Clinical Trial Results:
A phase 3 clinical trial to confirm efficacy and evaluate safety of twice-daily delgocitinib cream 20 mg/g compared with cream vehicle for a 16-week treatment period in adult subjects with moderate to severe chronic hand eczema (DELTA 1)
|
Summary
|
|
EudraCT number |
2020-002960-30 |
Trial protocol |
PL IT |
Global end of trial date |
31 Oct 2022
|
|
Results information
|
|
Results version number |
v1(current) |
This version publication date |
15 Nov 2023
|
First version publication date |
15 Nov 2023
|
Other versions |
|
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
|
|||
|
Trial identification
|
|||
Sponsor protocol code |
LP0133-1401
|
||
|
Additional study identifiers
|
|||
ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
|
Sponsors
|
|||
Sponsor organisation name |
LEO Pharma A/S
|
||
Sponsor organisation address |
Industriparken 55, Ballerup, Denmark, 2750
|
||
Public contact |
Clinical Disclosure, LEO Pharma A/S, disclosure@leo-pharma.com
|
||
Scientific contact |
Clinical Disclosure, LEO Pharma A/S, disclosure@leo-pharma.com
|
||
|
Paediatric regulatory details
|
|||
Is trial part of an agreed paediatric investigation plan (PIP) |
No
|
||
Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
|
||
|
Results analysis stage
|
|||
Analysis stage |
Final
|
||
Date of interim/final analysis |
17 Nov 2022
|
||
Is this the analysis of the primary completion data? |
Yes
|
||
Primary completion date |
31 Oct 2022
|
||
Global end of trial reached? |
Yes
|
||
Global end of trial date |
31 Oct 2022
|
||
Was the trial ended prematurely? |
No
|
||
|
General information about the trial
|
|||
Main objective of the trial |
To confirm the efficacy of twice-daily applications of delgocitinib cream 20 mg/g compared with cream vehicle in the treatment of adult subjects with moderate to severe chronic hand eczema (CHE).
|
||
Protection of trial subjects |
This clinical trial was conducted to conform to the principles of the Declaration of Helsinki, the International Council for Harmonisation (ICH) Good Clinical Practice (GCP) guidelines, in compliance with the approved protocol, and applicable regulatory requirements.
|
||
Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
10 May 2021
|
||
Long term follow-up planned |
No
|
||
Independent data monitoring committee (IDMC) involvement? |
No
|
||
|
Population of trial subjects
|
|||
Number of subjects enrolled per country |
|||
Country: Number of subjects enrolled |
Poland: 105
|
||
Country: Number of subjects enrolled |
France: 81
|
||
Country: Number of subjects enrolled |
Germany: 135
|
||
Country: Number of subjects enrolled |
Italy: 45
|
||
Country: Number of subjects enrolled |
Canada: 97
|
||
Country: Number of subjects enrolled |
United Kingdom: 24
|
||
Worldwide total number of subjects |
487
|
||
EEA total number of subjects |
366
|
||
Number of subjects enrolled per age group |
|||
In utero |
0
|
||
Preterm newborn - gestational age < 37 wk |
0
|
||
Newborns (0-27 days) |
0
|
||
Infants and toddlers (28 days-23 months) |
0
|
||
Children (2-11 years) |
0
|
||
Adolescents (12-17 years) |
0
|
||
Adults (18-64 years) |
451
|
||
From 65 to 84 years |
35
|
||
85 years and over |
1
|
||
|
||||||||||||||||||||||||||||
|
Recruitment
|
||||||||||||||||||||||||||||
Recruitment details |
487 participants from 51 sites in 6 countries (Canada, France, Germany, Italy, Poland, and United Kingdom) were randomised in this trial. The first participant was screened on 10-May-2021 and the last participant completed the trial on 31-Oct-2022. | |||||||||||||||||||||||||||
|
Pre-assignment
|
||||||||||||||||||||||||||||
Screening details |
566 participants were screened in this trial. Of these, 79 participants (14.0%) were excluded prior to randomisation. The main reason for exclusion prior to randomisation was screening failure (11.1%). | |||||||||||||||||||||||||||
|
Period 1
|
||||||||||||||||||||||||||||
Period 1 title |
Overall study (overall period)
|
|||||||||||||||||||||||||||
Is this the baseline period? |
Yes | |||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
|
|||||||||||||||||||||||||||
Blinding used |
Double blind | |||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator, Assessor | |||||||||||||||||||||||||||
Blinding implementation details |
This was a double-blind trial. The packaging and labelling of the IMPs contained no evidence of their identity. It was not considered possible to differentiate between the IMPs solely by sensory evaluation.
|
|||||||||||||||||||||||||||
|
Arms
|
||||||||||||||||||||||||||||
Are arms mutually exclusive |
Yes
|
|||||||||||||||||||||||||||
|
Arm title
|
Delgocitinib cream 20 mg/g | |||||||||||||||||||||||||||
Arm description |
- | |||||||||||||||||||||||||||
Arm type |
Experimental | |||||||||||||||||||||||||||
Investigational medicinal product name |
Delgocitinib cream
|
|||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||||
Pharmaceutical forms |
Cream
|
|||||||||||||||||||||||||||
Routes of administration |
Topical use
|
|||||||||||||||||||||||||||
Dosage and administration details |
A thin layer covering the affected areas twice daily for 16 weeks. The applications were to be performed approximately 12 hours apart to clean and dry skin of the affected areas of the hands and wrists.
|
|||||||||||||||||||||||||||
|
Arm title
|
Cream vehicle | |||||||||||||||||||||||||||
Arm description |
- | |||||||||||||||||||||||||||
Arm type |
Placebo | |||||||||||||||||||||||||||
Investigational medicinal product name |
Cream vehicle
|
|||||||||||||||||||||||||||
Investigational medicinal product code |
||||||||||||||||||||||||||||
Other name |
||||||||||||||||||||||||||||
Pharmaceutical forms |
Cream
|
|||||||||||||||||||||||||||
Routes of administration |
Topical use
|
|||||||||||||||||||||||||||
Dosage and administration details |
A thin layer covering the affected areas twice daily for 16 weeks. The applications were to be performed approximately 12 hours apart to clean and dry skin of the affected areas of the hands and wrists.
|
|||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Baseline characteristics reporting groups
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Delgocitinib cream 20 mg/g
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Cream vehicle
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
|
End points reporting groups
|
|||
Reporting group title |
Delgocitinib cream 20 mg/g
|
||
Reporting group description |
- | ||
Reporting group title |
Cream vehicle
|
||
Reporting group description |
- | ||
|
||||||||||
End point title |
Investigator’s Global Assessment for chronic hand eczema (IGA-CHE) score of 0 (clear) or 1 (almost clear) with at least a 2-step improvement from baseline (IGA-CHE treatment success [IGA-CHE TS]) at Week 16. | |||||||||
End point description |
IGA-CHE rates the severity of the participant's global disease and is based on a 5-point scale ranging from 0 (clear) to 4 (severe).
|
|||||||||
End point type |
Primary
|
|||||||||
End point timeframe |
Week 0 to Week 16
|
|||||||||
|
||||||||||
Statistical analysis title |
Delgocitinib cream 20 mg/g vs. cream vehicle | |||||||||
Statistical analysis description |
Based on the primary analysis of the primary estimand 'composite'. The difference in response rates between delgocitinib cream 20 mg/g and cream vehicle was analysed using the Cochran-Mantel-Haenszel test stratified by region and disease severity (baseline IGA-CHE score). Subjects with missing data, subjects who received rescue treatment, or subjects who permanently discontinued IMP were considered non-responders.
|
|||||||||
Comparison groups |
Delgocitinib cream 20 mg/g v Cream vehicle
|
|||||||||
Number of subjects included in analysis |
487
|
|||||||||
Analysis specification |
Pre-specified
|
|||||||||
Analysis type |
superiority | |||||||||
P-value |
= 0.006 [1] | |||||||||
Method |
Cochran-Mantel-Haenszel | |||||||||
Parameter type |
Risk difference (RD) | |||||||||
Point estimate |
9.8
|
|||||||||
Confidence interval |
||||||||||
level |
95% | |||||||||
sides |
2-sided
|
|||||||||
lower limit |
3.6 | |||||||||
upper limit |
16.1 | |||||||||
| Notes [1] - 5% significance level (two-sided). |
||||||||||
|
||||||||||
End point title |
IGA-CHE TS at Week 8. | |||||||||
End point description |
IGA-CHE rates the severity of the participant's global disease and is based on a 5-point scale ranging from 0 (clear) to 4 (severe).
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
Week 0 to Week 8
|
|||||||||
|
||||||||||
Statistical analysis title |
Delgocitinib cream 20 mg/g vs. cream vehicle | |||||||||
Statistical analysis description |
Based on the primary analysis of the primary estimand 'composite'. The difference in response rates between delgocitinib cream 20 mg/g and cream vehicle was analysed using the Cochran-Mantel-Haenszel test stratified by region and disease severity (baseline IGA-CHE score). Subjects with missing data, subjects who received rescue treatment, or subjects who permanently discontinued IMP were considered non-responders.
|
|||||||||
Comparison groups |
Delgocitinib cream 20 mg/g v Cream vehicle
|
|||||||||
Number of subjects included in analysis |
487
|
|||||||||
Analysis specification |
Pre-specified
|
|||||||||
Analysis type |
superiority | |||||||||
P-value |
= 0.001 [2] | |||||||||
Method |
Cochran-Mantel-Haenszel | |||||||||
Parameter type |
Risk difference (RD) | |||||||||
Point estimate |
12.3
|
|||||||||
Confidence interval |
||||||||||
level |
95% | |||||||||
sides |
2-sided
|
|||||||||
lower limit |
5.7 | |||||||||
upper limit |
18.9 | |||||||||
| Notes [2] - Evaluated at 4% significance level (two-sided) and significant as per testing hierarchy using hierarchical tests, alpha splitting and alpha recycling controlling overall type 1 error at 5% (two-sided). |
||||||||||
|
||||||||||
End point title |
IGA-CHE TS at Week 4. | |||||||||
End point description |
IGA-CHE rates the severity of the participant's global disease and is based on a 5-point scale ranging from 0 (clear) to 4 (severe).
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
Week 0 to Week 4
|
|||||||||
|
||||||||||
Statistical analysis title |
Delgocitinib cream 20 mg/g vs. cream vehicle | |||||||||
Statistical analysis description |
Based on the primary analysis of the primary estimand 'composite'. The difference in response rates between delgocitinib cream 20 mg/g and cream vehicle was analysed using the Cochran-Mantel-Haenszel test stratified by region and disease severity (baseline IGA-CHE score). Subjects with missing data, subjects who received rescue treatment, or subjects who permanently discontinued IMP were considered non-responders.
|
|||||||||
Comparison groups |
Delgocitinib cream 20 mg/g v Cream vehicle
|
|||||||||
Number of subjects included in analysis |
487
|
|||||||||
Analysis specification |
Pre-specified
|
|||||||||
Analysis type |
superiority | |||||||||
P-value |
< 0.001 [3] | |||||||||
Method |
Cochran-Mantel-Haenszel | |||||||||
Parameter type |
Risk difference (RD) | |||||||||
Point estimate |
10.4
|
|||||||||
Confidence interval |
||||||||||
level |
95% | |||||||||
sides |
2-sided
|
|||||||||
lower limit |
5.3 | |||||||||
upper limit |
15.6 | |||||||||
| Notes [3] - Evaluated at 4% significance level (two-sided) and significant as per testing hierarchy using hierarchical tests, alpha splitting and alpha recycling controlling overall type 1 error at 5% (two-sided). |
||||||||||
|
||||||||||
End point title |
At least 75% improvement in Hand Eczema Severity Index (HECSI) score from baseline (HECSI-75) at Week 16. | |||||||||
End point description |
HECSI is an instrument used in clinical trials to rate the severity of 6 clinical signs of hand eczema and the extent of the lesions on each of 5 hand areas by use of standard scales. The total HECSI score is based on a 4-point severity scale ranging from 0 (none/absent) to 3 (severe) and a 5-point scale rating the affected area(s) ranging from 0 (0% affected area) to 4 (76% to 100% affected area). The highest possible HECSI score is 360.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
Week 0 to Week 16
|
|||||||||
|
||||||||||
Statistical analysis title |
Delgocitinib cream 20 mg/g vs. cream vehicle | |||||||||
Statistical analysis description |
Based on the primary analysis of the primary estimand 'composite'. The difference in response rates between delgocitinib cream 20 mg/g and cream vehicle was analysed using the Cochran-Mantel-Haenszel test stratified by region and disease severity (baseline IGA-CHE score). Subjects with missing data, subjects who received rescue treatment, or subjects who permanently discontinued IMP were considered non-responders.
|
|||||||||
Comparison groups |
Delgocitinib cream 20 mg/g v Cream vehicle
|
|||||||||
Number of subjects included in analysis |
487
|
|||||||||
Analysis specification |
Pre-specified
|
|||||||||
Analysis type |
superiority | |||||||||
P-value |
< 0.001 [4] | |||||||||
Method |
Cochran-Mantel-Haenszel | |||||||||
Parameter type |
Risk difference (RD) | |||||||||
Point estimate |
25.7
|
|||||||||
Confidence interval |
||||||||||
level |
95% | |||||||||
sides |
2-sided
|
|||||||||
lower limit |
17.2 | |||||||||
upper limit |
34.3 | |||||||||
| Notes [4] - Evaluated at 1% significance level (two-sided) and significant as per testing hierarchy using hierarchical tests, alpha splitting and alpha recycling controlling overall type 1 error at 5% (two-sided). |
||||||||||
|
||||||||||
End point title |
HECSI-75 at Week 8. | |||||||||
End point description |
HECSI is an instrument used in clinical trials to rate the severity of 6 clinical signs of hand eczema and the extent of the lesions on each of 5 hand areas by use of standard scales. The total HECSI score is based on a 4-point severity scale ranging from 0 (none/absent) to 3 (severe) and a 5-point scale rating the affected area(s) ranging from 0 (0% affected area) to 4 (76% to 100% affected area). The highest possible HECSI score is 360.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
Week 0 to Week 8
|
|||||||||
|
||||||||||
Statistical analysis title |
Delgocitinib cream 20 mg/g vs. cream vehicle | |||||||||
Statistical analysis description |
Based on the primary analysis of the primary estimand 'composite'. The difference in response rates between delgocitinib cream 20 mg/g and cream vehicle was analysed using the Cochran-Mantel-Haenszel test stratified by region and disease severity (baseline IGA-CHE score). Subjects with missing data, subjects who received rescue treatment, or subjects who permanently discontinued IMP were considered non-responders.
|
|||||||||
Comparison groups |
Delgocitinib cream 20 mg/g v Cream vehicle
|
|||||||||
Number of subjects included in analysis |
487
|
|||||||||
Analysis specification |
Pre-specified
|
|||||||||
Analysis type |
superiority | |||||||||
P-value |
< 0.001 [5] | |||||||||
Method |
Cochran-Mantel-Haenszel | |||||||||
Parameter type |
Risk difference (RD) | |||||||||
Point estimate |
24.2
|
|||||||||
Confidence interval |
||||||||||
level |
95% | |||||||||
sides |
2-sided
|
|||||||||
lower limit |
15.5 | |||||||||
upper limit |
33 | |||||||||
| Notes [5] - Evaluated at 1% significance level (two-sided) and significant as per testing hierarchy using hierarchical tests, alpha splitting and alpha recycling controlling overall type 1 error at 5% (two-sided). |
||||||||||
|
||||||||||
End point title |
At least 90% improvement in HECSI score from baseline (HECSI-90) at Week 16. | |||||||||
End point description |
HECSI is an instrument used in clinical trials to rate the severity of 6 clinical signs of hand eczema and the extent of the lesions on each of 5 hand areas by use of standard scales. The total HECSI score is based on a 4-point severity scale ranging from 0 (none/absent) to 3 (severe) and a 5-point scale rating the affected area(s) ranging from 0 (0% affected area) to 4 (76% to 100% affected area). The highest possible HECSI score is 360.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
Week 0 to Week 16
|
|||||||||
|
||||||||||
Statistical analysis title |
Delgocitinib cream 20 mg/g vs. cream vehicle | |||||||||
Statistical analysis description |
Based on the primary analysis of the primary estimand 'composite'. The difference in response rates between delgocitinib cream 20 mg/g and cream vehicle was analysed using the Cochran-Mantel-Haenszel test stratified by region and disease severity (baseline IGA-CHE score). Subjects with missing data, subjects who received rescue treatment, or subjects who permanently discontinued IMP were considered non-responders.
|
|||||||||
Comparison groups |
Delgocitinib cream 20 mg/g v Cream vehicle
|
|||||||||
Number of subjects included in analysis |
487
|
|||||||||
Analysis specification |
Pre-specified
|
|||||||||
Analysis type |
superiority | |||||||||
P-value |
< 0.001 [6] | |||||||||
Method |
Cochran-Mantel-Haenszel | |||||||||
Parameter type |
Risk difference (RD) | |||||||||
Point estimate |
17.2
|
|||||||||
Confidence interval |
||||||||||
level |
95% | |||||||||
sides |
2-sided
|
|||||||||
lower limit |
10.1 | |||||||||
upper limit |
24.3 | |||||||||
| Notes [6] - Evaluated at 1% significance level (two-sided) and significant as per testing hierarchy using hierarchical tests, alpha splitting and alpha recycling controlling overall type 1 error at 5% (two-sided). |
||||||||||
|
|||||||||||||
End point title |
Percentage change in HECSI score from baseline to Week 16. | ||||||||||||
End point description |
HECSI is an instrument used in clinical trials to rate the severity of 6 clinical signs of hand eczema and the extent of the lesions on each of 5 hand areas by use of standard scales. The total HECSI score is based on a 4-point severity scale ranging from 0 (none/absent) to 3 (severe) and a 5-point scale rating the affected area(s) ranging from 0 (0% affected area) to 4 (76% to 100% affected area). The highest possible HECSI score is 360.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 0 to Week 16
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Delgocitinib cream 20 mg/g vs. cream vehicle | ||||||||||||
Statistical analysis description |
Primary analysis of primary estimand 'composite'. The percentage change from baseline was analysed using an ANCOVA model with effects of treatment group, region, baseline IGA-CHE score, and baseline HESCI value. Missing data for subjects who did not attend the visit was imputed as WOCF (including baseline value). For subjects who received rescue treatment or subjects who have permanently discontinued the IMP, observed data was considered non-response by using WOCF (including baseline value).
|
||||||||||||
Comparison groups |
Delgocitinib cream 20 mg/g v Cream vehicle
|
||||||||||||
Number of subjects included in analysis |
487
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.001 [7] | ||||||||||||
Method |
ANCOVA | ||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
-35.2
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-46.7 | ||||||||||||
upper limit |
-23.8 | ||||||||||||
| Notes [7] - Evaluated at 1% significance level (two-sided) and significant as per testing hierarchy using hierarchical tests, alpha splitting and alpha recycling controlling overall type 1 error at 5% (two-sided). |
|||||||||||||
|
||||||||||
End point title |
Reduction of Hand Eczema Symptom Diary (HESD) itch score (weekly average) of ≥4 points from baseline at Week 16. | |||||||||
End point description |
HESD is a 6-item PRO instrument designed to assess severity of CHE signs and symptoms. Participants assess the worst severity of 6 individual signs and symptoms of CHE over the past 24 hours using an 11-point numeric rating scale with anchors of 0 =‘no (symptom)’ and 10 =‘severe (symptom)’. The HESD score is derived as an average of the 6 items.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
Week 0 to Week 16
|
|||||||||
|
||||||||||
Statistical analysis title |
Delgocitinib cream 20 mg/g vs. cream vehicle | |||||||||
Statistical analysis description |
Based on the primary analysis of the primary estimand 'composite'. The difference in response rates between delgocitinib cream 20 mg/g and cream vehicle was analysed using the Cochran-Mantel-Haenszel test stratified by region and disease severity (baseline IGA-CHE score). Subjects with missing data, subjects who received rescue treatment, or subjects who permanently discontinued IMP were considered non-responders.
|
|||||||||
Comparison groups |
Cream vehicle v Delgocitinib cream 20 mg/g
|
|||||||||
Number of subjects included in analysis |
484
|
|||||||||
Analysis specification |
Pre-specified
|
|||||||||
Analysis type |
superiority [8] | |||||||||
P-value |
< 0.001 | |||||||||
Method |
Cochran-Mantel-Haenszel | |||||||||
Parameter type |
Risk difference (RD) | |||||||||
Point estimate |
24.1
|
|||||||||
Confidence interval |
||||||||||
level |
95% | |||||||||
sides |
2-sided
|
|||||||||
lower limit |
15.5 | |||||||||
upper limit |
32.6 | |||||||||
| Notes [8] - Evaluated at 5% significance level (two-sided) and significant as per testing hierarchy using hierarchical tests, alpha splitting and alpha recycling controlling overall type 1 error at 5% (two-sided). |
||||||||||
|
||||||||||
End point title |
Reduction of HESD itch score (weekly average) of ≥4 points from baseline at Week 8. | |||||||||
End point description |
HESD is a 6-item PRO instrument designed to assess severity of CHE signs and symptoms. Participants assess the worst severity of 6 individual signs and symptoms of CHE over the past 24 hours using an 11-point numeric rating scale with anchors of 0 =‘no (symptom)’ and 10 =‘severe (symptom)’. The HESD score is derived as an average of the 6 items.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
Week 0 to Week 8
|
|||||||||
|
||||||||||
Statistical analysis title |
Delgocitinib cream 20 mg/g vs. cream vehicle | |||||||||
Statistical analysis description |
Based on the primary analysis of the primary estimand 'composite'. The difference in response rates between delgocitinib cream 20 mg/g and cream vehicle was analysed using the Cochran-Mantel-Haenszel test stratified by region and disease severity (baseline IGA-CHE score). Subjects with missing data, subjects who received rescue treatment, or subjects who permanently discontinued IMP were considered non-responders.
|
|||||||||
Comparison groups |
Delgocitinib cream 20 mg/g v Cream vehicle
|
|||||||||
Number of subjects included in analysis |
484
|
|||||||||
Analysis specification |
Pre-specified
|
|||||||||
Analysis type |
superiority | |||||||||
P-value |
< 0.001 [9] | |||||||||
Method |
Cochran-Mantel-Haenszel | |||||||||
Parameter type |
Risk difference (RD) | |||||||||
Point estimate |
21
|
|||||||||
Confidence interval |
||||||||||
level |
95% | |||||||||
sides |
2-sided
|
|||||||||
lower limit |
12.6 | |||||||||
upper limit |
29.4 | |||||||||
| Notes [9] - Evaluated at 4% significance level (two-sided) and significant as per testing hierarchy using hierarchical tests, alpha splitting and alpha recycling controlling overall type 1 error at 5% (two-sided). |
||||||||||
|
||||||||||
End point title |
Reduction of HESD itch score (weekly average) of ≥4 points from baseline at Week 4. | |||||||||
End point description |
HESD is a 6-item PRO instrument designed to assess severity of CHE signs and symptoms. Participants assess the worst severity of 6 individual signs and symptoms of CHE over the past 24 hours using an 11-point numeric rating scale with anchors of 0 =‘no (symptom)’ and 10 =‘severe (symptom)’. The HESD score is derived as an average of the 6 items.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
Week 0 to Week 4
|
|||||||||
|
||||||||||
Statistical analysis title |
Delgocitinib cream 20 mg/g vs. cream vehicle | |||||||||
Statistical analysis description |
Based on the primary analysis of the primary estimand 'composite'. The difference in response rates between delgocitinib cream 20 mg/g and cream vehicle was analysed using the Cochran-Mantel-Haenszel test stratified by region and disease severity (baseline IGA-CHE score). Subjects with missing data, subjects who received rescue treatment, or subjects who permanently discontinued IMP were considered non-responders.
|
|||||||||
Comparison groups |
Delgocitinib cream 20 mg/g v Cream vehicle
|
|||||||||
Number of subjects included in analysis |
484
|
|||||||||
Analysis specification |
Pre-specified
|
|||||||||
Analysis type |
superiority | |||||||||
P-value |
< 0.001 [10] | |||||||||
Method |
Cochran-Mantel-Haenszel | |||||||||
Parameter type |
Risk difference (RD) | |||||||||
Point estimate |
19.5
|
|||||||||
Confidence interval |
||||||||||
level |
95% | |||||||||
sides |
2-sided
|
|||||||||
lower limit |
12.5 | |||||||||
upper limit |
26.5 | |||||||||
| Notes [10] - Evaluated at 4% significance level (two-sided) and significant as per testing hierarchy using hierarchical tests, alpha splitting and alpha recycling controlling overall type 1 error at 5% (two-sided). |
||||||||||
|
||||||||||
End point title |
Reduction of HESD itch score (weekly average) of ≥4 points from baseline at Week 2. | |||||||||
End point description |
HESD is a 6-item PRO instrument designed to assess severity of CHE signs and symptoms. Participants assess the worst severity of 6 individual signs and symptoms of CHE over the past 24 hours using an 11-point numeric rating scale with anchors of 0 =‘no (symptom)’ and 10 =‘severe (symptom)’. The HESD score is derived as an average of the 6 items.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
Week 0 to Week 2
|
|||||||||
|
||||||||||
Statistical analysis title |
Delgocitinib cream 20 mg/g vs. cream vehicle | |||||||||
Statistical analysis description |
Based on the primary analysis of the primary estimand 'composite'. The difference in response rates between delgocitinib cream 20 mg/g and cream vehicle was analysed using the Cochran-Mantel-Haenszel test stratified by region and disease severity (baseline IGA-CHE score). Subjects with missing data, subjects who received rescue treatment, or subjects who permanently discontinued IMP were considered non-responders.
|
|||||||||
Comparison groups |
Delgocitinib cream 20 mg/g v Cream vehicle
|
|||||||||
Number of subjects included in analysis |
484
|
|||||||||
Analysis specification |
Pre-specified
|
|||||||||
Analysis type |
superiority | |||||||||
P-value |
= 0.004 [11] | |||||||||
Method |
Cochran-Mantel-Haenszel | |||||||||
Parameter type |
Risk difference (RD) | |||||||||
Point estimate |
9.3
|
|||||||||
Confidence interval |
||||||||||
level |
95% | |||||||||
sides |
2-sided
|
|||||||||
lower limit |
3.8 | |||||||||
upper limit |
14.7 | |||||||||
| Notes [11] - Evaluated at 4% significance level (two-sided) and significant as per testing hierarchy using hierarchical tests, alpha splitting and alpha recycling controlling overall type 1 error at 5% (two-sided). |
||||||||||
|
|||||||||||||
End point title |
Change in HESD itch score (weekly average) from baseline to Week 16. | ||||||||||||
End point description |
HESD is a 6-item PRO instrument designed to assess severity of CHE signs and symptoms. Participants assess the worst severity of 6 individual signs and symptoms of CHE over the past 24 hours using an 11-point numeric rating scale with anchors of 0 =‘no (symptom)’ and 10 =‘severe (symptom)’. The HESD score is derived as an average of the 6 items.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 0 to Week 16
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Delgocitinib cream 20 mg/g vs. cream vehicle | ||||||||||||
Statistical analysis description |
Primary analysis of primary estimand 'composite'. The percentage change from baseline was analysed using an ANCOVA model with effects of treatment group, region, baseline IGA-CHE score, and baseline HESD itch value. Missing data for subjects who did not attend the visit was imputed as WOCF (including baseline value). For subjects who received rescue treatment or subjects who have permanently discontinued the IMP, observed data was considered non-response by using WOCF (including baseline value)
|
||||||||||||
Comparison groups |
Delgocitinib cream 20 mg/g v Cream vehicle
|
||||||||||||
Number of subjects included in analysis |
486
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.001 [12] | ||||||||||||
Method |
ANCOVA | ||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
-1.7
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-2.3 | ||||||||||||
upper limit |
-1.2 | ||||||||||||
| Notes [12] - Evaluated at 1% significance level (two-sided) and significant as per testing hierarchy using hierarchical tests, alpha splitting and alpha recycling controlling overall type 1 error at 5% (two-sided). |
|||||||||||||
|
||||||||||
End point title |
Reduction of HESD score (weekly average) of ≥4 points from baseline at Week 16. | |||||||||
End point description |
HESD is a 6-item PRO instrument designed to assess severity of CHE signs and symptoms. Participants assess the worst severity of 6 individual signs and symptoms of CHE over the past 24 hours using an 11-point numeric rating scale with anchors of 0 =‘no (symptom)’ and 10 =‘severe (symptom)’. The HESD score is derived as an average of the 6 items.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
Week 0 to Week 16
|
|||||||||
|
||||||||||
Statistical analysis title |
Delgocitinib cream 20 mg/g vs. cream vehicle | |||||||||
Statistical analysis description |
Based on the primary analysis of the primary estimand 'composite'. The difference in response rates between delgocitinib cream 20 mg/g and cream vehicle was analysed using the Cochran-Mantel-Haenszel test stratified by region and disease severity (baseline IGA-CHE score). Subjects with missing data, subjects who received rescue treatment, or subjects who permanently discontinued IMP were considered non-responders.
|
|||||||||
Comparison groups |
Delgocitinib cream 20 mg/g v Cream vehicle
|
|||||||||
Number of subjects included in analysis |
465
|
|||||||||
Analysis specification |
Pre-specified
|
|||||||||
Analysis type |
superiority | |||||||||
P-value |
< 0.001 [13] | |||||||||
Method |
Cochran-Mantel-Haenszel | |||||||||
Parameter type |
Risk difference (RD) | |||||||||
Point estimate |
22.8
|
|||||||||
Confidence interval |
||||||||||
level |
95% | |||||||||
sides |
2-sided
|
|||||||||
lower limit |
14 | |||||||||
upper limit |
31.7 | |||||||||
| Notes [13] - Evaluated at 5% significance level (two-sided) and significant as per testing hierarchy using hierarchical tests, alpha splitting and alpha recycling controlling overall type 1 error at 5% (two-sided). |
||||||||||
|
||||||||||
End point title |
Reduction of HESD score (weekly average) of ≥4 points from baseline at Week 8. | |||||||||
End point description |
HESD is a 6-item PRO instrument designed to assess severity of CHE signs and symptoms. Participants assess the worst severity of 6 individual signs and symptoms of CHE over the past 24 hours using an 11-point numeric rating scale with anchors of 0 =‘no (symptom)’ and 10 =‘severe (symptom)’. The HESD score is derived as an average of the 6 items.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
Week 0 to Week 8
|
|||||||||
|
||||||||||
Statistical analysis title |
Delgocitinib cream 20 mg/g vs. cream vehicle | |||||||||
Statistical analysis description |
Based on the primary analysis of the primary estimand 'composite'. The difference in response rates between delgocitinib cream 20 mg/g and cream vehicle was analysed using the Cochran-Mantel-Haenszel test stratified by region and disease severity (baseline IGA-CHE score). Subjects with missing data, subjects who received rescue treatment, or subjects who permanently discontinued IMP were considered non-responders.
|
|||||||||
Comparison groups |
Delgocitinib cream 20 mg/g v Cream vehicle
|
|||||||||
Number of subjects included in analysis |
465
|
|||||||||
Analysis specification |
Pre-specified
|
|||||||||
Analysis type |
superiority | |||||||||
P-value |
< 0.001 [14] | |||||||||
Method |
Cochran-Mantel-Haenszel | |||||||||
Parameter type |
Risk difference (RD) | |||||||||
Point estimate |
22.5
|
|||||||||
Confidence interval |
||||||||||
level |
95% | |||||||||
sides |
2-sided
|
|||||||||
lower limit |
14.4 | |||||||||
upper limit |
30.6 | |||||||||
| Notes [14] - Evaluated at 4% significance level (two-sided) and significant as per testing hierarchy using hierarchical tests, alpha splitting and alpha recycling controlling overall type 1 error at 5% (two-sided). |
||||||||||
|
||||||||||
End point title |
Reduction of HESD score (weekly average) of ≥4 points from baseline at Week 4. | |||||||||
End point description |
HESD is a 6-item PRO instrument designed to assess severity of CHE signs and symptoms. Participants assess the worst severity of 6 individual signs and symptoms of CHE over the past 24 hours using an 11-point numeric rating scale with anchors of 0 =‘no (symptom)’ and 10 =‘severe (symptom)’. The HESD score is derived as an average of the 6 items.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
Week 0 to Week 4
|
|||||||||
|
||||||||||
Statistical analysis title |
Delgocitinib cream 20 mg/g vs. cream vehicle | |||||||||
Statistical analysis description |
Based on the primary analysis of the primary estimand 'composite'. The difference in response rates between delgocitinib cream 20 mg/g and cream vehicle was analysed using the Cochran-Mantel-Haenszel test stratified by region and disease severity (baseline IGA-CHE score). Subjects with missing data, subjects who received rescue treatment, or subjects who permanently discontinued IMP were considered non-responders.
|
|||||||||
Comparison groups |
Delgocitinib cream 20 mg/g v Cream vehicle
|
|||||||||
Number of subjects included in analysis |
465
|
|||||||||
Analysis specification |
Pre-specified
|
|||||||||
Analysis type |
superiority | |||||||||
P-value |
< 0.001 [15] | |||||||||
Method |
Cochran-Mantel-Haenszel | |||||||||
Parameter type |
Risk difference (RD) | |||||||||
Point estimate |
19.5
|
|||||||||
Confidence interval |
||||||||||
level |
95% | |||||||||
sides |
2-sided
|
|||||||||
lower limit |
12.5 | |||||||||
upper limit |
26.5 | |||||||||
| Notes [15] - Evaluated at 4% significance level (two-sided) and significant as per testing hierarchy using hierarchical tests, alpha splitting and alpha recycling controlling overall type 1 error at 5% (two-sided). |
||||||||||
|
|||||||||||||
End point title |
Change in HESD score (weekly average) from baseline to Week 16. | ||||||||||||
End point description |
HESD is a 6-item PRO instrument designed to assess severity of CHE signs and symptoms. Participants assess the worst severity of 6 individual signs and symptoms of CHE over the past 24 hours using an 11-point numeric rating scale with anchors of 0 =‘no (symptom)’ and 10 =‘severe (symptom)’. The HESD score is derived as an average of the 6 items.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 0 to Week 16
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Delgocitinib cream 20 mg/g vs. cream vehicle | ||||||||||||
Statistical analysis description |
Primary analysis of primary estimand 'composite'. The percentage change from baseline was analysed using an ANCOVA model with effects of treatment group, region, baseline IGA-CHE score, and baseline HESD value. Missing data for subjects who did not attend the visit was imputed as WOCF (including baseline value). For subjects who received rescue treatment or subjects who have permanently discontinued the IMP, observed data was considered non-response by using WOCF (including baseline value).
|
||||||||||||
Comparison groups |
Delgocitinib cream 20 mg/g v Cream vehicle
|
||||||||||||
Number of subjects included in analysis |
486
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.001 [16] | ||||||||||||
Method |
ANCOVA | ||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
-1.7
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-2.2 | ||||||||||||
upper limit |
-1.2 | ||||||||||||
| Notes [16] - Evaluated at 1% significance level (two-sided) and significant as per testing hierarchy using hierarchical tests, alpha splitting and alpha recycling controlling overall type 1 error at 5% (two-sided). |
|||||||||||||
|
||||||||||
End point title |
Reduction of HESD pain score (weekly average) of ≥4 points from baseline at Week 16. | |||||||||
End point description |
HESD is a 6-item PRO instrument designed to assess severity of CHE signs and symptoms. Participants assess the worst severity of 6 individual signs and symptoms of CHE over the past 24 hours using an 11-point numeric rating scale with anchors of 0 =‘no (symptom)’ and 10 =‘severe (symptom)’. The HESD score is derived as an average of the 6 items.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
Week 0 to Week 16
|
|||||||||
|
||||||||||
Statistical analysis title |
Delgocitinib cream 20 mg/g vs. cream vehicle | |||||||||
Statistical analysis description |
Based on the primary analysis of the primary estimand 'composite'. The difference in response rates between delgocitinib cream 20 mg/g and cream vehicle was analysed using the Cochran-Mantel-Haenszel test stratified by region and disease severity (baseline IGA-CHE score). Subjects with missing data, subjects who received rescue treatment, or subjects who permanently discontinued IMP were considered non-responders.
|
|||||||||
Comparison groups |
Delgocitinib cream 20 mg/g v Cream vehicle
|
|||||||||
Number of subjects included in analysis |
440
|
|||||||||
Analysis specification |
Pre-specified
|
|||||||||
Analysis type |
superiority | |||||||||
P-value |
< 0.001 [17] | |||||||||
Method |
Cochran-Mantel-Haenszel | |||||||||
Parameter type |
Risk difference (RD) | |||||||||
Point estimate |
21.7
|
|||||||||
Confidence interval |
||||||||||
level |
95% | |||||||||
sides |
2-sided
|
|||||||||
lower limit |
12.4 | |||||||||
upper limit |
30.9 | |||||||||
| Notes [17] - Evaluated at 4% significance level (two-sided) and significant as per testing hierarchy using hierarchical tests, alpha splitting and alpha recycling controlling overall type 1 error at 5% (two-sided). |
||||||||||
|
||||||||||
End point title |
Reduction of HESD pain score (weekly average) of ≥4 points from baseline at Week 8. | |||||||||
End point description |
HESD is a 6-item PRO instrument designed to assess severity of CHE signs and symptoms. Participants assess the worst severity of 6 individual signs and symptoms of CHE over the past 24 hours using an 11-point numeric rating scale with anchors of 0 =‘no (symptom)’ and 10 =‘severe (symptom)’. The HESD score is derived as an average of the 6 items.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
Week 0 to Week 8
|
|||||||||
|
||||||||||
Statistical analysis title |
Delgocitinib cream 20 mg/g vs. cream vehicle | |||||||||
Statistical analysis description |
Based on the primary analysis of the primary estimand 'composite'. The difference in response rates between delgocitinib cream 20 mg/g and cream vehicle was analysed using the Cochran-Mantel-Haenszel test stratified by region and disease severity (baseline IGA-CHE score). Subjects with missing data, subjects who received rescue treatment, or subjects who permanently discontinued IMP were considered non-responders.
|
|||||||||
Comparison groups |
Delgocitinib cream 20 mg/g v Cream vehicle
|
|||||||||
Number of subjects included in analysis |
440
|
|||||||||
Analysis specification |
Pre-specified
|
|||||||||
Analysis type |
superiority | |||||||||
P-value |
< 0.001 [18] | |||||||||
Method |
Cochran-Mantel-Haenszel | |||||||||
Parameter type |
Risk difference (RD) | |||||||||
Point estimate |
23.9
|
|||||||||
Confidence interval |
||||||||||
level |
95% | |||||||||
sides |
2-sided
|
|||||||||
lower limit |
15.2 | |||||||||
upper limit |
32.7 | |||||||||
| Notes [18] - Evaluated at 4% significance level (two-sided) and significant as per testing hierarchy using hierarchical tests, alpha splitting and alpha recycling controlling overall type 1 error at 5% (two-sided). |
||||||||||
|
||||||||||
End point title |
Reduction of HESD pain score (weekly average) of ≥4 points from baseline at Week 4. | |||||||||
End point description |
HESD is a 6-item PRO instrument designed to assess severity of CHE signs and symptoms. Participants assess the worst severity of 6 individual signs and symptoms of CHE over the past 24 hours using an 11-point numeric rating scale with anchors of 0 =‘no (symptom)’ and 10 =‘severe (symptom)’. The HESD score is derived as an average of the 6 items.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
Week 0 to Week 4
|
|||||||||
|
||||||||||
Statistical analysis title |
Delgocitinib cream 20 mg/g vs. cream vehicle | |||||||||
Statistical analysis description |
Based on the primary analysis of the primary estimand 'composite'. The difference in response rates between delgocitinib cream 20 mg/g and cream vehicle was analysed using the Cochran-Mantel-Haenszel test stratified by region and disease severity (baseline IGA-CHE score). Subjects with missing data, subjects who received rescue treatment, or subjects who permanently discontinued IMP were considered non-responders.
|
|||||||||
Comparison groups |
Delgocitinib cream 20 mg/g v Cream vehicle
|
|||||||||
Number of subjects included in analysis |
440
|
|||||||||
Analysis specification |
Pre-specified
|
|||||||||
Analysis type |
superiority | |||||||||
P-value |
< 0.001 [19] | |||||||||
Method |
Cochran-Mantel-Haenszel | |||||||||
Parameter type |
Risk difference (RD) | |||||||||
Point estimate |
19.6
|
|||||||||
Confidence interval |
||||||||||
level |
95% | |||||||||
sides |
2-sided
|
|||||||||
lower limit |
11.8 | |||||||||
upper limit |
27.5 | |||||||||
| Notes [19] - Evaluated at 4% significance level (two-sided) and significant as per testing hierarchy using hierarchical tests, alpha splitting and alpha recycling controlling overall type 1 error at 5% (two-sided). |
||||||||||
|
|||||||||||||
End point title |
Change in HESD pain score (weekly average) from baseline to Week 16. | ||||||||||||
End point description |
HESD is a 6-item PRO instrument designed to assess severity of CHE signs and symptoms. Participants assess the worst severity of 6 individual signs and symptoms of CHE over the past 24 hours using an 11-point numeric rating scale with anchors of 0 =‘no (symptom)’ and 10 =‘severe (symptom)’. The HESD score is derived as an average of the 6 items.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 0 to Week 16
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Delgocitinib cream 20 mg/g vs. cream vehicle | ||||||||||||
Statistical analysis description |
Primary analysis of primary estimand 'composite'. The percentage change from baseline was analysed using an ANCOVA model with effects of treatment group, region, baseline IGA-CHE score, and baseline HESD pain value. Missing data for subjects who did not attend the visit was imputed as WOCF (including baseline value). For subjects who received rescue treatment or subjects who have permanently discontinued the IMP, observed data was considered non-response by using WOCF (including baseline value)
|
||||||||||||
Comparison groups |
Delgocitinib cream 20 mg/g v Cream vehicle
|
||||||||||||
Number of subjects included in analysis |
486
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.001 [20] | ||||||||||||
Method |
ANCOVA | ||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
-1.6
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-2.1 | ||||||||||||
upper limit |
-1 | ||||||||||||
| Notes [20] - Evaluated at 1% significance level (two-sided) and significant as per testing hierarchy using hierarchical tests, alpha splitting and alpha recycling controlling overall type 1 error at 5% (two-sided). |
|||||||||||||
|
||||||||||
End point title |
Reduction of Dermatology Life Quality Index (DLQI) score of ≥4 points from baseline at Week 16. | |||||||||
End point description |
DLQI is a validated questionnaire with content specific to those with dermatologic conditions. It consists of 10 items addressing the participant’s perception of the impact of their skin disease on different aspects of their quality of life over the last week. Each item is scored on a 4-point Likert scale ranging from 0 = ‘not at all ⁄not relevant’ to 3 = ‘very much’. The DLQI score is the sum of the 10 items (score ranging from 0 to 30); a high score is indicative of a poor quality of life.
|
|||||||||
End point type |
Secondary
|
|||||||||
End point timeframe |
Week 0 to Week 16
|
|||||||||
|
||||||||||
Statistical analysis title |
Delgocitinib cream 20 mg/g vs. cream vehicle | |||||||||
Statistical analysis description |
Based on the primary analysis of the primary estimand 'composite'. The difference in response rates between delgocitinib cream 20 mg/g and cream vehicle was analysed using the Cochran-Mantel-Haenszel test stratified by region and disease severity (baseline IGA-CHE score). Subjects with missing data, subjects who received rescue treatment, or subjects who permanently discontinued IMP were considered non-responders.
|
|||||||||
Comparison groups |
Delgocitinib cream 20 mg/g v Cream vehicle
|
|||||||||
Number of subjects included in analysis |
453
|
|||||||||
Analysis specification |
Pre-specified
|
|||||||||
Analysis type |
superiority | |||||||||
P-value |
< 0.001 [21] | |||||||||
Method |
Cochran-Mantel-Haenszel | |||||||||
Parameter type |
Risk difference (RD) | |||||||||
Point estimate |
24.5
|
|||||||||
Confidence interval |
||||||||||
level |
95% | |||||||||
sides |
2-sided
|
|||||||||
lower limit |
15 | |||||||||
upper limit |
33.9 | |||||||||
| Notes [21] - Evaluated at 1% significance level (two-sided) and significant as per testing hierarchy using hierarchical tests, alpha splitting and alpha recycling controlling overall type 1 error at 5% (two-sided). |
||||||||||
|
|||||||||||||
End point title |
Change in DLQI score from baseline to Week 16. | ||||||||||||
End point description |
DLQI is a validated questionnaire with content specific to those with dermatologic conditions. It consists of 10 items addressing the participant’s perception of the impact of their skin disease on different aspects of their quality of life over the last week. Each item is scored on a 4-point Likert scale ranging from 0 = ‘not at all ⁄not relevant’ to 3 = ‘very much’. The DLQI score is the sum of the 10 items (score ranging from 0 to 30); a high score is indicative of a poor quality of life.
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 0 to Week 16
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Delgocitinib cream 20 mg/g vs. cream vehicle | ||||||||||||
Statistical analysis description |
Primary analysis of primary estimand 'composite'. The percentage change from baseline was analysed using an ANCOVA model with effects of treatment group, region, baseline IGA-CHE score, and baseline DLQI value. Missing data for subjects who did not attend the visit was imputed as WOCF (including baseline value). For subjects who received rescue treatment or subjects who have permanently discontinued the IMP, observed data was considered non-response by using WOCF (including baseline value).
|
||||||||||||
Comparison groups |
Delgocitinib cream 20 mg/g v Cream vehicle
|
||||||||||||
Number of subjects included in analysis |
479
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.001 [22] | ||||||||||||
Method |
ANCOVA | ||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
-3.6
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-4.7 | ||||||||||||
upper limit |
-2.6 | ||||||||||||
| Notes [22] - Evaluated at 1% significance level (two-sided) and significant as per testing hierarchy using hierarchical tests, alpha splitting and alpha recycling controlling overall type 1 error at 5% (two-sided). |
|||||||||||||
|
|||||||||||||
End point title |
Change in Hand Eczema Impact Scale (HEIS) score from baseline to Week 16. | ||||||||||||
End point description |
HEIS includes 9 items addressing the participant’s perception of the impact of hand eczema on their daily activities, embarrassment, frustration, sleep, work, and physical functioning over the past 7 days. Each item is scored on a 5-point scale ranging from 0=‘not at all’ to 4=‘extremely’. The HEIS score is the average of the 9 items. The highest possible score is 4, and a high score is indicative of a high impact. 6 domain scores can be calculated for HEIS: Proximal Daily Activity Limitations (PDAL) (average of 3 items), embarrassment with the appearance of the hands (average of 2 items), frustration with CHE (1 item), sleep (1 item), work (1 item), and physical functioning (1 item).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 0 to Week 16
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Delgocitinib cream 20 mg/g vs. cream vehicle | ||||||||||||
Statistical analysis description |
Primary analysis of primary estimand 'composite'. The percentage change from baseline was analysed using an ANCOVA model with effects of treatment group, region, baseline IGA-CHE score, and baseline HEIS value. Missing data for subjects who did not attend the visit was imputed as WOCF (including baseline value). For subjects who received rescue treatment or subjects who have permanently discontinued the IMP, observed data was considered non-response by using WOCF (including baseline value).
|
||||||||||||
Comparison groups |
Delgocitinib cream 20 mg/g v Cream vehicle
|
||||||||||||
Number of subjects included in analysis |
479
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.001 [23] | ||||||||||||
Method |
ANCOVA | ||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
-0.64
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.83 | ||||||||||||
upper limit |
-0.45 | ||||||||||||
| Notes [23] - Evaluated at 1% significance level (two-sided) and significant as per testing hierarchy using hierarchical tests, alpha splitting and alpha recycling controlling overall type 1 error at 5% (two-sided). |
|||||||||||||
|
|||||||||||||
End point title |
Change in HEIS PDAL score from baseline to Week 16. | ||||||||||||
End point description |
HEIS includes 9 items addressing the participant’s perception of the impact of hand eczema on their daily activities, embarrassment, frustration, sleep, work, and physical functioning over the past 7 days. Each item is scored on a 5-point scale ranging from 0=‘not at all’ to 4=‘extremely’. The HEIS score is the average of the 9 items. The highest possible score is 4, and a high score is indicative of a high impact. 6 domain scores can be calculated for HEIS: Proximal Daily Activity Limitations (PDAL) (average of 3 items), embarrassment with the appearance of the hands (average of 2 items), frustration with CHE (1 item), sleep (1 item), work (1 item), and physical functioning (1 item).
|
||||||||||||
End point type |
Secondary
|
||||||||||||
End point timeframe |
Week 0 to Week 16
|
||||||||||||
|
|||||||||||||
Statistical analysis title |
Delgocitinib cream 20 mg/g vs. cream vehicle | ||||||||||||
Statistical analysis description |
Primary analysis of primary estimand 'composite'. The percentage change from baseline was analysed using an ANCOVA model with effects of treatment group, region, baseline IGA-CHE score, and baseline value. Missing data for subjects who did not attend the visit was imputed as WOCF (including baseline value). For subjects who received rescue treatment or subjects who have permanently discontinued the IMP, observed data was considered non-response by using WOCF (including baseline value).
|
||||||||||||
Comparison groups |
Delgocitinib cream 20 mg/g v Cream vehicle
|
||||||||||||
Number of subjects included in analysis |
479
|
||||||||||||
Analysis specification |
Pre-specified
|
||||||||||||
Analysis type |
superiority | ||||||||||||
P-value |
< 0.001 [24] | ||||||||||||
Method |
ANCOVA | ||||||||||||
Parameter type |
Mean difference (net) | ||||||||||||
Point estimate |
-0.6
|
||||||||||||
Confidence interval |
|||||||||||||
level |
95% | ||||||||||||
sides |
2-sided
|
||||||||||||
lower limit |
-0.79 | ||||||||||||
upper limit |
-0.4 | ||||||||||||
| Notes [24] - Evaluated at 1% significance level (two-sided) and significant as per testing hierarchy using hierarchical tests, alpha splitting and alpha recycling controlling overall type 1 error at 5% (two-sided). |
|||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Adverse events information
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Timeframe for reporting adverse events |
Week 0 to Week 16
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Assessment type |
Non-systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Dictionary used for adverse event reporting
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
24.0
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
Reporting groups
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Delgocitinib cream 20 mg/g
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Cream vehicle
|
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group description |
- | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Frequency threshold for reporting non-serious adverse events: 2% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|
|||
Substantial protocol amendments (globally) |
|||
| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
||
20 Aug 2021 |
This amendment was written to comply with requests from health authorities, to accommodate for the conduct of the trial in Russia, and to proceed with administrative and editorial changes. |
||
Interruptions (globally) |
|||
| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
|||
| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
