritus NRS were considered responders. Subjects with missing data or who received rescue medication from Week 2 to Week 16 were considered non-responders. Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity. The null hypothesis of no difference in response rate between tralokinumab 300 mg Q2W and placebo was tested against the 2-sided alternative that there is a difference.p-value: <0.00195% CI: [9.7, 31]Cochran-Mantel-Haenszel
Comparison: Subjects with at least 3-point reduction in Adolescent Worst Pruritus NRS were considered responders. Subjects with missing data or who received rescue medication from Week 2 to Week 16 were considered non-responders. Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity. The null hypothesis of no difference in response rate between tralokinumab 150 mg Q2W and placebo was tested against the 2-sided alternative that there is a difference.p-value: <0.00195% CI: [10.9, 32.7]Cochran-Mantel-Haenszel
Secondary
Presence of Anti-drug Antibodies
Anti-tralokinumab antibody levels were analysed using a validated bioanalytical method.
Time frame: From Week 0 to Week 16
Population: The analysis was performed on the safety analysis set. The safety analysis set comprised all subjects randomised to initial treatment, except for subjects randomised at the investigational sites where substantial quality/GCP issues were identified and subjects for whom no post-baseline safety data were available. The safety analysis set was identical to the full analysis set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Initial Treatment Period - Tralokinumab 300 mg Q2W | Presence of Anti-drug Antibodies | 1 Participants |
| Initial Treatment Period - Tralokinumab 150 mg Q2W | Presence of Anti-drug Antibodies | 7 Participants |
| Initial Treatment Period - Placebo | Presence of Anti-drug Antibodies | 2 Participants |
Secondary
Subjects With at Least 50% Reduction in Eczema Area and Severity Index (EASI50) at Week 16.
The EASI 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: At Week 16
Population: The full analysis set (FAS: All subjects randomised to initial treatment who were exposed to IMP and not randomised at the investigational sites where substantial quality/GCP issues were identified) was used for the primary analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Initial Treatment Period - Tralokinumab 300 mg Q2W | Subjects With at Least 50% Reduction in Eczema Area and Severity Index (EASI50) at Week 16. | 50 Participants |
| Initial Treatment Period - Tralokinumab 150 mg Q2W | Subjects With at Least 50% Reduction in Eczema Area and Severity Index (EASI50) at Week 16. | 45 Participants |
| Initial Treatment Period - Placebo | Subjects With at Least 50% Reduction in Eczema Area and Severity Index (EASI50) at Week 16. | 13 Participants |
Comparison: Subjects who achieved at least 50% reduction in EASI at Week 16 were considered responders. Subjects with missing data or subjects who received rescue medication from Week 2 to Week 16 were considered non-responders. Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity. The null hypothesis of no difference in response rate between tralokinumab 300 mg Q2W and placebo was tested against the 2-sided alternative that there is a difference.p-value: <0.00195% CI: [26.8, 50.2]Cochran-Mantel-Haenszel
Comparison: Subjects who achieved at least 50% reduction in EASI at Week 16 were considered responders. Subjects with missing data or subjects who received rescue medication from Week 2 to Week 16 were considered non-responders. Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity. The null hypothesis of no difference in response rate between tralokinumab 150 mg Q2W and placebo was tested against the 2-sided alternative that there is a difference.p-value: <0.00195% CI: [20.6, 44.1]Cochran-Mantel-Haenszel
Secondary
Subjects With at Least 50% Reduction in Scoring Atopic Dermatitis (SCORAD50) at Week 16
The SCORAD is a validated tool to evaluate the extent and severity of atopic dermatitis lesions, along with subjective symptoms. The score ranges from 0 to 103, with a higher values indicating a more extensive and/or severe condition.
Time frame: At Week 16
Population: The full analysis set (FAS: All subjects randomised to initial treatment who were exposed to IMP and not randomised at the investigational sites where substantial quality/GCP issues were identified) was used for the primary analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Initial Treatment Period - Tralokinumab 300 mg Q2W | Subjects With at Least 50% Reduction in Scoring Atopic Dermatitis (SCORAD50) at Week 16 | 30 Participants |
| Initial Treatment Period - Tralokinumab 150 mg Q2W | Subjects With at Least 50% Reduction in Scoring Atopic Dermatitis (SCORAD50) at Week 16 | 30 Participants |
| Initial Treatment Period - Placebo | Subjects With at Least 50% Reduction in Scoring Atopic Dermatitis (SCORAD50) at Week 16 | 5 Participants |
Comparison: Subjects who achieved at least 50% reduction in SCORAD at Week 16 were considered responders. Subjects with missing data or subjects who received rescue medication from Week 2 to Week 16 were considered non-responders. Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity. The null hypothesis of no difference in response rate between tralokinumab 300 mg Q2W and placebo was tested against the 2-sided alternative that there is a difference.p-value: <0.00195% CI: [16.1, 36.3]Cochran-Mantel-Haenszel
Comparison: Subjects who achieved at least 50% reduction in SCORAD at Week 16 were considered responders. Subjects with missing data or subjects who received rescue medication from Week 2 to Week 16 were considered non-responders. Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity. The null hypothesis of no difference in response rate between tralokinumab 150 mg Q2W and placebo was tested against the 2-sided alternative that there is a difference.p-value: <0.00195% CI: [15.3, 35.7]Cochran-Mantel-Haenszel
Secondary
Subjects With at Least 75% Reduction in Eczema Area and Severity Index (EASI75) at Week 52 Among Subjects With at Least 75% Reduction in EASI at Week 16 After Initial Randomisation to Tralokinumab and Without Use of Rescue From Week 2 to Week 16
The EASI 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: At Week 52
Population: Subjects in the full analysis set (FAS) who were re-randomised to maintenance treatment and achieved at Least 75% Reduction in Eczema Area and Severity Index (EASI75) at Week 16 without use of rescue medication from Week 2 to Week 16.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Initial Treatment Period - Tralokinumab 300 mg Q2W | Subjects With at Least 75% Reduction in Eczema Area and Severity Index (EASI75) at Week 52 Among Subjects With at Least 75% Reduction in EASI at Week 16 After Initial Randomisation to Tralokinumab and Without Use of Rescue From Week 2 to Week 16 | 4 Participants |
| Initial Treatment Period - Tralokinumab 150 mg Q2W | Subjects With at Least 75% Reduction in Eczema Area and Severity Index (EASI75) at Week 52 Among Subjects With at Least 75% Reduction in EASI at Week 16 After Initial Randomisation to Tralokinumab and Without Use of Rescue From Week 2 to Week 16 | 7 Participants |
| Initial Treatment Period - Placebo | Subjects With at Least 75% Reduction in Eczema Area and Severity Index (EASI75) at Week 52 Among Subjects With at Least 75% Reduction in EASI at Week 16 After Initial Randomisation to Tralokinumab and Without Use of Rescue From Week 2 to Week 16 | 7 Participants |
| Maintenance Treatment Period - Tralokinumab 150 mg Q4W | Subjects With at Least 75% Reduction in Eczema Area and Severity Index (EASI75) at Week 52 Among Subjects With at Least 75% Reduction in EASI at Week 16 After Initial Randomisation to Tralokinumab and Without Use of Rescue From Week 2 to Week 16 | 7 Participants |
Secondary
Subjects With at Least 75% Reduction in Scoring Atopic Dermatitis (SCORAD75) at Week 16
The SCORAD is a validated tool to evaluate the extent and severity of atopic dermatitis lesions, along with subjective symptoms. The score ranges from 0 to 103, with a higher values indicating a more extensive and/or severe condition.
Time frame: At Week 16
Population: The full analysis set (FAS: All subjects randomised to initial treatment who were exposed to IMP and not randomised at the investigational sites where substantial quality/GCP issues were identified) was used for the primary analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Initial Treatment Period - Tralokinumab 300 mg Q2W | Subjects With at Least 75% Reduction in Scoring Atopic Dermatitis (SCORAD75) at Week 16 | 12 Participants |
| Initial Treatment Period - Tralokinumab 150 mg Q2W | Subjects With at Least 75% Reduction in Scoring Atopic Dermatitis (SCORAD75) at Week 16 | 16 Participants |
| Initial Treatment Period - Placebo | Subjects With at Least 75% Reduction in Scoring Atopic Dermatitis (SCORAD75) at Week 16 | 1 Participants |
Comparison: Subjects who achieved at least 75% reduction in SCORAD at Week 16 were considered responders. Subjects with missing data or subjects who received rescue medication from Week 2 to Week 16 were considered non-responders. Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity. The null hypothesis of no difference in response rate between tralokinumab 300 mg Q2W and placebo was tested against the 2-sided alternative that there is a difference.p-value: 0.00295% CI: [4.5, 18.4]Cochran-Mantel-Haenszel
Comparison: Subjects who achieved at least 75% reduction in SCORAD at Week 16 were considered responders. Subjects with missing data or subjects who received rescue medication from Week 2 to Week 16 were considered non-responders. Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity. The null hypothesis of no difference in response rate between tralokinumab 150 mg Q2W and placebo was tested against the 2-sided alternative that there is a difference.p-value: <0.00195% CI: [7.8, 23.3]Cochran-Mantel-Haenszel
Secondary
Subjects With at Least 90% Reduction in Eczema Area and Severity Index (EASI90) at Week 16.
The EASI 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: At Week 16
Population: The full analysis set (FAS: All subjects randomised to initial treatment who were exposed to IMP and not randomised at the investigational sites where substantial quality/GCP issues were identified) was used for the primary analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Initial Treatment Period - Tralokinumab 300 mg Q2W | Subjects With at Least 90% Reduction in Eczema Area and Severity Index (EASI90) at Week 16. | 17 Participants |
| Initial Treatment Period - Tralokinumab 150 mg Q2W | Subjects With at Least 90% Reduction in Eczema Area and Severity Index (EASI90) at Week 16. | 19 Participants |
| Initial Treatment Period - Placebo | Subjects With at Least 90% Reduction in Eczema Area and Severity Index (EASI90) at Week 16. | 4 Participants |
Comparison: Subjects who achieved at least 90% reduction in EASI at Week 16 were considered responders. Subjects with missing data or subjects who received rescue medication from Week 2 to Week 16 were considered non-responders. Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity. The null hypothesis of no difference in response rate between tralokinumab 300 mg Q2W and placebo was tested against the 2-sided alternative that there is a difference.p-value: 0.00295% CI: [5.2, 22.2]Cochran-Mantel-Haenszel
Comparison: Subjects who achieved at least 90% reduction in EASI at Week 16 were considered responders. Subjects with missing data or subjects who received rescue medication from Week 2 to Week 16 were considered non-responders. Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity. The null hypothesis of no difference in response rate between tralokinumab 150 mg Q2W and placebo was tested against the 2-sided alternative that there is a difference.p-value: <0.00195% CI: [6.5, 24.1]Cochran-Mantel-Haenszel
Secondary
Subjects With Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Week 52 Among Subjects With IGA Score of 0 or 1 at Week 16 After Initial Randomisation to Tralokinumab and Without Use of Rescue From Week 2 to Week 16
The 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: At Week 52
Population: Subjects in the full analysis set (FAS) who were re-randomised to maintenance treatment and achieved an Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Week 16 without use of rescue medication from Week 2 to Week 16.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Initial Treatment Period - Tralokinumab 300 mg Q2W | Subjects With Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Week 52 Among Subjects With IGA Score of 0 or 1 at Week 16 After Initial Randomisation to Tralokinumab and Without Use of Rescue From Week 2 to Week 16 | 3 Participants |
| Initial Treatment Period - Tralokinumab 150 mg Q2W | Subjects With Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Week 52 Among Subjects With IGA Score of 0 or 1 at Week 16 After Initial Randomisation to Tralokinumab and Without Use of Rescue From Week 2 to Week 16 | 7 Participants |
| Initial Treatment Period - Placebo | Subjects With Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Week 52 Among Subjects With IGA Score of 0 or 1 at Week 16 After Initial Randomisation to Tralokinumab and Without Use of Rescue From Week 2 to Week 16 | 6 Participants |
| Maintenance Treatment Period - Tralokinumab 150 mg Q4W | Subjects With Investigator's Global Assessment (IGA) Score of 0 (Clear) or 1 (Almost Clear) at Week 52 Among Subjects With IGA Score of 0 or 1 at Week 16 After Initial Randomisation to Tralokinumab and Without Use of Rescue From Week 2 to Week 16 | 6 Participants |
Secondary
Subjects With Reduction of Adolescent Worst Pruritus Numeric Rating Scale (NRS) (Weekly Average) of at Least 4 From Baseline to Week 16
The Adolescent Worst Pruritus NRS is used by subjects to assess their worst itch over the past 24 hours using an 11-point NRS with 0 indicating 'no itch' and 10 indicating 'worst itch possible'.
Time frame: At Week 16
Population: Subjects in the full analysis set with baseline Adolescent Worst Pruritus weekly average ≥4. The full analysis set (FAS) comprised all subjects randomised to initial treatment who were exposed to IMP and not randomised at the investigational sites where substantial quality/GCP issues were identified.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Initial Treatment Period - Tralokinumab 300 mg Q2W | Subjects With Reduction of Adolescent Worst Pruritus Numeric Rating Scale (NRS) (Weekly Average) of at Least 4 From Baseline to Week 16 | 24 Participants |
| Initial Treatment Period - Tralokinumab 150 mg Q2W | Subjects With Reduction of Adolescent Worst Pruritus Numeric Rating Scale (NRS) (Weekly Average) of at Least 4 From Baseline to Week 16 | 22 Participants |
| Initial Treatment Period - Placebo | Subjects With Reduction of Adolescent Worst Pruritus Numeric Rating Scale (NRS) (Weekly Average) of at Least 4 From Baseline to Week 16 | 3 Participants |
Comparison: Subjects with at least 4-point reduction in Adolescent Worst Pruritus NRS were considered responders. Subjects with missing data or who received rescue medication from Week 2 to Week 16 were considered non-responders. Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity. The null hypothesis of no difference in response rate between tralokinumab 300 mg Q2W and placebo was tested against the 2-sided alternative that there is a difference.p-value: <0.00195% CI: [12.3, 31.1]Cochran-Mantel-Haenszel
Comparison: Subjects with at least 4-point reduction in Adolescent Worst Pruritus NRS were considered responders. Subjects with missing data or who received rescue medication from Week 2 to Week 16 were considered non-responders. Analysis was performed using Cochran-Mantel-Haenszel test stratified by region and baseline disease severity. The null hypothesis of no difference in response rate between tralokinumab 150 mg Q2W and placebo was tested against the 2-sided alternative that there is a difference.p-value: <0.00195% CI: [10.6, 29.2]Cochran-Mantel-Haenszel
Secondary
Tralokinumab Serum Trough Concentration at Week 16
Serum samples for determination of tralokinumab concentrations were analysed by a laboratory using a validated bioanalytical method.
Time frame: At Week 16
Population: Subjects in the full analysis set who were randomised to tralokinumab. The full analysis set (FAS) comprised all subjects randomised to initial treatment who were exposed to IMP and not randomised at the investigational sites where substantial quality/GCP issues were identified.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Initial Treatment Period - Tralokinumab 300 mg Q2W | Tralokinumab Serum Trough Concentration at Week 16 | 105.7 microgram/mL | Geometric Coefficient of Variation 39 |
| Initial Treatment Period - Tralokinumab 150 mg Q2W | Tralokinumab Serum Trough Concentration at Week 16 | 56.4 microgram/mL | Geometric Coefficient of Variation 35.4 |
Secondary
Tralokinumab Serum Trough Concentration at Week 66
Serum samples for determination of tralokinumab concentrations were analysed by a laboratory using a validated bioanalytical method.
Time frame: At Week 66
Population: 13 subjects in maintenance safety analysis set who were initially randomised to tralokinumab and completed the maintenance treatment period on treatment. 234 subjects in the open-label safety analysis set.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Initial Treatment Period - Tralokinumab 300 mg Q2W | Tralokinumab Serum Trough Concentration at Week 66 | 5.9 microgram/mL | — |
| Initial Treatment Period - Tralokinumab 150 mg Q2W | Tralokinumab Serum Trough Concentration at Week 66 | 1.0 microgram/mL | Geometric Coefficient of Variation 458 |
| Initial Treatment Period - Placebo | Tralokinumab Serum Trough Concentration at Week 66 | 1.5 microgram/mL | Geometric Coefficient of Variation 168.6 |
| Maintenance Treatment Period - Tralokinumab 150 mg Q4W | Tralokinumab Serum Trough Concentration at Week 66 | 2.6 microgram/mL | Geometric Coefficient of Variation 75.6 |
| Open-label Treatment -Tralokinumab 300 mg Q2W + Optional TCS | Tralokinumab Serum Trough Concentration at Week 66 | 4.4 microgram/mL | Geometric Coefficient of Variation 136.5 |