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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
462
Subcutaneous injection (SC) every 2 weeks
Subcutaneous injection (SC) every 2 weeks
Subcutaneous injection (SC) every 2 weeks
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
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
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
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Subcutaneous injection (SC) every 2 weeks
Subcutaneous injection (SC) every 2 weeks
Subcutaneous injection (SC) every 2 weeks
Ichnos Investigational Site 129
Birmingham, Alabama, United States
Ichnos Investigational Site 120
Clovis, California, United States
Ichnos Investigational Site 105
Rolling Hills Estates, California, United States
Ichnos Investigational Site 106
Bridgeport, Connecticut, United States
Ichnos Investigational Site 146
Danbury, Connecticut, United States
Ichnos Investigational Site 142
Brandon, Florida, United States
Ichnos Investigational Site 143
Fort Myers, Florida, United States
Ichnos Investigational Site 148
Lake City, Florida, United States
Ichnos Investigational Site 141
Lake Worth, Florida, United States
Ichnos Investigational Site 140
Miami, Florida, United States
...and 73 more locations
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
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
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
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
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
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
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
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
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
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
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
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
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
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