Atopic Dermatitis
Conditions
Keywords
Atopic Dermatitis, AMG 451, KHK 4083, Eczema, Rocatinlimab
Brief summary
The co-primary objectives of the study are to: * Evaluate the efficacy of rocatinlimab compared with placebo at Week 24, assessed using Validated Investigator's Global Assessment for Atopic Dermatitis (vIGA-AD). * Evaluate the efficacy of rocatinlimab compared with placebo at Week 24, assessed using Eczema Area and Severity Index (EASI).
Interventions
DRUGRocatinlimab
Rocatinlimab will be administered through a subcutaneous (SC) injection.
OTHERPlacebo
The matching placebo will be administered through a SC injection.
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years (or ≥ legal adult age within the country if it is older than 18 years at signing of informed consent) with a diagnosis of AD according to the AAD Consensus Criteria (2014) present for at least 12 months * History of inadequate response to TCS (Topical Corticosteroid) of medium or higher potency (with or without topical calcineurin inhibitors \[TCI\]) as appropriate or for whom topical treatments are otherwise medically inadvisable (eg, because of important side effects or safety risks). * EASI score ≥16 * vIGA-AD score ≥3 * ≥10% body surface area (BSA) of AD involvement * Worst pruritus numerical rating scale ≥ 4
Exclusion criteria
* Treatment with a biological product within 12 weeks or 5 half-lives, whichever is longer, prior to Day 1 * Treatment with any of the following medications or therapies within 4 weeks or 5 half-lives, whichever is longer, prior to Day 1: * Systemic corticosteroids * Systemic immunosuppressants * Phototherapy * Oral or topical Janus kinase inhibitors * Treatment with any of the following medications or therapies within 1 week, prior to Day 1: * TCS of any potency * TCI * Topical phosphodiesterase type 4 (PDE4) inhibitors * Other topical immunosuppressive agents * Combination agents including TCS of any potency or TCI, PDE4 inhibitors, or other immunosuppressive agents
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Achieved Validated Investigator's Global Assessment for AD (vIGA-AD) 1 Response With Presence of Only Barely Perceptible Erythema or vIGA-AD 0 Response (Revised Investigator's Global Assessment [rIGA] 0/1) at Week 24 | Baseline and Week 24 | vIGA-AD was a validated instrument rating AD severity on a 5-point scale (0 = Clear; 1 = Almost clear; 2 = Mild; 3 = Moderate; 4 = Severe), with higher scores indicating greater severity. Participants achieving a score of 0 or 1 with ≥2-point reduction from baseline were considered 'Clear' or 'Almost clear'. For rIGA 0/1, when vIGA-AD = 1, investigators answered: "Did participant have barely perceptible erythema, no induration/papulation, no lichenification, and no oozing/crusting?" If "Yes," the participant met rIGA 0/1; if "No," they did not. If vIGA-AD = 0, the participant met rIGA 0/1. Participants initiating rescue therapy for AD were classified as nonresponders at all subsequent time points. |
| Number of Participants Who Achieved ≥ 75% Reduction From Baseline in Eczema Area and Severity Index Score (EASI 75) at Week 24 | Baseline and Week 24 | EASI was designed and widely used to assess the severity and extent of AD across four anatomical regions. It evaluated key signs of inflammation, including erythema, induration/papulation, excoriation, and lichenification. The total EASI score ranged from 0 to 72, with higher scores indicating more severe disease. EASI 75 was defined as a ≥ 75% reduction from baseline in the total EASI score. Participants initiating rescue therapy for AD were classified as nonresponders at all subsequent time points. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Achieved EASI 75 at Week 16 | Baseline and Week 16 | EASI was designed and widely used to assess the severity and extent of AD across four anatomical regions. It evaluated key signs of inflammation, including erythema, induration/papulation, excoriation, and lichenification. The total EASI score ranged from 0 to 72, with higher scores indicating more severe disease. EASI 75 was defined as a ≥ 75% reduction from baseline in the total EASI score. Participants initiating rescue therapy for AD were classified as nonresponders at all subsequent time points. |
| Number of Participants Who Achieved a vIGA-AD Score of 0 (Clear) or 1 (Almost Clear) (vIGA-AD 0/1) at Week 16 | Baseline and Week 16 | The vIGA-AD was a validated assessment instrument used in clinical studies to globally rate the severity of AD on a 5-point scale ranging from 0 to 4, where 0 = Clear, 1 = Almost clear, 2 = Mild, 3 = Moderate, and 4 = Severe. Higher scores indicated greater disease severity. Participants who achieved a score of 0 or 1 with a ≥ 2-point reduction from baseline were considered to have achieved 'Clear' or 'Almost clear' status. Participants initiating rescue therapy for AD were classified as nonresponders at all subsequent time points. |
| Number of Participants Who Achieved a ≥ 4-point Reduction From Baseline in Weekly Average of Daily Worst Pruritus Numeric Rating Scale (NRS) Score at Week 16 in Participants With Baseline Weekly Average of Daily Worst Pruritus NRS Score ≥ 4 | Baseline and Week 16 | The Worst Pruritus was assessed daily using an NRS consisting of a single item ranging from 0 to 10, where 10 represented the highest intensity of itch. Participants were asked to rate the intensity of their worst itch using this scale. Participants initiating rescue therapy for AD were classified as nonresponders at all subsequent time points. |
| Number of Participants Who Achieved a ≥ 4-point Reduction From Baseline in Weekly Average of Daily Worst Pruritus NRS Score at Week 24 in Participants With Baseline Weekly Average of Daily Worst Pruritus NRS Score ≥ 4 | Baseline and Week 24 | The Worst Pruritus was assessed daily using an NRS consisting of a single item ranging from 0 to 10, where 10 represented the highest intensity of itch. Participants were asked to rate the intensity of their worst itch using this scale. Participants initiating rescue therapy for AD were classified as nonresponders at all subsequent time points. |
| Number of Participants Who Achieved ≥ 90% Reduction From Baseline in EASI Score (EASI 90) at Week 24 | Baseline and Week 24 | The EASI was designed and widely used to assess the severity and extent of AD across four anatomical regions. It evaluated key signs of inflammation, including erythema, induration/papulation, excoriation, and lichenification. The total EASI score ranged from 0 to 72, with higher scores indicating more severe disease. EASI 90 was defined as a ≥ 90% improvement from baseline in the total EASI score. Participants initiating rescue therapy for AD were classified as nonresponders at all subsequent time points. |
| Number of Participants Who Achieved ≥ 4-point Reduction From Baseline in Weekly Average of AD Skin Pain NRS Score at Week 24 in Participants With Baseline Weekly Average of AD Skin Pain NRS Score ≥ 4 | Baseline and Week 24 | AD skin pain was assessed using an NRS consisting of a single item ranging from 0 to 10, where 10 represented the highest intensity of AD skin pain. Participants initiating rescue therapy for AD were classified as nonresponders at all subsequent time points. |
| Number of Participants Who Achieved a vIGA-AD Score of 0 (Clear) or 1 (Almost Clear) With a ≥ 2-Point Reduction From Baseline (vIGA-AD 0/1) at Week 24 | Baseline and Week 24 | The vIGA-AD was a validated assessment instrument used in clinical studies to globally rate the severity of AD on a 5-point scale ranging from 0 to 4, where 0 = Clear, 1 = Almost clear, 2 = Mild, 3 = Moderate, and 4 = Severe. Higher scores indicated greater disease severity. Participants who achieved a score of 0 or 1 with a ≥ 2-point reduction from baseline were considered to have achieved 'Clear' or 'Almost clear' status. Participants initiating rescue therapy for AD were classified as nonresponders at all subsequent time points. |
| Number of Participants Who Achieved Facial AD Severity Score of Clear at Week 24 for Participants With Facial AD at Baseline | Baseline and Week 24 | The severity of facial AD was assessed using the Facial AD Severity Scale (FASS). The FASS was an instrument used to rate the overall severity of facial AD based on a 5-category scale: clear (0), almost clear (1), mild (2), moderate (3), and severe (4), with higher scores indicating more severe disease. Participants initiating rescue therapy for AD were classified as nonresponders at all subsequent time points. |
| Number of Participants Who Achieved Hand AD Severity Score of Clear at Week 24 for Participants With Hand AD at Baseline | Baseline and Week 24 | The severity of hand AD was assessed using the Hand Atopic Dermatitis Severity Scale (HASS). The HASS was an instrument used to rate the overall severity of hand AD based on a 5-category scale: clear (0), almost clear (1), mild (2), moderate (3), and severe (4), with higher scores indicating more severe disease. Participants initiating rescue therapy for AD were classified as nonresponders at all subsequent time points. |
| Change From Baseline in Weekly Average of Daily Worst Pruritus NRS Score at Week 16 | Baseline and Week 16 | The Worst Pruritus was assessed daily using an NRS consisting of a single item ranging from 0 to 10, where 10 represented the highest intensity of itch. Participants were asked to rate the intensity of their worst itch using this scale. Participants initiating rescue therapy for AD were included in the analysis, and each participant's worst observation, including baseline value, before initiation of rescue therapy for AD was carried forward (worst observation carried forward \[WOCF\]) to all subsequent time points. A negative change from baseline indicated a reduction in itch intensity. |
| Change From Baseline in Weekly Average of Daily Worst Pruritus NRS Score at Week 24 | Baseline and Week 24 | The Worst Pruritus was assessed daily using an NRS consisting of a single item ranging from 0 to 10, where 10 represented the highest intensity of itch. Participants were asked to rate the intensity of their worst itch using this scale. Participants initiating rescue therapy for AD were included in the analysis, and each participant's worst observation, including baseline value, before initiation of rescue therapy for AD was carried forward (WOCF) to all subsequent time points. A negative change from baseline indicated a reduction in itch intensity. |
| Change From Baseline in Severity Scoring (SCORing) of AD (SCORAD) Itch Visual Analogue Scale (VAS) Score at Week 16 | Baseline and Week 16 | The SCORAD Itch VAS was a component of the SCORAD tool used to assess the severity of AD using both physician and patient-reported data. Itch VAS scale ranged from 0 to 10, with a higher score indicating more severe AD. Participants initiating rescue therapy for AD were included in the analysis, and each participant's worst observation, including baseline value, before initiation of rescue therapy for AD was carried forward (WOCF) to all subsequent time points. A negative change from baseline indicated a reduction in AD severity. |
| Change From Baseline in SCORAD Itch VAS Score at Week 24 | Baseline and Week 24 | The SCORAD Itch VAS was a component of the SCORAD tool used to assess the severity of AD using both physician and patient-reported data. Itch VAS scale ranged from 0 to 10, with a higher score indicating more severe AD. Participants initiating rescue therapy for AD were included in the analysis, and each participant's worst observation, including baseline value, before initiation of rescue therapy for AD was carried forward (WOCF) to all subsequent time points. A negative change from baseline indicated a reduction in AD severity. |
| Number of Participants Who Achieved ≥ 4-point Reduction From Baseline in Dermatology Life Quality Index (DLQI) Score at Week 24 in Participants With Baseline DLQI ≥ 4 | Baseline and Week 24 | The DLQI was a 10-item, self-administered questionnaire, where the total score ranged from 0 to 30; higher scores represented a greater impact of AD. It was designed to measure the health-related quality of life of adult patients suffering from skin disease. The DLQI measured participants' perception of the impact of skin diseases on different aspects of their health-related quality of life over the previous week. Participants initiating rescue therapy for AD were classified as nonresponders at all subsequent time points. |
| Change From Baseline in DLQI Score at Week 24 | Baseline and Week 24 | The DLQI was a 10-item, self-administered questionnaire, where the total score ranged from 0 to 30; higher scores represented a greater impact of AD. It was designed to measure the health-related quality of life of adult patients suffering from skin disease. The DLQI measured patients' perception of the impact of skin diseases on different aspects of their health-related quality of life over the previous week. Participants initiating rescue therapy for AD were included in the analysis, and each participant's worst observation, including baseline value, before initiation of rescue therapy for AD was carried forward (WOCF) to all subsequent time points. A negative change from baseline indicated a reduction in the impact of AD on health-related quality of life. |
| Number of Participants Who Achieved ≥ 4-point Reduction From Baseline in Patient Oriented Eczema Measure (POEM) Score at Week 24 in Participants With Baseline POEM Score ≥ 4 | Baseline and Week 24 | The POEM was a 7-item validated questionnaire used to assess disease symptoms in children and adults, where the POEM total score ranged from 0 to 28; higher scores represented a greater impact of AD. It evaluated the time spent in the past week with AD signs and symptoms: individual items of bleeding, oozing, cracked, flaking, and dry/rough skin, and their impact on sleep. Participants initiating rescue therapy for AD were classified as nonresponders at all subsequent time points. |
| Change From Baseline in POEM Score at Week 24 | Baseline and Week 24 | The POEM was a 7-item validated questionnaire used to assess disease symptoms in children and adults, where the POEM total score ranged from 0 to 28; higher scores represented a greater impact of AD. It evaluated the time spent in the past week with AD signs and symptoms: individual items of bleeding, oozing, cracked, flaking, and dry/rough skin, and their impact on sleep. Participants initiating rescue therapy for AD were included in the analysis, and each participant's worst observation, including baseline value, before initiation of rescue therapy for AD was carried forward (WOCF) to all subsequent time points. A negative change from baseline indicated a reduction in the impact of AD. |
| Number of Participants Who Achieved ≥ 4-point Reduction From Baseline in Weekly Average of AD Skin Pain NRS Score at Week 16 in Participants With Baseline Weekly Average of AD Skin Pain NRS Score ≥ 4 | Baseline and Week 16 | AD skin pain was assessed using an NRS consisting of a single item ranging from 0 to 10, where 10 represented the highest intensity of AD skin pain. Participants initiating rescue therapy for AD were classified as nonresponders at all subsequent time points. |
| Change From Baseline in Weekly Average of Daily AD Skin Pain NRS Score at Week 24 | Baseline and Week 24 | AD skin pain was assessed daily using an NRS consisting of a single item ranging from 0 to 10, where 10 represented the highest intensity of AD skin pain. Participants initiating rescue therapy for AD were included in the analysis, and each participant's worst observation, including baseline value, before initiation of rescue therapy for AD was carried forward (WOCF) to all subsequent time points. A negative change from baseline indicated a reduction in AD skin pain intensity. |
| Change From Baseline in Weekly Average of Daily AD Skin Pain NRS Score at Week 16 | Baseline and Week 16 | AD skin pain was assessed daily using an NRS consisting of a single item ranging from 0 to 10, where 10 represented the highest intensity of AD skin pain. Participants initiating rescue therapy for AD were included in the analysis, and each participant's worst observation, including baseline value, before initiation of rescue therapy for AD was carried forward (WOCF) to all subsequent time points. A negative change from baseline indicated a reduction in AD skin pain intensity. |
| Number of Participants Who Achieved ≥ 3-point Reduction From Baseline in Weekly Average of Daily AD Skin Pain NRS Score at Week 24 in Participants With Baseline Weekly Average of Daily AD Skin Pain NRS Score ≥ 3 | Baseline and Week 24 | AD skin pain was assessed daily using an NRS consisting of a single item ranging from 0 to 10, where 10 represented the highest intensity of AD skin pain. Participants initiating rescue therapy for AD were classified as nonresponders at all subsequent time points. |
| Number of Participants Who Achieved ≥ 3-point Reduction From Baseline in Weekly Average of Daily AD Skin Pain NRS Score at Week 16 in Participants With Baseline Weekly Average of Daily AD Skin Pain NRS Score ≥ 3 | Baseline and Week 16 | AD skin pain was assessed daily using an NRS consisting of a single item ranging from 0 to 10, where 10 represented the highest intensity of AD skin pain. Participants initiating rescue therapy for AD were classified as nonresponders at all subsequent time points. |
| Change From Baseline in Weekly Average of Daily Sleep Disturbance NRS Score at Week 24 | Baseline and Week 24 | Weekly average of Daily Sleep Disturbance NRS Score was defined as the mean of daily scores reported by participants in an electronic diary assessing the quality of their sleep over the past 24 hours. Sleep disturbance was measured using an NRS consisting of a single item ranging from 0 to 10, where 10 indicated the highest level of sleep disturbance. Participants were asked to rate the intensity of their sleep disturbance using this scale each day. Participants initiating rescue therapy for AD were included in the analysis, and each participant's worst observation, including baseline value, before initiation of rescue therapy for AD was carried forward (WOCF) to all subsequent time points. A negative change from baseline indicated a reduction in level of sleep disturbance. |
| Number of Participants Who Achieved Hospital Anxiety and Depression Scale (HADS)-Anxiety Subscale Score < 8 at Week 24 in Participants With Baseline HADS-anxiety Subscale Score ≥ 8 | Baseline and Week 24 | HADS was defined as a self-assessment questionnaire used to detect states of anxiety and depression in hospital outpatient settings. The HADS-Anxiety subscale score ranged from 0 to 21, with higher scores representing a greater impact of AD. Anxiety severity was categorized as follows: 0 to 7 (Normal), 8 to 10 (Mild), 11 to 14 (Moderate), and 15 to 21 (Severe). Participants initiating rescue therapy for AD were classified as nonresponders at all subsequent time points. |
| Number of Participants Who Achieved HADS-depression Subscale Score < 8 at Week 24 in Participants With Baseline HADS-depression Subscale Score ≥ 8 | Baseline and Week 24 | HADS was defined as a self-assessment questionnaire used to detect states of anxiety and depression in hospital outpatient settings. The HADS-depression subscale score ranged from 0 to 21, with higher scores representing a greater impact of AD. Depression severity was categorized as follows: 0 to 7 (Normal), 8 to 10 (Mild), 11 to 14 (Moderate), and 15 to 21 (Severe). Participants initiating rescue therapy for AD were classified as nonresponders at all subsequent time points. |
| Change From Baseline in HADS-anxiety Subscale Score at Week 24 | Baseline and Week 24 | HADS was defined as a self-assessment questionnaire used to detect states of anxiety and depression in hospital outpatient settings. The HADS-Anxiety subscale score ranged from 0 to 21, with higher scores representing a greater impact of AD. Anxiety severity was categorized as follows: 0 to 7 (Normal), 8 to 10 (Mild), 11 to 14 (Moderate), and 15 to 21 (Severe). Participants initiating rescue therapy for AD were included in the analysis, and each participant's worst observation, including baseline value, before initiation of rescue therapy for AD was carried forward (WOCF) to all subsequent time points. A negative change from baseline indicated a reduction in the impact of AD. |
| Change From Baseline in HADS-depression Subscale Score at Week 24 | Baseline and Week 24 | HADS was defined as a self-assessment questionnaire used to detect states of anxiety and depression in hospital outpatient settings. The HADS-depression subscale score ranged from 0 to 21, with higher scores representing a greater impact of AD. Depression severity was categorized as follows: 0 to 7 (Normal), 8 to 10 (Mild), 11 to 14 (Moderate), and 15 to 21 (Severe). Participants initiating rescue therapy for AD were included in the analysis, and each participant's worst observation, including baseline value, before initiation of rescue therapy for AD was carried forward (WOCF) to all subsequent time points. A negative change from baseline indicated a reduction in the impact of AD. |
| Number of Participants Who Achieved a ≥ 8.7-point Reduction From Baseline in SCORAD Total Score at Week 24 in Participants With Baseline SCORAD Total Score ≥ 8.7 | Baseline and Week 24 | The SCORAD total score used to assess the severity of AD using both physician and patient-reported data. SCORAD total score ranged from 0 to 103 with a higher score indicating more severe AD. Participants initiating rescue therapy for AD were classified as nonresponders at all subsequent time points. |
Countries
Australia, Belgium, Brazil, Canada, Czechia, Denmark, Estonia, Finland, Germany, Japan, Mexico, Poland, Portugal, Romania, South Africa, South Korea, Spain, Sweden, Turkey (Türkiye), United Kingdom, United States
Contacts
STUDY_DIRECTORMD
Amgen
Participant flow
Recruitment details
This trial was conducted at 151 centers in North America, Europe, Asia, Oceania, Latin America, and Africa between 14 December 2022 to 27 August 2024.
Pre-assignment details
Participants with moderate-to-severe atopic dermatitis (AD) were randomized in a 3:1 ratio into two treatment groups for a duration of 24 weeks to receive either rocatinlimab or matching placebo.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 40.4 years STANDARD_DEVIATION 15.6 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 15 Participants |
| Race/Ethnicity, Customized Asian | 222 Participants |
| Race/Ethnicity, Customized Black or African American | 10 Participants |
| Race/Ethnicity, Customized Hispanic/Latino | 85 Participants |
| Race/Ethnicity, Customized Multiple | 3 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 2 Participants |
| Race/Ethnicity, Customized Not Hispanic/Latino | 161 Participants |
| Race/Ethnicity, Customized Other | 20 Participants |
| Race/Ethnicity, Customized White | 432 Participants |
| Sex: Female, Male Female | 329 Participants |
| Sex: Female, Male Male | 102 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 182 | 0 / 544 |
| other Total, other adverse events | 71 / 180 | 228 / 544 |
| serious Total, serious adverse events | 8 / 180 | 10 / 544 |
Outcome results
None listed