A Multicenter, Randomized, Parallel-Group, Double-Blind, Active-Controlled Study to Evaluate the Efficacy and Safety of Bimekizumab Compared to Ustekinumab in Children and Adolescents From 6 Years to Less Than 18 Years of Age With Moderate to Severe Plaque Psoriasis
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 176
- 试验地点
- 107
- 主要终点
- Investigator´s Global Assessment (IGA) 0/1 response at Week 16
研究概览
简要总结
The primary purpose of this study is to evaluate the efficacy of bimekizumab administered subcutaneously (sc) compared to active control (ustekinumab) in children and adolescents aged 6 to <18 years of age with moderate to severe plaque psoriasis (PSO).
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 6 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Study participant must be 6 to <18 years of age, inclusive, at the time of signing the informed consent/assent according to local regulation
- •Study participant has had a diagnosis of moderate to severe plaque psoriasis (PSO) for at least 3 months prior to the Screening Visit
- •Study participant meets the following at both the Screening and Baseline Visits:
- •Body surface area (BSA) affected by PSO ≥10%
- •. Investigator's Global Assessment (IGA) score ≥3 (on a scale from 0 to 4)
- •. Psoriasis Area and Severity Index (PASI) score ≥12 OR
- •PASI score ≥10 plus at least 1 of the following:
- •i) Clinically relevant facial involvement ii) Clinically relevant genital involvement iii) Clinically relevant hand and foot involvement
- •Study participant is a candidate for systemic PSO therapy and/or photo/chemotherapy and for treatment with ustekinumab per labeling
- •Study participant has body weight ≥15 kg and body mass index for age percentile of ≥5 at Screening
排除标准
- •Primary failure (no response within 12 weeks) to 1 or more interleukin-17 (IL-17) biologic response modifiers (eg, brodalumab, ixekizumab, secukinumab) OR more than 1 biologic response modifier other than an IL-17
- •Study participant has a presence of guttate, inverse, pustular, or erythrodermic PSO or other dermatological condition that may impact the clinical assessment of PSO
- •Study participant has a history of inflammatory bowel disease (IBD) or symptoms suggestive of IBD
- •History of active tuberculosis unless successfully treated, latent TB unless prophylactically treated
- •Study participant has an active infection or history of infections (such as serious infection, chronic infections, opportunistic infections, unusually severe infections)
- •Study participant has previously received bimekizumab
- •Study participant has previously received ustekinumab
- •Study participant has received drugs outside the specified timeframes relative to the Baseline Visit or receives prohibited concomitant treatments
- •Study participant has the presence of active suicidal ideation, or positive suicide behavior
- •Study participant diagnosed with severe depression in the past 6 months (prior to Screening) should be excluded
- •Study participant has a history of psychiatric inpatient hospitalization within the past year before enrolling into the study
研究组 & 干预措施
bimekizumab
Study participants randomized to this arm receive bimekizumab dosage regimen 1 at pre-specified timepoints during the Initial Treatment Period (16 weeks). They continue to receive bimekizumab dosage regimen 2 in the Maintenance Period (32 weeks). Under certain conditions study participants may be offered to continue on bimekizumab dosage regimen 2 in the Open-label Extension (OLE) Period (104 weeks).
干预措施: placebo (Drug)
bimekizumab
Study participants randomized to this arm receive bimekizumab dosage regimen 1 at pre-specified timepoints during the Initial Treatment Period (16 weeks). They continue to receive bimekizumab dosage regimen 2 in the Maintenance Period (32 weeks). Under certain conditions study participants may be offered to continue on bimekizumab dosage regimen 2 in the Open-label Extension (OLE) Period (104 weeks).
干预措施: bimekizumab (Drug)
ustekinumab
Study participants randomized to this arm receive ustekinumab at pre-specified timepoints during the Initial Treatment Period (16 weeks) and during the Maintenance Period. Under certain conditions participants may switch to bimekizumab dosage regimen 1 (16 weeks) and continue with bimekizumab dosage regimen 2 in the last 16 weeks of the Maintenance Period. Under certain conditions study participants may be offered to participate in the OLE Period also receiving bimekizumab dosage regimen 2.
干预措施: bimekizumab (Drug)
ustekinumab
Study participants randomized to this arm receive ustekinumab at pre-specified timepoints during the Initial Treatment Period (16 weeks) and during the Maintenance Period. Under certain conditions participants may switch to bimekizumab dosage regimen 1 (16 weeks) and continue with bimekizumab dosage regimen 2 in the last 16 weeks of the Maintenance Period. Under certain conditions study participants may be offered to participate in the OLE Period also receiving bimekizumab dosage regimen 2.
干预措施: ustekinumab (Drug)
ustekinumab
Study participants randomized to this arm receive ustekinumab at pre-specified timepoints during the Initial Treatment Period (16 weeks) and during the Maintenance Period. Under certain conditions participants may switch to bimekizumab dosage regimen 1 (16 weeks) and continue with bimekizumab dosage regimen 2 in the last 16 weeks of the Maintenance Period. Under certain conditions study participants may be offered to participate in the OLE Period also receiving bimekizumab dosage regimen 2.
干预措施: placebo (Drug)
结局指标
主要结局
Investigator´s Global Assessment (IGA) 0/1 response at Week 16
时间窗: Week 16
The Investigator's Global Assessment (IGA) measures the overall psoriasis severity following a 5-point scale (0-4), where scale 0= clear, no signs of psoriasis; presence of post-inflammatory hyperpigmentation, scale 1= almost clear, no thickening; normal to pink coloration; no to minimal focal scaling, scale 2= mild, just detectable to mild thickening; pink to light red coloration; predominately fine scaling, 3= moderate, clearly distinguishable to moderate thickening; dull to bright red; moderate scaling and 4= severe, severe thickening with hard edges; bright to deep dark red coloration; severe/coarse scaling covering almost all or all lesions. IGA response (Clear or Almost Clear) is defined as clear \[0\] or almost clear \[1\] with at least a two-category improvement from Baseline.
Psoriasis Area Severity Index 90 (PASI90) response at Week 16
时间窗: Week 16
The PASI90 response assessments are based on at least 90% improvement in the PASI score from Baseline. This is a scoring system that averages the redness, thickness, and scaliness of the psoriatic lesions (on a 0-4 scale), and weights the resulting score by the area of skin involved. Body divided into 4 areas: head, arms, trunk to groin, and legs to top of buttocks. Assignment of an average score for the redness, thickness, and scaling for each of the 4 body areas with a score of 0 (clear) to 4 (very marked). Determining the percentage of skin covered with PSO for each of the body areas and converting to a 0 to 6 scale. Final PASI= average redness, thickness, and scaliness of the psoriatic skin lesions, multiplied by the involved psoriasis area score of the respective section, and weighted by the percentage of the person's affected skin for the respective section. The minimum possible PASI score is 0= no disease, the maximum score is 72= maximal disease.
次要结局
- Change from Baseline in hematology parameters (erythrocytes)(From Baseline (Week 0) up to Week 48)
- Change from Baseline in hematology parameters (hemoglobin)(From Baseline (Week 0) up to Week 48)
- Incidence of TEAEs predefined as safety topics of interest(From Baseline (Week 0) to Week 48 and to End of Safety Follow-up (up to Week 164))
- Change from Baseline in vital signs (pulse rate)(From Baseline (Week 0) up to Week 48)
- Incidence of treatment-emergent adverse events (TEAE)s(From Baseline (Week 0) to End of Safety Follow-up (up to Week 164))
- PASI100 response at Week 48(Week 48)
- Change from Baseline in vital signs (diastolic blood pressure)(From Baseline (Week 0) up to Week 48)
- Change from Baseline in height (growth assessment)(From Baseline (Week 0) up to Week 48)
- Change from Baseline in weight (growth assessment)(From Baseline (Week 0) up to Week 48.)
- Change from Baseline in biochemistry parameters (total bilirubin and direct bilirubin, total protein, blood urea nitrogen, and creatinine)(From Baseline (Week 0) up to Week 48)
- Change from Baseline in Children's Dermatology Life Quality Index (CDLQI) total score at Week 16(Week 16, compared to Baseline)
- PASI75 response at Week 4(Week 4)
- PASI100 response at Week 16(Week 16)
- Incidence of serious TEAEs(From Baseline (Week 0) to End of Safety Follow-up (up to Week 164))
- Incidence of TEAEs leading to withdrawal from the study(From Baseline (Week 0) to End of Safety Follow-up (up to Week 164))
- IGA 0/1 response at Week 48(Week 48)
- Incidence of TEAEs leading to discontinuation of Investigational Medicinal Product (IMP)(From Baseline (Week 0) to End of Safety Follow-up (up to Week 164))
- Change from Baseline in vital signs (systolic blood pressure)(From Baseline (Week 0) up to Week 48)
- Incidence of clinically significant physical examination findings reported as TEAEs(From Baseline (Week 0) up to Week 48)
- Change from Baseline in hematology parameters (hematocrit)(From Baseline (Week 0) up to Week 48)
- PASI90 response at Week 48(Week 48)
- IGA 0 response at Week 16(Week 16)
- IGA 0 response at Week 48(Week 48)
- Change from Baseline in hematology parameters (platelet count)(From Baseline (Week 0) up to Week 48)
- Change from Baseline in biochemistry parameters (alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase)(From Baseline (Week 0) up to Week 48)
- Change from Baseline in hematology parameters (basophils, eosinophils, lymphocytes, monocytes, neutrophils, leukocytes)(From Baseline (Week 0) up to Week 48)
- Change from Baseline in biochemistry parameters (glucose, potassium, sodium, calcium)(From Baseline (Week 0) up to Week 48)
- Plasma anti-bimekizumab antibodies prior to and following IMP administration over the Initial Treatment Period, over the Maintenance Period, and over the OLE Period(From Baseline to End of OLE Period (up to 144 weeks))
- Plasma bimekizumab concentrations prior to and following IMP administration over the Initial Treatment Period, over the Maintenance Period, and over the OLE Period(From Baseline to End of OLE Period (up to 144 weeks))
- Change from Baseline in Children's Dermatology Life Quality Index (CDLQI) total score at Week 48(Week 48, compared to Baseline)
- Change from Baseline in Childhood Health Assessment Questionnaire (CHAQ) disability index at Week 16 for study participants with juvenile PsA prior to Baseline(Week 16, compared to Baseline)
- Change from Baseline in Peak Pruritus numerical rating scale (NRS) score at Week 16(Week 16, compared to Baseline)