Phase 2b Study to Evaluate the Efficacy and Safety of ISB 830 in Adults With Moderate to Severe Atopic Dermatitis
- Conditions
- Moderate to Severe Atopic Dermatitis
- Interventions
- Drug: ISB 830 - Part 2 Group 5Drug: ISB 830 - Part 1 Group 2Drug: ISB 830 - Part 1 Group 3Drug: Placebo - Part 1 Group 4Drug: ISB 830 - Part 1 Group 1Drug: Placebo - Part 2 Group 6
- Registration Number
- NCT03568162
- Lead Sponsor
- Ichnos Sciences SA
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 462
- 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.
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description ISB 830 - Part 2 Group 5 ISB 830 - Part 2 Group 5 Subcutaneous (SC) administration of ISB 830 as a loading dose, followed by SC maintenance dose of ISB 830. ISB 830 - Part 1 Group 2 ISB 830 - Part 1 Group 2 Subcutaneous (SC) administration of ISB 830 as a loading dose, followed by SC maintenance dose of ISB 830 or placebo. ISB 830 - Part 1 Group 3 ISB 830 - Part 1 Group 3 Subcutaneous (SC) administration of ISB 830 as a loading dose, followed by SC maintenance dose of ISB 830 or placebo. Placebo - Part 1 Group 4 Placebo - Part 1 Group 4 Subcutaneous (SC) administration of placebo, followed by SC maintenance dose of placebo. ISB 830 - Part 1 Group 1 ISB 830 - Part 1 Group 1 Subcutaneous (SC) administration of ISB 830 as a loading dose, followed by SC maintenance dose of ISB 830. Placebo - Part 2 Group 6 Placebo - Part 2 Group 6 Subcutaneous (SC) administration of placebo, followed by SC maintenance dose of placebo.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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).
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".
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 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.
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).
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 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.
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).
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.
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.
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 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.
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.
Trial Locations
- Locations (83)
Ichnos Investigational Site 144
🇺🇸Las Vegas, Nevada, United States
Ichnos Investigational Site 148
🇺🇸Lake City, Florida, United States
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 146
🇺🇸Danbury, Connecticut, United States
Ichnos Investigational Site 106
🇺🇸Bridgeport, Connecticut, United States
Ichnos Investigational Site 143
🇺🇸Fort Myers, Florida, United States
Ichnos Investigational Site 142
🇺🇸Brandon, Florida, United States
Ichnos Investigational Site 140
🇺🇸Miami, Florida, United States
Ichnos Investigational Site 141
🇺🇸Lake Worth, Florida, United States
Ichnos Investigational Site 147
🇺🇸Ormond Beach, Florida, United States
Ichnos Investigational Site 139
🇺🇸Savannah, Georgia, United States
Ichnos Investigational site 101
🇺🇸Tampa, Florida, United States
Ichnos Investigational Site 135
🇺🇸Tampa, Florida, United States
Ichnos Investigational Site 115
🇺🇸Newnan, Georgia, United States
Ichnos Investigational Site 112
🇺🇸Plainfield, Indiana, United States
Ichnos Investigational Site109
🇺🇸New Orleans, Louisiana, United States
Ichnos Investigational Site 126
🇺🇸Saint Louis, Missouri, United States
Ichnos Investigational Site 125
🇺🇸West Des Moines, Iowa, United States
Glenmark Investigational Site 102
🇺🇸Forest Hills, New York, United States
Ichnos Investigational Site 117
🇺🇸Verona, New Jersey, United States
Ichnos Investigational Site 114
🇺🇸Medford, Oregon, United States
Ichnos Investigational Site 133
🇺🇸Hazleton, Pennsylvania, United States
Ichnos Investigational Site 122
🇺🇸Philadelphia, Pennsylvania, United States
Ichnos Investigational Site 119
🇺🇸Houston, Texas, United States
Ichnos Investigational Site 138
🇺🇸Pflugerville, Texas, United States
Ichnos Investigational Site 136
🇺🇸Spokane, Washington, United States
Ichnos Investigational Site 110
🇺🇸Waco, Texas, United States
Ichnos Investigational Site 131
🇺🇸Richmond, Virginia, United States
Ichnos Investigational Site 103
🇺🇸Newport News, Virginia, United States
Ichnos Investigational Site 202
🇨🇦Calgary, Alberta, Canada
Ichnos Investigational Site 207
🇨🇦Winnipeg, Manitoba, Canada
Ichnos Investigational Site 208
🇨🇦Ottawa, Ontario, Canada
Ichnos Investigational Site 204
🇨🇦Markham, Ontario, Canada
Ichnos Investigational Site 214
🇨🇦Hamilton, Ontario, Canada
Ichnos Investigational Site 206
🇨🇦Ottawa, Ontario, Canada
Ichnos Investigational Site 402
🇨🇿Náchod, Královéhradecký Kraj, Czechia
Ichnos Investigational Site 201
🇨🇦Richmond Hill, Ontario, Canada
Ichnos Investigational Site 404
🇨🇿Brno, Brno-město, Czechia
Ichnos Investigational Site 403
🇨🇿Praha, Praha 3, Czechia
Ichnos Investigational Site 401
🇨🇿Ostrava, Czechia
Ichnos Investigational Site 405
🇨🇿Pardubice, Czechia
Ichnos Investigational Site 313
🇩🇪Friedrichshafen, Baden-Württemberg, Germany
Ichnos Investigational Site 407
🇨🇿Praha 1, Czechia
Ichnos Investigational Site 406
🇨🇿Svitavy, Czechia
Ichnos Investigational Site 311
🇩🇪Erlangen, Bayern, Germany
Ichnos Investigational Site 314
🇩🇪Osnabrück, Niedersachsen, Germany
Ichnos Investigational Site 322
🇩🇪Bielefeld, Nordrhein-Westfalen, Germany
Ichnos Investigational Site 302
🇩🇪Dresden, Sachsen, Germany
Ichnos Investigational Site 318
🇩🇪Bochum, Nordrhein-Westfalen, Germany
Ichnos Investigational Site 309
🇩🇪Dresden, Sachsen, Germany
Ichnos Investigational Site 315
🇩🇪Lübeck, Schleswig-Holstein, Germany
Ichnos Investigational Site 319
🇩🇪Berlin, Germany
Ichnos Investigational Site 304
🇩🇪Berlin, Germany
Ichnos Investigational Site 326
🇩🇪Berlin, Germany
Ichnos Investigational Site 310
🇩🇪Hamburg, Germany
Ichnos Investigational Site 308
🇩🇪Hamburg, Germany
Ichnos Investigational Site 521
🇵🇱Warszawa, Mazowieckie, Poland
Ichnos Investigational Site 512
🇵🇱Warszawa, Mazowieckie, Poland
Ichnos Investigational Site 517
🇵🇱Iwonicz-Zdrój, Podkarpackie, Poland
Ichnos Investigational Site 520
🇵🇱Gdynia, Pomorskie, Poland
Ichnos Investigational Site 519
🇵🇱Gdynia, Pomorskie, Poland
Ichnos Investigational Site 514
🇵🇱Poznań, Wielkopolskie, Poland
Ichnos Investigational Site 508
🇵🇱Skarzysko-Kamienna, Poland
Ichnos Investigational Site 505
🇵🇱Kraków, Poland
Ichnos Investigational Site 507
🇵🇱Warszawa, Poland
Ichnos Investigational Site 501
🇵🇱Kraków, Malopolskie, Poland
Ichnos Investigational Site 509
🇵🇱Warszawa, Mazowieckie, Poland
Ichnos Investigational Site 513
🇵🇱Szczecin, Zachodniopomorskie, Poland
Ichnos Investigational Site 504
🇵🇱Wroclaw, Dolnoslaskie, Poland
Ichnos Investigational Site 510
🇵🇱Krakow, Malopolskie, Poland
Ichnos Investigational Site 502
🇵🇱Kraków, Malopolskie, Poland
Ichnos Investigational Site 503
🇵🇱Katowice, Poland
Ichnos Investigational Site 511
🇵🇱Krakow, Malopolskie, Poland
Ichnos Investigational Site 506
🇵🇱Warszawa, Mazowieckie, Poland
Ichnos Investigational Site 305
🇩🇪Langenau, Baden-Württemberg, Germany
Ichnos Investigational Site 518
🇵🇱Poznań, Wielkopolskie, Poland
Ichnos Investigational Site 116
🇺🇸San Antonio, Texas, United States
Ichnos Investigational Site 211
🇨🇦Drummondville, Quebec, Canada
Ichnos Investigational Site 123
🇺🇸Miami, Florida, United States
Ichnos Investigational Site 132
🇺🇸Chattanooga, Tennessee, United States
Ichnos Investigational Site 203
🇨🇦Surrey, British Columbia, Canada