Phase 2b Study to Evaluate the Efficacy and Safety of ISB 830 in Adults With Moderate to Severe Atopic Dermatitis

Study Overview
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Brief Summary
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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.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study of ISB 830 in Adult Subjects With Moderate to Severe Atopic Dermatitis.

Conditions
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Moderate to Severe Atopic Dermatitis

Intervention / Treatment
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* Drug: ISB 830 - Part 1 Group 1
* Drug: ISB 830 - Part 1 Group 2
* Drug: ISB 830 - Part 1 Group 3
* Drug: Placebo - Part 1 Group 4
* Drug: ISB 830 - Part 2 Group 5
* Drug: Placebo - Part 2 Group 6


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ISB 830 - Part 1 Group 1<br>Subcutaneous (SC) administration of ISB 830 as a loading dose, followed by SC maintenance dose of ISB 830. | Drug: ISB 830 - Part 1 Group 1<br>* Subcutaneous injection (SC) every 2 weeks<br>|
| Experimental: ISB 830 - Part 1 Group 2<br>Subcutaneous (SC) administration of ISB 830 as a loading dose, followed by SC maintenance dose of ISB 830 or placebo. | Drug: ISB 830 - Part 1 Group 2<br>* Subcutaneous injection (SC) every 2 weeks<br>|
| Experimental: ISB 830 - Part 1 Group 3<br>Subcutaneous (SC) administration of ISB 830 as a loading dose, followed by SC maintenance dose of ISB 830 or placebo. | Drug: ISB 830 - Part 1 Group 3<br>* Subcutaneous injection (SC) every 2 weeks<br>|
| Placebo Comparator: Placebo - Part 1 Group 4<br>Subcutaneous (SC) administration of placebo, followed by SC maintenance dose of placebo. | Drug: Placebo - Part 1 Group 4<br>* Subcutaneous injection (SC) every 2 weeks<br>|
| Experimental: ISB 830 - Part 2 Group 5<br>Subcutaneous (SC) administration of ISB 830 as a loading dose, followed by SC maintenance dose of ISB 830. | Drug: ISB 830 - Part 2 Group 5<br>* Subcutaneous injection (SC) every 2 weeks<br>|
| Placebo Comparator: Placebo - Part 2 Group 6<br>Subcutaneous (SC) administration of placebo, followed by SC maintenance dose of placebo. | Drug: Placebo - Part 2 Group 6<br>* Subcutaneous injection (SC) every 2 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline, Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline, Week 16 | 
| 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). | Baseline, Week 16 | 
| 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. | Baseline, Week 16 | 
| 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. | Baseline, Week 16 | 
| 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). | Baseline, Week 16 | 
| 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. | Baseline, Week 16 | 
| 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). | Baseline, Week 16 | 
| 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. | Baseline, Week 16 | 
| 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). | Baseline, Week 16 | 
| 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. | Baseline, Week 16 | 
| 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. | Baseline, Week 16 | 
| 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. | Week 16 | 
| Maximum Observed Serum Concentration (Cmax) of ISB 830 | Cmax is the maximum concentration of ISB 830 observed in serum | 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 | 
| 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. | 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 | 
| 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. | Baseline through Week 16 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ISB 830, OX40, atopic dermatitis