Study to Assess the Efficacy and Safety of Orismilast in Atopic Dermatitis (ADESOS)

Percentage of Participants Achieving a Score of Clear (0) or Almost Clear (1) and At Least a 2-point Improvement in Investigator Global Assessment for Atopic Dermatitis (IGA-AD) at Weeks 2, 4, 8, 12, and 20

The IGA-AD is a measure used by physicians to determine a patient's overall severity of disease. The static version was used for measurement at a single point in time. The Investigator rated the severity of the patient's AD on a 5-point scale ranging from 0 (clear) to 4 (severe).

Time frame: At Weeks 2, 4, 8, 12, and 20

Number of Participants Achieving 75% Reduction in Eczema Area and Severity Index (EASI 75) at Weeks 2, 4, 8, 12, and 20

The EASI is an investigator-assessed instrument measuring the severity of clinical signs and the percentage of affected BSA in patients with AD. EASI scores range from 0 to 72, with higher scores reflecting greater disease severity. The extent of affected skin in each body region is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement).

Time frame: At Weeks 2, 4, 8, 12, and 20

Number of Participants Achieving 50% Reduction in Eczema Area and Severity Index (EASI 50) at Weeks 2, 4, 8, 12, 16, and 20

The EASI is an investigator-assessed instrument measuring the severity of clinical signs and the percentage of affected BSA in patients with AD. EASI scores range from 0 to 72, with higher scores reflecting greater disease severity. The extent of affected skin in each body region is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement).

Time frame: At Weeks 2, 4, 8, 12, 16, and 20

Number of Participants Achieving 90% Reduction in Eczema Area and Severity Index (EASI 90) at Weeks 2, 4, 8, 12, 16, and 20

The EASI is an investigator-assessed instrument measuring the severity of clinical signs and the percentage of affected BSA in patients with AD. EASI scores range from 0 to 72, with higher scores reflecting greater disease severity. The extent of affected skin in each body region is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement).

Time frame: At Weeks 2, 4, 8, 12, 16, and 20

Percent Change From Baseline in Eczema Area and Severity Index (EASI) at Weeks 2, 4, 8, 12, and 20

The EASI is a tool to measure the severity of clinical signs and the percentage of affected BSA in patients with AD. The EASI is a composite scoring system to evaluate the degree of erythema, induration/papulation, excoriation, and lichenification (each scored separately) for each of 4 body regions, with adjustment for the percentage of BSA involved for each body region and for the proportion of the body region to the whole body. EASI scores range from 0 to 72, with higher scores reflecting greater disease severity. Erythema, induration/papulation, excoriation, and lichenification are scored on a scale of 0 (absent) to 3 (severe) for each body region: head and neck, upper limbs (including the external axillae and hands), trunk (including the internal axillae and groin), and lower limbs (including the buttocks and feet). The extent of affected skin in each body region is scored on a scale of 0 (no involvement) to 6 (90% to 100% involvement).

Time frame: Baseline and Weeks 2, 4, 8, 12, and 20

Change From Baseline in the Peak Pruritus Numerical Rating Scale (NRS) Score at Weeks 1, 2, 4, 8, 12, 16, and 20

The severity of itch (pruritus) due to AD was assessed using a horizontal 11-point NRS. Patients were asked to assess their "worst itching due to AD over the past 24 hours" on an NRS anchored by the terms "no itching" (0) and "worst possible itching" (10).

Time frame: Baseline, Weeks 1, 2, 4, 8, 12, 16, and 20

Percentage of Participants Achieving At Least a 4-point Improvement in the Peak Pruritus Numerical Rating Scale (NRS) From Baseline at Weeks 1, 2, 4, 8, 12, 16, and 20

The severity of itch (pruritus) due to AD was assessed using a horizontal 11-point NRS. Patients were asked to assess their "worst itching due to AD over the past 24 hours" on an NRS anchored by the terms "no itching" (0) and "worst possible itching" (10).

Time frame: At Weeks 1, 2, 4, 8, 12, 16 and 20

Change From Baseline in Affected Body Surface Area (BSA) at Weeks 2, 4, 8, 12, 16, and 20

The BSA assessment estimated the extent of disease or skin affected by AD and was expressed as a percentage of total BSA. BSA was determined by the Investigator or designee using the participant's hand (palm + fingers) = 1% BSA rule.

Time frame: Baseline and Weeks 2, 4, 8, 12, 16, and 20

Change From Baseline in Dermatology Life Quality Index (DLQI) Score at Weeks 8, 16, and 20

The DLQI is a 10-item validated questionnaire completed by the patient and used to assess the effect of skin disease on the patient's quality of life during the previous week. The 10 questions cover the following topics: symptoms; embarrassment; interference with shopping and home care, clothing choices, social and leisure activities, sports participation, work or study, close relationships, and sex; and treatment. Each question is scored from 0 to 3 ("not at all," "a little," "a lot," and "very much," respectively), giving a total score ranging from 0 to 30. A high score is indicative of a poor quality of life.

Time frame: Baseline and Weeks 8, 16, and 20

Change From Baseline in Patient Oriented Eczema Measure (POEM) Score at Weeks 2, 4, 8, 12, 16, and 20

The POEM is a 7-item, validated questionnaire completed by the patient to assess disease symptoms. Patients were asked to respond to questions on frequency of sleep loss and skin dryness, itching, flaking, cracking, bleeding, and weeping over the past week. All answers carry equal weight, with a total possible score ranging from 0 to 28. A high score is indicative of a poor quality of life.

Time frame: Baseline and Weeks 2, 4, 8, 12, 16, and 20

Change From Baseline in Patient Global Impression of Severity Scale (PGIS) Score at Weeks 2, 4, 8, 12, 16, and 20

The PGIS scale is a single question asking the patient how he or she would rate his or her overall AD symptoms over the past 24 hours. The 5 categories of responses are (0) "no symptoms", (1) "very mild", (2) "mild", (3) "moderate", and (4) "severe."

Time frame: Baseline and Weeks 2, 4, 8, 12, 16, and 20

Change From Baseline in Patient Global Impression of Change (PGIC) Score at Weeks 2, 4, 8, 12, 16, and 20

The PGIC scale measures change in clinical status of AD. The PGIC is based on a 7-point scale, and the patient will rate the change from the start of treatment as 1 "very much improved," 2 "much improved," 3 "minimally improved," 4 "no change," 5 "minimally worse," 6 "much worse," and 7 "very much worse."

Time frame: Baseline and Weeks 2, 4, 8, 12, 16, and 20

Change From Baseline in Sleep Disturbance Numerical Rating Scale (NRS) Score at Weeks 1, 2, 4, 8, 12, 16, and 20

The sleep disturbance NRS is a scale used by the patients to report their degree of sleep loss related to AD. Patients were asked the following question in their local language: how would you rate your sleep last night? On a scale of 0 to 10, with 0 being "no sleep loss related to signs/symptoms of AD" and 10 being "I cannot sleep at all because of the signs/symptoms of AD". Higher scores indicate worse outcomes.

Time frame: Baseline and Weeks 1, 2, 4, 8, 12, 16, and 20

Change From Baseline in Skin Pain Numerical Rating Scale (NRS) at Weeks 1, 2, 4, 8, 12, 16, and 20

The skin pain NRS is a patient-administered, 11-point horizontal scale anchored at 0 and 10, with 0 representing "no pain" and 10 representing "worst pain imaginable." Overall severity of a participant's skin pain is indicated by selecting the number that best describes the worst level of skin pain in the past 24 hours.

Time frame: Baseline and Weeks 1, 2, 4, 8, 12, 16, and 20

Number of Participants With Treatment Emergent Adverse Events (TEAE)

An adverse event (AE) is any symptom, physical sign, syndrome, or disease that either emerges during the study or, if present at screening, worsens during the study, regardless of the suspected cause of the event.

Time frame: From Baseline through Week 20

Number of Participants With Abnormal Clinically Significant Findings in Physical Examination at Weeks 16

A complete physical examination (a check of the head, eyes, ears, nose, and throat; heart; lungs; abdomen; skin; cervical and axillary lymph nodes; and neurological and musculoskeletal systems) was performed at screening (Visit 1) and Weeks 16.

Time frame: At Week 16

Change From Baseline in Body Temperature at Weeks 16 and 20

A complete physical examination that included body temperature measurement was performed at screening (Visit 1) and Weeks 16 and 20.

Time frame: Baseline and Weeks 16 and 20

Change From Baseline in Respiration Rate at Weeks 16 and 20

A complete physical examination that included respiration rate measurement was performed at screening (Visit 1) and Weeks 16 and 20.

Time frame: Baseline and Weeks 16 and 20

Change From Baseline in Heart Rate at Weeks 16 and 20

A complete physical examination that included heart rate measurement was performed at screening (Visit 1) and Weeks 16 and 20.

Time frame: Baseline and Weeks 16 and 20

Change From Baseline in Systolic and Diastolic Blood Pressure at Weeks 16 and 20

A complete physical examination that included systolic and diastolic blood pressure measurements was performed at screening (Visit 1) and Weeks 16 and 20.

Time frame: Baseline and Weeks 16 and 20

Change From Baseline in Body Mass Index (BMI) at Weeks 16 and 20

A complete physical examination that included BMI measurements was performed at screening (Visit 1) and Weeks 16 and 20.

Time frame: Baseline and Weeks 16 and 20

Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) at Week 16

Electrocardiograms were assessed by the investigators based on automatically generated parameters.

Time frame: At Week 16

Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin Concentration at Week 16

Laboratory parameters including hematology was evaluated at baseline and at Week 16.

Time frame: Baseline and Week 16

Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Hemoglobin at Week 16

Laboratory parameters including hematology was evaluated at baseline and at Week 16.

Time frame: Baseline and Week 16

Change From Baseline in Hematology Parameter: Erythrocytes Mean Corpuscular Volume at Week 16

Laboratory parameters including hematology was evaluated at baseline and at Week 16.

Time frame: Baseline and Week 16

Change From Baseline in Hematology Parameter: Hematocrit at Week 16

Laboratory parameters including hematology was evaluated at baseline and at Week 16.

Time frame: Baseline and Week 16

Change From Baseline in Hematology Parameter: Hemoglobin at Week 16

Laboratory parameters including hematology was evaluated at baseline and at Week 16.

Time frame: Baseline and Week 16

Change From Baseline in Hematology Parameter: Basophils, Eosinophils, Leukocytes, Lymphocytes, Monocytes, and Neutrophils at Week 16

Laboratory parameters including hematology was evaluated at baseline and at Week 16.

Time frame: Baseline and Week 16

Change From Baseline in Hematology Parameter: Platelets at Week 16

Laboratory parameters including hematology was evaluated at baseline and at Week 16.

Time frame: Baseline and Week 16

Change From Baseline in Hematology Parameter: Reticulocytes at Week 16

Laboratory parameters including hematology was evaluated at baseline and at Week 16.

Time frame: Baseline and Week 16

Change From Baseline in Hematology Parameter: Basophils/Leukocytes at Week 16

Laboratory parameters including hematology was evaluated at baseline and at Week 16.

Time frame: Baseline and Week 16

Change From Baseline in Hematology Parameter: Eosinophils/Leukocytes at Week 16

Laboratory parameters including hematology was evaluated at baseline and at Week 16.

Time frame: Baseline and Week 16

Change From Baseline in Hematology Parameter: Lymphocytes/Leukocytes at Week 16

Laboratory parameters including hematology was evaluated at baseline and at Week 16.

Time frame: Baseline and Week 16

Change From Baseline in Hematology Parameter: Monocytes/Leukocytes at Week 16

Laboratory parameters including hematology was evaluated at baseline and at Week 16.

Time frame: Baseline and Week 16

Change From Baseline in Hematology Parameter: Neutrophils/Leukocytes at Week 16

Laboratory parameters including hematology was evaluated at baseline and at Week 16.

Time frame: Baseline and Week 16

Change From Baseline in Chemistry Parameter: Alanine Aminotransferase, Alkaline Phosphatase, Aspartate Aminotransferase, Gamma Glutamyl Transferase, Lactate Dehydrogenase at Week 16

Laboratory parameters including chemistry was evaluated at baseline and at Week 16.

Time frame: Baseline and Week 16

Change From Baseline in Chemistry Parameter: Albumin at Week 16

Laboratory parameters including chemistry was evaluated at baseline and at Week 16.

Time frame: Baseline and Week 16

Change From Baseline in Chemistry Parameter: Bilirubin, Creatinine, and Direct Bilirubin at Week 16

Laboratory parameters including chemistry was evaluated at baseline and at Week 16.

Time frame: Baseline and Week 16

Change From Baseline in Chemistry Parameter: Calcium, Chloride, Potassium, Sodium, and Urea Nitrogen at Week 16

Laboratory parameters including chemistry was evaluated at baseline and at Week 16.

Time frame: Baseline and Week 16

Change From Baseline in Chemistry Parameter: Phosphate at Week 16

Laboratory parameters including chemistry was evaluated at baseline and at Week 16.

Time frame: Baseline and Week 16

Number of Participants With Worst Case Post-Baseline Urinalysis at Week 16

Laboratory parameters including chemistry was evaluated at baseline and at Week 16.

Time frame: At Week 16

Change From Baseline in Hospital Anxiety and Depression Scale (HADS) at Weeks 2, 4, 8, 12, 16, and 20

The HADS is a patient reported outcome, comprises of 7 questions for anxiety and 7 questions for depression, with each answer graded from 0 to 3 with a higher score indicating a worse condition. For each group of questions, scores of 7 or less indicate cases without anxiety or depression, whereas scores of 8 to 10, 11 to 14, and 15 to 21 indicate mild, moderate, and severe cases, respectively.

Time frame: Baseline and Weeks 2, 4, 8, 12, 16, and 20

Number of Participants With Suicidal Ideation, Suicidal Behavior, and Self-Injurious Behavior Without Suicidal Intent Based on the Columbia-Suicide Severity Rating Scale (C-SSRS)

The C-SSRS, Investigator-administered version, was designed to provide a prospective, standardized measure of suicidality. C-SSRS is administered in the form of a clinical interview. The C-SSRS categories have been re-ordered from the actual scale to facilitate the definitions of the endpoints, and to enable clarity in the presentation of the results: Category 1 - Wish to be Dead, Category 2 - Non-specific Active Suicidal Thoughts, Category 3 - Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act, Category 4 - Active Suicidal Ideation with Some Intent to Act, without Specific Plan, Category 5 - Active Suicidal Ideation with Specific Plan and Intent, Category 6 - Preparatory Acts or Behavior, Category 7 - Aborted Attempt, Category 8 - Interrupted Attempt, Category 9 - Actual Attempt (non-fatal), Category 10 - Completed Suicide.

Time frame: At Weeks 2, 4, 8, 12, 16, and 20