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

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

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 Overview

• Status: Completed
• Conditions: Moderate to Severe Atopic Dermatitis
• Intervention / Treatment: 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

• Study Type: Interventional
• Enrollment (Actual): 462
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T3A 2N1
      • Ichnos Investigational Site 202
  • British Columbia
    • Surrey, British Columbia, Canada, V3V 0C6
      • Ichnos Investigational Site 203
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3M 3Z4
      • Ichnos Investigational Site 207
  • Ontario
    • Hamilton, Ontario, Canada, L8N 3Z5
      • Ichnos Investigational Site 214
    • Markham, Ontario, Canada, L3P 1X2
      • Ichnos Investigational Site 204
    • Ottawa, Ontario, Canada, K1G 6C6
      • Ichnos Investigational Site 206
    • Ottawa, Ontario, Canada, K2C 3N2
      • Ichnos Investigational Site 208
    • Richmond Hill, Ontario, Canada, L4C 9M7
      • Ichnos Investigational Site 201
  • Quebec
    • Drummondville, Quebec, Canada, QC, J2B 5L
      • Ichnos Investigational Site 211
• Czechia
  • Ostrava, Czechia, 702 00
    • Ichnos Investigational Site 401
  • Pardubice, Czechia, 530 02
    • Ichnos Investigational Site 405
  • Praha 1, Czechia, 110 00
    • Ichnos Investigational Site 407
  • Svitavy, Czechia, 568 02
    • Ichnos Investigational Site 406
  • Brno-město
    • Brno, Brno-město, Czechia, 602 00
      • Ichnos Investigational Site 404
  • Královéhradecký Kraj
    • Náchod, Královéhradecký Kraj, Czechia, 547 01
      • Ichnos Investigational Site 402
  • Praha 3
    • Praha, Praha 3, Czechia, 130 00
      • Ichnos Investigational Site 403
• Germany
  • Berlin, Germany, 10117
    • Ichnos Investigational Site 319
  • Berlin, Germany, 10789
    • Ichnos Investigational Site 304
  • Berlin, Germany, 14050
    • Ichnos Investigational Site 326
  • Hamburg, Germany, 22143
    • Ichnos Investigational Site 310
  • Hamburg, Germany, 22391
    • Ichnos Investigational Site 308
  • Baden-Württemberg
    • Friedrichshafen, Baden-Württemberg, Germany, 88045
      • Ichnos Investigational Site 313
    • Langenau, Baden-Württemberg, Germany, 89129
      • Ichnos Investigational Site 305
  • Bayern
    • Erlangen, Bayern, Germany, 91054
      • Ichnos Investigational Site 311
  • Niedersachsen
    • Osnabrück, Niedersachsen, Germany, 49074
      • Ichnos Investigational Site 314
  • Nordrhein-Westfalen
    • Bielefeld, Nordrhein-Westfalen, Germany, 33647
      • Ichnos Investigational Site 322
    • Bochum, Nordrhein-Westfalen, Germany, 44793
      • Ichnos Investigational Site 318
  • Sachsen
    • Dresden, Sachsen, Germany, 01097
      • Ichnos Investigational Site 302
    • Dresden, Sachsen, Germany, 1069
      • Ichnos Investigational Site 309
  • Schleswig-Holstein
    • Lübeck, Schleswig-Holstein, Germany, 23538
      • Ichnos Investigational Site 315
• Poland
  • Katowice, Poland, 40-851
    • Ichnos Investigational Site 503
  • Kraków, Poland, 31-513
    • Ichnos Investigational Site 505
  • Skarzysko-Kamienna, Poland, 26-110
    • Ichnos Investigational Site 508
  • Warszawa, Poland, 02-777
    • Ichnos Investigational Site 507
  • Dolnoslaskie
    • Wroclaw, Dolnoslaskie, Poland, 51-124
      • Ichnos Investigational Site 504
  • Malopolskie
    • Krakow, Malopolskie, Poland, 31-002
      • Ichnos Investigational Site 511
    • Krakow, Malopolskie, Poland, 31-011
      • Ichnos Investigational Site 510
    • Kraków, Malopolskie, Poland, 30-033
      • Ichnos Investigational Site 502
    • Kraków, Malopolskie, Poland, 31-209
      • Ichnos Investigational Site 501
  • Mazowieckie
    • Warszawa, Mazowieckie, Poland, 01-817
      • Ichnos Investigational Site 509
    • Warszawa, Mazowieckie, Poland, 02-625
      • Ichnos Investigational Site 521
    • Warszawa, Mazowieckie, Poland, 02-758
      • Ichnos Investigational Site 512
    • Warszawa, Mazowieckie, Poland, 04-141
      • Ichnos Investigational Site 506
  • Podkarpackie
    • Iwonicz-Zdrój, Podkarpackie, Poland, 38-440
      • Ichnos Investigational Site 517
  • Pomorskie
    • Gdynia, Pomorskie, Poland, 81-338
      • Ichnos Investigational Site 519
    • Gdynia, Pomorskie, Poland, 81-384
      • Ichnos Investigational Site 520
  • Wielkopolskie
    • Poznań, Wielkopolskie, Poland, 60-702
      • Ichnos Investigational Site 518
    • Poznań, Wielkopolskie, Poland, 60-848
      • Ichnos Investigational Site 514
  • Zachodniopomorskie
    • Szczecin, Zachodniopomorskie, Poland, 71-270
      • Ichnos Investigational Site 513
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
      • Ichnos Investigational Site 129
  • California
    • Clovis, California, United States, 93711
      • Ichnos Investigational Site 120
    • Rolling Hills Estates, California, United States, 90274
      • Ichnos Investigational Site 105
  • Connecticut
    • Bridgeport, Connecticut, United States, 06606
      • Ichnos Investigational Site 106
    • Danbury, Connecticut, United States, 06810
      • Ichnos Investigational Site 146
  • Florida
    • Brandon, Florida, United States, 33511
      • Ichnos Investigational Site 142
    • Fort Myers, Florida, United States, 33912
      • Ichnos Investigational Site 143
    • Lake City, Florida, United States, 32055
      • Ichnos Investigational Site 148
    • Lake Worth, Florida, United States, 33461
      • Ichnos Investigational Site 141
    • Miami, Florida, United States, 33156
      • Ichnos Investigational Site 140
    • Miami, Florida, United States, 33175
      • Ichnos Investigational Site 123
    • Ormond Beach, Florida, United States, 32174
      • Ichnos Investigational Site 147
    • Tampa, Florida, United States, 33607
      • Ichnos Investigational site 101
    • Tampa, Florida, United States, 33612
      • Ichnos Investigational Site 135
  • Georgia
    • Newnan, Georgia, United States, 30263
      • Ichnos Investigational Site 115
    • Savannah, Georgia, United States, 31406
      • Ichnos Investigational Site 139
  • Indiana
    • Plainfield, Indiana, United States, 46168
      • Ichnos Investigational Site 112
  • Iowa
    • West Des Moines, Iowa, United States, 50265
      • Ichnos Investigational Site 125
  • Louisiana
    • New Orleans, Louisiana, United States, 70115
      • Ichnos Investigational Site109
  • Missouri
    • Saint Louis, Missouri, United States, 63141
      • Ichnos Investigational Site 126
  • Nevada
    • Las Vegas, Nevada, United States, 89120
      • Ichnos Investigational Site 144
  • New Jersey
    • Verona, New Jersey, United States, 07044-2946
      • Ichnos Investigational Site 117
  • New York
    • Forest Hills, New York, United States, 11375
      • Glenmark Investigational Site 102
  • Oregon
    • Medford, Oregon, United States, 97504-9741
      • Ichnos Investigational Site 114
  • Pennsylvania
    • Hazleton, Pennsylvania, United States, 18201
      • Ichnos Investigational Site 133
    • Philadelphia, Pennsylvania, United States, 19103
      • Ichnos Investigational Site 122
  • Tennessee
    • Chattanooga, Tennessee, United States, 37421
      • Ichnos Investigational Site 132
  • Texas
    • Houston, Texas, United States, 77004
      • Ichnos Investigational Site 119
    • Pflugerville, Texas, United States, 78660
      • Ichnos Investigational Site 138
    • San Antonio, Texas, United States, 78258
      • Ichnos Investigational Site 116
    • Waco, Texas, United States, 76710
      • Ichnos Investigational Site 110
  • Virginia
    • Newport News, Virginia, United States, 23606-4537
      • Ichnos Investigational Site 103
    • Richmond, Virginia, United States, 23220
      • Ichnos Investigational Site 131
  • Washington
    • Spokane, Washington, United States, 99224
      • Ichnos Investigational Site 136

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ISB 830 - Part 1 Group 1; 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; Subcutaneous injection (SC) every 2 weeks
Experimental: 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.	Drug: ISB 830 - Part 1 Group 2; Subcutaneous injection (SC) every 2 weeks
Experimental: 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.	Drug: ISB 830 - Part 1 Group 3; Subcutaneous injection (SC) every 2 weeks
Placebo Comparator: Placebo - Part 1 Group 4; Subcutaneous (SC) administration of placebo, followed by SC maintenance dose of placebo.	Drug: Placebo - Part 1 Group 4; Subcutaneous injection (SC) every 2 weeks
Experimental: ISB 830 - Part 2 Group 5; 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; Subcutaneous injection (SC) every 2 weeks
Placebo Comparator: Placebo - Part 2 Group 6; Subcutaneous (SC) administration of placebo, followed by SC maintenance dose of placebo.	Drug: Placebo - Part 2 Group 6; Subcutaneous injection (SC) every 2 weeks

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Ichnos Sciences SA
• Collaborators: Glenmark Pharmaceuticals S.A.
• Investigators: Study Director: Andrea Acocella, MD, MBA, Ichnos Sciences

Study record dates

Study Major Dates

• Study Start (Actual): May 31, 2018
• Primary Completion (Actual): August 11, 2020
• Study Completion (Actual): August 3, 2021

Study Registration Dates

• First Submitted: May 31, 2018
• First Submitted That Met QC Criteria: June 22, 2018
• First Posted (Actual): June 26, 2018

Study Record Updates

• Last Update Posted (Actual): August 23, 2022
• Last Update Submitted That Met QC Criteria: July 26, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: ISB 830, OX40, atopic dermatitis
• Additional Relevant MeSH Terms: Skin Diseases; Immune System Diseases; Hypersensitivity, Immediate; Genetic Diseases, Inborn; Skin Diseases, Genetic; Hypersensitivity; Skin Diseases, Eczematous; Dermatitis; Eczema; Dermatitis, Atopic
• Other Study ID Numbers: GBR 830-204; 2018-000783-29 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No