A Study to Evaluate Rocatinlimab (AMG 451) in Adolescent Subjects With Moderate-to-severe Atopic Dermatitis (AD)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of rocatinlimab in monotherapy and combination therapy treatment in adolescent subjects.

Official Title
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A Phase 3, Randomized, 52-week, Placebo-controlled, Double-blind Study With Rerandomization to Assess the Efficacy, Safety, and Tolerability of Rocatinlimab (AMG 451) in Adolescent Subjects With Moderate-to-severe Atopic Dermatitis (AD) (ROCKET-ASTRO)

Conditions
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Atopic Dermatitis

Intervention / Treatment
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* Drug: Rocatinlimab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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: Systemic corticosteroids Non-biologic, non-targeted 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 4 inhibitors Other topical immunosuppressive agents

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A: Dose 1<br>Part 1 (Initial Period); Week 0 to Week 24: Rocatinlimab Dose 1 every 4 weeks (Q4W) for 24 weeks with loading dose at Week 2 (+ topical corticosteroids (TCS)/ topical calcineurin inhibitor (TCI) if within combination therapy cohort). Part 2 (Maintenance Period); Week 24 to Week 52: Part 1 Responders will be rerandomised at Week 24 to Rocatinlimab Dose 1 Q4W or every 8 weeks (Q8W) for 28 weeks (+ TCS/TCI if within combination therapy cohort). | Drug: Rocatinlimab<br>* Subcutaneous (SC) injection<br>* Other names: AMG 451;|
| Experimental: Arm B: Dose 2<br>Part 1 (Initial Period); Week 0 to Week 24: Rocatinlimab Dose 2 Q4W for 24 weeks with loading dose at Week 2 (+TCS/TCI if within combination therapy cohort). Part 2 (Maintenance Period); Week 24 to Week 52: Part 1 Responders will be rerandomised at Week 24 to Rocatinlimab Dose 2 Q4W or Q8W for 28 weeks (with TCS/TCI if within combination therapy cohort). | Drug: Rocatinlimab<br>* Subcutaneous (SC) injection<br>* Other names: AMG 451;|
| Experimental: Arm C: Placebo<br>Part 1 (Initial Period); Week 0 to Week 24: Placebo Q4W for 24 weeks with loading dose at Week 2 (+TCS/TCI if within combination therapy cohort). Part 2 (Maintenance Period); Week 24 to Week 52: Part 1 Responders will be reassigned at Week 24 with Placebo Q4W for 28 weeks (with TCS/TCI if within combination therapy cohort). | Drug: Placebo<br>* SC injection<br>|
| Experimental: Arm D: Open-Label Dose 1<br>Part 2; Week 24 to Week 52: Part 1 Non-Responders will be reassigned at Week 24 with Rocatinlimab Open-label Dose 1 Q4W for 28 weeks (with TCS/TCI if within combination therapy cohort). Participants in Arms A, B or C Maintenance Period will be reassigned with Rocatinlimab Open-label Dose 1 Q4W (with TCS/TCI if within combination therapy cohort) upon relapse after Week 24. | Drug: Rocatinlimab<br>* Subcutaneous (SC) injection<br>* Other names: AMG 451;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Achievement of vIGA-AD 0/1 at Week 24 |  | Baseline and Week 24 | 
| Achievement of EASI 75 at Week 24 |  | Baseline and Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Achievement of EASI 75 at Week 16 |  | Baseline and Week 16 | 
| Achievement of a vIGA-AD 0/1 at Week 16 |  | Baseline and Week 16 | 
| Achievement of a ≥ 4-point Reduction From Baseline in Weekly Average of Daily Worst Pruritus Numeric Rating Scale (NRS) Score at Week 16 in Subjects with Baseline Weekly Average of Daily Worst Pruritus NRS Score ≥ 4 |  | Baseline and Week 16 | 
| Achievement of a ≥ 4-point Reduction From Baseline in Weekly Average of Daily Worst Pruritus NRS Score at Week 24 in Subjects with Baseline Weekly Average of Daily Worst Pruritus NRS Score ≥ 4 |  | Baseline and Week 24 | 
| Achievement of ≥ 90% Reduction From Baseline in EASI Score (EASI 90) at Week 24 |  | Baseline and Week 24 | 
| Change From Baseline in Weekly Average of Daily AD Skin Pain NRS Score at Week 24 |  | Baseline to Week 24 | 
| Achievement of a vIGA-AD Score of 1 with presence of only barely perceptible erythema or vIGA-AD Score of 0 at Week 24 |  | Baseline and Week 24 | 
| Change From Baseline in Weekly Average of Daily Worst Pruritus NRS Score at Week 16 |  | Baseline to Week 16 | 
| Change From Baseline in Weekly Average of Daily Worst Pruritus NRS Score at Week 24 |  | Baseline to Week 24 | 
| Change From Baseline in Scoring of Atopic Dermatitis (SCORAD) Itch Visual Analog Scale (VAS) Score at Week 16 |  | Baseline to Week 16 | 
| Change From Baseline in SCORAD Itch VAS Score at Week 24 |  | Baseline to Week 24 | 
| Achievement of a ≥ 4-point Reduction from Baseline in Dermatology Life Quality Index (DLQI) Score at Week 24 in Subjects with Baseline DLQI ≥ 4 (Children's Dermatology Life Quality Index [CDLQI] in Subjects < 16 Years of Age at Screening) |  | Baseline and Week 24 | 
| Change From Baseline in DLQI or CDLQI Score at Week 24 |  | Baseline to Week 24 | 
| Achievement of a ≥ 4-point Reduction From Baseline in Patient Oriented Eczema Measure (POEM) Score at Week 24 in Subjects with Baseline POEM Score ≥ 4 |  | Baseline and Week 24 | 
| Change From Baseline in POEM Score at Week 24 |  | Baseline to Week 24 | 
| Change From Baseline in Weekly Average of Sleep Disturbance NRS Score at Week 24 |  | Baseline to Week 24 | 
| Achievement of a Hospital Anxiety and Depression Scale (HADS)-anxiety Subscale Score < 8 at Week 24 in Subjects with Baseline HADS-anxiety Subscale Score ≥ 8 |  | Baseline and Week 24 | 
| Change From Baseline in HADS-anxiety Subscale Score at Week 24 |  | Baseline to Week 24 | 
| Achievement of a HADS-depression Subscale Score < 8 at Week 24 in Subjects with Baseline HADS-depression Subscale Score ≥ 8 |  | Baseline and Week 24 | 
| Change From Baseline in HADS-depression Subscale Score at Week 24 |  | Baseline to Week 24 | 
| Achievement of a ≥ 8.7-point Reduction from Baseline in Severity SCORAD Score at Week 24 in Subjects with Baseline SCORAD Score ≥ 8.7 |  | Baseline and Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Atopic Dermatitis, AMG 451, KHK4083, Rocatinlimab