Atopic Dermatitis
Conditions
Brief summary
This is an up to 22-week clinical study in adult participants with moderate to severe atopic dermatitis (AD). The purpose of the study is to test a new tablet (LEO 152020) to see if it improves AD and what the side effects are when compared with a placebo tablet with no medical ingredient. During the study, there will be a 16-week treatment period during which the participants will be asked to take the tablets. The participants will regularly visit the clinic for tests and the study doctor will evaluate their AD. The participants will also be asked to answer questions about their AD symptoms, itch, sleep, and quality of life.
Interventions
LEO 152020 is a small drug molecule which can bind to the histamine 4 receptor (H4R) and prevent histamine from binding to the receptor. LEO 152020 is a tablet for oral administration.
DRUGLEO 152020 placebo tablet
LEO 152020 placebo tablet contains the same excipients in the same concentration as LEO 152020 tablet, except that it does not contain the medical ingredient LEO 152020. LEO 152020 placebo is a tablet for oral administration.
Sponsors
LEO Pharma
JW Pharmaceutical
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Masking description
The outcome assessor is considered to be the person/people who will assess the outcome of the data/study and will in this study therefore be the sponsor. To ensure masking across the interventions, each dose of treatment in the LEO 152020 tablet - Dose regimen 2 and LEO 152020 tablet - Dose regimen 3 arms will consist of a combination of LEO 152020 and LEO 152020 placebo tablets. In these arms, placebo will be used as a masking aid and is therefore considered neither a control nor an intervention.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult, age 18 years or older at screening. * Diagnosis of chronic atopic dermatitis (AD). * History of AD ≥1 year prior to baseline. * Recent (within 6 months prior to baseline) documented history of inadequate response to topical AD treatments or subject for whom topical AD treatments are medically inadvisable. * 7.1≤ Eczema Area and Severity Index (EASI) ≤50 at baseline. * Validated Investigator Global Assessment Scale for Atopic Dermatitis (vIGA-AD) score ≥3 at baseline.
Exclusion criteria
* Previous treatment with an oral histidine 4 receptor (H4R) antagonist (including LEO 152020) within 6 months prior to baseline. * Previous treatment with 3 or more systemic AD treatments prior to screening. * Women who are pregnant, intend to become pregnant, or are lactating.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in EASI From Baseline to Week 16 | Week 0 to Week 16 | The Eczema Area and Severity Index (EASI) is a validated measure used in clinical trials to evaluate the extent and severity of atopic dermatitis. EASI is a composite score ranging from 0 to 72 with higher scores indicating a more extensive or severe condition. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Adverse Events From Baseline to Week 16+3 Days Per Subject | Week 0 to Week 16+3 days | Only treatment-emergent adverse events will be reported for this outcome measure. An adverse event will be considered treatment emergent if occurring after the first dose of treatment (Week 0) and up until 3 days after the last dose of treatment (Week 16+3 days for a participant completing the 16-week treatment period). |
Countries
Australia, Canada, Czechia, Germany, Japan, Poland, Spain, United States
Participant flow
Recruitment details
This trial was conducted at 45 sites that screened subjects in 8 countries (Australia, Canada, Czech Republic (Czechia), Germany, Japan, Poland, Spain and the United States).
Pre-assignment details
285 subjects were screened and 216 were randomized in a 4:3:3:4 ratio into the 4 treatment groups.
Participants by arm
| Arm | Count |
|---|---|
| LEO 152020 - Dosing Regimen 1 (Higher Dose) Subjects administered themselves daily for 16 weeks a fixed treatment of LEO 152020 - higher dose. Film coated tablets, administered orally. | 61 |
| LEO 152020 - Dosing Regimen 2 (Middle Dose) Subjects administered themselves daily for 16 weeks a fixed treatment of LEO 152020 - middle dose. Film coated tablets, administered orally. | 45 |
| LEO 152020 - Dosing Regimen 3 (Lower Dose) Subjects administered themselves daily for 16 weeks a fixed treatment of LEO 152020 and LEO 152020 placebo - lower dose. Film coated tablets, administered orally. | 49 |
| LEO 152020 - Placebo Subjects administered themselves daily for 16 weeks a fixed treatment of LEO 152020 placebo. Film coated tablets, administered orally. | 61 |
| Total | 216 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 3 | 5 | 6 | 1 |
| Overall Study | Lack of Efficacy | 4 | 5 | 2 | 6 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 1 |
| Overall Study | Other | 2 | 1 | 3 | 1 |
| Overall Study | Withdrawal by Subject | 8 | 5 | 5 | 6 |
Baseline characteristics
| Characteristic | LEO 152020 - Dosing Regimen 2 (Middle Dose) | LEO 152020 - Dosing Regimen 3 (Lower Dose) | LEO 152020 - Dosing Regimen 1 (Higher Dose) | LEO 152020 - Placebo | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 2 Participants | 2 Participants | 0 Participants | 0 Participants | 4 Participants |
| Age, Categorical >=65 years | 3 Participants | 1 Participants | 2 Participants | 2 Participants | 8 Participants |
| Age, Categorical Between 18 and 65 years | 40 Participants | 46 Participants | 59 Participants | 59 Participants | 204 Participants |
| Age, Continuous | 35.2 years STANDARD_DEVIATION 15 | 35.2 years STANDARD_DEVIATION 13.5 | 36.2 years STANDARD_DEVIATION 13.3 | 33.4 years STANDARD_DEVIATION 12.9 | 35.0 years STANDARD_DEVIATION 13.5 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 9 Participants | 15 Participants | 17 Participants | 14 Participants | 55 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 2 Participants | 7 Participants | 2 Participants | 14 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 33 Participants | 30 Participants | 36 Participants | 45 Participants | 144 Participants |
| Region of Enrollment Australia | 1 participants | 6 participants | 3 participants | 4 participants | 14 participants |
| Region of Enrollment Canada | 6 participants | 8 participants | 14 participants | 6 participants | 34 participants |
| Region of Enrollment Czechia | 7 participants | 4 participants | 5 participants | 12 participants | 28 participants |
| Region of Enrollment Germany | 9 participants | 2 participants | 8 participants | 8 participants | 27 participants |
| Region of Enrollment Japan | 7 participants | 9 participants | 10 participants | 10 participants | 36 participants |
| Region of Enrollment Poland | 11 participants | 11 participants | 12 participants | 14 participants | 48 participants |
| Region of Enrollment Spain | 0 participants | 1 participants | 2 participants | 1 participants | 4 participants |
| Region of Enrollment United States | 4 participants | 8 participants | 7 participants | 6 participants | 25 participants |
| Sex: Female, Male Female | 21 Participants | 30 Participants | 32 Participants | 35 Participants | 118 Participants |
| Sex: Female, Male Male | 24 Participants | 19 Participants | 29 Participants | 26 Participants | 98 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 61 | 0 / 45 | 0 / 49 | 0 / 61 |
| other Total, other adverse events | 29 / 61 | 24 / 45 | 23 / 49 | 24 / 61 |
| serious Total, serious adverse events | 0 / 61 | 2 / 45 | 1 / 49 | 0 / 61 |
Outcome results
Primary
Change in EASI From Baseline to Week 16
The Eczema Area and Severity Index (EASI) is a validated measure used in clinical trials to evaluate the extent and severity of atopic dermatitis. EASI is a composite score ranging from 0 to 72 with higher scores indicating a more extensive or severe condition.
Time frame: Week 0 to Week 16
Population: FAS, full analysis set.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| LEO 152020 - Dosing Regimen 1 (Higher Dose) | Change in EASI From Baseline to Week 16 | -9.99 score on a scale |
| LEO 152020 - Dosing Regimen 2 (Middle Dose) | Change in EASI From Baseline to Week 16 | -8.83 score on a scale |
| LEO 152020 - Dosing Regimen 3 (Lower Dose) | Change in EASI From Baseline to Week 16 | -8.87 score on a scale |
| LEO 152020 - Placebo | Change in EASI From Baseline to Week 16 | -9.11 score on a scale |
Secondary
Number of Adverse Events From Baseline to Week 16+3 Days Per Subject
Only treatment-emergent adverse events will be reported for this outcome measure. An adverse event will be considered treatment emergent if occurring after the first dose of treatment (Week 0) and up until 3 days after the last dose of treatment (Week 16+3 days for a participant completing the 16-week treatment period).
Time frame: Week 0 to Week 16+3 days
Population: SAF, safety analysis set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LEO 152020 - Dosing Regimen 1 (Higher Dose) | Number of Adverse Events From Baseline to Week 16+3 Days Per Subject | 109 events |
| LEO 152020 - Dosing Regimen 2 (Middle Dose) | Number of Adverse Events From Baseline to Week 16+3 Days Per Subject | 67 events |
| LEO 152020 - Dosing Regimen 3 (Lower Dose) | Number of Adverse Events From Baseline to Week 16+3 Days Per Subject | 80 events |
| LEO 152020 - Placebo | Number of Adverse Events From Baseline to Week 16+3 Days Per Subject | 75 events |