A Phase 3, Randomized, 52-week, Placebo-controlled, Double-blind Study With Re-randomization to Assess the Efficacy, Safety, and Tolerability of Rocatinlimab (AMG 451) in Adolescent Subjects With Moderate-to-severe Atopic Dermatitis (AD) (ROCKET-ASTRO)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 532
- 试验地点
- 486
- 主要终点
- Achievement of a Validated Investigator's Global Assessment for Atopic Dermatitis Score of 0 (Clear) or 1 (Almost Clear) with a ≥ 2 Point Reduction From Baseline (vIGA-AD 0/1) at Week 24
研究概览
简要总结
The purpose of this study is to evaluate the efficacy and safety of rocatinlimab in monotherapy and combination therapy treatment in adolescent participants.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 12 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 12 to < 18 years at Day
- •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
- •vIGA-AD score ≥
- •≥10% body surface area of AD involvement.
- •Worst pruritus NRS ≥ 4.
排除标准
- •Treatment with a biological product within 12 weeks or 5 half-lives, whichever is longer, prior to Day
- •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
- •Topical phosphodiesterase 4 inhibitors
- •Other topical immunosuppressive agents
研究组 & 干预措施
Arm B: Dose 2
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).
干预措施: Rocatinlimab (Drug)
Arm D: Open-Label Dose 1
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.
干预措施: Rocatinlimab (Drug)
Arm C: Placebo
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).
干预措施: Placebo (Drug)
Arm A: Dose 1
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).
干预措施: Rocatinlimab (Drug)
结局指标
主要结局
Achievement of a Validated Investigator's Global Assessment for Atopic Dermatitis Score of 0 (Clear) or 1 (Almost Clear) with a ≥ 2 Point Reduction From Baseline (vIGA-AD 0/1) at Week 24
时间窗: Baseline and Week 24
Achievement of ≥ 75% Reduction From Baseline in EASI Score (EASI 75) at Week 24
时间窗: Baseline and Week 24
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
时间窗: 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
时间窗: 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.
次要结局
- 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 Participants 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 Participants 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)
- Achievement of a ≥ 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)
- Achievement of a vIGA-AD Score of 1 with Presence of Only Barely Perceptible Erythema or vIGA-AD Score of 0 (revised Investigator's Global Assessment [rIGA™] 0/1) at Week 24(Baseline and Week 24)
- Initiation of rescue therapy for AD at or before Week 16(Baseline to Week 16)
- Initiation of rescue therapy for AD at or before Week 24(Baseline to 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 Participants with Baseline DLQI ≥ 4 in Participants ≥ 16 Years of Age at Enrollment(Baseline and Week 24)
- Change From Baseline in DLQI Score at Week 24 in Participants ≥ 16 Years of Age at Enrollment(Baseline to Week 24)
- Change From Baseline in CDLQI Score at Week 24 in Participants < 16 Years of Age at Enrollment(Baseline to Week 24)
- Achievement of a ≥ 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)
- Change From Baseline in POEM Score at Week 24(Baseline to Week 24)
- Achievement of a ≥ 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 Daily AD Skin Pain NRS Score ≥ 4(Baseline and Week 16)
- Achievement of a ≥ 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)
- Achievement of a ≥ 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)
- 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 Participants 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 Participants 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 Participants with Baseline SCORAD Score ≥ 8.7(Baseline and Week 24)
- Change From Baseline in Weekly Average of Daily AD Skin Pain NRS Score at Week 24(Baseline and Week 24)
- Change From Baseline in Weekly Average of Daily AD Skin Pain NRS Score at Week 16(Baseline and Week 16)
- Number of Participants Who Achieved EASI 75 at Week 16(Baseline and Week 16)
- Number of Participants Who Achieved vIGA-AD 0/1 at Week 16(Baseline and Week 16)
- 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)
- Number of Participants Who Achieved vIGA-AD 0/1 at Week 24(Baseline and Week 24)
- 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)
- Number of Participants Who Achieved ≥ 90% Reduction From Baseline in EASI Score (EASI 90) at Week 24(Baseline and Week 24)
- 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)
- 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 at or Before Week 24(Up to Week 24)
- Change From Baseline in Weekly Average of Daily Worst Pruritus NRS Score at Week 16(Baseline and Week 16)
- Change From Baseline in Weekly Average of Daily Worst Pruritus NRS Score at Week 24(Baseline and Week 24)
- 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)
- Change From Baseline in Severity Scoring (SCORing) of AD (SCORAD) Itch Visual Analogue Scale (VAS) Score at Week 16(Baseline and Week 16)
- Change From Baseline in SCORAD Itch VAS Score at Week 24(Baseline and Week 24)
- 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)
- Change From Baseline in DLQI Score at Week 24 For Participants ≥ 16 Years Old at Enrollment(Baseline and Week 24)
- 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)
- Change From Baseline in POEM Score at Week 24(Baseline and Week 24)
- 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)
- 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)
- 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)
- Change From Baseline in Weekly Average of Daily Sleep Disturbance NRS Score at Week 24(Baseline and Week 24)
- 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)
- 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)
- Change From Baseline in HADS-anxiety Subscale Score at Week 24(Baseline and Week 24)
- Change From Baseline in HADS-depression Subscale Score at Week 24(Baseline and Week 24)
- 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)