Atopic Dermatitis
Conditions
Brief summary
This is a double-blind, multi-centre, randomised, 5-arm, vehicle-controlled, parallel-group trial. The trial is designed to establish a dose-response signal and investigate the efficacy and safety of delgocitinib cream in the treatment of adult subjects with mild to severe atopic dermatitis (AD).
Interventions
Cream for topical application
The cream vehicle is similar to the delgocitinib cream except that it does not contain any active ingredient.
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 years and above. * Diagnosis of AD as defined by the Hanifin and Rajka 1980 criteria for AD. * History of AD for ≥1 year. * AD involvement of 5-50% treatable body surface area at screening and at baseline (excluding scalp). * Disease severity graded as mild to severe according to vIGA-AD (i.e. vIGA-AD ≥2) at screening and baseline. Key
Exclusion criteria
* AD lesion(s) on scalp at screening and/or baseline. * Active dermatologic conditions that may confound the diagnosis of AD or would interfere with assessment of treatment, such as scabies, cutaneous lymphoma, rosacea, urticaria, or psoriasis. * Known active allergic or irritant contact dermatitis that is likely to interfere with the assessment of severity of AD. * Use of tanning beds or phototherapy within 4 weeks prior to baseline. * Systemic treatment with immunosuppressive/modulating drugs or corticosteroids within 4 weeks prior to baseline or 3 or more bleach baths any week within 4 weeks prior to baseline. * Treatment with topical corticosteroids, topical calcineurin inhibitors, topical phosphodiesterase-4 inhibitors, or oral antibiotics within 2 weeks prior to baseline. * Change in systemic antihistamine therapy within 2 weeks prior to baseline i.e. the subjects must not start antihistamine treatment or change the current dosage regime within 2 weeks prior to baseline. * Receipt of live attenuated vaccines within 4 weeks prior to baseline. * Treatment with any marketed or investigational biologic agents within 6 months or 5 half-lives prior to baseline, or until cell counts return to normal, whichever is longer. * History of any active skin infection within 1 week prior to baseline. * Clinically significant infection (systemic infection or serious skin infection requiring parenteral treatment) within 4 weeks prior to baseline.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline (Week 0) to Week 8 in Eczema Area and Severity Index (EASI) Score. | Week 0 to Week 8 | 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 or more extensive condition. The multiple comparison procedure - modelling (MCP-Mod) approach was used to guide dose selection. Mixed Model for Repeated Measurements (MMRM) analysis was used to determine the difference in the continuous endpoint between the active delgocitinib doses and delgocitinib cream vehicle. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Validated Investigator Global Assessment Scale for Atopic Dermatitis (vIGA-AD) Score of 0 (Clear) or 1 (Almost Clear) With ≥2-step Improvement (vIGA-AD TS) From Baseline to Week 8. | Week 0 to Week 8 | vIGA-AD is an instrument used in clinical trials to assess the subject's global disease severity and is based on a 5-point scale ranging from 0 (clear) to 4 (severe). The multiple comparison procedure - modelling (MCP-Mod) approach was used to guide dose-selection. Cochran-Mantel-Haenszel analysis was used to determine the difference in response rates between the active delgocitinib cream doses and the delgocitinib cream vehicle. |
| EASI75 at Week 8 | Week 0 to Week 8 | EASI75 is defined as at least 75% reduction in EASI from baseline. |
| Time to vIGA-AD TS | Week 0 to Week 8 | The time to vIGA-AD TS response is defined as the time from baseline to first assessment of a vIGA-AD score of 0 (Clear) or 1 (Almost Clear) with ≥2-step improvement |
Countries
Australia, Canada, United States
Participant flow
Recruitment details
251 participants from 31 sites in 3 countries (U.S., Canada and Australia) were randomised in this trial. The first participant was screened on 29-Nov-2018 and the last participant completed the trial on 19-May-2020.
Pre-assignment details
326 participants were screened for this trial. Of these, 75 participants (23.0%) were screening failures. The main reason for screening failure was failure to meet eligibility criteria (18.4%).
Participants by arm
| Arm | Count |
|---|---|
| Delgocitinib Cream 1 mg/g Delgocitinib cream applied twice daily for 8 weeks
Delgocitinib cream: Cream for topical application | 49 |
| Delgocitinib Cream 3 mg/g Delgocitinib cream applied twice daily for 8 weeks
Delgocitinib cream: Cream for topical application | 50 |
| Delgocitinib Cream 8 mg/g Delgocitinib cream applied twice daily for 8 weeks
Delgocitinib cream: Cream for topical application | 50 |
| Delgocitinib Cream 20 mg/g Delgocitinib cream applied twice daily for 8 weeks
Delgocitinib cream: Cream for topical application | 52 |
| Delgocitinib Cream Vehicle Delgocitinib cream vehicle applied twice daily for 8 weeks
Delgocitinib cream vehicle: The cream vehicle is similar to the delgocitinib cream except that it does not contain any active ingredient. | 50 |
| Total | 251 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 2 | 1 | 0 | 6 |
| Overall Study | COVID-19 situation | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Lack of Efficacy | 2 | 1 | 2 | 0 | 2 |
| Overall Study | Lost to Follow-up | 3 | 1 | 2 | 2 | 1 |
| Overall Study | Personal reasons | 0 | 0 | 1 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 4 | 1 | 0 | 4 | 4 |
Baseline characteristics
| Characteristic | Delgocitinib Cream 1 mg/g | Delgocitinib Cream 3 mg/g | Delgocitinib Cream 8 mg/g | Delgocitinib Cream 20 mg/g | Delgocitinib Cream Vehicle | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 43.8 years STANDARD_DEVIATION 16.1 | 38.5 years STANDARD_DEVIATION 16.6 | 42.0 years STANDARD_DEVIATION 17.4 | 37.4 years STANDARD_DEVIATION 14.7 | 41.3 years STANDARD_DEVIATION 19.6 | 40.5 years STANDARD_DEVIATION 17 |
| Baseline EASI score | 9.3 units on a scale STANDARD_DEVIATION 5.2 | 10.9 units on a scale STANDARD_DEVIATION 9.1 | 8.6 units on a scale STANDARD_DEVIATION 4.6 | 9.9 units on a scale STANDARD_DEVIATION 6.9 | 11.2 units on a scale STANDARD_DEVIATION 7.3 | 10.0 units on a scale STANDARD_DEVIATION 6.8 |
| Baseline vIGA-AD score 0 - Clear | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Baseline vIGA-AD score 1 - Almost clear | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Baseline vIGA-AD score 2 - Mild | 18 Participants | 18 Participants | 18 Participants | 19 Participants | 17 Participants | 90 Participants |
| Baseline vIGA-AD score 3 - Moderate | 27 Participants | 28 Participants | 28 Participants | 28 Participants | 29 Participants | 140 Participants |
| Baseline vIGA-AD score 4 - Severe | 4 Participants | 4 Participants | 4 Participants | 5 Participants | 4 Participants | 21 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 6 Participants | 5 Participants | 8 Participants | 1 Participants | 25 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 44 Participants | 44 Participants | 45 Participants | 44 Participants | 49 Participants | 226 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized American Indian or Alaska native | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Asian | 12 Participants | 9 Participants | 19 Participants | 15 Participants | 14 Participants | 69 Participants |
| Race/Ethnicity, Customized Black or African American | 3 Participants | 11 Participants | 5 Participants | 4 Participants | 8 Participants | 31 Participants |
| Race/Ethnicity, Customized Native Hawaiian or other Pacific islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized Other | 7 Participants | 2 Participants | 3 Participants | 4 Participants | 1 Participants | 17 Participants |
| Race/Ethnicity, Customized White | 27 Participants | 28 Participants | 23 Participants | 28 Participants | 26 Participants | 132 Participants |
| Region of Enrollment Australia | 11 participants | 12 participants | 12 participants | 13 participants | 11 participants | 59 participants |
| Region of Enrollment Canada | 15 participants | 9 participants | 19 participants | 15 participants | 14 participants | 72 participants |
| Region of Enrollment United States | 23 participants | 29 participants | 19 participants | 24 participants | 25 participants | 120 participants |
| Sex: Female, Male Female | 34 Participants | 33 Participants | 32 Participants | 37 Participants | 36 Participants | 172 Participants |
| Sex: Female, Male Male | 15 Participants | 17 Participants | 18 Participants | 15 Participants | 14 Participants | 79 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 |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 49 | 0 / 50 | 0 / 50 | 0 / 51 | 0 / 50 |
| other Total, other adverse events | 12 / 49 | 11 / 50 | 8 / 50 | 12 / 51 | 11 / 50 |
| serious Total, serious adverse events | 1 / 49 | 1 / 50 | 0 / 50 | 0 / 51 | 1 / 50 |
Outcome results
Primary
Change From Baseline (Week 0) to Week 8 in Eczema Area and Severity Index (EASI) Score.
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 or more extensive condition. The multiple comparison procedure - modelling (MCP-Mod) approach was used to guide dose selection. Mixed Model for Repeated Measurements (MMRM) analysis was used to determine the difference in the continuous endpoint between the active delgocitinib doses and delgocitinib cream vehicle.
Time frame: Week 0 to Week 8
Population: FAS (defined as all randomized subjects exposed to investigational medicinal product)
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Delgocitinib Cream 1 mg/g | Change From Baseline (Week 0) to Week 8 in Eczema Area and Severity Index (EASI) Score. | -5.0 score on a scale | Standard Error 0.7 |
| Delgocitinib Cream 3 mg/g | Change From Baseline (Week 0) to Week 8 in Eczema Area and Severity Index (EASI) Score. | -4.9 score on a scale | Standard Error 0.7 |
| Delgocitinib Cream 8 mg/g | Change From Baseline (Week 0) to Week 8 in Eczema Area and Severity Index (EASI) Score. | -5.8 score on a scale | Standard Error 0.7 |
| Delgocitinib Cream 20 mg/g | Change From Baseline (Week 0) to Week 8 in Eczema Area and Severity Index (EASI) Score. | -7.6 score on a scale | Standard Error 0.7 |
| Delgocitinib Cream Vehicle | Change From Baseline (Week 0) to Week 8 in Eczema Area and Severity Index (EASI) Score. | -1.9 score on a scale | Standard Error 0.8 |
Comparison: The primary endpoint was evaluated by determining if there was a dose-response relationship between the change from baseline to Week 8 in EASI score and the dose administered using the Multiple Comparison Procedure - Modelling (MCP-Mod) methodology. Several candidate parametric models were assumed and multiple comparison techniques were used to choose the model(s) likely to present the true underlying dose-response curve.p-value: <0.0001Multiple contrast test
Comparison: Least square (LS) means were calculated using a mixed model response model (MMRM) on post-baseline responses up to Week 8 with an unstructured covariance matrix, Kenward-Roger approximation to estimate denominator degrees of freedom and the mean modelled as follows:~Change from baseline in EASI = treatment x visit + baseline EASI x visit + region + baseline vIGA-AD.~The primary comparison between each active delgocitinib dose and delgocitinib cream vehicle was at Week 8.p-value: <0.0195% CI: [-5, -1.3]Mixed Models Analysis
Comparison: Least square (LS) means were calculated using a mixed model response model (MMRM) on post-baseline responses up to Week 8 with an unstructured covariance matrix, Kenward-Roger approximation to estimate denominator degrees of freedom and the mean modelled as follows:~Change from baseline in EASI = treatment x visit + baseline EASI x visit + region + baseline vIGA-AD.~The primary comparison between each active delgocitinib dose and delgocitinib cream vehicle was at Week 8.p-value: <0.0595% CI: [-4.8, -1.2]Mixed Models Analysis
Comparison: Least square (LS) means were calculated using a mixed model response model (MMRM) on post-baseline responses up to Week 8 with an unstructured covariance matrix, Kenward-Roger approximation to estimate denominator degrees of freedom and the mean modelled as follows:~Change from baseline in EASI = treatment x visit + baseline EASI x visit + region + baseline vIGA-AD.~The primary comparison between each active delgocitinib dose and delgocitinib cream vehicle was at Week 8.p-value: <0.000195% CI: [-5.8, -2.1]Mixed Models Analysis
Comparison: Least square (LS) means were calculated using a mixed model response model (MMRM) on post-baseline responses up to Week 8 with an unstructured covariance matrix, Kenward-Roger approximation to estimate denominator degrees of freedom and the mean modelled as follows:~Change from baseline in EASI = treatment x visit + baseline EASI x visit + region + baseline vIGA-AD.~The primary comparison between each active delgocitinib dose and delgocitinib cream vehicle was at Week 8.p-value: <0.000195% CI: [-7.5, -3.9]Mixed Models Analysis
Secondary
EASI75 at Week 8
EASI75 is defined as at least 75% reduction in EASI from baseline.
Time frame: Week 0 to Week 8
Population: FAS (defined as all randomized subjects exposed to investigational medicinal product).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Delgocitinib Cream 1 mg/g | EASI75 at Week 8 | 20 Participants |
| Delgocitinib Cream 3 mg/g | EASI75 at Week 8 | 21 Participants |
| Delgocitinib Cream 8 mg/g | EASI75 at Week 8 | 28 Participants |
| Delgocitinib Cream 20 mg/g | EASI75 at Week 8 | 33 Participants |
| Delgocitinib Cream Vehicle | EASI75 at Week 8 | 10 Participants |
Comparison: This endpoint was evaluated by determining if there was a dose-response relationship between EASI75 at Week 8 and the dose administered using the Multiple Comparison Procedure - Modelling (MCP-Mod) methodology. Several candidate parametric models were assumed and multiple comparison techniques were used to choose the model(s) most likely to represent the true underlying dose-responsep-value: <0.0001Multiple contrast test
Comparison: The difference in response rates between the active delgocitinib cream doses and delgocitinib cream vehicle was analysed separately for each of the active dose groups using the Cochran-Mantel-Haenszel test stratified by region and disease severity (baseline vIGA-AD score). The null hypothesis of no difference in response rates between the delgocitinib cream active doses and delgocitinib cream vehicle was tested against the 2-sided alternative test that there is a differencep-value: <0.0595% CI: [1.8, 37.6]Cochran-Mantel-Haenszel
Comparison: The difference in response rates between the active delgocitinib cream doses and delgocitinib cream vehicle was analysed separately for each of the active dose groups using the Cochran-Mantel-Haenszel test stratified by region and disease severity (baseline vIGA-AD score). The null hypothesis of no difference in response rates between the delgocitinib cream active doses and delgocitinib cream vehicle was tested against the 2-sided alternative test that there is a differencep-value: <0.0595% CI: [5.8, 41.2]Cochran-Mantel-Haenszel
Comparison: The difference in response rates between the active delgocitinib cream doses and delgocitinib cream vehicle was analysed separately for each of the active dose groups using the Cochran-Mantel-Haenszel test stratified by region and disease severity (baseline vIGA-AD score). The null hypothesis of no difference in response rates between the delgocitinib cream active doses and delgocitinib cream vehicle was tested against the 2-sided alternative test that there is a differencep-value: <0.000595% CI: [17.5, 53.2]Cochran-Mantel-Haenszel
Comparison: The difference in response rates between the active delgocitinib cream doses and delgocitinib cream vehicle was analysed separately for each of the active dose groups using the Cochran-Mantel-Haenszel test stratified by region and disease severity (baseline vIGA-AD score). The null hypothesis of no difference in response rates between the delgocitinib cream active doses and delgocitinib cream vehicle was tested against the 2-sided alternative test that there is a differencep-value: <0.000195% CI: [28.1, 62.8]Cochran-Mantel-Haenszel
Secondary
Time to vIGA-AD TS
The time to vIGA-AD TS response is defined as the time from baseline to first assessment of a vIGA-AD score of 0 (Clear) or 1 (Almost Clear) with ≥2-step improvement
Time frame: Week 0 to Week 8
Population: FAS (defined as all randomized subjects exposed to investigational medicinal product)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Delgocitinib Cream 1 mg/g | Time to vIGA-AD TS | 64 Days |
| Delgocitinib Cream 3 mg/g | Time to vIGA-AD TS | NA Days |
| Delgocitinib Cream 8 mg/g | Time to vIGA-AD TS | 64 Days |
| Delgocitinib Cream 20 mg/g | Time to vIGA-AD TS | 44 Days |
| Delgocitinib Cream Vehicle | Time to vIGA-AD TS | NA Days |
Comparison: Time to vIGA-AD TS was def. as time from date of first IMP applic. to first assess. of vIGA-AD TS. Subjects without baseline observation were censored at date of first IMP applic. Subjects with baseline observation not achieving vIGA-AD TS during treatment period were censored at date of last visit with a valid post-baseline assess. on or prior to date of discont. of IMP or initiation of rescue med, whichever occurred first. Subjects affected by COVID-19 pandemic were handled in the same manner.p-value: >0.05Log Rank
Comparison: Time to vIGA-AD TS was def. as time from date of first IMP applic. to first assess. of vIGA-AD TS. Subjects without baseline observation were censored at date of first IMP applic. Subjects with baseline observation not achieving vIGA-AD TS during treatment period were censored at date of last visit with a valid post-baseline assess. on or prior to date of discont. of IMP or initiation of rescue med, whichever occurred first. Subjects affected by COVID-19 pandemic were handled in the same manner.p-value: >0.05Log Rank
Comparison: Time to vIGA-AD TS was def. as time from date of first IMP applic. to first assess. of vIGA-AD TS. Subjects without baseline observation were censored at date of first IMP applic. Subjects with baseline observation not achieving vIGA-AD TS during treatment period were censored at date of last visit with a valid post-baseline assess. on or prior to date of discont. of IMP or initiation of rescue med, whichever occurred first. Subjects affected by COVID-19 pandemic were handled in the same mannerp-value: >0.05Log Rank
Comparison: Time to vIGA-AD TS was def. as time from date of first IMP applic. to first assess. of vIGA-AD TS. Subjects without baseline observation were censored at date of first IMP applic. Subjects with baseline observation not achieving vIGA-AD TS during treatment period were censored at date of last visit with a valid post-baseline assess. on or prior to date of discont. of IMP or initiation of rescue med, whichever occurred first. Subjects affected by COVID-19 pandemic were handled in the same mannerp-value: <0.001Log Rank
Secondary
Validated Investigator Global Assessment Scale for Atopic Dermatitis (vIGA-AD) Score of 0 (Clear) or 1 (Almost Clear) With ≥2-step Improvement (vIGA-AD TS) From Baseline to Week 8.
vIGA-AD is an instrument used in clinical trials to assess the subject's global disease severity and is based on a 5-point scale ranging from 0 (clear) to 4 (severe). The multiple comparison procedure - modelling (MCP-Mod) approach was used to guide dose-selection. Cochran-Mantel-Haenszel analysis was used to determine the difference in response rates between the active delgocitinib cream doses and the delgocitinib cream vehicle.
Time frame: Week 0 to Week 8
Population: FAS (defined as all randomized subjects exposed to investigational medicinal product).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Delgocitinib Cream 1 mg/g | Validated Investigator Global Assessment Scale for Atopic Dermatitis (vIGA-AD) Score of 0 (Clear) or 1 (Almost Clear) With ≥2-step Improvement (vIGA-AD TS) From Baseline to Week 8. | 9 Participants |
| Delgocitinib Cream 3 mg/g | Validated Investigator Global Assessment Scale for Atopic Dermatitis (vIGA-AD) Score of 0 (Clear) or 1 (Almost Clear) With ≥2-step Improvement (vIGA-AD TS) From Baseline to Week 8. | 14 Participants |
| Delgocitinib Cream 8 mg/g | Validated Investigator Global Assessment Scale for Atopic Dermatitis (vIGA-AD) Score of 0 (Clear) or 1 (Almost Clear) With ≥2-step Improvement (vIGA-AD TS) From Baseline to Week 8. | 15 Participants |
| Delgocitinib Cream 20 mg/g | Validated Investigator Global Assessment Scale for Atopic Dermatitis (vIGA-AD) Score of 0 (Clear) or 1 (Almost Clear) With ≥2-step Improvement (vIGA-AD TS) From Baseline to Week 8. | 24 Participants |
| Delgocitinib Cream Vehicle | Validated Investigator Global Assessment Scale for Atopic Dermatitis (vIGA-AD) Score of 0 (Clear) or 1 (Almost Clear) With ≥2-step Improvement (vIGA-AD TS) From Baseline to Week 8. | 5 Participants |
Comparison: This endpoint was evaluated by determining if there was a dose-response relationship between the vIGA-AD response rate at Week 8 and the dose administered using the Multiple Comparison Procedure - Modelling (MCP-Mod) methodology. Several candidate parametric models were assumed and multiple comparison techniques were used to choose the model(s) most likely to represent the true underlying dose-response.p-value: <0.0001Multiple contrast test
Comparison: The difference in response rates between the active delgocitinib cream doses and delgocitinib cream vehicle was analysed separately for each of the active dose groups using the Cochran-Mantel-Haenszel test stratified by region and disease severity (baseline vIGA-AD score). The null hypothesis of no difference in response rates between the delgocitinib cream active doses and delgocitinib cream vehicle was tested against the 2-sided alternative test that there is a difference.p-value: >0.0595% CI: [-5.6, 21.9]Cochran-Mantel-Haenszel
Comparison: The difference in response rates between the active delgocitinib cream doses and delgocitinib cream vehicle was analysed separately for each of the active dose groups using the Cochran-Mantel-Haenszel test stratified by region and disease severity (baseline vIGA-AD score). The null hypothesis of no difference in response rates between the delgocitinib cream active doses and delgocitinib cream vehicle was tested against the 2-sided alternative test that there is a difference.p-value: <0.0595% CI: [3.9, 34.6]Cochran-Mantel-Haenszel
Comparison: The difference in response rates between the active delgocitinib cream doses and delgocitinib cream vehicle was analysed separately for each of the active dose groups using the Cochran-Mantel-Haenszel test stratified by region and disease severity (baseline vIGA-AD score). The null hypothesis of no difference in response rates between the delgocitinib cream active doses and delgocitinib cream vehicle was tested against the 2-sided alternative test that there is a differencep-value: <0.0595% CI: [5.4, 35.2]Cochran-Mantel-Haenszel
Comparison: The difference in response rates between the active delgocitinib cream doses and delgocitinib cream vehicle was analysed separately for each of the active dose groups using the Cochran-Mantel-Haenszel test stratified by region and disease severity (baseline vIGA-AD score). The null hypothesis of no difference in response rates between the delgocitinib cream active doses and delgocitinib cream vehicle was tested against the 2-sided alternative test that there is a differencep-value: <0.000195% CI: [22.3, 54.3]Cochran-Mantel-Haenszel