A Phase 3b Exploratory Multicenter Open-Label Study to Evaluate the Effect of Bimekizumab on Gene Expression Biomarkers in Study Participants 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
- 89
- 试验地点
- 30
- 主要终点
- Change from Baseline in composite gene expression score using reverse transcription-polymerase chain reaction (RT-PCR) in lesional skin at Week 48
研究概览
简要总结
The purpose of this study is to evaluate the effect of bimekizumab on gene expression biomarkers at Week 48 in a subset of study participants with moderate to severe plaque psoriasis (PSO) and moderate to severe plaque PSO with concomitant active psoriatic arthritis (PsA) who have provided skin biopsies for reverse transcription-polymerase chain reaction (RT-PCR).
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
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Cohort A and Cohort B
- •Study participant must be at least 18 years of age inclusive at the time of signing the Informed Consent Form (ICF)
- •Study participant must have:
- •Cohort A and Cohort B: Plaque psoriasis (PSO) diagnosed for at least 6 months prior to the Screening Visit
- •Cohort B only: In addition to the criteria specified above, study participant has a documented diagnosis of adult-onset psoriatic arthritis (PsA) and meets the CASPAR classification criteria for at least 6 months prior to Screening for active PsA and must have ≥1 tender joint count (TJC) out of 68 and ≥1 swollen joint count (SJC) out of 66 at Screening or up to 3 months before Screening (documented evidence)
- •Study participant must have Psoriasis Area and Severity Index (PASI) score ≥12 and body surface area (BSA) affected by PSO ≥10% and Investigator's Global Assessment (IGA) score ≥3 on a 5 point scale
- •Study participant must be a candidate for systemic PSO therapy and/or phototherapy
- •Study participant agrees not to change their usual sun exposure during the course of the study and to use ultraviolet A/ultraviolet B sunscreens if unavoidable exposure occurs
- •Study participant has body weight <120 kg
- •A female study participant is eligible to participate if they are not pregnant, not breastfeeding, and at least 1 of the following conditions applies:
- •Not a woman of childbearing potential (WOCBP) OR A WOCBP who agrees to follow the contraceptive guidance during the Run In Treatment Period, the Randomized Treatment Extension Period, theTreatment Extension Period, the Escape Treatment Period, and for 17 weeks after the final dose of investigational medicinal product (IMP)
- •Control Cohort
- •Study participant must be ≥18 years of age at the time of signing the informed consent
- •Study participants who are overtly healthy as determined by medical evaluation including medical history, physical examination, and vital signs
- •Study participant has body weight <120 kg
- •Female study participant is eligible to participate if they are not pregnant and not breastfeeding
排除标准
- •Cohort A and Cohort B
- •Study participant has a form of PSO other than plaque type (eg, pustular, erythrodermic and guttate PSO, or drug induced PSO)
- •Study participant has an active infection or history of infection(s) as follows:
- •Any active systemic infection within 14 days prior to Baseline
- •A serious infection, defined as requiring hospitalization or intravenous anti-infective(s) within 2 months prior to the Baseline Visit
- •A history of opportunistic, recurrent, or chronic infections that, in the opinion of the investigator, might cause this study to be detrimental to the study participant
- •At investigator's discretion, study participant with chronic (medically controlled) viral hepatitis B or C or human immunodeficiency virus (HIV) infection, or history of hepatitis B.
- •Study participant has any of the following:
- •Known active tuberculosis (TB) disease.
- •History of active TB involving any organ system unless adequately treated
- •High risk of acquiring TB infection
- •Study participant has a verified diagnosis of inflammatory conditions other than PSO or PsA, including but not limited to rheumatoid arthritis (RA), sarcoidosis, inflammatory bowel diseases (IBD), or systemic lupus erythematosus. Note: Study participants with a diagnosis of IBD are allowed if they have no active symptomatic disease at Screening or Baseline
- •Study participant has any active malignancy or history of malignancy within 5 years prior to the Screening Visit EXCEPT treated and considered cured cutaneous squamous or basal cell carcinoma, or in situ cervical cancer
- •Study participant has any medical or psychiatric condition that, in the opinion of the investigator, could jeopardize or would compromise the study participant's ability to participate in this study
- •Study participant has a known hypersensitivity to any components of the IMP as stated in this protocol
- •Study participant has a history of primary failure to any biologic (ie, no response within the first 12 weeks of treatment)
- •Study participant has laboratory abnormalities at Screening
- •Study participant has a current history of alcohol or drug use disorder, as defined in Diagnostic and Statistical Manual of Mental Disorders (DSM) V, within the previous 6 months prior to Screening, as evaluated by the investigator based on medical history, and/or site interview
- •Control Cohort
- •- Study participant has any systemic disease (eg, cardiovascular, neurological, renal, liver, metabolic, gastrointestinal, hematological, coagulation disorders, immunological) considered by the investigator to be uncontrolled, unstable, or likely to progress to a clinically significant degree during the course of the study
研究组 & 干预措施
Control Cohort
Healthy participants, who will not receive IMP during the study.
Cohort A
Study participants with moderate to severe plaque PSO without concomitant active PsA (Cohort A) receive bimekizumab dosage regimen 1 from Baseline up to Week 16 and bimekizumab regimen 2 from Week 16 up to Week 48. Study participants, fulfilling randomization criteria receive bimekizumab dosage regimen 2 or 3 from Week 48 to Week 96. Study participants who do not meet the criteria for randomization receive bimekizumab dosage regimen 2 to Week 96.
干预措施: bimekizumab (Drug)
Cohort B
Study participants with moderate to severe plaque PSO with concomitant active PsA (Cohort B) receive bimekizumab dosage regimen 1 from Baseline up to Week 16 and bimekizumab regimen 2 from Week 16 up to Week 48. Study participants, fulfilling randomization criteria receive bimekizumab dosage regimen 2 or 3 from Week 48 to Week 96. Study participants who do not meet the criteria for randomization receive bimekizumab dosage regimen 2 to Week 96.
干预措施: bimekizumab (Drug)
结局指标
主要结局
Change from Baseline in composite gene expression score using reverse transcription-polymerase chain reaction (RT-PCR) in lesional skin at Week 48
时间窗: Week 48, compared to Baseline
Composite gene expression score using RT-PCR in lesional skin at Baseline and Week 48 using preselected genes based on bimekizumab mechanism of action and PSO disease biology pathways.
次要结局
- Treatment-emergent adverse events (TEAEs) from Baseline to the end of the Safety Follow-Up (SFU)(From Baseline to End of SFU (up to Week 100))
- Treatment-emergent serious adverse event (TESAEs) from Baseline to the end of the SFU(From Baseline to End of SFU (up to Week 100))
- TEAEs leading to permanent discontinuation of IMP from Baseline to the end of the SFU(From Baseline to End of SFU (up to Week 100))