Dermatitis, Atopic
Conditions
Keywords
Atopic Dermatitis, BMS-986166, BMS-986195, Branebrutinib
Brief summary
The purpose of this study is to evaluate the efficacy, safety, and tolerability of BMS-986166 and of branebrutinib, each versus placebo, for the treatment of participants with moderate to severe atopic dermatitis.
Interventions
DRUGBMS-986166
Specified dose on specified days
DRUGBranebrutinib
Specified dose on specified days
OTHERPlacebo
Specified dose on specified days
Sponsors
Bristol-Myers Squibb
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Chronic atopic dermatitis (AD) diagnosed according to the Eichenfield modification of Hanifin's and Rajka's (E-HR) criteria at Screening * Disease duration of at least 24 months since diagnosis by any criteria * Documented history of inadequate control of AD by a stable regimen (≥ 4 weeks) of topical corticosteroids, calcineurin inhibitors or biologics, within 6 months of randomization, or inappropriateness of therapy due to side effects or safety risks leading to prior discontinuation * Application of fixed doses of an additive-free, basic bland emollient twice-daily for ≥ 7 days before baseline visit and for the duration of the study
Exclusion criteria
* Any major illness/condition or evidence of an unstable clinical condition or local active infection/infectious illness that, in the investigator's judgment, will substantially increase the risk to the participant if he or she participates in the study or interfere with the interpretation of study results * Clinically relevant cardiovascular conditions or pulmonary conditions * High likelihood - based on participant history, and investigator judgement - of requiring rescue therapy in \< 4 weeks prior to randomization * Evidence of acute flare between the Screening and Baseline/ Randomization * Skin lesion(s) and/or pruritus due to conditions other than AD that would interfere with the study specified assessments Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Percentage Change From Baseline in EASI Score at Week 16 | From baseline and 16 weeks | The Eczema Area and Severity Index (EASI) is a validated, composite scoring system assessed by the investigator based on the extent of each of the 4 body regions (head and neck, upper limbs, lower limbs, and trunk) affected with AD and the intensity of each of 4 key signs of AD (erythema, induration/papulation, excoriation, and lichenification) and is based on a 4-point scale of 0 (absent), 1 (mild), 2 (moderate), and 3 (severe). For each of the 4 body regions, the mean intensity of inflamed lesions for each of the 4 signs is recorded. Xerosis, scaling, urticaria, or post-inflammatory pigmentation changes are not included. The total EASI score ranges from 0 to 72. The lower the score the better. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Exhibiting a ≥ 50% (EASI-50) Reduction From Baseline in EASI Score at Week 16 | From baseline and 16 weeks | The Eczema Area and Severity Index (EASI) is a validated, composite scoring system assessed by the investigator based on the extent of each of the 4 body regions (head and neck, upper limbs, lower limbs, and trunk) affected with AD and the intensity of each of 4 key signs of AD (erythema, induration/papulation, excoriation, and lichenification) and is based on a 4-point scale of 0 (absent), 1 (mild), 2 (moderate), and 3 (severe). For each of the 4 body regions, the mean intensity of inflamed lesions for each of the 4 signs is recorded. Xerosis, scaling, urticaria, or post-inflammatory pigmentation changes are not included. The total EASI score ranges from 0 to 72. The lower the score the better. |
| Percentage of Participants Exhibiting a ≥ 4-point Improvement From Baseline in Pruritus NRS at Week 16 | From baseline and 16 weeks | Participants will complete a daily diary recording the intensity of their pruritus they experienced during the preceding 24 hours. The intensity of pruritus will be assessed using a validated 11-point NRS, ranging from 0 (no itching) to 10 (the worst itching imaginable). The lower the score the better. |
| Mean Percentage Change From Baseline in Pruritus NRS Score at Week 16 | From baseline and 16 weeks | Participants will complete a daily diary recording the intensity of their pruritus and the average quality of sleep they experienced during the preceding 24 hours. The intensity of pruritus will be assessed using a validated 11-point NRS, ranging from 0 (no itching) to 10 (the worst itching imaginable). The quality of sleep will be assessed using a validated 11-point NRS ranging from 0 (the best possible sleep) to 10 (the worst possible sleep). The lower the score the better. |
| Mean Change From Baseline in Percentage of Affected BSA at Week 16 | From baseline and 16 weeks | A widely used method of measuring Body Surface Area (BSA) involvement by AD, is the rule of nines in which for each section of the body (the possible highest score for each region is: head and neck \[9%\], anterior trunk \[18%\], back \[18%\], upper limbs \[18%\], lower limbs \[36%\], genitals \[1%\]) and will be reported as a percentage of all major body sections combined. |
| Number of Participants With Mild Moderate or Severe AEs | From initial treatment to 30 days post discontinuation, approximately 29 weeks | An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a clinical investigation participant administered study treatment that does not necessarily have a causal relationship with this treatment. Mild: An event that is easily tolerated by the participant, causing minimal discomfort and not interfering with everyday activities. Moderate: An event that causes sufficient discomfort and interferes with normal everyday activities. Severe: An event that prevents normal everyday activities. An AE that is assessed as severe should not be confused with an SAE. Severe is a category utilized for rating the intensity of an event, and both AEs and SAEs can be assessed as severe. |
| Percentage of Participants Exhibiting a Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) Score of 0 (Cleared) or 1 (Almost Cleared) AND a ≥ 2 Point Reduction From Baseline at Week 16 | From baseline and 16 weeks | The vIGA-AD is a static 5-point assessment intended to assess the global severities of key acute clinical signs of AD, including erythema, induration/papulation, and oozing/crusting (lichenification excluded). The rating of cleared (0), almost cleared (1), mild (2), moderate (3), and severe (4) will be assessed. |
| Number of Participants With Clinically Relevant ECG Abnormalities | Week 24 after initial treatment | 12 Lead Electrocardiogram (ECG). The participant will remain supine for 5 to 10 minutes prior to the ECG and must have lab work done after the tracing so that the ECG results remain as accurate as possible. |
| Number of Participants With Clinically Relevant OCT Abnormalities | Week 24 after initial treatment | Optical coherence tomography (OCT) is a non-invasive imaging test. It uses light waves to take cross-section pictures of your retina. Diagnosis is made by an ophthalmologist. |
| Number of Participants With Clinically Relevant PFT Abnormalities | Week 24 after initial treatment | Pulmonary function tests (PFT) include: forced expiratory volume (FEV1), percent predicted FEV1, forced vital capacity (FVC), percent predicted FVC, and Diffusion capacity of carbon monoxide (DLCO). |
| Number of Participants With Clinically Meaningful Changes in Vital Signs | Week 24 after initial treatment | The following vital signs will be assessed: systolic blood pressure, diastolic blood pressure, heart rate, respiratory rate and body temperature. |
| Number of Participants With Clinically Relevant Changes in LFTs | Week 24 after initial treatment | Liver Function Tests (LFTs) will include the following measurements: * ALT OR AST \> 3 X ULN * ALT OR AST \> 5 X ULN * ALT OR AST \> 8 X ULN * TOTAL BILIRUBIN \> 2 X ULN * ALT OR AST \> 3 X ULN AND (TOTAL BILIRUBIN \> 2 X ULN OR INR \>1.5) AST = aspartate aminotransferase ALT = alanine aminotransferase ULN = Upper limit number INR = International Normalized Ratio |
| Number of Participants With Mild Moderate or Severe SAEs | From initial treatment to 30 days post discontinuation, approximately 29 weeks | A Serious Adverse Event (SAE) is defined as any untoward medical occurrence that, at any dose: * Results in death * is life threatening * Requires inpatient hospitalization or causes prolongation of existing hospitalization * Results in persistent or significant disability * Is a congenital anomaly/birth defect. * Is an important medical event |
Countries
Australia, Austria, Canada, Germany, Poland, Spain, United States
Participant flow
Pre-assignment details
17 participants randomized and treated
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo | 4 |
| Treatment 1 BMS-986166 0.25mg POQD | 3 |
| Treatment 2 BMS-986166 0.5mg POQD | 4 |
| Treatment 3 BMS-986166 0.75mg POQD | 3 |
| Treatment 4 Branebrutinib 9mg POQD | 3 |
| Total | 17 |
Baseline characteristics
| Characteristic | Placebo | Treatment 1 | Treatment 2 | Treatment 3 | Treatment 4 | Total |
|---|---|---|---|---|---|---|
| Age, Continuous | 30.5 Years STANDARD_DEVIATION 11.3 | 36.0 Years STANDARD_DEVIATION 6.2 | 29.5 Years STANDARD_DEVIATION 14.6 | 46.7 Years STANDARD_DEVIATION 8.3 | 36.7 Years STANDARD_DEVIATION 17.8 | 35.2 Years STANDARD_DEVIATION 12.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 3 Participants | 3 Participants | 2 Participants | 2 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 3 Participants | 3 Participants | 2 Participants | 3 Participants | 3 Participants | 14 Participants |
| Sex: Female, Male Female | 3 Participants | 1 Participants | 3 Participants | 2 Participants | 2 Participants | 11 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 1 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 3 | 0 / 4 | 0 / 3 | 0 / 3 |
| other Total, other adverse events | 2 / 4 | 3 / 3 | 2 / 4 | 1 / 3 | 1 / 3 |
| serious Total, serious adverse events | 0 / 4 | 1 / 3 | 0 / 4 | 0 / 3 | 0 / 3 |
Outcome results
Primary
Mean Percentage Change From Baseline in EASI Score at Week 16
The Eczema Area and Severity Index (EASI) is a validated, composite scoring system assessed by the investigator based on the extent of each of the 4 body regions (head and neck, upper limbs, lower limbs, and trunk) affected with AD and the intensity of each of 4 key signs of AD (erythema, induration/papulation, excoriation, and lichenification) and is based on a 4-point scale of 0 (absent), 1 (mild), 2 (moderate), and 3 (severe). For each of the 4 body regions, the mean intensity of inflamed lesions for each of the 4 signs is recorded. Xerosis, scaling, urticaria, or post-inflammatory pigmentation changes are not included. The total EASI score ranges from 0 to 72. The lower the score the better.
Time frame: From baseline and 16 weeks
Population: mITT population with evaluable EASI score at baseline and week 16. mITT: Modified Intent-To-Treat (All participants who are randomized and received at least one dose of study treatment)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | Mean Percentage Change From Baseline in EASI Score at Week 16 | -83.1 Percentage change |
| Treatment 4 | Mean Percentage Change From Baseline in EASI Score at Week 16 | -92.3 Percentage change |
Secondary
Mean Change From Baseline in Percentage of Affected BSA at Week 16
A widely used method of measuring Body Surface Area (BSA) involvement by AD, is the rule of nines in which for each section of the body (the possible highest score for each region is: head and neck \[9%\], anterior trunk \[18%\], back \[18%\], upper limbs \[18%\], lower limbs \[36%\], genitals \[1%\]) and will be reported as a percentage of all major body sections combined.
Time frame: From baseline and 16 weeks
Population: mITT population with evaluable baseline and week 16 BSA measurement. mITT: Modified Intent-To-Treat (All participants who are randomized and received at least one dose of study treatment)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | Mean Change From Baseline in Percentage of Affected BSA at Week 16 | -17.00 Percentage change |
| Treatment 4 | Mean Change From Baseline in Percentage of Affected BSA at Week 16 | -12.10 Percentage change |
Secondary
Mean Percentage Change From Baseline in Pruritus NRS Score at Week 16
Participants will complete a daily diary recording the intensity of their pruritus and the average quality of sleep they experienced during the preceding 24 hours. The intensity of pruritus will be assessed using a validated 11-point NRS, ranging from 0 (no itching) to 10 (the worst itching imaginable). The quality of sleep will be assessed using a validated 11-point NRS ranging from 0 (the best possible sleep) to 10 (the worst possible sleep). The lower the score the better.
Time frame: From baseline and 16 weeks
Population: mITT population with evaluable Pruritus NRS at baseline and week 16. mITT: Modified Intent-To-Treat (All participants who are randomized and received at least one dose of study treatment)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | Mean Percentage Change From Baseline in Pruritus NRS Score at Week 16 | -89.6 Percentage change |
| Treatment 3 | Mean Percentage Change From Baseline in Pruritus NRS Score at Week 16 | -100 Percentage change |
| Treatment 4 | Mean Percentage Change From Baseline in Pruritus NRS Score at Week 16 | -86.8 Percentage change |
Secondary
Number of Participants With Clinically Meaningful Changes in Vital Signs
The following vital signs will be assessed: systolic blood pressure, diastolic blood pressure, heart rate, respiratory rate and body temperature.
Time frame: Week 24 after initial treatment
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Clinically Meaningful Changes in Vital Signs | Systolic Blood Pressure | 0 Participants |
| Placebo | Number of Participants With Clinically Meaningful Changes in Vital Signs | Heart Rate | 0 Participants |
| Placebo | Number of Participants With Clinically Meaningful Changes in Vital Signs | Respiratory Rate | 2 Participants |
| Placebo | Number of Participants With Clinically Meaningful Changes in Vital Signs | Diastolic Blood Pressure | 0 Participants |
| Placebo | Number of Participants With Clinically Meaningful Changes in Vital Signs | Body Temperature | 0 Participants |
| Treatment 1 | Number of Participants With Clinically Meaningful Changes in Vital Signs | Diastolic Blood Pressure | 0 Participants |
| Treatment 1 | Number of Participants With Clinically Meaningful Changes in Vital Signs | Heart Rate | 0 Participants |
| Treatment 1 | Number of Participants With Clinically Meaningful Changes in Vital Signs | Body Temperature | 0 Participants |
| Treatment 1 | Number of Participants With Clinically Meaningful Changes in Vital Signs | Respiratory Rate | 1 Participants |
| Treatment 1 | Number of Participants With Clinically Meaningful Changes in Vital Signs | Systolic Blood Pressure | 0 Participants |
| Treatment 2 | Number of Participants With Clinically Meaningful Changes in Vital Signs | Respiratory Rate | 2 Participants |
| Treatment 2 | Number of Participants With Clinically Meaningful Changes in Vital Signs | Body Temperature | 0 Participants |
| Treatment 2 | Number of Participants With Clinically Meaningful Changes in Vital Signs | Heart Rate | 0 Participants |
| Treatment 2 | Number of Participants With Clinically Meaningful Changes in Vital Signs | Diastolic Blood Pressure | 0 Participants |
| Treatment 2 | Number of Participants With Clinically Meaningful Changes in Vital Signs | Systolic Blood Pressure | 0 Participants |
| Treatment 3 | Number of Participants With Clinically Meaningful Changes in Vital Signs | Respiratory Rate | 3 Participants |
| Treatment 3 | Number of Participants With Clinically Meaningful Changes in Vital Signs | Heart Rate | 0 Participants |
| Treatment 3 | Number of Participants With Clinically Meaningful Changes in Vital Signs | Diastolic Blood Pressure | 0 Participants |
| Treatment 3 | Number of Participants With Clinically Meaningful Changes in Vital Signs | Systolic Blood Pressure | 0 Participants |
| Treatment 3 | Number of Participants With Clinically Meaningful Changes in Vital Signs | Body Temperature | 0 Participants |
| Treatment 4 | Number of Participants With Clinically Meaningful Changes in Vital Signs | Diastolic Blood Pressure | 0 Participants |
| Treatment 4 | Number of Participants With Clinically Meaningful Changes in Vital Signs | Heart Rate | 0 Participants |
| Treatment 4 | Number of Participants With Clinically Meaningful Changes in Vital Signs | Respiratory Rate | 3 Participants |
| Treatment 4 | Number of Participants With Clinically Meaningful Changes in Vital Signs | Body Temperature | 0 Participants |
| Treatment 4 | Number of Participants With Clinically Meaningful Changes in Vital Signs | Systolic Blood Pressure | 0 Participants |
Secondary
Number of Participants With Clinically Relevant Changes in LFTs
Liver Function Tests (LFTs) will include the following measurements: * ALT OR AST \> 3 X ULN * ALT OR AST \> 5 X ULN * ALT OR AST \> 8 X ULN * TOTAL BILIRUBIN \> 2 X ULN * ALT OR AST \> 3 X ULN AND (TOTAL BILIRUBIN \> 2 X ULN OR INR \>1.5) AST = aspartate aminotransferase ALT = alanine aminotransferase ULN = Upper limit number INR = International Normalized Ratio
Time frame: Week 24 after initial treatment
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Clinically Relevant Changes in LFTs | ALT OR AST > 3 X ULN | 0 Participants |
| Placebo | Number of Participants With Clinically Relevant Changes in LFTs | ALT OR AST > 5 X ULN | 0 Participants |
| Placebo | Number of Participants With Clinically Relevant Changes in LFTs | ALT OR AST > 8 X ULN | 0 Participants |
| Placebo | Number of Participants With Clinically Relevant Changes in LFTs | TOTAL BILIRUBIN > 2 X ULN | 0 Participants |
| Placebo | Number of Participants With Clinically Relevant Changes in LFTs | ALT OR AST > 3 X ULN AND (TOTAL BILIRUBIN > 2 X ULN OR INR >1.5) | 0 Participants |
| Placebo | Number of Participants With Clinically Relevant Changes in LFTs | ALT OR AST > 5 X ULN WITH CONFIRMATION, WITHIN 2 WEEKS | 0 Participants |
| Treatment 1 | Number of Participants With Clinically Relevant Changes in LFTs | ALT OR AST > 3 X ULN AND (TOTAL BILIRUBIN > 2 X ULN OR INR >1.5) | 0 Participants |
| Treatment 1 | Number of Participants With Clinically Relevant Changes in LFTs | ALT OR AST > 5 X ULN WITH CONFIRMATION, WITHIN 2 WEEKS | 0 Participants |
| Treatment 1 | Number of Participants With Clinically Relevant Changes in LFTs | ALT OR AST > 3 X ULN | 0 Participants |
| Treatment 1 | Number of Participants With Clinically Relevant Changes in LFTs | ALT OR AST > 8 X ULN | 0 Participants |
| Treatment 1 | Number of Participants With Clinically Relevant Changes in LFTs | TOTAL BILIRUBIN > 2 X ULN | 0 Participants |
| Treatment 1 | Number of Participants With Clinically Relevant Changes in LFTs | ALT OR AST > 5 X ULN | 0 Participants |
| Treatment 2 | Number of Participants With Clinically Relevant Changes in LFTs | TOTAL BILIRUBIN > 2 X ULN | 0 Participants |
| Treatment 2 | Number of Participants With Clinically Relevant Changes in LFTs | ALT OR AST > 3 X ULN AND (TOTAL BILIRUBIN > 2 X ULN OR INR >1.5) | 0 Participants |
| Treatment 2 | Number of Participants With Clinically Relevant Changes in LFTs | ALT OR AST > 3 X ULN | 0 Participants |
| Treatment 2 | Number of Participants With Clinically Relevant Changes in LFTs | ALT OR AST > 8 X ULN | 0 Participants |
| Treatment 2 | Number of Participants With Clinically Relevant Changes in LFTs | ALT OR AST > 5 X ULN | 0 Participants |
| Treatment 2 | Number of Participants With Clinically Relevant Changes in LFTs | ALT OR AST > 5 X ULN WITH CONFIRMATION, WITHIN 2 WEEKS | 0 Participants |
| Treatment 3 | Number of Participants With Clinically Relevant Changes in LFTs | TOTAL BILIRUBIN > 2 X ULN | 0 Participants |
| Treatment 3 | Number of Participants With Clinically Relevant Changes in LFTs | ALT OR AST > 5 X ULN | 0 Participants |
| Treatment 3 | Number of Participants With Clinically Relevant Changes in LFTs | ALT OR AST > 8 X ULN | 0 Participants |
| Treatment 3 | Number of Participants With Clinically Relevant Changes in LFTs | ALT OR AST > 5 X ULN WITH CONFIRMATION, WITHIN 2 WEEKS | 0 Participants |
| Treatment 3 | Number of Participants With Clinically Relevant Changes in LFTs | ALT OR AST > 3 X ULN AND (TOTAL BILIRUBIN > 2 X ULN OR INR >1.5) | 0 Participants |
| Treatment 3 | Number of Participants With Clinically Relevant Changes in LFTs | ALT OR AST > 3 X ULN | 0 Participants |
| Treatment 4 | Number of Participants With Clinically Relevant Changes in LFTs | ALT OR AST > 3 X ULN AND (TOTAL BILIRUBIN > 2 X ULN OR INR >1.5) | 0 Participants |
| Treatment 4 | Number of Participants With Clinically Relevant Changes in LFTs | ALT OR AST > 8 X ULN | 0 Participants |
| Treatment 4 | Number of Participants With Clinically Relevant Changes in LFTs | ALT OR AST > 5 X ULN | 0 Participants |
| Treatment 4 | Number of Participants With Clinically Relevant Changes in LFTs | ALT OR AST > 5 X ULN WITH CONFIRMATION, WITHIN 2 WEEKS | 0 Participants |
| Treatment 4 | Number of Participants With Clinically Relevant Changes in LFTs | TOTAL BILIRUBIN > 2 X ULN | 0 Participants |
| Treatment 4 | Number of Participants With Clinically Relevant Changes in LFTs | ALT OR AST > 3 X ULN | 0 Participants |
Secondary
Number of Participants With Clinically Relevant ECG Abnormalities
12 Lead Electrocardiogram (ECG). The participant will remain supine for 5 to 10 minutes prior to the ECG and must have lab work done after the tracing so that the ECG results remain as accurate as possible.
Time frame: Week 24 after initial treatment
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Clinically Relevant ECG Abnormalities | 0 Participants |
| Treatment 1 | Number of Participants With Clinically Relevant ECG Abnormalities | 0 Participants |
| Treatment 2 | Number of Participants With Clinically Relevant ECG Abnormalities | 0 Participants |
| Treatment 3 | Number of Participants With Clinically Relevant ECG Abnormalities | 0 Participants |
| Treatment 4 | Number of Participants With Clinically Relevant ECG Abnormalities | 0 Participants |
Secondary
Number of Participants With Clinically Relevant OCT Abnormalities
Optical coherence tomography (OCT) is a non-invasive imaging test. It uses light waves to take cross-section pictures of your retina. Diagnosis is made by an ophthalmologist.
Time frame: Week 24 after initial treatment
Population: Safety population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Clinically Relevant OCT Abnormalities | 0 Participants |
| Treatment 1 | Number of Participants With Clinically Relevant OCT Abnormalities | 0 Participants |
| Treatment 2 | Number of Participants With Clinically Relevant OCT Abnormalities | 1 Participants |
| Treatment 3 | Number of Participants With Clinically Relevant OCT Abnormalities | 0 Participants |
| Treatment 4 | Number of Participants With Clinically Relevant OCT Abnormalities | 0 Participants |
Secondary
Number of Participants With Clinically Relevant PFT Abnormalities
Pulmonary function tests (PFT) include: forced expiratory volume (FEV1), percent predicted FEV1, forced vital capacity (FVC), percent predicted FVC, and Diffusion capacity of carbon monoxide (DLCO).
Time frame: Week 24 after initial treatment
Population: Safety Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Placebo | Number of Participants With Clinically Relevant PFT Abnormalities | 0 Participants |
| Treatment 1 | Number of Participants With Clinically Relevant PFT Abnormalities | 0 Participants |
| Treatment 2 | Number of Participants With Clinically Relevant PFT Abnormalities | 0 Participants |
| Treatment 3 | Number of Participants With Clinically Relevant PFT Abnormalities | 0 Participants |
| Treatment 4 | Number of Participants With Clinically Relevant PFT Abnormalities | 0 Participants |
Secondary
Number of Participants With Mild Moderate or Severe AEs
An Adverse Event (AE) is defined as any new untoward medical occurrence or worsening of a pre-existing medical condition in a clinical investigation participant administered study treatment that does not necessarily have a causal relationship with this treatment. Mild: An event that is easily tolerated by the participant, causing minimal discomfort and not interfering with everyday activities. Moderate: An event that causes sufficient discomfort and interferes with normal everyday activities. Severe: An event that prevents normal everyday activities. An AE that is assessed as severe should not be confused with an SAE. Severe is a category utilized for rating the intensity of an event, and both AEs and SAEs can be assessed as severe.
Time frame: From initial treatment to 30 days post discontinuation, approximately 29 weeks
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Mild Moderate or Severe AEs | Mild | 1 Participants |
| Placebo | Number of Participants With Mild Moderate or Severe AEs | Severe | 0 Participants |
| Placebo | Number of Participants With Mild Moderate or Severe AEs | Moderate | 1 Participants |
| Treatment 1 | Number of Participants With Mild Moderate or Severe AEs | Moderate | 3 Participants |
| Treatment 1 | Number of Participants With Mild Moderate or Severe AEs | Mild | 2 Participants |
| Treatment 1 | Number of Participants With Mild Moderate or Severe AEs | Severe | 0 Participants |
| Treatment 2 | Number of Participants With Mild Moderate or Severe AEs | Moderate | 1 Participants |
| Treatment 2 | Number of Participants With Mild Moderate or Severe AEs | Mild | 1 Participants |
| Treatment 2 | Number of Participants With Mild Moderate or Severe AEs | Severe | 0 Participants |
| Treatment 3 | Number of Participants With Mild Moderate or Severe AEs | Mild | 1 Participants |
| Treatment 3 | Number of Participants With Mild Moderate or Severe AEs | Severe | 0 Participants |
| Treatment 3 | Number of Participants With Mild Moderate or Severe AEs | Moderate | 1 Participants |
| Treatment 4 | Number of Participants With Mild Moderate or Severe AEs | Moderate | 0 Participants |
| Treatment 4 | Number of Participants With Mild Moderate or Severe AEs | Mild | 1 Participants |
| Treatment 4 | Number of Participants With Mild Moderate or Severe AEs | Severe | 0 Participants |
Secondary
Number of Participants With Mild Moderate or Severe SAEs
A Serious Adverse Event (SAE) is defined as any untoward medical occurrence that, at any dose: * Results in death * is life threatening * Requires inpatient hospitalization or causes prolongation of existing hospitalization * Results in persistent or significant disability * Is a congenital anomaly/birth defect. * Is an important medical event
Time frame: From initial treatment to 30 days post discontinuation, approximately 29 weeks
Population: Safety Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Placebo | Number of Participants With Mild Moderate or Severe SAEs | Moderate | 0 Participants |
| Placebo | Number of Participants With Mild Moderate or Severe SAEs | Mild | 0 Participants |
| Placebo | Number of Participants With Mild Moderate or Severe SAEs | Severe | 0 Participants |
| Treatment 1 | Number of Participants With Mild Moderate or Severe SAEs | Moderate | 1 Participants |
| Treatment 1 | Number of Participants With Mild Moderate or Severe SAEs | Mild | 0 Participants |
| Treatment 1 | Number of Participants With Mild Moderate or Severe SAEs | Severe | 0 Participants |
| Treatment 2 | Number of Participants With Mild Moderate or Severe SAEs | Moderate | 0 Participants |
| Treatment 2 | Number of Participants With Mild Moderate or Severe SAEs | Mild | 0 Participants |
| Treatment 2 | Number of Participants With Mild Moderate or Severe SAEs | Severe | 0 Participants |
| Treatment 3 | Number of Participants With Mild Moderate or Severe SAEs | Mild | 0 Participants |
| Treatment 3 | Number of Participants With Mild Moderate or Severe SAEs | Severe | 0 Participants |
| Treatment 3 | Number of Participants With Mild Moderate or Severe SAEs | Moderate | 0 Participants |
| Treatment 4 | Number of Participants With Mild Moderate or Severe SAEs | Moderate | 0 Participants |
| Treatment 4 | Number of Participants With Mild Moderate or Severe SAEs | Mild | 0 Participants |
| Treatment 4 | Number of Participants With Mild Moderate or Severe SAEs | Severe | 0 Participants |
Secondary
Percentage of Participants Exhibiting a ≥ 4-point Improvement From Baseline in Pruritus NRS at Week 16
Participants will complete a daily diary recording the intensity of their pruritus they experienced during the preceding 24 hours. The intensity of pruritus will be assessed using a validated 11-point NRS, ranging from 0 (no itching) to 10 (the worst itching imaginable). The lower the score the better.
Time frame: From baseline and 16 weeks
Population: mITT population with evaluable baseline pruritis NRS greater than or equal to 4. mITT: Modified Intent-To-Treat (All participants who are randomized and received at least one dose of study treatment)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Exhibiting a ≥ 4-point Improvement From Baseline in Pruritus NRS at Week 16 | 25.0 Percentage of participants |
| Treatment 1 | Percentage of Participants Exhibiting a ≥ 4-point Improvement From Baseline in Pruritus NRS at Week 16 | 0 Percentage of participants |
| Treatment 2 | Percentage of Participants Exhibiting a ≥ 4-point Improvement From Baseline in Pruritus NRS at Week 16 | 0 Percentage of participants |
| Treatment 3 | Percentage of Participants Exhibiting a ≥ 4-point Improvement From Baseline in Pruritus NRS at Week 16 | 50 Percentage of participants |
| Treatment 4 | Percentage of Participants Exhibiting a ≥ 4-point Improvement From Baseline in Pruritus NRS at Week 16 | 50 Percentage of participants |
Secondary
Percentage of Participants Exhibiting a ≥ 50% (EASI-50) Reduction From Baseline in EASI Score at Week 16
The Eczema Area and Severity Index (EASI) is a validated, composite scoring system assessed by the investigator based on the extent of each of the 4 body regions (head and neck, upper limbs, lower limbs, and trunk) affected with AD and the intensity of each of 4 key signs of AD (erythema, induration/papulation, excoriation, and lichenification) and is based on a 4-point scale of 0 (absent), 1 (mild), 2 (moderate), and 3 (severe). For each of the 4 body regions, the mean intensity of inflamed lesions for each of the 4 signs is recorded. Xerosis, scaling, urticaria, or post-inflammatory pigmentation changes are not included. The total EASI score ranges from 0 to 72. The lower the score the better.
Time frame: From baseline and 16 weeks
Population: mITTpopulationIntent-To-Treat (All participants who are randomized and received at least one dose of study treatment)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Exhibiting a ≥ 50% (EASI-50) Reduction From Baseline in EASI Score at Week 16 | 25 Percentage of participants |
| Treatment 1 | Percentage of Participants Exhibiting a ≥ 50% (EASI-50) Reduction From Baseline in EASI Score at Week 16 | 0 Percentage of participants |
| Treatment 2 | Percentage of Participants Exhibiting a ≥ 50% (EASI-50) Reduction From Baseline in EASI Score at Week 16 | 0 Percentage of participants |
| Treatment 3 | Percentage of Participants Exhibiting a ≥ 50% (EASI-50) Reduction From Baseline in EASI Score at Week 16 | 0 Percentage of participants |
| Treatment 4 | Percentage of Participants Exhibiting a ≥ 50% (EASI-50) Reduction From Baseline in EASI Score at Week 16 | 33.3 Percentage of participants |
Secondary
Percentage of Participants Exhibiting a Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) Score of 0 (Cleared) or 1 (Almost Cleared) AND a ≥ 2 Point Reduction From Baseline at Week 16
The vIGA-AD is a static 5-point assessment intended to assess the global severities of key acute clinical signs of AD, including erythema, induration/papulation, and oozing/crusting (lichenification excluded). The rating of cleared (0), almost cleared (1), mild (2), moderate (3), and severe (4) will be assessed.
Time frame: From baseline and 16 weeks
Population: mITT population with evaluable vIGA-AD at baseline. mITT: Modified Intent-To-Treat (All participants who are randomized and received at least one dose of study treatment)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | Percentage of Participants Exhibiting a Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) Score of 0 (Cleared) or 1 (Almost Cleared) AND a ≥ 2 Point Reduction From Baseline at Week 16 | 0 Percentage of participants |
| Treatment 1 | Percentage of Participants Exhibiting a Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) Score of 0 (Cleared) or 1 (Almost Cleared) AND a ≥ 2 Point Reduction From Baseline at Week 16 | 0 Percentage of participants |
| Treatment 2 | Percentage of Participants Exhibiting a Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) Score of 0 (Cleared) or 1 (Almost Cleared) AND a ≥ 2 Point Reduction From Baseline at Week 16 | 0 Percentage of participants |
| Treatment 3 | Percentage of Participants Exhibiting a Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) Score of 0 (Cleared) or 1 (Almost Cleared) AND a ≥ 2 Point Reduction From Baseline at Week 16 | 0 Percentage of participants |
| Treatment 4 | Percentage of Participants Exhibiting a Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) Score of 0 (Cleared) or 1 (Almost Cleared) AND a ≥ 2 Point Reduction From Baseline at Week 16 | 0 Percentage of participants |