Atopic Dermatitis
Conditions
Brief summary
This clinical trial will investigate the effectiveness and safety of a new active ingredient (LEO 138559) in the treatment of moderate to severe atopic dermatitis (AD). It is given by subcutaneous injection. Some people in the trial will instead receive Dupixent® which is an approved treatment for moderate to severe AD. Dupixent® is also given by subcutaneous injection. The main aim of this clinical trial is to investigate which changes in biomarkers in the skin are caused by LEO 138559 and Dupixent®. The trial includes a screening phase of up to 4 weeks, followed by a treatment period of 16 weeks, and a safety follow-up period of 16 weeks.
Interventions
DRUGLEO 138559
LEO 138559 is an antibody given by subcutaneous injection.
DRUGDupixent®
Dupixent® is an antibody given by subcutaneous injection.
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 64 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of AD \[as defined by the American Academy of Dermatology (AAD) Consensus Criteria\] that has been present for ≥1 year prior to screening. * Subjects who have a recent history (within 6 months before screening) of inadequate response to treatment with topical medication, or for whom topical treatments are otherwise medically inadvisable. * EASI score ≥12 at screening and ≥16 at baseline. * vIGA-AD score ≥3 at screening and baseline. * Body surface area (BSA) of AD involvement ≥10% at screening and baseline. * Worst Daily Pruritus NRS (weekly average) of ≥3 points at baseline.
Exclusion criteria
* Treatment with systemic immunosuppressive/immunomodulating medication (excluding systemic antihistamines if taken at stable dose already before baseline), e.g., JAK inhibitors, immunoglobulin/blood products, or phototherapy within 4 weeks or 5 half-lives prior to baseline, whichever is longer. * Treatment with systemic corticosteroids within 4 weeks prior to baseline (NOTE: Inhaled or intranasal steroids equivalent to doses including and up to 500 µg beclometasone (or equivalent) daily is allowed). * Treatment with biologics within 5 half-lives (if known) or 16 weeks prior to baseline, whichever is longer. * Treatment with TCS, TCI, or topical PDE-4 inhibitor within 1 week prior to baseline (NOTE: Patient may be rescreened (one time) if failed for this criterion. * Intake of nonsteroidal anti-inflammatory drugs (NSAIDs) within 1 week prior to baseline. Intake of paracetamol will be allowed. * Treatment with a live (attenuated) vaccine within 12 weeks prior to baseline. * Clinically significant active chronic or acute infection requiring systemic treatment within 4 weeks prior to baseline that may compromise the safety of the subject. * Clinically significant abnormalities detected on vital signs or ECG (apart from 1st degree atrioventricular (AV) block that is allowed). * Serious heart conditions, chronic lung diseases. * Acute asthma, acute bronchospasm, moderate to severe asthma. * Skin infection within 1 week prior to the baseline visit. * Presence of hepatitis B or C infection at screening. * Active inflammatory bowel disease (IBD) or history of IBD, anaphylaxis, immune complex disease, pancreatic disease, zoster infections, viral skin infections (including eczema herpeticum) or known or suspected history of immunosuppressive disorder. * History of human immunodeficiency virus (HIV) infection or positive HIV serology at screening. * Subject has a positive test for tuberculosis at screening. * Subject is pregnant or lactating.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Gene Expression Typically Associated With Atopic Dermatitis in Lesional Skin Biopsies From Baseline to Week 4 | From baseline to week 4 | Lesional skin biopsies will be evaluated by single cell RNA sequencing to evaluate global gene expression |
Secondary
| Measure | Time frame |
|---|---|
| Number of Treatment-emergent Adverse Events From Baseline to Week 16 Per Subject | Between baseline and week 16 |
Countries
Austria
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| LEO 138559 Participants will receive injections of LEO 138559 from Week 0 (baseline) to Week 16 (end of treatment).
LEO 138559: LEO 138559 is an antibody given by subcutaneous injection. | 9 |
| Dupixent® Participants will receive injections of Dupixent® from Week 0 (baseline) to Week 16 (end of treatment).
Dupixent®: Dupixent® is an antibody given by subcutaneous injection. | 4 |
| Total | 13 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | LEO 138559 | Total | Dupixent® |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 9 Participants | 13 Participants | 4 Participants |
| Age, Continuous | 32.6 years STANDARD_DEVIATION 11.3 | 30.5 years STANDARD_DEVIATION 10.2 | 26.0 years STANDARD_DEVIATION 5.9 |
| Baseline height (cm) | 176.1 cm STANDARD_DEVIATION 11.1 | 174.5 cm STANDARD_DEVIATION 9.7 | 171.0 cm STANDARD_DEVIATION 4.7 |
| Baseline weight (kg) | 82.49 kg STANDARD_DEVIATION 13.61 | 79.18 kg STANDARD_DEVIATION 13.23 | 71.75 kg STANDARD_DEVIATION 9.98 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants | 13 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 12 Participants | 4 Participants |
| Region of Enrollment Austria | 9 participants | 13 participants | 4 participants |
| Sex: Female, Male Female | 3 Participants | 4 Participants | 1 Participants |
| Sex: Female, Male Male | 6 Participants | 9 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 4 |
| other Total, other adverse events | 8 / 9 | 3 / 4 |
| serious Total, serious adverse events | 0 / 9 | 0 / 4 |
Outcome results
Primary
Change in Gene Expression Typically Associated With Atopic Dermatitis in Lesional Skin Biopsies From Baseline to Week 4
Lesional skin biopsies will be evaluated by single cell RNA sequencing to evaluate global gene expression
Time frame: From baseline to week 4
Population: The analysis population consists of individuals with AD, and the gene expression analysis is based on lesional skin biopsies obtained from these individuals at baseline and week 4. The gene expression values used in the analysis are averaged expression values for each identity class. These values were calculated using the AverageExpression function on the basis of normalized data from the respective Seurat object.~In LEO 138559 Arm group, 1 participant screened but not included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| LEO 138559 | Change in Gene Expression Typically Associated With Atopic Dermatitis in Lesional Skin Biopsies From Baseline to Week 4 | Keratinocytes S100A7 | 0.212 fold change | Standard Deviation 7.692 |
| LEO 138559 | Change in Gene Expression Typically Associated With Atopic Dermatitis in Lesional Skin Biopsies From Baseline to Week 4 | Keratinocytes S100A8 | 0.155 fold change | Standard Deviation 6.308 |
| LEO 138559 | Change in Gene Expression Typically Associated With Atopic Dermatitis in Lesional Skin Biopsies From Baseline to Week 4 | Keratinocytes S100A9 | 0.149 fold change | Standard Deviation 5.52 |
| LEO 138559 | Change in Gene Expression Typically Associated With Atopic Dermatitis in Lesional Skin Biopsies From Baseline to Week 4 | Keratinocytes KRT6A | 0.164 fold change | Standard Deviation 4.08 |
| LEO 138559 | Change in Gene Expression Typically Associated With Atopic Dermatitis in Lesional Skin Biopsies From Baseline to Week 4 | Keratinocytes KRT16 | 0.246 fold change | Standard Deviation 2.75 |
| LEO 138559 | Change in Gene Expression Typically Associated With Atopic Dermatitis in Lesional Skin Biopsies From Baseline to Week 4 | Keratinocytes KRT1 | 1.355 fold change | Standard Deviation 1.748 |
| Dupixent® | Change in Gene Expression Typically Associated With Atopic Dermatitis in Lesional Skin Biopsies From Baseline to Week 4 | Keratinocytes KRT16 | 0.094 fold change | Standard Deviation 1.731 |
| Dupixent® | Change in Gene Expression Typically Associated With Atopic Dermatitis in Lesional Skin Biopsies From Baseline to Week 4 | Keratinocytes S100A7 | 0.043 fold change | Standard Deviation 8.899 |
| Dupixent® | Change in Gene Expression Typically Associated With Atopic Dermatitis in Lesional Skin Biopsies From Baseline to Week 4 | Keratinocytes KRT6A | 0.088 fold change | Standard Deviation 1.459 |
| Dupixent® | Change in Gene Expression Typically Associated With Atopic Dermatitis in Lesional Skin Biopsies From Baseline to Week 4 | Keratinocytes S100A8 | 0.048 fold change | Standard Deviation 5.367 |
| Dupixent® | Change in Gene Expression Typically Associated With Atopic Dermatitis in Lesional Skin Biopsies From Baseline to Week 4 | Keratinocytes KRT1 | 0.851 fold change | Standard Deviation 5.008 |
| Dupixent® | Change in Gene Expression Typically Associated With Atopic Dermatitis in Lesional Skin Biopsies From Baseline to Week 4 | Keratinocytes S100A9 | 0.02 fold change | Standard Deviation 13.99 |
Secondary
Number of Treatment-emergent Adverse Events From Baseline to Week 16 Per Subject
Time frame: Between baseline and week 16
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| LEO 138559 | Number of Treatment-emergent Adverse Events From Baseline to Week 16 Per Subject | 17 Events |
| Dupixent® | Number of Treatment-emergent Adverse Events From Baseline to Week 16 Per Subject | 8 Events |