Atopic Dermatitis, Atopic Hand Eczema
Conditions
Brief summary
The purpose of this study is to test if treatment with tralokinumab is safe and efficacious in treating moderate-to-severe atopic hand eczema. This will be judged by a range of assessments that rate the severity and extent of atopic hand eczema and its symptoms, as well as general health status and quality of life. The trial will last for up to 40 weeks for each participant. There will be up to 15 visits for each participant, 3 of which will be conducted by phone. The first part of the trial is called a screening period and will last up to 4 weeks. For the first 16 weeks after screening, trial participants will receive either tralokinumab or dummy injections every two weeks. After the first 16 weeks, all trial participants will receive tralokinumab injections every two weeks for 16 weeks. The last part of the trial is a period of 4 weeks after the end of treatment period, where trial participants will not receive tralokinumab but are monitored for safety.
Interventions
DRUGPlacebo
After a loading dose under the skin (s.c.) at baseline, trial participants are administered a placebo dose every two weeks for 16 weeks
DRUGTralokinumab
After a loading dose of 600 mg under the skin (s.c.) at baseline, trial participants are administered a dose of 300 mg every two weeks for 32 weeks
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
* Age 18 years or above at screening * Diagnosis of atopic dermatitis (AD) as by the Hanifin and Rajka (1980) criteria for AD * History of AD for ≥1 year * Presence of atopic hand eczema (AHE) that has persisted for more than 3 months or returned twice or more within the last 12 months, with avoidance of any known and relevant irritants and allergens * AD involvement of at least one body location other than the hands and wrists at screening * An Investigator's Global Assessment AHE score of 3 or 4 (moderate to severe) at screening and baseline * A HESD itch score (weekly average) of ≥4 at baseline * Subjects who have a documented recent history (within 12 months before the screening visit) of inadequate response to treatment of AHE with topical prescription medications or for whom topical treatments are otherwise medically inadvisable (e.g., due to important side effects or safety risks)
Exclusion criteria
* Subjects must not enter the trial if they have active subtypes of hand eczema other than AHE that are considered to be the predominant cause of the current hand eczema including: * Active irritant contact dermatitis * Active allergic contact dermatitis * Active protein contact dermatitis/contact urticaria * Active hyperkeratotic hand eczema * Active vesicular hand eczema (pompholyx) * Active dermatologic conditions that may confound the diagnosis of AD or AHE, or that would interfere with the assessment of treatment * Use of tanning beds or phototherapy (e.g., UVB, UVA1, PUVA), or Grenz ray therapy on the hands or wrists within 28 days prior to baseline or use of bleach baths on the hands or wrists within 7 days prior to baseline * Treatment with systemic immunosuppressive/immunomodulating drugs and/or systemic corticosteroids within 28 days prior to baseline * Treatment with topical corticosteroids, topical calcineurin inhibitors, topical phosphodiesterase 4 inhibitors, or topical Janus kinase inhibitors within 7 days prior to baseline * Receipt of any marketed biological therapy (i.e. immunoglobulin, anti immunoglobulin E) including dupilumab or investigational biologic agents 3 to 6 months prior to baseline
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With IGA-AHE Score of 0 (Clear) or 1 (Almost Clear) | At Week 16 | IGA-AHE: The Investigator's Global Assessment for atopic hand eczema (IGA-AHE) is an instrument to rate the severity of the subject's AHE and is based on a 5-point scale ranging from 0 (clear) to 4 (severe). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Having a ≥2-point Reduction in IGA-AHE Score | From baseline to Week 16 | IGA-AHE: The Investigator's Global Assessment for atopic hand eczema (IGA-AHE) is an instrument to rate the severity of the subject's AHE and is based on a 5-point scale ranging from 0 (clear) to 4 (severe). |
| Percentage of Participants Having a Decrease in HECSI of at Least 75% (HECSI-75) | From baseline (Day 1) to Week 16 | The Hand Eczema Severity Index (HECSI) is an instrument used in clinical trials to rate the severity of 6 clinical signs (erythema, infiltration/papulation, vesicles, fissures, scaling, and oedema) and the extent of the lesions in each of the 5 hand regions (fingertips, fingers \[except fingertips\], palm of hands, back of hands, and wrists) by use of standard scales. The HECSI score will range from 0 (lowest possible score) to 360 (highest possible score), with a higher score indicating greater severity. HECSI-75 is defined as at least 75% improvement in HECSI score from baseline. |
| Percentage of Participants Having a Decrease in HECSI of at Least 50% (HECSI-50) | From baseline to Week 16 | The Hand Eczema Severity Index (HECSI) is an instrument used in clinical trials to rate the severity of 6 clinical signs (erythema, infiltration/papulation, vesicles, fissures, scaling, and oedema) and the extent of the lesions in each of the 5 hand regions (fingertips, fingers \[except fingertips\], palm of hands, back of hands, and wrists) by use of standard scales. The HECSI score will range from 0 (lowest possible score) to 360 (highest possible score), with a higher score indicating greater severity. HECSI-50 is defined as at least 50% improvement in HECSI score from baseline. |
| Percentage of Participants Having a Decrease in HECSI of at Least 90% (HECSI-90) | From baseline to Week 16 | The Hand Eczema Severity Index (HECSI) is an instrument used in clinical trials to rate the severity of 6 clinical signs (erythema, infiltration/papulation, vesicles, fissures, scaling, and oedema) and the extent of the lesions in each of the 5 hand regions (fingertips, fingers \[except fingertips\], palm of hands, back of hands, and wrists) by use of standard scales. The HECSI score will range from 0 (lowest possible score) to 360 (highest possible score), with a higher score indicating greater severity. HECSI-90 is defined as at least 90% improvement in HECSI score from baseline. |
| Percentage Change in HECSI Score | From baseline to Week 16 | The Hand Eczema Severity Index (HECSI) is an instrument used in clinical trials to rate the severity of 6 clinical signs (erythema, infiltration/papulation, vesicles, fissures, scaling, and oedema) and the extent of the lesions in each of the 5 hand regions (fingertips, fingers \[except fingertips\], palm of hands, back of hands, and wrists) by use of standard scales. The HECSI score will range from 0 (lowest possible score) to 360 (highest possible score), with a higher score indicating greater severity. |
| Percentage of Participants With Reduction in HESD Itch Score (Weekly Average) of ≥4 Points | From baseline to Week 16 | The Hand Eczema Symptom Diary (HESD) is a 6-item patient-reported outcome where the subject assesses the worst severity of 6 individual signs and symptoms of hand eczema over the past 24 hours using an 11-point numeric rating scale with anchors of 0 ='no (symptom)' and 10 ='severe (symptom)' throughout the trial on a daily basis. This endpoint assessed only the 'itch' component and will be evaluated among participants with a baseline HESD itch score (weekly average) ≥4 points. |
| Percentage Change in HESD Itch Score (Weekly Average) | From baseline to Week 16 | The Hand Eczema Symptom Diary (HESD) is a 6-item patient-reported outcome where the subject assesses the worst severity of 6 individual signs and symptoms of hand eczema over the past 24 hours using an 11-point numeric rating scale with anchors of 0 ='no (symptom)' and 10 ='severe (symptom)' throughout the trial on a daily basis. This endpoint assessed only the 'itch' component and will be evaluated among participants with a baseline HESD itch score (weekly average) ≥4 points. |
| Percentage of Participants With Reduction in HESD Pain Score (Weekly Average) of ≥4 Points | From baseline to Week 16 | The Hand Eczema Symptom Diary (HESD) is a 6-item patient-reported outcome where the subject assesses the worst severity of 6 individual signs and symptoms of hand eczema over the past 24 hours using an 11-point numeric rating scale with anchors of 0 ='no (symptom)' and 10 ='severe (symptom)' throughout the trial on a daily basis. This endpoint assessed only the 'pain' component and will be evaluated among participants with a baseline HESD pain score (weekly average) ≥4 points. |
| Percentage Change in HESD Pain Score (Weekly Average) | From baseline to Week 16 | The Hand Eczema Symptom Diary (HESD) is a 6-item patient-reported outcome where the subject assesses the worst severity of 6 individual signs and symptoms of hand eczema over the past 24 hours using an 11-point numeric rating scale with anchors of 0 ='no (symptom)' and 10 ='severe (symptom)' throughout the trial on a daily basis. This endpoint assessed only the 'pain' component and will be evaluated among participants with a baseline HESD pain score (weekly average) ≥4 points. |
| Percentage Change in HEIS Score | From baseline to Week 16 | HEIS: The Hand Eczema Impact Scale (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 (0='not at all', 1='a little', 2='moderately', 3='a lot', 4='extremely'). The HEIS score is the average of the 9 items. |
| Percentage Change in DLQI Score | From baseline to Week 16 | The Dermatology Life Quality Index (DLQI) consists of 10 items addressing the subject's perception of the impact of their skin disease on different aspects of their quality of life over the last week. 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. |
| Change in WPAI+CIQ:AHE Domain Scores | From baseline to Week 16 | The impact of AHE on the subject's ability to work/school and perform regular activities was assessed by Work Productivity and Activity Impairment plus Classroom Impairment Questionnaire in atopic hand eczema (WPAI+CIQ:AHE), which is an instrument to measure impairments in both paid work and unpaid work/school attendance. Only domain scores where an estimand analysis was possible are presented. Scores are on a scale from 0 to 100 and reflect the percentage impairment due to AHE during the past 7 days, with higher numbers indicating greater impairment and less productivity/school attendance. |
| Number of Participants With IGA-AHE Score of 0 (Clear) or 1 (Almost Clear) | At Week 32 | The Investigator's Global Assessment for atopic hand eczema (IGA-AHE) is an instrument to rate the severity of the subject's AHE and is based on a 5-point scale ranging from 0 (clear) to 4 (severe). |
| Number of Participants Having a Decrease in HECSI of at Least 75% (HECSI-75) | From baseline to Week 32 | The Hand Eczema Severity Index (HECSI) is an instrument used in clinical trials to rate the severity of 6 clinical signs (erythema, infiltration/papulation, vesicles, fissures, scaling, and oedema) and the extent of the lesions in each of the 5 hand regions (fingertips, fingers \[except fingertips\], palm of hands, back of hands, and wrists) by use of standard scales. The HECSI score ranges from 0 (lowest possible score) to 360 (highest possible score), with a higher score indicating greater severity. HECSI-75 is defined as at least 75% improvement in HECSI score from baseline. |
| Number of Participants With Reduction in HESD Itch Score (Weekly Average) of ≥4 Points | From baseline to Week 32 | The Hand Eczema Symptom Diary (HESD) is a 6-item patient-reported outcome where the subject assesses the worst severity of 6 individual signs and symptoms of hand eczema over the past 24 hours using an 11-point numeric rating scale with anchors of 0 ='no (symptom)' and 10 ='severe (symptom)' throughout the trial on a daily basis. This endpoint assessed only the 'itch' component and will be evaluated among participants with a baseline HESD itch score (weekly average) ≥4 points. |
| Number of Participants With Reduction in HESD Pain Score (Weekly Average) of ≥4 Points | From baseline to Week 32 | The Hand Eczema Symptom Diary (HESD) is a 6-item patient-reported outcome where the subject assesses the worst severity of 6 individual signs and symptoms of hand eczema over the past 24 hours using an 11-point numeric rating scale with anchors of 0 ='no (symptom)' and 10 ='severe (symptom)' throughout the trial on a daily basis. This endpoint assessed only the 'itch' component and will be evaluated among participants with a baseline HESD itch score (weekly average) ≥4 points. |
| Number of Treatment-emergent Adverse Events | From baseline to Week 16 | An event was considered treatment-emergent if started after the first use of IMP or if started before the first use of IMP and worsened in severity after first dose of IMP. |
| Number of Treatment-emergent Adverse Events During the Open-label Treatment Period | Week 16 to Week 32 | An event was considered treatment-emergent if started after the first use of IMP or if started before the first use of IMP and worsened in severity after first dose of IMP. |
Countries
Belgium, Canada, France, Germany, Netherlands, Poland, South Korea, Spain, United Kingdom, United States
Contacts
STUDY_DIRECTORMedical Expert
LEO Pharma
Participant flow
Recruitment details
This trial was conducted at sites in Asia, Europe, and North America.
Pre-assignment details
Participants were randomized 2:1 to treatment with tralokinumab or placebo.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 41.5 years STANDARD_DEVIATION 13.7 |
| DLQI Score | 14.2 units on a scale STANDARD_DEVIATION 7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 8 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 71 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| HECSI Score | 77.7 units on a scale STANDARD_DEVIATION 41.4 |
| HEIS Score | 2.69 units on a scale STANDARD_DEVIATION 0.85 |
| HESD Itch Score (Weekly Average) | 7.36 units on a scale STANDARD_DEVIATION 1.62 |
| HESD Pain Score (Weekly Average) | 7.07 units on a scale STANDARD_DEVIATION 2.15 |
| Investigator's Global Assessment - AHE Moderate disease | 114 Participants |
| Investigator's Global Assessment - AHE Severe disease | 42 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 17 Participants |
| Race (NIH/OMB) Black or African American | 15 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 104 Participants |
| Region of Enrollment Belgium | 1 Participants |
| Region of Enrollment Canada | 56 Participants |
| Region of Enrollment France | 5 Participants |
| Region of Enrollment Germany | 6 Participants |
| Region of Enrollment Netherlands | 3 Participants |
| Region of Enrollment Poland | 22 Participants |
| Region of Enrollment South Korea | 11 Participants |
| Region of Enrollment Spain | 7 Participants |
| Region of Enrollment United Kingdom | 5 Participants |
| Region of Enrollment United States | 72 Participants |
| Sex: Female, Male Female | 55 Participants |
| Sex: Female, Male Male | 24 Participants |
| WPAI:AHE Absenteeism Score | 8.33 units on a scale STANDARD_DEVIATION 19.41 |
| WPAI:AHE Presenteeism Score | 48.77 units on a scale STANDARD_DEVIATION 29.73 |
| WPAI:AHE Work Productivity | 50.72 units on a scale STANDARD_DEVIATION 30.4 |
| WPAI+CIQ:AHE Activity Impairment Score | 58.48 units on a scale STANDARD_DEVIATION 26.96 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 156 | 0 / 79 | 0 / 214 |
| other Total, other adverse events | 50 / 156 | 19 / 79 | 31 / 214 |
| serious Total, serious adverse events | 3 / 156 | 1 / 79 | 4 / 214 |
Outcome results
None listed