Moderate to Severe Atopic Dermatitis
Conditions
Keywords
ISB 830, OX40, atopic dermatitis
Brief summary
Phase 2b, randomized, double-blinded, placebo-controlled dose range finding study to evaluate the efficacy, safety and tolerability of ISB 830 in adults with moderate to severe atopic dermatitis. The study will be conducted in 2 Parts, with dosing Groups 1-4 comprising Part 1, and dosing Groups 5-6 comprising Part 2. All subjects will receive open-label ISB 830 after a 16 week blinded treatment period.
Interventions
DRUGISB 830 - Part 1 Group 1
Subcutaneous injection (SC) every 2 weeks
DRUGISB 830 - Part 1 Group 2
Subcutaneous injection (SC) every 2 weeks
DRUGISB 830 - Part 1 Group 3
Subcutaneous injection (SC) every 2 weeks
DRUGPlacebo - Part 1 Group 4
Subcutaneous injection (SC) every 2 weeks
DRUGISB 830 - Part 2 Group 5
Subcutaneous injection (SC) every 2 weeks
DRUGPlacebo - Part 2 Group 6
Subcutaneous injection (SC) every 2 weeks
Sponsors
Ichnos Sciences SA
Glenmark Pharmaceuticals S.A.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double-blind
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female subjects aged ≥18 years with physician diagnosis of atopic dermatitis for \>1 year as defined by American Academy of Dermatology Consensus Criteria. * Atopic dermatitis involvement of ≥10% of body surface area at screening and baseline. * EASI score of ≥12 at screening or ≥16 at baseline. * IGA score of ≥3 at screening and baseline (on the 0 to 4 IGA scale, in which 3 is moderate and 4 is severe) * Baseline Pruritus Numerical Rating Scale (NRS) score for maximum itch intensity ≥3 over the previous 24 hours.
Exclusion criteria
* Pregnant or lactating women. * Prior treatment with ISB 830 * Treatment with biologics * Systemic corticosteroids, immunosuppressive/immunomodulatory drugs or phototherapy within 4 weeks of baseline * Active chronic or acute infection requiring systemic treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in Eczema Area and Severity Index (EASI) Clinical Score at Week 16 | Baseline, Week 16 | In EASI, four disease characteristics of atopic dermatitis (AD) (erythema, edema/papulation, excoriation, and lichenification) are assessed for severity on a scale of 0 (absent), 1 (mild), 2 (moderate), 3 (severe). The scores are added up for each of the four body regions (Head and neck, trunk, arms, and legs). The assigned percentages of body surface area (BSA) for each section of the body are 10% for head and neck, 20% for arms, 30% for trunk, and 40% for legs. Each subtotal score is multiplied by the BSA represented by that region. In addition, an area score of 0 to 6 is assigned for each body region, depending on the percentage of AD-affected skin in that area: 0 (none), 1 (1% to 9%), 2 (10% to 29%), 3 (30% to 49%), 4 (50% to 69%), 5 (70% to 89%), or 6 (90% to 100%). Each of the body area scores are multiplied by the area affected. The resulting EASI score ranges from 0 to 72 points, with the highest score indicating worse severity of AD. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Achieving Both Investigator's Global Assessment (IGA) Clinical Score of 0 or 1 and an IGA Reduction From Baseline of ≥ 2 Points at Week 16 | Baseline, Week 16 | The IGA is an assessment scale used in clinical studies to determine severity of AD based on a 5-point scale ranging from 0 (clear) to 4 (severe/very severe). |
| Percentage of Participants With Improvement (Reduction) in Pruritus Numerical Rating Scale (NRS) Score of ≥ 4 From Baseline at Week 16 | Baseline, Week 16 | Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on a daily basis using an 11-point scale from 0 (no itch) to 10 (worst imaginable itch). Pruritus NRS was analyzed based on weekly rolling averages of daily scores. |
| Percentage of Participants Achieving a 50% Reduction From Baseline in EASI Score (EASI-50) at Week 16 | Baseline, Week 16 | In EASI, 4 disease characteristics of AD are assessed for severity on a scale of 0 (absent), 1 (mild), 2 (moderate), 3 (severe). The scores are added up for each of the 4 body regions (Head and neck, trunk, arms, and legs). The assigned percentages of BSA for each section of the body are 10% for head and neck, 20% for arms, 30% for trunk, and 40% for legs. Each subtotal score is multiplied by the BSA represented by that region. In addition, an area score of 0 to 6 is assigned for each body region, depending on the percentage of AD-affected skin: 0 (none), 1 (1% to 9%), 2 (10% to 29%), 3 (30% to 49%), 4 (50% to 69%), 5 (70% to 89%), or 6 (90% to 100%). Each of the body area scores are multiplied by the area affected. The resulting EASI score ranges from 0 to 72 points, with the highest score indicating worse severity of AD. |
| Percent Change From Baseline in SCORAD Score at Week 16 | Baseline, Week 16 | SCORAD (Severity scoring of Atopic Dermatitis) is composite severity index comprising a) the amount/extent of BSA affected; b) subjective symptom visual analog assessments for pruritis ( 0 \[no itching\] to 3 \[severe itching\]) and sleep disturbance (0 \[no sleep disturbance\] to 3 \[severe sleep disturbance\]); and c) 6 disease intensity assessments \[dryness/scaling, erythema, induration/papulation, excoriation, lichenification and oozing/weeping/crusting, each graded from 0 to (none) to 3 (severe). A SCORAD score ranges from 0 (no AD present) to 103 (severe). |
| Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 16 | Baseline, Week 16 | The DLQI is a 10-item validated questionnaire used to assess the impact of AD disease symptoms and treatment on quality of life (QoL). It consists of 10 questions evaluating impact of skin diseases on different aspects of a participant's QoL over the prior week, including symptoms and feelings, daily activities, leisure, work or school, personal relationships, and the side effects of treatment. Each item is scored on a 4-point scale (0 = not at all/not relevant; 1 = a little; 2 = a lot; and 3 = very much). Item scores are added to provide a total score, ranging from 0 to 30, with higher scores indicating greater impairment of QoL. |
| Change From Baseline in Global Individual Signs Score (GISS) at Week 16 | Baseline, Week 16 | GISS assesses AD lesions for erythema, excoriations, lichenification and infiltration/papulation. Each component is rated on a global basis (over the entire body surface rather than region) using a 4-point scale (0=none, 1=mild, 2=moderate, and 3=severe) according to the EASI grading severity. Total score ranges from 0 to 12 (no disease to most severe disease, respectively). |
| Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Subscale Scores at Week 16 | Baseline, Week 16 | The HADS is a 14-item questionnaire, with 7 items related to anxiety (HADS-A) and 7 items related to depression (HADS-D). Each item is scored from 0 to 3; scores for each subscale range from 0 to 21, with higher scores indicating more distress. For each subscale, scores 7 or lower are considered normal, 8 to 10 are borderline, and 11 or higher indicate clinical anxiety or depression. |
| Percentage of Participants Achieving a 75% Reduction From Baseline in EASI Score (EASI-75) at Week 16 | Baseline, Week 16 | In EASI, 4 disease characteristics of AD are assessed for severity on a scale of 0 (absent), 1 (mild), 2 (moderate), 3 (severe). The scores are added up for each of the 4 body regions (Head and neck, trunk, arms, and legs). The assigned percentages of BSA for each section of the body are 10% for head and neck, 20% for arms, 30% for trunk, and 40% for legs. Each subtotal score is multiplied by the BSA represented by that region. In addition, an area score of 0 to 6 is assigned for each body region, depending on the percentage of AD-affected skin: 0 (none), 1 (1% to 9%), 2 (10% to 29%), 3 (30% to 49%), 4 (50% to 69%), 5 (70% to 89%), or 6 (90% to 100%). Each of the body area scores are multiplied by the area affected. The resulting EASI score ranges from 0 to 72 points, with the highest score indicating worse severity of AD. |
| Change From Baseline in Patient Global Assessment (PGA) of Disease and Treatment at Week 16 | Baseline, Week 16 | For PGA of disease, participants rated their overall wellbeing on a 5-point Likert scale from 0 (poor) to 4 (excellent). Participants were asked: Considering all the ways in which your disease affects you, indicate how well you are doing. Response choices were: Poor; Fair; Good; Very Good; Excellent. For PGA of treatment, participants rated their satisfaction with the study treatment on a 5-point Likert scale from 0 (poor) to 4 (excellent). Subjects were asked: How would you rate the way your disease responded to the study medication? Response choices were: Poor; Fair; Good; Very Good; Excellent. |
| Percentage Change From Baseline in PGA of Disease and Treatment at Week 16 | Baseline, Week 16 | For PGA of disease, participants rated their overall wellbeing on a 5-point Likert scale from 0 (poor) to 4 (excellent). Participants were asked: Considering all the ways in which your disease affects you, indicate how well you are doing. Response choices were: Poor; Fair; Good; Very Good; Excellent. For PGA of treatment, participants rated their satisfaction with the study treatment on a 5-point Likert scale from 0 (poor) to 4 (excellent). Subjects were asked: How would you rate the way your disease responded to the study medication? Response choices were: Poor; Fair; Good; Very Good; Excellent. |
| Number of Missed Work or School Days at Week 16 | Week 16 | Participants who were employed or enrolled in school were asked to report the number of sick leave and/or missed school days due to AD (eg, versus due to an accident) in the last 4 weeks. |
| Maximum Observed Serum Concentration (Cmax) of ISB 830 | Predose (within 15 minutes prior to dose), 4, 24, 96, 120, 168, and 336 hours postdose on Day 1 and predose (within 15 minutes prior to dose), 4, 24, 96, 120, and 168 hours postdose on Day 85 | Cmax is the maximum concentration of ISB 830 observed in serum |
| Area Under Curve From Time Zero to the End of Dosing Interval (AUC0-tau) | Predose (within 15 minutes prior to dose), 4, 24, 96, 120, 168, and 336 hours postdose on Day 1 and predose (within 15 minutes prior to dose), and at 4, 24, 96, 120, 168 hours postdose on Day 85 | AUC0-tau is the area under the curve from time zero to the end of the dosing interval of ISB 830. |
| Percentage of Participants With Anti-Drug Antibody (ADA) at Week 16 | Baseline through Week 16 | Participants with ADA were those with at least 1 treatment-induced or treatment-boosted ADA-positive sample at any time during the treatment or follow-up observation period (up to Week 16). Treatment-emergent ADA referred to percentage of the total number of evaluable participants who were ADA-negative at baseline but developed ADA following biologic drug administration. Treatment-boosted ADA referred to percentage of the total number of evaluable participants who were ADA positive at baseline with at least 4-fold increase in ADA titer after biologic drug administration. |
| Change From Baseline in Patient-Oriented Eczema Measure (POEM) at Week 16 | Baseline, Week 16 | The POEM is a 7-item, validated questionnaire used to assess disease symptoms in both children and adults. Participants respond to 7 questions, including dryness, itching, flaking, cracking, sleep loss, bleeding, and weeping, each scored on a 5-point scale based on frequency of occurrence during the previous week: 0 = no days, 1 = 1 to 2 days, 2 = 3 to 4 days, 3 = 5 to 6 days, and 4 = all days. Item scores are added to provide a total score ranging from 0 (clear) to 28 (very severe atopic eczema). |
Countries
Canada, Czechia, Germany, Poland, United States
Participant flow
Recruitment details
The study was conducted in 4 phases: a Screening phase (28 days before randomization), a Blinded Treatment Phase (up to Week 16), an Open-label Treatment Phase (Week 16 to Week 54), and a Follow-up Phase (Week 54 to Week 66)
Pre-assignment details
During Blinded Treatment Phase, participants received placebo-controlled treatment with ISB 830 administered subcutaneously (SC) for 16 weeks at different dose levels. During the Open-label Treatment Phase, participants received treatment with ISB 830 administered SC every other week (q2w) for 38 weeks.
Participants by arm
| Arm | Count |
|---|---|
| ISB 830 300 mg q2w Blinded Treatment Phase: ISB 830 administered at dose of 600 mg via SC injection (2 × 300 mg) on Day 1, followed by ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection every 2 weeks (q2w) starting from Day 15 (Week 2) up to Week 14.
Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66. | 76 |
| ISB 830 300 mg q4w Blinded Treatment Phase: ISB 830 administered at dose of 600 mg via SC injection (2 × 300 mg) on Day 1, followed by ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection every 4 weeks (q4w) starting from Day 29 (Week 4) up to Week 12 and placebo administered via SC injection q4w starting from Day 15 (Week 2) up to Week 14.
Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66. | 78 |
| ISB 830 75 mg q4w Blinded Treatment Phase: ISB 830 administered at dose of 150 mg via SC injection (2 × 75 mg) on Day 1, followed by ISB 830 administered at dose of 75 mg (1 × 75 mg) via SC injection q4w starting from Day 29 (Week 4) up to Week 12 and placebo administered via SC injection q4w starting from Day 15 (Week 2) up to Week 14.
Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66. | 77 |
| Placebo - 1 Blinded Treatment Phase: Placebo administered via SC injection (2 injections) q2w starting from Day 1 up to Week 14.
Open-label Treatment Phase: ISB 830 administered at dose of 300 mg (1 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66. | 80 |
| ISB 830 600 mg q2w Blinded Treatment Phase: ISB 830 administered at dose of 1200 mg via SC injection (4 × 300 mg) on Day 1, followed by ISB 830 administered at dose of 600 mg (2 × 300 mg) via SC injection q2w starting from Day 15 (Week 2) up to Week 14.
Open-label Treatment Phase: ISB 830 administered at dose of 600 mg (2 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66. | 75 |
| Placebo - 2 Blinded Treatment Phase: Placebo administered via SC injection (4 injections) q2w starting from Day 1 up to Week 14.
Open-label Treatment Phase: ISB 830 administered at dose of 600 mg (2 × 300 mg) via SC injection q2w starting from Week 16 up to Week 52 (or until participant withdrawal). Participants were followed up for 12 weeks after treatment discontinuation, maximum up to Week 66. | 74 |
| Total | 460 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 2 | 0 | 0 | 1 |
| Overall Study | Death | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Lost to Follow-up | 3 | 2 | 4 | 2 | 3 | 2 |
| Overall Study | Others | 3 | 4 | 1 | 4 | 2 | 1 |
| Overall Study | Physician Decision | 0 | 1 | 1 | 0 | 1 | 0 |
| Overall Study | Pregnancy | 0 | 0 | 0 | 1 | 0 | 0 |
| Overall Study | Protocol Violation | 1 | 0 | 1 | 1 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 15 | 15 | 26 | 22 | 6 | 9 |
Baseline characteristics
| Characteristic | ISB 830 75 mg q4w | Total | Placebo - 2 | ISB 830 600 mg q2w | ISB 830 300 mg q4w | ISB 830 300 mg q2w | Placebo - 1 |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 38.4 Years STANDARD_DEVIATION 16.87 | 37.55 Years STANDARD_DEVIATION 14.21 | 36.0 Years STANDARD_DEVIATION 13.75 | 37.9 Years STANDARD_DEVIATION 13.31 | 36.6 Years STANDARD_DEVIATION 14.77 | 40.2 Years STANDARD_DEVIATION 13.1 | 36.3 Years STANDARD_DEVIATION 13.05 |
| Baseline Eczema Area and Severity Index (EASI) Score | 28.42 units on a scale STANDARD_DEVIATION 11.602 | 30.84 units on a scale STANDARD_DEVIATION 13.63 | 31.81 units on a scale STANDARD_DEVIATION 14.34 | 29.86 units on a scale STANDARD_DEVIATION 13.223 | 33.84 units on a scale STANDARD_DEVIATION 14.91 | 30.42 units on a scale STANDARD_DEVIATION 14.11 | 30.65 units on a scale STANDARD_DEVIATION 13.173 |
| Baseline Severity scoring of Atopic Dermatitis (SCORAD) Score | 66.22 units on a scale STANDARD_DEVIATION 12.408 | 67.16 units on a scale STANDARD_DEVIATION 13.25 | 67.66 units on a scale STANDARD_DEVIATION 13.56 | 66.40 units on a scale STANDARD_DEVIATION 12.3 | 69.09 units on a scale STANDARD_DEVIATION 14.284 | 67.50 units on a scale STANDARD_DEVIATION 14.325 | 66.12 units on a scale STANDARD_DEVIATION 12.658 |
| BMI | 26.32 kg/m^2 STANDARD_DEVIATION 6.199 | 27.05 kg/m^2 STANDARD_DEVIATION 6.27 | 26.50 kg/m^2 STANDARD_DEVIATION 5.434 | 26.03 kg/m^2 STANDARD_DEVIATION 5.167 | 27.49 kg/m^2 STANDARD_DEVIATION 6.167 | 28.72 kg/m^2 STANDARD_DEVIATION 7.538 | 27.20 kg/m^2 STANDARD_DEVIATION 6.608 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 15 Participants | 0 Participants | 3 Participants | 3 Participants | 5 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 75 Participants | 444 Participants | 73 Participants | 72 Participants | 75 Participants | 71 Participants | 78 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 23 Participants | 1 Participants | 2 Participants | 4 Participants | 5 Participants | 7 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants | 58 Participants | 4 Participants | 6 Participants | 14 Participants | 13 Participants | 15 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 3 Participants | 0 Participants | 0 Participants | 1 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 | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 65 Participants | 375 Participants | 69 Participants | 66 Participants | 59 Participants | 58 Participants | 58 Participants |
| Sex: Female, Male Female | 41 Participants | 245 Participants | 47 Participants | 37 Participants | 44 Participants | 32 Participants | 44 Participants |
| Sex: Female, Male Male | 36 Participants | 215 Participants | 27 Participants | 38 Participants | 34 Participants | 44 Participants | 36 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 | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 76 | 0 / 78 | 0 / 77 | 0 / 80 | 0 / 60 | 1 / 75 | 0 / 74 | 0 / 67 |
| other Total, other adverse events | 68 / 76 | 56 / 78 | 64 / 77 | 57 / 80 | 43 / 60 | 65 / 75 | 37 / 74 | 38 / 67 |
| serious Total, serious adverse events | 4 / 76 | 6 / 78 | 4 / 77 | 1 / 80 | 2 / 60 | 1 / 75 | 0 / 74 | 2 / 67 |
Outcome results
Primary
Percent Change From Baseline in Eczema Area and Severity Index (EASI) Clinical Score at Week 16
In EASI, four disease characteristics of atopic dermatitis (AD) (erythema, edema/papulation, excoriation, and lichenification) are assessed for severity on a scale of 0 (absent), 1 (mild), 2 (moderate), 3 (severe). The scores are added up for each of the four body regions (Head and neck, trunk, arms, and legs). The assigned percentages of body surface area (BSA) for each section of the body are 10% for head and neck, 20% for arms, 30% for trunk, and 40% for legs. Each subtotal score is multiplied by the BSA represented by that region. In addition, an area score of 0 to 6 is assigned for each body region, depending on the percentage of AD-affected skin in that area: 0 (none), 1 (1% to 9%), 2 (10% to 29%), 3 (30% to 49%), 4 (50% to 69%), 5 (70% to 89%), or 6 (90% to 100%). Each of the body area scores are multiplied by the area affected. The resulting EASI score ranges from 0 to 72 points, with the highest score indicating worse severity of AD.
Time frame: Baseline, Week 16
Population: Full Analysis Set (FAS) included all participants who were randomized and received at least 1 dose of study medication. Participants were analyzed according to the treatment group assigned. Here, 'Overall Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ISB 830 300 mg q2w | Percent Change From Baseline in Eczema Area and Severity Index (EASI) Clinical Score at Week 16 | -57.589 percentage change | Standard Deviation 36.2014 |
| ISB 830 300 mg q4w | Percent Change From Baseline in Eczema Area and Severity Index (EASI) Clinical Score at Week 16 | -56.734 percentage change | Standard Deviation 32.5395 |
| ISB 830 75 mg q4w | Percent Change From Baseline in Eczema Area and Severity Index (EASI) Clinical Score at Week 16 | -38.099 percentage change | Standard Deviation 39.6857 |
| Placebo - 1 | Percent Change From Baseline in Eczema Area and Severity Index (EASI) Clinical Score at Week 16 | -42.142 percentage change | Standard Deviation 38.1945 |
| ISB 830 600 mg q2w | Percent Change From Baseline in Eczema Area and Severity Index (EASI) Clinical Score at Week 16 | -59.737 percentage change | Standard Deviation 27.1176 |
| Placebo - 2 | Percent Change From Baseline in Eczema Area and Severity Index (EASI) Clinical Score at Week 16 | -43.252 percentage change | Standard Deviation 41.2404 |
p-value: =0.00895% CI: [-34.944, 5.439]Mixed Models Analysis
p-value: =0.06195% CI: [-29.552, 0.674]Mixed Models Analysis
p-value: =0.69195% CI: [-12.41, 18.698]Mixed Models Analysis
Comparison: The analysis was conducted using a MMRM model for percent change from baseline in EASI with the corresponding baseline value as covariate, and treatment group, region, disease severity, visit as fixed effect factors, and interactions of treatment-by-visit, baseline-by-visit.p-value: =0.00895% CI: [-29.895, -4.503]Mixed Models Analysis
Secondary
Area Under Curve From Time Zero to the End of Dosing Interval (AUC0-tau)
AUC0-tau is the area under the curve from time zero to the end of the dosing interval of ISB 830.
Time frame: Predose (within 15 minutes prior to dose), 4, 24, 96, 120, 168, and 336 hours postdose on Day 1 and predose (within 15 minutes prior to dose), and at 4, 24, 96, 120, 168 hours postdose on Day 85
Population: Pharmacokinetic Analysis Set (PKAS) included all participants who received at least 1 dose of ISB 830, did not had any major protocol deviation affecting pharmacokinetic (PK), and for whom at least 1 sample with detectable plasma concentration with known time of dosing and the time of sampling was available. 'Overall Number of Participants Analyzed' = number of participants evaluable for this outcome measure; 'Number Analyzed' = number of participants evaluable at specified time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| ISB 830 300 mg q2w | Area Under Curve From Time Zero to the End of Dosing Interval (AUC0-tau) | Day 85 | 12990 h*µg/mL | Geometric Coefficient of Variation 40.3 |
| ISB 830 300 mg q2w | Area Under Curve From Time Zero to the End of Dosing Interval (AUC0-tau) | Day 1 | 12170 h*µg/mL | Geometric Coefficient of Variation 49.9 |
| ISB 830 300 mg q4w | Area Under Curve From Time Zero to the End of Dosing Interval (AUC0-tau) | Day 1 | 20340 h*µg/mL | Geometric Coefficient of Variation 34.1 |
| ISB 830 300 mg q4w | Area Under Curve From Time Zero to the End of Dosing Interval (AUC0-tau) | Day 85 | 13120 h*µg/mL | Geometric Coefficient of Variation 49.5 |
| ISB 830 75 mg q4w | Area Under Curve From Time Zero to the End of Dosing Interval (AUC0-tau) | Day 85 | 3448 h*µg/mL | Geometric Coefficient of Variation 97.8 |
| ISB 830 75 mg q4w | Area Under Curve From Time Zero to the End of Dosing Interval (AUC0-tau) | Day 1 | 6671 h*µg/mL | Geometric Coefficient of Variation 40.2 |
| Placebo - 1 | Area Under Curve From Time Zero to the End of Dosing Interval (AUC0-tau) | Day 85 | 39420 h*µg/mL | Geometric Coefficient of Variation 2.6 |
| Placebo - 1 | Area Under Curve From Time Zero to the End of Dosing Interval (AUC0-tau) | Day 1 | 26930 h*µg/mL | — |
Secondary
Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 16
The DLQI is a 10-item validated questionnaire used to assess the impact of AD disease symptoms and treatment on quality of life (QoL). It consists of 10 questions evaluating impact of skin diseases on different aspects of a participant's QoL over the prior week, including symptoms and feelings, daily activities, leisure, work or school, personal relationships, and the side effects of treatment. Each item is scored on a 4-point scale (0 = not at all/not relevant; 1 = a little; 2 = a lot; and 3 = very much). Item scores are added to provide a total score, ranging from 0 to 30, with higher scores indicating greater impairment of QoL.
Time frame: Baseline, Week 16
Population: Full Analysis Set (FAS) included all participants who were randomized and received at least 1 dose of study medication. Participants were analyzed according to the treatment group assigned. Here, 'Overall Number of Participants Analyzed' signifies the number of participants analyzed for this outcome measure and 'Number Analyzed' signifies the number of participants analyzed at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ISB 830 300 mg q2w | Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 16 | Baseline | 15.2 units on a scale | Standard Deviation 6.8 |
| ISB 830 300 mg q2w | Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 16 | Change at Week 16 | -7.3 units on a scale | Standard Deviation 7.58 |
| ISB 830 300 mg q4w | Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 16 | Baseline | 15.4 units on a scale | Standard Deviation 7.14 |
| ISB 830 300 mg q4w | Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 16 | Change at Week 16 | -6.7 units on a scale | Standard Deviation 6.16 |
| ISB 830 75 mg q4w | Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 16 | Baseline | 14.3 units on a scale | Standard Deviation 7.18 |
| ISB 830 75 mg q4w | Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 16 | Change at Week 16 | -4.1 units on a scale | Standard Deviation 6.13 |
| Placebo - 1 | Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 16 | Baseline | 14.3 units on a scale | Standard Deviation 6.77 |
| Placebo - 1 | Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 16 | Change at Week 16 | -4.7 units on a scale | Standard Deviation 7 |
| ISB 830 600 mg q2w | Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 16 | Baseline | 14.1 units on a scale | Standard Deviation 6.02 |
| ISB 830 600 mg q2w | Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 16 | Change at Week 16 | -6.6 units on a scale | Standard Deviation 6.19 |
| Placebo - 2 | Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 16 | Baseline | 14.7 units on a scale | Standard Deviation 6.78 |
| Placebo - 2 | Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 16 | Change at Week 16 | -5.5 units on a scale | Standard Deviation 5.1 |
Secondary
Change From Baseline in Global Individual Signs Score (GISS) at Week 16
GISS assesses AD lesions for erythema, excoriations, lichenification and infiltration/papulation. Each component is rated on a global basis (over the entire body surface rather than region) using a 4-point scale (0=none, 1=mild, 2=moderate, and 3=severe) according to the EASI grading severity. Total score ranges from 0 to 12 (no disease to most severe disease, respectively).
Time frame: Baseline, Week 16
Population: Full Analysis Set (FAS) included all participants who were randomized and received at least 1 dose of study medication. Participants were analyzed according to the treatment group assigned. Here, 'Overall Number of Participants Analyzed' signifies the number of participants analyzed for this outcome measure and 'Number Analyzed' signifies the number of participants analyzed at specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ISB 830 300 mg q2w | Change From Baseline in Global Individual Signs Score (GISS) at Week 16 | Baseline | 9.1 units on a scale | Standard Deviation 1.81 |
| ISB 830 300 mg q2w | Change From Baseline in Global Individual Signs Score (GISS) at Week 16 | Change at Week 16 | -3.4 units on a scale | Standard Deviation 2.52 |
| ISB 830 300 mg q4w | Change From Baseline in Global Individual Signs Score (GISS) at Week 16 | Baseline | 9.4 units on a scale | Standard Deviation 1.71 |
| ISB 830 300 mg q4w | Change From Baseline in Global Individual Signs Score (GISS) at Week 16 | Change at Week 16 | -3.2 units on a scale | Standard Deviation 2.81 |
| ISB 830 75 mg q4w | Change From Baseline in Global Individual Signs Score (GISS) at Week 16 | Baseline | 9.1 units on a scale | Standard Deviation 1.71 |
| ISB 830 75 mg q4w | Change From Baseline in Global Individual Signs Score (GISS) at Week 16 | Change at Week 16 | -2.4 units on a scale | Standard Deviation 2.52 |
| Placebo - 1 | Change From Baseline in Global Individual Signs Score (GISS) at Week 16 | Baseline | 8.9 units on a scale | Standard Deviation 1.77 |
| Placebo - 1 | Change From Baseline in Global Individual Signs Score (GISS) at Week 16 | Change at Week 16 | -2.2 units on a scale | Standard Deviation 2.49 |
| ISB 830 600 mg q2w | Change From Baseline in Global Individual Signs Score (GISS) at Week 16 | Baseline | 9.0 units on a scale | Standard Deviation 1.66 |
| ISB 830 600 mg q2w | Change From Baseline in Global Individual Signs Score (GISS) at Week 16 | Change at Week 16 | -3.5 units on a scale | Standard Deviation 2.52 |
| Placebo - 2 | Change From Baseline in Global Individual Signs Score (GISS) at Week 16 | Baseline | 8.9 units on a scale | Standard Deviation 1.63 |
| Placebo - 2 | Change From Baseline in Global Individual Signs Score (GISS) at Week 16 | Change at Week 16 | -2.3 units on a scale | Standard Deviation 2.21 |
Secondary
Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Subscale Scores at Week 16
The HADS is a 14-item questionnaire, with 7 items related to anxiety (HADS-A) and 7 items related to depression (HADS-D). Each item is scored from 0 to 3; scores for each subscale range from 0 to 21, with higher scores indicating more distress. For each subscale, scores 7 or lower are considered normal, 8 to 10 are borderline, and 11 or higher indicate clinical anxiety or depression.
Time frame: Baseline, Week 16
Population: Full Analysis Set (FAS) included all participants who were randomized and received at least 1 dose of study medication. Participants were analyzed according to the treatment group assigned. Here, 'Overall Number of Participants Analyzed' signifies the number of participants analyzed for this outcome measure and 'Number Analyzed' signifies the number of participants analyzed for specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ISB 830 300 mg q2w | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Subscale Scores at Week 16 | HADS-D Baseline | 4.3 units on a scale | Standard Deviation 3.9 |
| ISB 830 300 mg q2w | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Subscale Scores at Week 16 | HADS-D Change at Week 16 | -1.1 units on a scale | Standard Deviation 2.62 |
| ISB 830 300 mg q2w | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Subscale Scores at Week 16 | HADS-A Change at Week 16 | -1.8 units on a scale | Standard Deviation 3.34 |
| ISB 830 300 mg q2w | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Subscale Scores at Week 16 | HADS-A Baseline | 6.1 units on a scale | Standard Deviation 4.47 |
| ISB 830 300 mg q4w | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Subscale Scores at Week 16 | HADS-D Change at Week 16 | -1.0 units on a scale | Standard Deviation 4.05 |
| ISB 830 300 mg q4w | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Subscale Scores at Week 16 | HADS-A Change at Week 16 | -0.9 units on a scale | Standard Deviation 3.54 |
| ISB 830 300 mg q4w | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Subscale Scores at Week 16 | HADS-A Baseline | 6.1 units on a scale | Standard Deviation 4.82 |
| ISB 830 300 mg q4w | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Subscale Scores at Week 16 | HADS-D Baseline | 4.8 units on a scale | Standard Deviation 4.38 |
| ISB 830 75 mg q4w | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Subscale Scores at Week 16 | HADS-A Baseline | 6.1 units on a scale | Standard Deviation 4.15 |
| ISB 830 75 mg q4w | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Subscale Scores at Week 16 | HADS-A Change at Week 16 | -1.0 units on a scale | Standard Deviation 3.16 |
| ISB 830 75 mg q4w | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Subscale Scores at Week 16 | HADS-D Baseline | 4.9 units on a scale | Standard Deviation 4.19 |
| ISB 830 75 mg q4w | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Subscale Scores at Week 16 | HADS-D Change at Week 16 | -0.6 units on a scale | Standard Deviation 2.58 |
| Placebo - 1 | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Subscale Scores at Week 16 | HADS-D Baseline | 4.2 units on a scale | Standard Deviation 3.16 |
| Placebo - 1 | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Subscale Scores at Week 16 | HADS-A Baseline | 6.2 units on a scale | Standard Deviation 3.74 |
| Placebo - 1 | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Subscale Scores at Week 16 | HADS-A Change at Week 16 | -0.8 units on a scale | Standard Deviation 3.39 |
| Placebo - 1 | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Subscale Scores at Week 16 | HADS-D Change at Week 16 | -0.1 units on a scale | Standard Deviation 2.62 |
| ISB 830 600 mg q2w | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Subscale Scores at Week 16 | HADS-D Change at Week 16 | -0.9 units on a scale | Standard Deviation 3.6 |
| ISB 830 600 mg q2w | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Subscale Scores at Week 16 | HADS-A Baseline | 6.0 units on a scale | Standard Deviation 4.41 |
| ISB 830 600 mg q2w | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Subscale Scores at Week 16 | HADS-D Baseline | 4.7 units on a scale | Standard Deviation 3.81 |
| ISB 830 600 mg q2w | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Subscale Scores at Week 16 | HADS-A Change at Week 16 | -1.8 units on a scale | Standard Deviation 3.8 |
| Placebo - 2 | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Subscale Scores at Week 16 | HADS-D Baseline | 5.0 units on a scale | Standard Deviation 4.26 |
| Placebo - 2 | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Subscale Scores at Week 16 | HADS-A Change at Week 16 | -1.9 units on a scale | Standard Deviation 3.85 |
| Placebo - 2 | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Subscale Scores at Week 16 | HADS-A Baseline | 6.7 units on a scale | Standard Deviation 4.12 |
| Placebo - 2 | Change From Baseline in Hospital Anxiety and Depression Scale (HADS) Subscale Scores at Week 16 | HADS-D Change at Week 16 | -1.2 units on a scale | Standard Deviation 2.97 |
Secondary
Change From Baseline in Patient Global Assessment (PGA) of Disease and Treatment at Week 16
For PGA of disease, participants rated their overall wellbeing on a 5-point Likert scale from 0 (poor) to 4 (excellent). Participants were asked: Considering all the ways in which your disease affects you, indicate how well you are doing. Response choices were: Poor; Fair; Good; Very Good; Excellent. For PGA of treatment, participants rated their satisfaction with the study treatment on a 5-point Likert scale from 0 (poor) to 4 (excellent). Subjects were asked: How would you rate the way your disease responded to the study medication? Response choices were: Poor; Fair; Good; Very Good; Excellent.
Time frame: Baseline, Week 16
Population: Full Analysis Set (FAS) included all participants who were randomized and received at least 1 dose of study medication. Participants were analyzed according to the treatment group assigned. Here, 'Overall Number of Participants Analyzed' signifies the number of participants analyzed for this outcome measure and 'Number Analyzed' signifies the number of participants analyzed for specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ISB 830 300 mg q2w | Change From Baseline in Patient Global Assessment (PGA) of Disease and Treatment at Week 16 | PGA of Disease Baseline | 2.0 units on a scale | Standard Deviation 0.89 |
| ISB 830 300 mg q2w | Change From Baseline in Patient Global Assessment (PGA) of Disease and Treatment at Week 16 | PGA of Treatment Baseline | 2.1 units on a scale | Standard Deviation 0.98 |
| ISB 830 300 mg q2w | Change From Baseline in Patient Global Assessment (PGA) of Disease and Treatment at Week 16 | PGA of Disease Change at Week 16 | 1.1 units on a scale | Standard Deviation 0.98 |
| ISB 830 300 mg q2w | Change From Baseline in Patient Global Assessment (PGA) of Disease and Treatment at Week 16 | PGA of Treatment Change at Week 16 | 0.9 units on a scale | Standard Deviation 0.87 |
| ISB 830 300 mg q4w | Change From Baseline in Patient Global Assessment (PGA) of Disease and Treatment at Week 16 | PGA of Disease Change at Week 16 | 1.2 units on a scale | Standard Deviation 1.17 |
| ISB 830 300 mg q4w | Change From Baseline in Patient Global Assessment (PGA) of Disease and Treatment at Week 16 | PGA of Treatment Baseline | 2.0 units on a scale | Standard Deviation 1.07 |
| ISB 830 300 mg q4w | Change From Baseline in Patient Global Assessment (PGA) of Disease and Treatment at Week 16 | PGA of Disease Baseline | 1.9 units on a scale | Standard Deviation 0.84 |
| ISB 830 300 mg q4w | Change From Baseline in Patient Global Assessment (PGA) of Disease and Treatment at Week 16 | PGA of Treatment Change at Week 16 | 1.1 units on a scale | Standard Deviation 0.98 |
| ISB 830 75 mg q4w | Change From Baseline in Patient Global Assessment (PGA) of Disease and Treatment at Week 16 | PGA of Treatment Change at Week 16 | 0.7 units on a scale | Standard Deviation 0.75 |
| ISB 830 75 mg q4w | Change From Baseline in Patient Global Assessment (PGA) of Disease and Treatment at Week 16 | PGA of Disease Change at Week 16 | 0.8 units on a scale | Standard Deviation 0.8 |
| ISB 830 75 mg q4w | Change From Baseline in Patient Global Assessment (PGA) of Disease and Treatment at Week 16 | PGA of Treatment Baseline | 2.1 units on a scale | Standard Deviation 0.98 |
| ISB 830 75 mg q4w | Change From Baseline in Patient Global Assessment (PGA) of Disease and Treatment at Week 16 | PGA of Disease Baseline | 2.1 units on a scale | Standard Deviation 0.97 |
| Placebo - 1 | Change From Baseline in Patient Global Assessment (PGA) of Disease and Treatment at Week 16 | PGA of Disease Baseline | 1.9 units on a scale | Standard Deviation 0.79 |
| Placebo - 1 | Change From Baseline in Patient Global Assessment (PGA) of Disease and Treatment at Week 16 | PGA of Treatment Change at Week 16 | 0.7 units on a scale | Standard Deviation 0.84 |
| Placebo - 1 | Change From Baseline in Patient Global Assessment (PGA) of Disease and Treatment at Week 16 | PGA of Treatment Baseline | 2.0 units on a scale | Standard Deviation 1.05 |
| Placebo - 1 | Change From Baseline in Patient Global Assessment (PGA) of Disease and Treatment at Week 16 | PGA of Disease Change at Week 16 | 1.1 units on a scale | Standard Deviation 0.97 |
| ISB 830 600 mg q2w | Change From Baseline in Patient Global Assessment (PGA) of Disease and Treatment at Week 16 | PGA of Disease Change at Week 16 | 1.1 units on a scale | Standard Deviation 0.88 |
| ISB 830 600 mg q2w | Change From Baseline in Patient Global Assessment (PGA) of Disease and Treatment at Week 16 | PGA of Treatment Change at Week 16 | 1.0 units on a scale | Standard Deviation 0.88 |
| ISB 830 600 mg q2w | Change From Baseline in Patient Global Assessment (PGA) of Disease and Treatment at Week 16 | PGA of Treatment Baseline | 2.2 units on a scale | Standard Deviation 1.02 |
| ISB 830 600 mg q2w | Change From Baseline in Patient Global Assessment (PGA) of Disease and Treatment at Week 16 | PGA of Disease Baseline | 2.0 units on a scale | Standard Deviation 0.76 |
| Placebo - 2 | Change From Baseline in Patient Global Assessment (PGA) of Disease and Treatment at Week 16 | PGA of Treatment Baseline | 1.9 units on a scale | Standard Deviation 1.03 |
| Placebo - 2 | Change From Baseline in Patient Global Assessment (PGA) of Disease and Treatment at Week 16 | PGA of Disease Change at Week 16 | 0.8 units on a scale | Standard Deviation 0.83 |
| Placebo - 2 | Change From Baseline in Patient Global Assessment (PGA) of Disease and Treatment at Week 16 | PGA of Treatment Change at Week 16 | 0.7 units on a scale | Standard Deviation 0.92 |
| Placebo - 2 | Change From Baseline in Patient Global Assessment (PGA) of Disease and Treatment at Week 16 | PGA of Disease Baseline | 2.1 units on a scale | Standard Deviation 0.92 |
Secondary
Change From Baseline in Patient-Oriented Eczema Measure (POEM) at Week 16
The POEM is a 7-item, validated questionnaire used to assess disease symptoms in both children and adults. Participants respond to 7 questions, including dryness, itching, flaking, cracking, sleep loss, bleeding, and weeping, each scored on a 5-point scale based on frequency of occurrence during the previous week: 0 = no days, 1 = 1 to 2 days, 2 = 3 to 4 days, 3 = 5 to 6 days, and 4 = all days. Item scores are added to provide a total score ranging from 0 (clear) to 28 (very severe atopic eczema).
Time frame: Baseline, Week 16
Population: Full Analysis Set (FAS) included all participants who were randomized and received at least 1 dose of study medication. Participants were analyzed according to the treatment group assigned. Here, 'Overall Number of Participants Analyzed' signifies the number of participants analyzed for this outcome measure and 'Number Analyzed' signifies the number of participants analyzed for specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ISB 830 300 mg q2w | Change From Baseline in Patient-Oriented Eczema Measure (POEM) at Week 16 | Baseline | 20.2 units on a scale | Standard Deviation 5.78 |
| ISB 830 300 mg q2w | Change From Baseline in Patient-Oriented Eczema Measure (POEM) at Week 16 | Change at Week 16 | -7.1 units on a scale | Standard Deviation 6.44 |
| ISB 830 300 mg q4w | Change From Baseline in Patient-Oriented Eczema Measure (POEM) at Week 16 | Baseline | 20.9 units on a scale | Standard Deviation 5.56 |
| ISB 830 300 mg q4w | Change From Baseline in Patient-Oriented Eczema Measure (POEM) at Week 16 | Change at Week 16 | -4.8 units on a scale | Standard Deviation 8.79 |
| ISB 830 75 mg q4w | Change From Baseline in Patient-Oriented Eczema Measure (POEM) at Week 16 | Baseline | 19.8 units on a scale | Standard Deviation 5.27 |
| ISB 830 75 mg q4w | Change From Baseline in Patient-Oriented Eczema Measure (POEM) at Week 16 | Change at Week 16 | -3.8 units on a scale | Standard Deviation 6.51 |
| Placebo - 1 | Change From Baseline in Patient-Oriented Eczema Measure (POEM) at Week 16 | Baseline | 21.2 units on a scale | Standard Deviation 5.4 |
| Placebo - 1 | Change From Baseline in Patient-Oriented Eczema Measure (POEM) at Week 16 | Change at Week 16 | -5.0 units on a scale | Standard Deviation 6.94 |
| ISB 830 600 mg q2w | Change From Baseline in Patient-Oriented Eczema Measure (POEM) at Week 16 | Baseline | 20.7 units on a scale | Standard Deviation 4.63 |
| ISB 830 600 mg q2w | Change From Baseline in Patient-Oriented Eczema Measure (POEM) at Week 16 | Change at Week 16 | -7.0 units on a scale | Standard Deviation 7.37 |
| Placebo - 2 | Change From Baseline in Patient-Oriented Eczema Measure (POEM) at Week 16 | Baseline | 21.1 units on a scale | Standard Deviation 4.79 |
| Placebo - 2 | Change From Baseline in Patient-Oriented Eczema Measure (POEM) at Week 16 | Change at Week 16 | -5.5 units on a scale | Standard Deviation 7.33 |
Secondary
Maximum Observed Serum Concentration (Cmax) of ISB 830
Cmax is the maximum concentration of ISB 830 observed in serum
Time frame: Predose (within 15 minutes prior to dose), 4, 24, 96, 120, 168, and 336 hours postdose on Day 1 and predose (within 15 minutes prior to dose), 4, 24, 96, 120, and 168 hours postdose on Day 85
Population: Pharmacokinetic Analysis Set (PKAS) included all participants who received at least 1 dose of ISB 830, did not had any major protocol deviation affecting pharmacokinetic (PK), and for whom at least 1 sample with detectable plasma concentration with known time of dosing and the time of sampling was available. 'Overall Number of Participants Analyzed' = number of participants evaluable for this outcome measure; 'Number Analyzed' = number of participants evaluable at specified time point.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| ISB 830 300 mg q2w | Maximum Observed Serum Concentration (Cmax) of ISB 830 | Day 1 | 46.98 micrograms per milliliters (µg/mL) | Geometric Coefficient of Variation 46.5 |
| ISB 830 300 mg q2w | Maximum Observed Serum Concentration (Cmax) of ISB 830 | Day 85 | 52.33 micrograms per milliliters (µg/mL) | Geometric Coefficient of Variation 45.8 |
| ISB 830 300 mg q4w | Maximum Observed Serum Concentration (Cmax) of ISB 830 | Day 85 | 31.20 micrograms per milliliters (µg/mL) | Geometric Coefficient of Variation 60.4 |
| ISB 830 300 mg q4w | Maximum Observed Serum Concentration (Cmax) of ISB 830 | Day 1 | 49.95 micrograms per milliliters (µg/mL) | Geometric Coefficient of Variation 33.1 |
| ISB 830 75 mg q4w | Maximum Observed Serum Concentration (Cmax) of ISB 830 | Day 85 | 8.8 micrograms per milliliters (µg/mL) | Geometric Coefficient of Variation 73.6 |
| ISB 830 75 mg q4w | Maximum Observed Serum Concentration (Cmax) of ISB 830 | Day 1 | 16.62 micrograms per milliliters (µg/mL) | Geometric Coefficient of Variation 32.6 |
| Placebo - 1 | Maximum Observed Serum Concentration (Cmax) of ISB 830 | Day 85 | 144.80 micrograms per milliliters (µg/mL) | Geometric Coefficient of Variation 6.8 |
| Placebo - 1 | Maximum Observed Serum Concentration (Cmax) of ISB 830 | Day 1 | 92.84 micrograms per milliliters (µg/mL) | Geometric Coefficient of Variation 12.3 |
Secondary
Number of Missed Work or School Days at Week 16
Participants who were employed or enrolled in school were asked to report the number of sick leave and/or missed school days due to AD (eg, versus due to an accident) in the last 4 weeks.
Time frame: Week 16
Population: Full Analysis Set (FAS) included all participants who were randomized and received at least 1 dose of study medication. Participants were analyzed according to the treatment group assigned. Here, 'Overall Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ISB 830 300 mg q2w | Number of Missed Work or School Days at Week 16 | 1.2 days | Standard Deviation 3.73 |
| ISB 830 300 mg q4w | Number of Missed Work or School Days at Week 16 | 0.5 days | Standard Deviation 0.92 |
| ISB 830 75 mg q4w | Number of Missed Work or School Days at Week 16 | 0.5 days | Standard Deviation 1.26 |
| Placebo - 1 | Number of Missed Work or School Days at Week 16 | 0.5 days | Standard Deviation 1.29 |
| ISB 830 600 mg q2w | Number of Missed Work or School Days at Week 16 | 4.9 days | Standard Deviation 14.92 |
| Placebo - 2 | Number of Missed Work or School Days at Week 16 | 1.4 days | Standard Deviation 5.31 |
Secondary
Percentage Change From Baseline in PGA of Disease and Treatment at Week 16
For PGA of disease, participants rated their overall wellbeing on a 5-point Likert scale from 0 (poor) to 4 (excellent). Participants were asked: Considering all the ways in which your disease affects you, indicate how well you are doing. Response choices were: Poor; Fair; Good; Very Good; Excellent. For PGA of treatment, participants rated their satisfaction with the study treatment on a 5-point Likert scale from 0 (poor) to 4 (excellent). Subjects were asked: How would you rate the way your disease responded to the study medication? Response choices were: Poor; Fair; Good; Very Good; Excellent.
Time frame: Baseline, Week 16
Population: Full Analysis Set (FAS) included all participants who were randomized and received at least 1 dose of study medication. Participants were analyzed according to the treatment group assigned. Here, 'Overall Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure and 'Number Analyzed' signifies the number of participants evaluable for specified category.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| ISB 830 300 mg q2w | Percentage Change From Baseline in PGA of Disease and Treatment at Week 16 | PGA of Disease: Percent Change at Week 16 | 72.2 percentage change | Standard Deviation 93.51 |
| ISB 830 300 mg q2w | Percentage Change From Baseline in PGA of Disease and Treatment at Week 16 | PGA of Treatment: Percent Change at Week 16 | 42.3 percentage change | Standard Deviation 75.61 |
| ISB 830 300 mg q4w | Percentage Change From Baseline in PGA of Disease and Treatment at Week 16 | PGA of Disease: Percent Change at Week 16 | 73.3 percentage change | Standard Deviation 114.18 |
| ISB 830 300 mg q4w | Percentage Change From Baseline in PGA of Disease and Treatment at Week 16 | PGA of Treatment: Percent Change at Week 16 | 50.6 percentage change | Standard Deviation 97.24 |
| ISB 830 75 mg q4w | Percentage Change From Baseline in PGA of Disease and Treatment at Week 16 | PGA of Disease: Percent Change at Week 16 | 33.3 percentage change | Standard Deviation 87.25 |
| ISB 830 75 mg q4w | Percentage Change From Baseline in PGA of Disease and Treatment at Week 16 | PGA of Treatment: Percent Change at Week 16 | 16.0 percentage change | Standard Deviation 64.62 |
| Placebo - 1 | Percentage Change From Baseline in PGA of Disease and Treatment at Week 16 | PGA of Disease: Percent Change at Week 16 | 76.2 percentage change | Standard Deviation 101.89 |
| Placebo - 1 | Percentage Change From Baseline in PGA of Disease and Treatment at Week 16 | PGA of Treatment: Percent Change at Week 16 | 21.3 percentage change | Standard Deviation 56.76 |
| ISB 830 600 mg q2w | Percentage Change From Baseline in PGA of Disease and Treatment at Week 16 | PGA of Disease: Percent Change at Week 16 | 69.2 percentage change | Standard Deviation 92.85 |
| ISB 830 600 mg q2w | Percentage Change From Baseline in PGA of Disease and Treatment at Week 16 | PGA of Treatment: Percent Change at Week 16 | 55.0 percentage change | Standard Deviation 93.81 |
| Placebo - 2 | Percentage Change From Baseline in PGA of Disease and Treatment at Week 16 | PGA of Disease: Percent Change at Week 16 | 40.4 percentage change | Standard Deviation 76.89 |
| Placebo - 2 | Percentage Change From Baseline in PGA of Disease and Treatment at Week 16 | PGA of Treatment: Percent Change at Week 16 | 15.2 percentage change | Standard Deviation 61.29 |
Secondary
Percentage of Participants Achieving a 50% Reduction From Baseline in EASI Score (EASI-50) at Week 16
In EASI, 4 disease characteristics of AD are assessed for severity on a scale of 0 (absent), 1 (mild), 2 (moderate), 3 (severe). The scores are added up for each of the 4 body regions (Head and neck, trunk, arms, and legs). The assigned percentages of BSA for each section of the body are 10% for head and neck, 20% for arms, 30% for trunk, and 40% for legs. Each subtotal score is multiplied by the BSA represented by that region. In addition, an area score of 0 to 6 is assigned for each body region, depending on the percentage of AD-affected skin: 0 (none), 1 (1% to 9%), 2 (10% to 29%), 3 (30% to 49%), 4 (50% to 69%), 5 (70% to 89%), or 6 (90% to 100%). Each of the body area scores are multiplied by the area affected. The resulting EASI score ranges from 0 to 72 points, with the highest score indicating worse severity of AD.
Time frame: Baseline, Week 16
Population: Full Analysis Set (FAS) included all participants who were randomized and received at least 1 dose of study medication. Participants were analyzed according to the treatment group assigned. Any participant who received a rescue medication for AD during Part 1, had missing Week 16 assessment, or withdrew before Week 16 was considered Nonresponder
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ISB 830 300 mg q2w | Percentage of Participants Achieving a 50% Reduction From Baseline in EASI Score (EASI-50) at Week 16 | 48.7 percentage of participants |
| ISB 830 300 mg q4w | Percentage of Participants Achieving a 50% Reduction From Baseline in EASI Score (EASI-50) at Week 16 | 34.6 percentage of participants |
| ISB 830 75 mg q4w | Percentage of Participants Achieving a 50% Reduction From Baseline in EASI Score (EASI-50) at Week 16 | 27.3 percentage of participants |
| Placebo - 1 | Percentage of Participants Achieving a 50% Reduction From Baseline in EASI Score (EASI-50) at Week 16 | 27.5 percentage of participants |
| ISB 830 600 mg q2w | Percentage of Participants Achieving a 50% Reduction From Baseline in EASI Score (EASI-50) at Week 16 | 44.0 percentage of participants |
| Placebo - 2 | Percentage of Participants Achieving a 50% Reduction From Baseline in EASI Score (EASI-50) at Week 16 | 33.8 percentage of participants |
Secondary
Percentage of Participants Achieving a 75% Reduction From Baseline in EASI Score (EASI-75) at Week 16
In EASI, 4 disease characteristics of AD are assessed for severity on a scale of 0 (absent), 1 (mild), 2 (moderate), 3 (severe). The scores are added up for each of the 4 body regions (Head and neck, trunk, arms, and legs). The assigned percentages of BSA for each section of the body are 10% for head and neck, 20% for arms, 30% for trunk, and 40% for legs. Each subtotal score is multiplied by the BSA represented by that region. In addition, an area score of 0 to 6 is assigned for each body region, depending on the percentage of AD-affected skin: 0 (none), 1 (1% to 9%), 2 (10% to 29%), 3 (30% to 49%), 4 (50% to 69%), 5 (70% to 89%), or 6 (90% to 100%). Each of the body area scores are multiplied by the area affected. The resulting EASI score ranges from 0 to 72 points, with the highest score indicating worse severity of AD.
Time frame: Baseline, Week 16
Population: Full Analysis Set (FAS) included all participants who were randomized and received at least 1 dose of study medication. Participants were analyzed according to the treatment group assigned. Any participant who received a rescue medication for AD during Part 1, had missed Week 16 assessment, or withdrew before Week 16 was considered Non-responder.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ISB 830 300 mg q2w | Percentage of Participants Achieving a 75% Reduction From Baseline in EASI Score (EASI-75) at Week 16 | 23.7 percentage of participants |
| ISB 830 300 mg q4w | Percentage of Participants Achieving a 75% Reduction From Baseline in EASI Score (EASI-75) at Week 16 | 20.5 percentage of participants |
| ISB 830 75 mg q4w | Percentage of Participants Achieving a 75% Reduction From Baseline in EASI Score (EASI-75) at Week 16 | 11.7 percentage of participants |
| Placebo - 1 | Percentage of Participants Achieving a 75% Reduction From Baseline in EASI Score (EASI-75) at Week 16 | 11.3 percentage of participants |
| ISB 830 600 mg q2w | Percentage of Participants Achieving a 75% Reduction From Baseline in EASI Score (EASI-75) at Week 16 | 25.3 percentage of participants |
| Placebo - 2 | Percentage of Participants Achieving a 75% Reduction From Baseline in EASI Score (EASI-75) at Week 16 | 18.9 percentage of participants |
Secondary
Percentage of Participants Achieving Both Investigator's Global Assessment (IGA) Clinical Score of 0 or 1 and an IGA Reduction From Baseline of ≥ 2 Points at Week 16
The IGA is an assessment scale used in clinical studies to determine severity of AD based on a 5-point scale ranging from 0 (clear) to 4 (severe/very severe).
Time frame: Baseline, Week 16
Population: Full Analysis Set (FAS) included all participants who were randomized and received at least 1 dose of study medication. Participants were analyzed according to the treatment group assigned. Any participant who received a rescue medication for AD during Part 1, had missed Week 16 assessment, or withdrew before Week 16 was considered Non-responder.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ISB 830 300 mg q2w | Percentage of Participants Achieving Both Investigator's Global Assessment (IGA) Clinical Score of 0 or 1 and an IGA Reduction From Baseline of ≥ 2 Points at Week 16 | 13.2 percentage of participants |
| ISB 830 300 mg q4w | Percentage of Participants Achieving Both Investigator's Global Assessment (IGA) Clinical Score of 0 or 1 and an IGA Reduction From Baseline of ≥ 2 Points at Week 16 | 10.3 percentage of participants |
| ISB 830 75 mg q4w | Percentage of Participants Achieving Both Investigator's Global Assessment (IGA) Clinical Score of 0 or 1 and an IGA Reduction From Baseline of ≥ 2 Points at Week 16 | 6.5 percentage of participants |
| Placebo - 1 | Percentage of Participants Achieving Both Investigator's Global Assessment (IGA) Clinical Score of 0 or 1 and an IGA Reduction From Baseline of ≥ 2 Points at Week 16 | 5.0 percentage of participants |
| ISB 830 600 mg q2w | Percentage of Participants Achieving Both Investigator's Global Assessment (IGA) Clinical Score of 0 or 1 and an IGA Reduction From Baseline of ≥ 2 Points at Week 16 | 12.0 percentage of participants |
| Placebo - 2 | Percentage of Participants Achieving Both Investigator's Global Assessment (IGA) Clinical Score of 0 or 1 and an IGA Reduction From Baseline of ≥ 2 Points at Week 16 | 5.4 percentage of participants |
Secondary
Percentage of Participants With Anti-Drug Antibody (ADA) at Week 16
Participants with ADA were those with at least 1 treatment-induced or treatment-boosted ADA-positive sample at any time during the treatment or follow-up observation period (up to Week 16). Treatment-emergent ADA referred to percentage of the total number of evaluable participants who were ADA-negative at baseline but developed ADA following biologic drug administration. Treatment-boosted ADA referred to percentage of the total number of evaluable participants who were ADA positive at baseline with at least 4-fold increase in ADA titer after biologic drug administration.
Time frame: Baseline through Week 16
Population: Safety Analysis Set (SAS) included all participants who were randomized and received at least 1 dose of study medication. Participants were analyzed according to the treatment they received. Here, 'Overall Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ISB 830 300 mg q2w | Percentage of Participants With Anti-Drug Antibody (ADA) at Week 16 | 13.3 percentage of participants |
| ISB 830 300 mg q4w | Percentage of Participants With Anti-Drug Antibody (ADA) at Week 16 | 29.9 percentage of participants |
| ISB 830 75 mg q4w | Percentage of Participants With Anti-Drug Antibody (ADA) at Week 16 | 50.6 percentage of participants |
| Placebo - 1 | Percentage of Participants With Anti-Drug Antibody (ADA) at Week 16 | 5.1 percentage of participants |
| ISB 830 600 mg q2w | Percentage of Participants With Anti-Drug Antibody (ADA) at Week 16 | 10.7 percentage of participants |
| Placebo - 2 | Percentage of Participants With Anti-Drug Antibody (ADA) at Week 16 | 6.8 percentage of participants |
Secondary
Percentage of Participants With Improvement (Reduction) in Pruritus Numerical Rating Scale (NRS) Score of ≥ 4 From Baseline at Week 16
Participants were asked to rate itch (pruritus) intensity at its worst during the past 24 hours on a daily basis using an 11-point scale from 0 (no itch) to 10 (worst imaginable itch). Pruritus NRS was analyzed based on weekly rolling averages of daily scores.
Time frame: Baseline, Week 16
Population: Full Analysis Set (FAS) included all participants who were randomized and received at least 1 dose of study medication. Participants were analyzed according to the treatment group assigned. Any participant who received a rescue medication for AD during Part 1, had missed Week 16 assessment or withdrew before Week 16 was considered Non-responder.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| ISB 830 300 mg q2w | Percentage of Participants With Improvement (Reduction) in Pruritus Numerical Rating Scale (NRS) Score of ≥ 4 From Baseline at Week 16 | 7.9 percentage of participants |
| ISB 830 300 mg q4w | Percentage of Participants With Improvement (Reduction) in Pruritus Numerical Rating Scale (NRS) Score of ≥ 4 From Baseline at Week 16 | 11.5 percentage of participants |
| ISB 830 75 mg q4w | Percentage of Participants With Improvement (Reduction) in Pruritus Numerical Rating Scale (NRS) Score of ≥ 4 From Baseline at Week 16 | 5.2 percentage of participants |
| Placebo - 1 | Percentage of Participants With Improvement (Reduction) in Pruritus Numerical Rating Scale (NRS) Score of ≥ 4 From Baseline at Week 16 | 10.0 percentage of participants |
| ISB 830 600 mg q2w | Percentage of Participants With Improvement (Reduction) in Pruritus Numerical Rating Scale (NRS) Score of ≥ 4 From Baseline at Week 16 | 13.3 percentage of participants |
| Placebo - 2 | Percentage of Participants With Improvement (Reduction) in Pruritus Numerical Rating Scale (NRS) Score of ≥ 4 From Baseline at Week 16 | 9.5 percentage of participants |
Secondary
Percent Change From Baseline in SCORAD Score at Week 16
SCORAD (Severity scoring of Atopic Dermatitis) is composite severity index comprising a) the amount/extent of BSA affected; b) subjective symptom visual analog assessments for pruritis ( 0 \[no itching\] to 3 \[severe itching\]) and sleep disturbance (0 \[no sleep disturbance\] to 3 \[severe sleep disturbance\]); and c) 6 disease intensity assessments \[dryness/scaling, erythema, induration/papulation, excoriation, lichenification and oozing/weeping/crusting, each graded from 0 to (none) to 3 (severe). A SCORAD score ranges from 0 (no AD present) to 103 (severe).
Time frame: Baseline, Week 16
Population: Full Analysis Set (FAS) included all participants who were randomized and received at least 1 dose of study medication. Participants were analyzed according to the treatment group assigned. Here, 'Overall Number of Participants Analyzed' signifies the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| ISB 830 300 mg q2w | Percent Change From Baseline in SCORAD Score at Week 16 | -26.519 percentage change | Standard Deviation 18.1662 |
| ISB 830 300 mg q4w | Percent Change From Baseline in SCORAD Score at Week 16 | -26.108 percentage change | Standard Deviation 21.4476 |
| ISB 830 75 mg q4w | Percent Change From Baseline in SCORAD Score at Week 16 | -18.405 percentage change | Standard Deviation 15.8756 |
| Placebo - 1 | Percent Change From Baseline in SCORAD Score at Week 16 | -19.440 percentage change | Standard Deviation 17.4296 |
| ISB 830 600 mg q2w | Percent Change From Baseline in SCORAD Score at Week 16 | -27.401 percentage change | Standard Deviation 14.4471 |
| Placebo - 2 | Percent Change From Baseline in SCORAD Score at Week 16 | -18.847 percentage change | Standard Deviation 14.4472 |