A Phase 3, Randomized, Multicenter, Double-Blind, Placebo-Controlled Trial to Evaluate the Efficacy, Safety, Tolerability, and Pharmacokinetics of Zasocitinib in Pediatric Participants Aged 4 to Less Than 18 Years With Moderate-to-Severe Plaque Psoriasis
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 110
- 试验地点
- 45
- 主要终点
- Part B: Maximum Observed Plasma Concentration (Cmax) of Zasocitinib
研究概览
简要总结
The main aim of this study is to see how well the medicine zasocitinib works, how safe it is, and how children and teenagers aged 4 to under 18 with moderate-to-severe plaque psoriasis respond to it.
The study will be done in 2 parts: Part A will include both children and teenagers, while part B will only include children.
At first, only teenagers who meet the study rules can participate in this study. Children may only start to participate once enough information has been collected from other studies with zasocitinib.
Participants in Part A will initially be assigned to receive either zasocitinib or placebo for the first 16 weeks of treatment, then all participants will receive zasocitinib through the end of the study. All participants in Part B will be assigned to receive treatment with zasocitinib throughout the study.
Participants will be in the study for up to 4 years and 2 months (217 weeks), including up to 35 days for the screening period, 208 weeks of treatment (Part A and Part B) and a 4-week safety follow-up period. During the study, participants will visit their study site multiple times.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
Part A: Double-blinded and Open-label; Part B: Open-label
入排标准
- 年龄范围
- 4 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant has a diagnosis of chronic plaque psoriasis for greater than or equal to (>=) 6 months prior to the screening visit.
- •Participant has stable plaque psoriasis defined as no significant flare or change in morphology (as assessed by the investigator) in psoriasis for >=6 months before screening.
- •Participant has moderate-to-severe plaque psoriasis as defined by a Psoriasis Area and Severity Index (PASI) score >=12 and a Static Physician's Global Assessment (sPGA) score >=3 at screening and Day
- •Participant has plaque psoriasis covering >=10 percent (%) of total body surface area (BSA) at screening and Day
- •Participant must be a candidate for phototherapy or systemic therapy.
- •Inclusion Criteria for Part A Cohort 1: The participant is male or female and aged 12 to less than (<) 18 years, inclusive.
- •Inclusion Criteria for Part A Cohort 2 and for Part B: The participant is male or female and aged 4 to <12 years, inclusive.
- •Inclusion Criteria for Part A Cohort 1: The participant must weigh >=40 kilograms (kg) at the time of screening.
排除标准
- •Participant has evidence of nonplaque psoriasis (erythrodermic, pustular, predominantly guttate psoriasis, predominantly inverse, or drug-induced psoriasis). If a participant meets criteria for inclusion based on typical plaque psoriasis presentation, a limited amount of inverse psoriasis is not exclusionary.
- •Participant requires systemic treatment, other than nonsteroidal anti-inflammatory drugs (NSAIDs), during the trial period for an immune-related disease.
- •Participant has concomitant comorbid skin condition that, in the opinion of the investigator, would interfere with the trial assessments.
- •Participant has history of active TB infection, regardless of treatment status and has signs or symptoms of active TB or evidence of latent tuberculosis infection (LTBI).
- •Participant has active herpes virus infection, including herpes zoster or herpes simplex 1 and 2 or a history of serious herpetic infection.
- •Participant has a history of chronic or recurrent bacterial disease.
- •Participant has a history of opportunistic infections (for example, Pneumocystis jirovecii pneumonia, histoplasmosis, coccidiomycosis).
- •Participant has any clinically significant medical condition, evidence of an unstable clinical condition or vital signs/physical examination/laboratory/ECG abnormality that would, in the opinion of the investigator, put the participant at undue risk or interfere with interpretation of trial results.
- •Participant has any previous exposure to zasocitinib (also known as TAK-279 or NDI-034858) or other TYK2 inhibitors or participated in any trial that included a tyrosine kinase 2 (TYK2) inhibitor, unless participant has documentation of posttrial unblinding that confirms the participant did not receive a TYK2 inhibitor.
- •Participant is not up to date on all required vaccinations according to current immunization guidelines as noted by country-specific pediatric authorities.
- •Other protocol-defined inclusion/exclusion criteria apply.
研究组 & 干预措施
Part A (Cohort 1 and Cohort 2): Placebo
Participants in Cohort 1 (Adolescent aged 12 to <18 years) and Cohort 2 (Children aged 4 to <12 years) will receive zasocitinib matching placebo QD from Week 1 to Week 16 during the double-blind placebo-controlled period.
干预措施: Placebo (Drug)
Part A (Cohort 1): Zasocitinib (Dose A)
Participants (Adolescent) aged 12 to less than (<)18 years will receive zasocitinib Dose A once daily (QD), orally, from Week 1 to Week 16 during the double-blind placebo-controlled period followed by zasocitinib, from Week 16 to Week 208 during the open-label period.
干预措施: Zasocitinib (Drug)
Part B: Zasocitinib (Multiple Doses)
Participants (Children) aged 4 to <12 years will receive zasocitinib, orally, doses based on weight, from Week 1 to Week 208 during the open-label period.
干预措施: Zasocitinib (Drug)
Part A (Cohort 2): Zasocitinib (Multiple Doses)
Participants (Children) aged 4 to <12 years will receive zasocitinib, orally, doses based on weight, from Week 1 to Week 16 during the double-blind placebo-controlled period followed by zasocitinib from Week 16 to Week 208 during the open-label period.
干预措施: Zasocitinib (Drug)
结局指标
主要结局
Part B: Maximum Observed Plasma Concentration (Cmax) of Zasocitinib
时间窗: Pre-dose and Post-dose on Day 7
Cmax of zasocitinib in plasma will be assessed.
Part A: Percentage of Participants Achieving a Static Physician's Global Assessment (sPGA) of Clear (0) or Almost Clear (1) With a Greater than or Equal to (>=) 2-Point Decrease From Baseline at Week 16
时间窗: At Week 16
The sPGA is an assessment by the investigator of the overall disease severity at the time of evaluation. Erythema (E), induration (I), and desquamation (D) are scored on a 5-point scale ranging from 0 (none) to 4 (severe). The sPGA composite score ranges from 0 to 4 and is calculated as Clear (0) = 0 for all three; Almost clear (1) = mean greater than (\>) 0, less than (\<) 1.5; Mild (2) = mean \>= 1.5, \<2.5; Moderate (3) = mean \>=2.5, \<3.5; and Severe (4) = mean \>=3.5. The percentage of participants achieving an sPGA of Clear (0) or Almost Clear (1) with a \>= 2-point decrease from baseline at Week 16 will be reported.
Part A: Percentage of Participants Achieving >= 75 Percent (%) Improvement From Baseline in Psoriasis Area and Severity Index (PASI) Score at Week 16
时间窗: At Week 16
The PASI is a measure of the average redness, thickness and scaliness of psoriatic skin lesions (each graded on a 0 to 4 scale; 0 = none to 4 = very severe), weighted by the area of involvement (head, upper extremities, trunk, and lower extremities). The PASI score ranges from 0 to 72, with higher PASI scores denoting more severe disease activity (less than or equal to \[\<=\] 3 representing mild disease, \>= 3 to 15 representing moderate disease, and \>= 15 indicating severe disease). The PASI-75 is defined as 75% improvement from baseline in PASI score. The percentage of participants achieving \>= 75% improvement from baseline in PASI score at Week 16 will be reported.
Part B: Time to Maximum Concentration (Tmax) of Zasocitinib
时间窗: Pre-dose and Post-dose on Day 7
Tmax of zasocitinib in plasma will be assessed.
Part B: Area Under the Concentration-Time Curve From Time 0 to the Time of Last Quantifiable Concentration (AUC0-Last) of Zasocitinib
时间窗: Pre-dose and Post-dose on Day 7
AUC0-Last of zasocitinib in plasma will be assessed.
次要结局
- Part A: Percentage of Participants Achieving PASI-90 Response at Week 16(At Week 16)
- Part A: Percentage of Participants Achieving PASI-100 Response at Week 16(At Week 16)
- Part A: Change From Baseline in Body Surface Area (BSA) Affected by Psoriasis at Week 16(Baseline, Week 16)
- Part A: Percentage of Participants Achieving an Enhanced sPGA Response of Clear (0) at Week 16(At Week 16)
- Part A: Percent Change From Baseline in BSA Affected by Psoriasis at Week 16(Baseline, Week 16)
- Part A: Percentage of Participants Achieving a Scalp-specific Physician's Global Assessment (ssPGA) Response of Clear (0) or Almost Clear (1) With a >=2-Point Decrease From Baseline for Participants With a Baseline ssPGA >=3 at Week 16(At Week 16)
- Part A: Percentage of Participants With a Baseline Children's Dermatology Life Quality Index (CDLQI) Score >=2 who Achieve CDLQI Score of 0 or 1 at Week 16(At Week 16)
- Part A: Change From Baseline in DLQI at Week 16(Baseline, Week 16)
- Part A: Change From Baseline in CDLQI at Week 16(Baseline, Week 16)
- Part A (Cohort 1): Percentage of Participants in Cohort 1 with a Baseline Itch Numerical Rating Scale (NRS) Score >=4 who Achieve a >= 4-Point Improvement in Itch NRS Score at Week 16(At Week 16)
- Part A (Cohort 1): Change From Baseline in Itch NRS at Week 16(Baseline, Week 16)
- Part A (Cohort 1): Percent Change From Baseline in Itch NRS at Week 16(Baseline, Week 16)
- Part A: Percentage of Participants with a Baseline Dermatology Life Quality Index (DLQI) Score >=2 who Achieve DLQI Score of Zero (0) or One (1) at Week 16(At Week 16)
- Parts A and B: Percentage of Participants Achieving PASI-75 Response During Open-Label Period(Part A: Week 16 to Week 208; Part B: Week 1 to Week 208)
- Parts A and B: Percentage of Participants Achieving PASI-90 During Open-Label Period(Part A: Week 16 to Week 208; Part B: Week 1 to Week 208)
- Parts A and B: Percentage of Participants Achieving PASI-100 During Open-Label Period(Part A: Week 16 to Week 208; Part B: Week 1 to Week 208)
- Parts A and B: Percentage of Participants Achieving an sPGA of Clear (0) or Almost Clear (1) With a >=2-Point Decrease From Baseline(Part A: Week 16 to Week 208; Part B: Week 1 to Week 208)
- Parts A and B: Percentage of Participants Achieving an Enhanced sPGA of Clear (0) During Open-Label Period(Part A: Week 16 to Week 208; Part B: Week 1 to Week 208)
- Parts A and B: Percentage of Participants Achieving an ssPGA Response of Clear (0) or Almost Clear (1) with a >=2-point Decrease From Baseline for Participants with a Baseline ssPGA >=3 During Open-Label Period(Part A: Week 16 to Week 208)
- Parts A and B: Change From Baseline in BSA Affected by Psoriasis During Open-Label Period(Part A: Week 16 to Week 208; Part B: Week 1 to Week 208)
- Parts A and B: Percent Change From Baseline in BSA Affected by Psoriasis During Open-Label Period(Part A: Week 16 to Week 208; Part B: Week 1 to Week 208)
- Parts A and B: Percentage of Participants With a Baseline DLQI Score >=2 who Achieve DLQI Score of 0 or 1 During Open-Label Period(Part A: Week 16 to Week 208; Part B: Week 1 to Week 208)
- Parts A and B: Percentage of Participants With a Baseline CDLQI Score >=2 who Achieve CDLQI Score of 0 or 1 During Open-Label Period(Part A: Week 16 to Week 208; Part B: Week 1 to Week 208)
- Parts A and B: Change From Baseline in DLQI During Open-Label Period(Part A: Week 16 to Week 208; Part B: Week 1 to Week 208)
- Parts A and B: Change From Baseline in CDLQI During Open-Label Period(Part A: Week 16 to Week 208; Part B: Week 1 to Week 208)
- Part A (Cohort 1): Percentage of Participants with a Baseline Itch Numerical Rating Scale (NRS) Score >=4 who Achieve a >= 4-Point Improvement in Itch NRS Score During Open-Label Period(Part A: Week 16 to Week 208)
- Part A (Cohort 1): Change From Baseline in Itch NRS for Participants in Cohort 1 During Open-Label Period(Part A: Baseline, Week 16 to Week 208)
- Part A (Cohort 1): Percent Change From Baseline in Itch NRS for Participants in Cohort 1 During Open-Label Period(Part A: Baseline, Week 16 to Week 208)
- Part A: Plasma Concentrations of Zasocitinib in Participants Receiving Active Treatment(Part A: Week 1 to Week 208)
- Part B: Zasocitinib Acceptability and Palatability Assessment Scores of Participants(Day 1, Day 7 and Day 14)