Dermatitis, Atopic, Eczema
Conditions
Keywords
Atopic Dermatitis, Cendakimab, CC-93538
Brief summary
The purpose of this study is to evaluate the effectiveness and safety of 3 dose regimen of CC-93538 in adult participants with moderate to severe Atopic Dermatitis (AD).
Interventions
DRUGCC-93538
Specified dosages on specified days
OTHERPlacebo
Specified dosages on specified days
Sponsors
Celgene
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 75 Years
Healthy volunteers
No
Inclusion criteria
Participants must satisfy the following criteria to be enrolled in the study: 1. Participant must be ≥ 18 years and ≤ 75 years of age and have a body weight of ≥ 40 kg (88.2 lb) at the time of signing the informed consent form (ICF). 2. Participant has chronic atopic dermatitis (AD) as defined by Hanifin and Rajka that has been present for ≥ 1 year prior to the baseline visit (Day 1). 3. Participant has moderate to severe, active, and symptomatic AD defined by meeting all of the following criteria on the day of the baseline visit (Day 1): 1. Body Surface Area (BSA) ≥ 10%, and 2. EASI score ≥ 16, and 3. vIGA-AD ≥ 3, and 4. Pruritus Numeric Rating Scale (NRS) severity score ≥ 4. 4. Participant must have a documented history of inadequate response to treatment with topical medications for at least 4 weeks, unless topical treatments are otherwise medically inadvisable or has required systemic therapy for control of disease. 5. Participant must be willing to apply a stable dose of topical emollient (eg, over-the-counter moisturizer, non-medicated emollient, etc.) twice daily for ≥ 7 days prior to the Baseline visit and continue application throughout the study. 6. Participant must commit to avoid prolonged exposure to the sun and not to use tanning booths, sun lamps or other ultraviolet light sources during the study. 7. Participants currently receiving concomitant medications for any reason other than AD, such as inhaled corticosteroids, leukotriene receptor antagonists (eg, montelukast), or mast cell stabilizers (eg, cromolyn sodium) for asthma, must be on a stable regimen, which is defined as not starting a new drug, changing, or stopping dosage within 7 days or 5 half-lives (whichever is longer) prior to Day 1 and through the treatment duration of the study. 8. Female participants of childbearing potential must agree to practice a highly effective method of contraception.
Exclusion criteria
1. The presence of any of the following will exclude a participant from enrollment: Evidence of an active and/or concurrent inflammatory skin condition (eg, seborrheic dermatitis, psoriasis, acute allergic contact dermatitis, etc.) that would interfere with the Investigator or participant-driven evaluations of AD. 2. Evidence of acute AD flare between the Screening and Baseline/ Randomization (eg, doubling of the EASI score between Screening and Baseline). 3. Use of topical treatments that could affect the assessment of AD (eg, corticosteroids, calcineurin inhibitors, tars, antibiotic creams, topical antihistamines) within 7 days of the Day 1 visit. 4. Received phototherapy narrowband UVB (NB-UVB) or broad band phototherapy within 4 weeks prior to the Baseline visit. 5. Evidence of immunosuppression, participant is receiving, or has received systemic immunosuppressive or immunomodulating drugs (eg, azathioprine, cyclosporine, systemic corticosteroids, interferon gamma (IFN-γ), Janus kinase inhibitors, methotrexate, mycophenolate-mofetil, etc.) within 4 weeks prior to the Baseline visit. 6. Treatment with immunomodulatory biologics 7. Concurrent treatment with another IP 8. Received a live attenuated vaccine within 1 month prior to the first Screening Visit or anticipates the need to be vaccinated with a live attenuated vaccine during the study. 9. Active parasitic/helminthic infection or a suspected parasitic/helminthic infection. 10. Ongoing infection 11. A history of idiopathic anaphylaxis or a major immunologic reaction (such as anaphylactic reaction, anaphylactoid reaction, or serum sickness) to an immunoglobulin G (IgG) containing agent. A known hypersensitivity to any ingredient in the investigational product (IP) is also exclusionary.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Percentage Change From Baseline in EASI at Week 16 | From initial EASI measurement to week 16 | The Eczema Area and Severity Index (EASI) is a composite scoring system assessed by the Investigator based on the proportion of each of the 4 body regions (head and neck, upper limbs, lower limbs, and trunk) affected with Atopic Dermatitis (AD) and the intensity of each of 4 main signs of AD (eg, erythema, induration/papulation, excoriation, and lichenification) and is based on a 4-point scale of 0 (none), 1 (mild), 2 (moderate), and 3 (severe). The sum of the scores is totaled (0 to 72), the lower the score the better. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of EASI-75 Responders at Week 16 | From initial EASI measurement to week 16 | The EASI is a composite scoring system assessed by the Investigator based on the proportion 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 main signs of AD (eg, erythema, induration/papulation, excoriation, and lichenification) and is based on a 4-point scale of 0 (none), 1 (mild), 2 (moderate), and 3 (severe). The sum of the scores is totaled (0 to 72), the lower the score the better. Percentage of responders calculated using Multiple Imputation (MI) approach. For participants discontinued study drug, whose EASI-75 response at Week 16 are missing or cannot be adequately determined (including missing due to COVID-19) without use of rescue therapy/prohibited medication prior to Week 16, their outcomes will be handled using a MI approach assuming missing at random (MAR). |
| Percentage of EASI-90 Responders at Week 16 | From initial EASI measurement to week 16 | The Eczema Area and Severity Index (EASI) is a composite scoring system assessed by the Investigator based on the proportion of each of the 4 body regions (head and neck, upper limbs, lower limbs, and trunk) affected with Atopic Dermatitis (AD) and the intensity of each of 4 main signs of AD (eg, erythema, induration/papulation, excoriation, and lichenification) and is based on a 4-point scale of 0 (none), 1 (mild), 2 (moderate), and 3 (severe). The sum of the scores is totaled (0 to 72), the lower the score the better. Percentage of responders calculated using Multiple Imputation (MI) approach. For participants discontinued study drug, whose EASI-90 response at Week 16 are missing or cannot be adequately determined (including missing due to COVID-19) without use of rescue therapy/prohibited medication prior to Week 16, their outcomes will be handled using a MI approach assuming missing at random (MAR). |
| Percent Change in Mean SCORAD Scores From Baseline at Week 16 | From initial SCORAD measurement to week 16 | The SCORAD is a validated scoring index for atopic dermatitis, which combines extent (0 to 100), severity (0 to 18), and subjective symptoms (0 to 20) based on pruritus and sleep loss, each scored (0 to 10). The subject will assess the subjective symptoms (itch and sleepless) part of the assessment. SCORing Atopic Dermatitis Index (SCORAD) score ranges from 0 to 103, higher scores indicate more severe disease. |
| Percent Change From Baseline in Pruritus NRS at Week 16 | From initial NRS measurement to week 16 | Pruritus will be assessed by the subject using the Pruritus NRS, which was developed and validated as a single item, patient reported outcome (PRO) of itch severity. Clinical response is indicated by a ≥ 2 to 4-point change from baseline in Peak Pruritus NRS score. The intensity of pruritus will be assessed based on last 24 hours using a validated 11-point NRS, ranging from 0 (no pruritus) to 10 (the worst pruritus imaginable). |
| Percentage of Participants With a Response and Pruritus NRS Change of ≥ 4 Points From Baseline at Week 16 | From initial NRS assessment to week 16 | Pruritus will be assessed by the subject using the Pruritus NRS, which was developed and validated as a single item, patient reported outcome (PRO) of itch severity. Clinical response is indicated by a ≥ 2 to 4-point change from baseline in Peak Pruritus NRS score. The intensity of pruritus will be assessed based on last 24 hours using a validated 11-point NRS, ranging from 0 (no pruritus) to 10 (the worst pruritus imaginable). Percentage of responders calculated using Multiple Imputation (MI) approach. For participants discontinued study drug, whose pruritus NRS response at Week 16 are missing or cannot be adequately determined (including missing due to COVID-19) without use of rescue therapy/prohibited medication prior to Week 16, their outcomes will be handled using a MI approach assuming missing at random (MAR). |
| Percentage of Responders With an vIGA-AD Score of 0 (Clear) or 1 (Almost Clear) and a Reduction ≥ 2 Points From Baseline at Week 16 | From initial vIGA-AD assessment to week 16 | The Validated Investigator Global Assessment (vIGA-AD) is a validated 5-point assessment intended to assess the global severities of key acute clinical signs of AD, including erythema, induration/papulation, oozing/crusting (lichenification excluded). The rating of clear (0), almost clear (1), mild (2), moderate (3) and severe (4), will be assessed at scheduled visits. The vIGA-AD must be conducted before the EASI assessment. The vIGA-AD is a static evaluation conducted without regard to the score obtained at a previous visit. Percentage of responders calculated using Multiple Imputation (MI) approach. For participants discontinued study drug, whose vIGA-AD response at Week 16 are missing or cannot be adequately determined (including missing due to COVID-19) without use of rescue therapy/prohibited medication prior to Week 16, their outcomes will be handled using a MI approach assuming missing at random (MAR). |
| Adjust Mean Percentage Change in BSA in Atopic Dermatitis From Baseline at Week 16 | From initial BSA assessment to week 16 | Body Surface Area involvement will be calculated from the sum of the number of handprints of skin afflicted with atopic dermatitis in a body region. The number of handprints of skin afflicted with atopic dermatitis in a body region can be used to determine the extent (%) to which a body region is involved with AD. When measuring, the handprint unit refers to the size of each individual subject's hand with fingers in a closed position. BSA will be calculated by the Investigator or qualified designee using the 1% handprint rule, in which the area represented by the palm with all 5 digits adducted together is approximately 1% of the subject's BSA. |
| Number of Participants With Treatment Emergent Adverse Events | From first treatment to the end of follow up, approximately 32 weeks | Treatment emergent adverse events |
| Number of Participants With the Presence of Serum Antibodies to CC-93538 | From first treatment to the end of follow up, approximately 32 weeks | — |
| Serum Trough Concentration at Week 16 | At week 16 | A serum trough concentration (Ctrough) is the concentration reached by a drug immediately before the next dose is administered. Serum trough concentrations (Ctrough) of CC-93538 will be summarized with descriptive statistics by treatment and visit. |
| Number of Participants With Clinically Significant Laboratory Abnormalities | From first treatment to the end of follow up, approximately 32 weeks | — |
| Time to Achieve at Least 4 Points of Improvement in the Severity of Pruritus NRS Scale. | From initial NRS pruritus response up to study day 127 (127 days) | Pruritus will be assessed by the subject using the Pruritus NRS, which was developed and validated as a single item, patient reported outcome (PRO) of itch severity. Clinical response is indicated by a ≥ 2 to 4-point change from baseline in Peak Pruritus NRS score. The intensity of pruritus will be assessed based on last 24 hours using a validated 11-point NRS, ranging from 0 (no pruritus) to 10 (the worst pruritus imaginable). |
Countries
Canada, China, Czechia, Japan, Poland, United States
Participant flow
Pre-assignment details
221 participants Randomized, 220 Participants Treated
Participants by arm
| Arm | Count |
|---|---|
| Treatment 1 CC-93538 High Dose QW | 55 |
| Treatment 2 CC-93538 High Dose Q2W | 55 |
| Treatment 3 CC-93538 Low Dose Q2W | 55 |
| Placebo Placebo | 56 |
| Total | 221 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Randomization | Did not receive study treatment | 1 | 0 | 0 | 0 |
| Treatment Period | Adverse Event | 4 | 2 | 1 | 2 |
| Treatment Period | Lack of Efficacy | 1 | 0 | 0 | 3 |
| Treatment Period | Lost to Follow-up | 0 | 1 | 2 | 2 |
| Treatment Period | Other Reasons | 0 | 2 | 0 | 1 |
| Treatment Period | Withdrawal by participant | 0 | 0 | 0 | 4 |
Baseline characteristics
| Characteristic | Treatment 1 | Total | Placebo | Treatment 3 | Treatment 2 |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 12 Participants | 3 Participants | 4 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 53 Participants | 209 Participants | 53 Participants | 51 Participants | 52 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 6 Participants | 3 Participants | 0 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 53 Participants | 214 Participants | 53 Participants | 55 Participants | 53 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| modified Intent to treat population (mITT) | 54 Participants | 220 Participants | 56 Participants | 55 Participants | 55 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 19 Participants | 60 Participants | 13 Participants | 14 Participants | 14 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 23 Participants | 6 Participants | 5 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 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 |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 30 Participants | 136 Participants | 37 Participants | 36 Participants | 33 Participants |
| Sex: Female, Male Female | 19 Participants | 95 Participants | 21 Participants | 29 Participants | 26 Participants |
| Sex: Female, Male Male | 36 Participants | 126 Participants | 35 Participants | 26 Participants | 29 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 / 54 | 0 / 55 | 0 / 55 | 0 / 56 |
| other Total, other adverse events | 34 / 54 | 35 / 55 | 29 / 55 | 34 / 56 |
| serious Total, serious adverse events | 2 / 54 | 1 / 55 | 2 / 55 | 4 / 56 |
Outcome results
Primary
Mean Percentage Change From Baseline in EASI at Week 16
The Eczema Area and Severity Index (EASI) is a composite scoring system assessed by the Investigator based on the proportion of each of the 4 body regions (head and neck, upper limbs, lower limbs, and trunk) affected with Atopic Dermatitis (AD) and the intensity of each of 4 main signs of AD (eg, erythema, induration/papulation, excoriation, and lichenification) and is based on a 4-point scale of 0 (none), 1 (mild), 2 (moderate), and 3 (severe). The sum of the scores is totaled (0 to 72), the lower the score the better.
Time frame: From initial EASI measurement to week 16
Population: Modified Intent to Treat (mITT) Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment 1 | Mean Percentage Change From Baseline in EASI at Week 16 | -84.41 Percent Change | Standard Error 5.07 |
| Treatment 2 | Mean Percentage Change From Baseline in EASI at Week 16 | -76.03 Percent Change | Standard Error 4.2 |
| Treatment 3 | Mean Percentage Change From Baseline in EASI at Week 16 | -78.93 Percent Change | Standard Error 4.53 |
| Placebo | Mean Percentage Change From Baseline in EASI at Week 16 | -62.65 Percent Change | Standard Error 5.53 |
p-value: 0.00395% CI: [-35.81, -7.7]ANCOVA
p-value: 0.05795% CI: [-27.19, 0.43]ANCOVA
p-value: 0.02995% CI: [-30.88, -1.68]ANCOVA
Secondary
Adjust Mean Percentage Change in BSA in Atopic Dermatitis From Baseline at Week 16
Body Surface Area involvement will be calculated from the sum of the number of handprints of skin afflicted with atopic dermatitis in a body region. The number of handprints of skin afflicted with atopic dermatitis in a body region can be used to determine the extent (%) to which a body region is involved with AD. When measuring, the handprint unit refers to the size of each individual subject's hand with fingers in a closed position. BSA will be calculated by the Investigator or qualified designee using the 1% handprint rule, in which the area represented by the palm with all 5 digits adducted together is approximately 1% of the subject's BSA.
Time frame: From initial BSA assessment to week 16
Population: Modified Intent to Treat (mITT) Population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment 1 | Adjust Mean Percentage Change in BSA in Atopic Dermatitis From Baseline at Week 16 | -78.85 mean percentage | Standard Error 6.13 |
| Treatment 2 | Adjust Mean Percentage Change in BSA in Atopic Dermatitis From Baseline at Week 16 | -64.01 mean percentage | Standard Error 5.3 |
| Treatment 3 | Adjust Mean Percentage Change in BSA in Atopic Dermatitis From Baseline at Week 16 | -66.60 mean percentage | Standard Error 6.03 |
| Placebo | Adjust Mean Percentage Change in BSA in Atopic Dermatitis From Baseline at Week 16 | -55.73 mean percentage | Standard Error 6.9 |
95% CI: [-41.48, -4.76]ANCOVA
95% CI: [-25.16, 8.59]ANCOVA
95% CI: [-29.39, 7.66]ANCOVA
Secondary
Number of Participants With Clinically Significant Laboratory Abnormalities
Time frame: From first treatment to the end of follow up, approximately 32 weeks
Population: Modified Intent to Treat Population (mITT)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment 1 | Number of Participants With Clinically Significant Laboratory Abnormalities | 0 Participants |
| Treatment 2 | Number of Participants With Clinically Significant Laboratory Abnormalities | 0 Participants |
| Treatment 3 | Number of Participants With Clinically Significant Laboratory Abnormalities | 0 Participants |
| Placebo | Number of Participants With Clinically Significant Laboratory Abnormalities | 0 Participants |
Secondary
Number of Participants With the Presence of Serum Antibodies to CC-93538
Time frame: From first treatment to the end of follow up, approximately 32 weeks
Population: Modified Intent to Treat (mITT) Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment 1 | Number of Participants With the Presence of Serum Antibodies to CC-93538 | Post Baseline Positive | 22 Participants |
| Treatment 1 | Number of Participants With the Presence of Serum Antibodies to CC-93538 | Baseline ADA Positive | 0 Participants |
| Treatment 1 | Number of Participants With the Presence of Serum Antibodies to CC-93538 | Post Baseline Negative | 32 Participants |
| Treatment 2 | Number of Participants With the Presence of Serum Antibodies to CC-93538 | Post Baseline Positive | 35 Participants |
| Treatment 2 | Number of Participants With the Presence of Serum Antibodies to CC-93538 | Baseline ADA Positive | 3 Participants |
| Treatment 2 | Number of Participants With the Presence of Serum Antibodies to CC-93538 | Post Baseline Negative | 20 Participants |
| Treatment 3 | Number of Participants With the Presence of Serum Antibodies to CC-93538 | Baseline ADA Positive | 1 Participants |
| Treatment 3 | Number of Participants With the Presence of Serum Antibodies to CC-93538 | Post Baseline Negative | 27 Participants |
| Treatment 3 | Number of Participants With the Presence of Serum Antibodies to CC-93538 | Post Baseline Positive | 28 Participants |
Secondary
Number of Participants With Treatment Emergent Adverse Events
Treatment emergent adverse events
Time frame: From first treatment to the end of follow up, approximately 32 weeks
Population: Modified Intent to Treat (mITT) Population
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Treatment 1 | Number of Participants With Treatment Emergent Adverse Events | Any TEAE | 40 Participants |
| Treatment 1 | Number of Participants With Treatment Emergent Adverse Events | Any TEAE leading to discontinuation | 4 Participants |
| Treatment 1 | Number of Participants With Treatment Emergent Adverse Events | Any TEAE of special interest | 9 Participants |
| Treatment 1 | Number of Participants With Treatment Emergent Adverse Events | Any TESAE | 2 Participants |
| Treatment 2 | Number of Participants With Treatment Emergent Adverse Events | Any TEAE leading to discontinuation | 2 Participants |
| Treatment 2 | Number of Participants With Treatment Emergent Adverse Events | Any TEAE of special interest | 10 Participants |
| Treatment 2 | Number of Participants With Treatment Emergent Adverse Events | Any TESAE | 1 Participants |
| Treatment 2 | Number of Participants With Treatment Emergent Adverse Events | Any TEAE | 41 Participants |
| Treatment 3 | Number of Participants With Treatment Emergent Adverse Events | Any TEAE of special interest | 8 Participants |
| Treatment 3 | Number of Participants With Treatment Emergent Adverse Events | Any TEAE leading to discontinuation | 1 Participants |
| Treatment 3 | Number of Participants With Treatment Emergent Adverse Events | Any TESAE | 2 Participants |
| Treatment 3 | Number of Participants With Treatment Emergent Adverse Events | Any TEAE | 38 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events | Any TESAE | 4 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events | Any TEAE leading to discontinuation | 2 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events | Any TEAE | 41 Participants |
| Placebo | Number of Participants With Treatment Emergent Adverse Events | Any TEAE of special interest | 10 Participants |
Secondary
Percentage of EASI-75 Responders at Week 16
The EASI is a composite scoring system assessed by the Investigator based on the proportion 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 main signs of AD (eg, erythema, induration/papulation, excoriation, and lichenification) and is based on a 4-point scale of 0 (none), 1 (mild), 2 (moderate), and 3 (severe). The sum of the scores is totaled (0 to 72), the lower the score the better. Percentage of responders calculated using Multiple Imputation (MI) approach. For participants discontinued study drug, whose EASI-75 response at Week 16 are missing or cannot be adequately determined (including missing due to COVID-19) without use of rescue therapy/prohibited medication prior to Week 16, their outcomes will be handled using a MI approach assuming missing at random (MAR).
Time frame: From initial EASI measurement to week 16
Population: modified Intent to Treat (mITT) population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment 1 | Percentage of EASI-75 Responders at Week 16 | 50.0 Percentage of Participants |
| Treatment 2 | Percentage of EASI-75 Responders at Week 16 | 48.2 Percentage of Participants |
| Treatment 3 | Percentage of EASI-75 Responders at Week 16 | 52.7 Percentage of Participants |
| Placebo | Percentage of EASI-75 Responders at Week 16 | 26.3 Percentage of Participants |
p-value: 0.01895% CI: [6.2, 41.2]Cochran-Mantel-Haenszel
p-value: 0.03395% CI: [4.3, 39.3]Cochran-Mantel-Haenszel
p-value: 0.00695% CI: [9.3, 44]Cochran-Mantel-Haenszel
Secondary
Percentage of EASI-90 Responders at Week 16
The Eczema Area and Severity Index (EASI) is a composite scoring system assessed by the Investigator based on the proportion of each of the 4 body regions (head and neck, upper limbs, lower limbs, and trunk) affected with Atopic Dermatitis (AD) and the intensity of each of 4 main signs of AD (eg, erythema, induration/papulation, excoriation, and lichenification) and is based on a 4-point scale of 0 (none), 1 (mild), 2 (moderate), and 3 (severe). The sum of the scores is totaled (0 to 72), the lower the score the better. Percentage of responders calculated using Multiple Imputation (MI) approach. For participants discontinued study drug, whose EASI-90 response at Week 16 are missing or cannot be adequately determined (including missing due to COVID-19) without use of rescue therapy/prohibited medication prior to Week 16, their outcomes will be handled using a MI approach assuming missing at random (MAR).
Time frame: From initial EASI measurement to week 16
Population: Modified Intent to Treat (mITT) Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment 1 | Percentage of EASI-90 Responders at Week 16 | 31.5 Percentage of participants |
| Treatment 2 | Percentage of EASI-90 Responders at Week 16 | 24.0 Percentage of participants |
| Treatment 3 | Percentage of EASI-90 Responders at Week 16 | 29.1 Percentage of participants |
| Placebo | Percentage of EASI-90 Responders at Week 16 | 13.4 Percentage of participants |
95% CI: [2.3, 33.9]Cochran-Mantel-Haenszel
95% CI: [-4.6, 25.7]Cochran-Mantel-Haenszel
95% CI: [0.4, 31.4]Cochran-Mantel-Haenszel
Secondary
Percentage of Participants With a Response and Pruritus NRS Change of ≥ 4 Points From Baseline at Week 16
Pruritus will be assessed by the subject using the Pruritus NRS, which was developed and validated as a single item, patient reported outcome (PRO) of itch severity. Clinical response is indicated by a ≥ 2 to 4-point change from baseline in Peak Pruritus NRS score. The intensity of pruritus will be assessed based on last 24 hours using a validated 11-point NRS, ranging from 0 (no pruritus) to 10 (the worst pruritus imaginable). Percentage of responders calculated using Multiple Imputation (MI) approach. For participants discontinued study drug, whose pruritus NRS response at Week 16 are missing or cannot be adequately determined (including missing due to COVID-19) without use of rescue therapy/prohibited medication prior to Week 16, their outcomes will be handled using a MI approach assuming missing at random (MAR).
Time frame: From initial NRS assessment to week 16
Population: Modified Intent to Treat (mITT) Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment 1 | Percentage of Participants With a Response and Pruritus NRS Change of ≥ 4 Points From Baseline at Week 16 | 33.3 Percentage of Participants |
| Treatment 2 | Percentage of Participants With a Response and Pruritus NRS Change of ≥ 4 Points From Baseline at Week 16 | 34.5 Percentage of Participants |
| Treatment 3 | Percentage of Participants With a Response and Pruritus NRS Change of ≥ 4 Points From Baseline at Week 16 | 32.7 Percentage of Participants |
| Placebo | Percentage of Participants With a Response and Pruritus NRS Change of ≥ 4 Points From Baseline at Week 16 | 14.8 Percentage of Participants |
p-value: 0.04295% CI: [2.7, 34.3]Cochran-Mantel-Haenszel
p-value: 0.02995% CI: [4.1, 35.7]Cochran-Mantel-Haenszel
p-value: 0.05295% CI: [2.3, 33.6]Cochran-Mantel-Haenszel
Secondary
Percentage of Responders With an vIGA-AD Score of 0 (Clear) or 1 (Almost Clear) and a Reduction ≥ 2 Points From Baseline at Week 16
The Validated Investigator Global Assessment (vIGA-AD) is a validated 5-point assessment intended to assess the global severities of key acute clinical signs of AD, including erythema, induration/papulation, oozing/crusting (lichenification excluded). The rating of clear (0), almost clear (1), mild (2), moderate (3) and severe (4), will be assessed at scheduled visits. The vIGA-AD must be conducted before the EASI assessment. The vIGA-AD is a static evaluation conducted without regard to the score obtained at a previous visit. Percentage of responders calculated using Multiple Imputation (MI) approach. For participants discontinued study drug, whose vIGA-AD response at Week 16 are missing or cannot be adequately determined (including missing due to COVID-19) without use of rescue therapy/prohibited medication prior to Week 16, their outcomes will be handled using a MI approach assuming missing at random (MAR).
Time frame: From initial vIGA-AD assessment to week 16
Population: Modified Intent to Treat (mITT) Population
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment 1 | Percentage of Responders With an vIGA-AD Score of 0 (Clear) or 1 (Almost Clear) and a Reduction ≥ 2 Points From Baseline at Week 16 | 33.3 Percentage of Participants |
| Treatment 2 | Percentage of Responders With an vIGA-AD Score of 0 (Clear) or 1 (Almost Clear) and a Reduction ≥ 2 Points From Baseline at Week 16 | 24.4 Percentage of Participants |
| Treatment 3 | Percentage of Responders With an vIGA-AD Score of 0 (Clear) or 1 (Almost Clear) and a Reduction ≥ 2 Points From Baseline at Week 16 | 38.2 Percentage of Participants |
| Placebo | Percentage of Responders With an vIGA-AD Score of 0 (Clear) or 1 (Almost Clear) and a Reduction ≥ 2 Points From Baseline at Week 16 | 9.4 Percentage of Participants |
p-value: 0.00495% CI: [8.8, 39.2]Cochran-Mantel-Haenszel
p-value: 0.06195% CI: [0.8, 29.8]Cochran-Mantel-Haenszel
p-value: <0.00195% CI: [13.6, 44.2]Cochran-Mantel-Haenszel
Secondary
Percent Change From Baseline in Pruritus NRS at Week 16
Pruritus will be assessed by the subject using the Pruritus NRS, which was developed and validated as a single item, patient reported outcome (PRO) of itch severity. Clinical response is indicated by a ≥ 2 to 4-point change from baseline in Peak Pruritus NRS score. The intensity of pruritus will be assessed based on last 24 hours using a validated 11-point NRS, ranging from 0 (no pruritus) to 10 (the worst pruritus imaginable).
Time frame: From initial NRS measurement to week 16
Population: Modified Intent to Treat (mITT) population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment 1 | Percent Change From Baseline in Pruritus NRS at Week 16 | -55.48 Percent Change | Standard Error 6.22 |
| Treatment 2 | Percent Change From Baseline in Pruritus NRS at Week 16 | -46.15 Percent Change | Standard Error 5.32 |
| Treatment 3 | Percent Change From Baseline in Pruritus NRS at Week 16 | -49.30 Percent Change | Standard Error 5.89 |
| Placebo | Percent Change From Baseline in Pruritus NRS at Week 16 | -32.98 Percent Change | Standard Error 7.46 |
95% CI: [-41.46, -3.54]ANCOVA
95% CI: [-30.67, 4.33]ANCOVA
95% CI: [-36.4, 3.75]ANCOVA
Secondary
Percent Change in Mean SCORAD Scores From Baseline at Week 16
The SCORAD is a validated scoring index for atopic dermatitis, which combines extent (0 to 100), severity (0 to 18), and subjective symptoms (0 to 20) based on pruritus and sleep loss, each scored (0 to 10). The subject will assess the subjective symptoms (itch and sleepless) part of the assessment. SCORing Atopic Dermatitis Index (SCORAD) score ranges from 0 to 103, higher scores indicate more severe disease.
Time frame: From initial SCORAD measurement to week 16
Population: Modified Intent to Treat (mITT) population
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment 1 | Percent Change in Mean SCORAD Scores From Baseline at Week 16 | -69.28 Percent Change | Standard Error 4.64 |
| Treatment 2 | Percent Change in Mean SCORAD Scores From Baseline at Week 16 | -55.47 Percent Change | Standard Error 4.08 |
| Treatment 3 | Percent Change in Mean SCORAD Scores From Baseline at Week 16 | -60.19 Percent Change | Standard Error 4.38 |
| Placebo | Percent Change in Mean SCORAD Scores From Baseline at Week 16 | -41.11 Percent Change | Standard Error 5.61 |
95% CI: [-41.89, -14.44]ANCOVA
95% CI: [-27.26, -1.46]ANCOVA
95% CI: [-33.53, -4.62]ANCOVA
Secondary
Serum Trough Concentration at Week 16
A serum trough concentration (Ctrough) is the concentration reached by a drug immediately before the next dose is administered. Serum trough concentrations (Ctrough) of CC-93538 will be summarized with descriptive statistics by treatment and visit.
Time frame: At week 16
Population: Pharmacokinetic Population
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Treatment 1 | Serum Trough Concentration at Week 16 | Week 6 | 220561.6 ng/mL | Geometric Coefficient of Variation 55.2 |
| Treatment 1 | Serum Trough Concentration at Week 16 | Week 2 | 120157.8 ng/mL | Geometric Coefficient of Variation 29.8 |
| Treatment 1 | Serum Trough Concentration at Week 16 | Week 10 | 279538.4 ng/mL | Geometric Coefficient of Variation 34.9 |
| Treatment 1 | Serum Trough Concentration at Week 16 | Week 8 | 253107.2 ng/mL | Geometric Coefficient of Variation 56.7 |
| Treatment 1 | Serum Trough Concentration at Week 16 | Week 16 | 274180.6 ng/mL | Geometric Coefficient of Variation 88 |
| Treatment 1 | Serum Trough Concentration at Week 16 | Week 14 | 266531.3 ng/mL | Geometric Coefficient of Variation 102.3 |
| Treatment 1 | Serum Trough Concentration at Week 16 | Week 4 | 192521.4 ng/mL | Geometric Coefficient of Variation 32.8 |
| Treatment 1 | Serum Trough Concentration at Week 16 | Week 1 | 66107.2 ng/mL | Geometric Coefficient of Variation 31.5 |
| Treatment 1 | Serum Trough Concentration at Week 16 | Week 12 | 310649.1 ng/mL | Geometric Coefficient of Variation 36.1 |
| Treatment 2 | Serum Trough Concentration at Week 16 | Week 14 | 128517.9 ng/mL | Geometric Coefficient of Variation 79.4 |
| Treatment 2 | Serum Trough Concentration at Week 16 | Week 2 | 54957.8 ng/mL | Geometric Coefficient of Variation 38.2 |
| Treatment 2 | Serum Trough Concentration at Week 16 | Week 4 | 92827.7 ng/mL | Geometric Coefficient of Variation 37.6 |
| Treatment 2 | Serum Trough Concentration at Week 16 | Week 6 | 108474.6 ng/mL | Geometric Coefficient of Variation 48.3 |
| Treatment 2 | Serum Trough Concentration at Week 16 | Week 8 | 121185.1 ng/mL | Geometric Coefficient of Variation 45.9 |
| Treatment 2 | Serum Trough Concentration at Week 16 | Week 10 | 136972.4 ng/mL | Geometric Coefficient of Variation 35.6 |
| Treatment 2 | Serum Trough Concentration at Week 16 | Week 12 | 137656.3 ng/mL | Geometric Coefficient of Variation 40.5 |
| Treatment 2 | Serum Trough Concentration at Week 16 | Week 16 | 140413.6 ng/mL | Geometric Coefficient of Variation 44 |
| Treatment 3 | Serum Trough Concentration at Week 16 | Week 10 | 60839.6 ng/mL | Geometric Coefficient of Variation 43.6 |
| Treatment 3 | Serum Trough Concentration at Week 16 | Week 4 | 40802.8 ng/mL | Geometric Coefficient of Variation 69.8 |
| Treatment 3 | Serum Trough Concentration at Week 16 | Week 16 | 57046.4 ng/mL | Geometric Coefficient of Variation 106.8 |
| Treatment 3 | Serum Trough Concentration at Week 16 | Week 12 | 57197.5 ng/mL | Geometric Coefficient of Variation 104.2 |
| Treatment 3 | Serum Trough Concentration at Week 16 | Week 2 | 26651.4 ng/mL | Geometric Coefficient of Variation 35.3 |
| Treatment 3 | Serum Trough Concentration at Week 16 | Week 8 | 54975.0 ng/mL | Geometric Coefficient of Variation 45.5 |
| Treatment 3 | Serum Trough Concentration at Week 16 | Week 6 | 43613.1 ng/mL | Geometric Coefficient of Variation 99.7 |
| Treatment 3 | Serum Trough Concentration at Week 16 | Week 14 | 67212.2 ng/mL | Geometric Coefficient of Variation 38.9 |
Secondary
Time to Achieve at Least 4 Points of Improvement in the Severity of Pruritus NRS Scale.
Pruritus will be assessed by the subject using the Pruritus NRS, which was developed and validated as a single item, patient reported outcome (PRO) of itch severity. Clinical response is indicated by a ≥ 2 to 4-point change from baseline in Peak Pruritus NRS score. The intensity of pruritus will be assessed based on last 24 hours using a validated 11-point NRS, ranging from 0 (no pruritus) to 10 (the worst pruritus imaginable).
Time frame: From initial NRS pruritus response up to study day 127 (127 days)
Population: Modified Intent to Treat (mITT) Population
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Treatment 1 | Time to Achieve at Least 4 Points of Improvement in the Severity of Pruritus NRS Scale. | 54.0 Days |
| Treatment 2 | Time to Achieve at Least 4 Points of Improvement in the Severity of Pruritus NRS Scale. | 76.0 Days |
| Treatment 3 | Time to Achieve at Least 4 Points of Improvement in the Severity of Pruritus NRS Scale. | 50.0 Days |
| Placebo | Time to Achieve at Least 4 Points of Improvement in the Severity of Pruritus NRS Scale. | 123.0 Days |