Atopic Dermatitis
Conditions
Keywords
Atopic Dermatitis, AMG 451, KHK4083, Rocatinlimab
Brief summary
The purpose of this study is to evaluate the efficacy and safety of rocatinlimab in monotherapy and combination therapy treatment in adolescent participants.
Interventions
DRUGRocatinlimab
Subcutaneous (SC) injection
DRUGPlacebo
SC injection
Sponsors
Amgen
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
12 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Age ≥ 12 to \< 18 years at Day 1. * Diagnosis of AD (according to American Academy of Dermatology Consensus Criteria \[Eichenfield et al, 2014\]) that has been present for at least 12 months before signing of informed consent. * Body weight ≥ 40 kg at screening. * History of inadequate response to TCS of medium to higher potency (with or without TCI). * EASI score ≥ 12 at initial screening. * EASI score ≥ 16 at Day 1. * vIGA-AD score ≥ 3. * ≥10% body surface area of AD involvement. * Worst pruritus NRS ≥ 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: 1. Systemic corticosteroids 2. Non-biologic, non-targeted systemic immunosuppressants 3. Phototherapy 4. Oral or Topical Janus kinase inhibitors * Treatment with any of the following medications or therapies within 1 week, prior to Day 1: 1. TCS of any potency 2. TCI 3. Topical phosphodiesterase 4 inhibitors 4. Other topical immunosuppressive agents
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Achieved 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," participant met rIGA 0/1; if "No," they did not. If vIGA-AD = 0, 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 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 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 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 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. Only 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 by modifying the Psoriasis Area and Severity Index, 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. |
| Percentage of Participants Who Initiated Rescue Therapy for AD at or Before Week 16 | Up to Week 16 | Percentage of participants who initiated rescue therapy for AD were provided by each treatment group descriptively during initiation treatment period. |
| Percentage of Participants Who Initiated Rescue Therapy for AD at or Before Week 24 | Up to Week 24 | Percentage of participants who initiated rescue therapy for AD were provided by each treatment group descriptively during initiation treatment period. |
| Change From Baseline in Weekly Average of Daily Worst Pruritus NRS Score at Week 16 | Baseline and Week 16 | The Worst Pruritus was assessed 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 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 symptoms of 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 symptoms of 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 ≥ 16 Years Old at Enrollment 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 adolescent 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 For Participants ≥ 16 Years Old at Enrollment | 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 adolescent 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. |
| Change From Baseline in Children's Dermatology Life Quality Index (CDLQI) Score at Week 24 For Participants < 16 Years Old at Enrollment | Baseline and Week 24 | The CDLQI was a 10-item 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 child patients suffering from skin disease. The CDLQI 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 Daily 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 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 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 | 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 worse anxiety. 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 worse depression. 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 worse anxiety. 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 anxiety. |
| 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 worse depression. 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 depression. |
| 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
Belgium, Brazil, Canada, Chile, China, Croatia, France, Germany, Greece, Hungary, Israel, Italy, Japan, Mexico, Poland, Puerto Rico, Romania, South Korea, Spain, Taiwan, Thailand, United States
Contacts
STUDY_DIRECTORMD
Amgen
Participant flow
Recruitment details
This trial was conducted at 247 centers in Asia, Europe, Latin America, and North America between April 2023 to November 2025. Adolescent participants with moderate to severe atopic dermatitis (AD) were randomized 4:3:3 into 3 treatment groups during initiation period (24 Weeks).
Pre-assignment details
Based on achieving validated investigator's global assessment for AD score of 0 (clear) or 1 (almost clear) with a ≥ 2-point reduction from baseline (vIGA-AD 0/1) or achievement of ≥ 75% reduction from baseline in eczema area and severity index score (EASI 75) at Week 24, and whether therapies consistent with AD rescue were used, participants were assigned to either maintenance period or open-label period.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 14.7 years STANDARD_DEVIATION 1.7 |
| Race/Ethnicity, Customized Asian | 198 Participants |
| Race/Ethnicity, Customized Black or African American | 14 Participants |
| Race/Ethnicity, Customized Hispanic/Latino | 34 Participants |
| Race/Ethnicity, Customized Not Hispanic/Latino | 450 Participants |
| Race/Ethnicity, Customized Other | 6 Participants |
| Race/Ethnicity, Customized White | 91 Participants |
| Sex: Female, Male Female | 109 Participants |
| Sex: Female, Male Male | 108 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk | EG011 affected / at risk | EG012 affected / at risk | EG013 affected / at risk | EG014 affected / at risk | EG015 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 157 | 0 / 157 | 0 / 218 | 0 / 34 | 0 / 48 | 0 / 43 | 0 / 33 | 0 / 88 | 0 / 15 | 0 / 7 | 0 / 5 | 0 / 7 | 0 / 14 | 0 / 107 | 0 / 53 | 0 / 82 |
| other Total, other adverse events | 65 / 157 | 88 / 156 | 122 / 216 | 13 / 34 | 22 / 48 | 21 / 43 | 13 / 33 | 28 / 88 | 7 / 15 | 2 / 7 | 1 / 5 | 2 / 7 | 6 / 14 | 45 / 107 | 24 / 53 | 39 / 81 |
| serious Total, serious adverse events | 6 / 157 | 2 / 156 | 4 / 216 | 1 / 34 | 1 / 48 | 1 / 43 | 1 / 33 | 1 / 88 | 0 / 15 | 0 / 7 | 0 / 5 | 0 / 7 | 0 / 14 | 5 / 107 | 1 / 53 | 1 / 81 |
Outcome results
None listed