A Multicenter, Phase 2A, Randomized, Investigator-Blind, Subject-Blind, Parallel-Group Study to Evaluate the Efficacy and Safety of Bimekizumab and Certolizumab Pegol in Subjects With Active Ankylosing Spondylitis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 76
- 试验地点
- 34
- 主要终点
- Change From Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) at Week 12
研究概览
简要总结
The purpose of the study is to evaluate the efficacy and safety of bimekizumab compared to certolizumab pegol in the treatment of subjects with active ankylosing spondylitis (AS).
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)
盲法说明
This is an investigator-blind and subject-blind study.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Documented diagnosis of active adult-onset ankylosing spondylitis (AS) as defined by documented radiologic evidence (X-ray) fulfilling the Modified New York criteria for AS (1984) of at least 3 months' symptom duration and age of onset <45 years
- •Subject has moderate to severe active disease at the Screening Visit as defined by each of the following:
- •Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score >=4
- •Spinal pain >=4 on a 0 to 10 numeric rating scale (NRS) (from BASDAI Item 2)
- •Subjects must have had an inadequate response to, have a contraindication to, or have been intolerant to at least 2 nonsteroidal anti-inflammatory drugs (NSAIDs)
- •Subjects taking corticosteroids must be on a maximum daily dose of <=10mg/day oral prednisolone or equivalent
- •Subjects taking methotrexate (MTX; <=25 mg/week) are allowed to continue their medication if they received a stable dose for at least 12 weeks before randomization
- •Subjects taking sulfasalazine (up to 3 grams/day) or hydroxychloroquine (up to 400 mg per day total) are allowed to continue their medication if started at least 12 weeks prior to randomization
- •Subject who has been on an anti-tumor necrosis factor alpha (TNFα) agent must have experienced an inadequate response to previous or current treatment given at an approved dose for at least 3 months or have been intolerant to at least 1 administration of an anti-TNFα agent. Subjects may not have been on more than 1 anti-TNFα agent
- •Subject has high-sensitive C-Reactive Protein (hsCRP) levels >=3 mg/L at the Screening Visit
- •Female subjects must be postmenopausal, permanently sterilized or, if of childbearing potential, must be willing to use a highly effective method of contraception up till 20 weeks after last administration of investigational medicinal product (IMP)
- •Male subjects with a partner of childbearing potential must be willing to use a condom when sexually active, up till 20 weeks after the last administration of IMP
排除标准
- •Subject has received previous or current biological treatment other than TNFα inhibitor treatment
- •Subjects with a total ankylosis of the spine, or a diagnosis of any other inflammatory arthritis eg, rheumatoid arthritis (RA), sarcoidosis, systemic lupus erythematosus, or reactive arthritis
- •Subjects with any current sign or symptom that may indicate an active infection (except for the common cold)
- •Subject has received previous or current biological treatment other than TNFα inhibitor treatment
- •Subject has chronic, recurrent, recent serious / life-threatening or current infection, as defined in the protocol
- •Subject has history of certain atypical infections, viral hepatitides, human immunodeficiency virus (HIV) infection, tuberculosis, as defined in the protocol
- •Subjects receiving any live vaccination within the 8 weeks prior to Baseline
- •Subjects with known tuberculosis (TB) infection, at high risk of acquiring TB infection, with latent TB infection or current or history of nontuberculous mycobacteria (NTMB) infection
- •Subject has immunosuppressive condition or treatment, recent history of malignancy (some exceptions) or demyelinating disease
- •Subjects with concurrent malignancy or a history of malignancy during the past 5 years will be excluded, with following exceptions that may be included:
- •<= 3 excised or ablated basal cell carcinomas of the skin
- •One squamous cell carcinoma of the skin (stage T1 maximum) successfully excised, or ablated only (other treatments, ie, chemotherapy, do not apply), with no signs of recurrence or metastases for more than 2 years prior to Screening
- •Actinic keratosis (-es)
- •Squamous cell carcinoma-in-situ of the skin successfully excised, or ablated, more than 6 months prior to Screening
- •Subject has history of psychiatric disorder, including suicidality (as defined in the protocol
- •Subject has major abnormalities on laboratory testing, as defined in the protocol
研究组 & 干预措施
Bimekizumab
Subjects will receive several bimekizumab administrations on pre-defined time points. Placebo will be provided in this arm to mask the certolizumab pegol loading dose.
干预措施: Bimekizumab (Drug)
Bimekizumab
Subjects will receive several bimekizumab administrations on pre-defined time points. Placebo will be provided in this arm to mask the certolizumab pegol loading dose.
干预措施: Placebo (Other)
Certolizumab pegol
Subjects will receive several certolizumab pegol administrations on pre-defined time points.
干预措施: Certolizumab pegol (Drug)
结局指标
主要结局
Change From Baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS) at Week 12
时间窗: From Baseline to Week 12
ASDAS was calculated as the sum of the results from the following components: 0.121xTotal spinal pain (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) Question 2 result), 0.058xDuration of morning stiffness (BASDAI Question 6 result), 0.110xPGADA, 0.073xPeripheral pain/swelling (BASDAI Question 3 result), 0.579x(natural logarithm of the CRP \[mg/L\] + 1), Spinal pain, PGADA, duration of morning stiffness, peripheral pain/swelling were all assessed on a numerical scale (0 to 10 units). There is a minimum score of 0.980 for ASDAS (as a fixed value of 2 was assumed for values of hs-CRP below the LLOQ), but no defined upper score. The change from Baseline is calculated, a negative value indicating improvement and a positive value worsening. Posterior means and 95% credible intervals in each group are presented.
Number of Participants With Adverse Events (AE) During the Study Conduct
时间窗: From Baseline until Safety Follow-Up Visit (up to Week 64)
An AE was any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A treatment-emergent adverse event (TEAE) was defined as any AE with a start date/time at the time of or after the first dose of IMP up until 140 days after the last dose of IMP.
Number of Participants With Serious Adverse Events (SAEs) During the Study Conduct
时间窗: From Baseline until Safety Follow-Up Visit (up to Week 64)
An SAE was any untoward medical occurrence that at any dose: - Resulted in death - Is life-threatening - Required in patient hospitalisation or prolongation of existing hospitalisation - Is a congenital anomaly or birth defect - Is an infection that requires treatment with parenteral antibiotics - Other important medical events which based on medical or scientific judgement may jeopardised the participants, or may require medical or surgical intervention to prevent any of the above. A TEAE was defined as any AE with a start date/time at the time of or after the first dose of IMP up until 140 days after the last dose of IMP.
Number of Participants Who Withdrew Due to an Adverse Event (AE) During the Study Conduct
时间窗: From Baseline until Safety Follow-Up Visit (up to Week 64)
An AE was any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. A TEAE was defined as any AE with a start date/time at the time of or after the first dose of IMP up until 140 days after the last dose of IMP.
次要结局
- Number of Participants With Ankylosing Spondylitis Disease Activity Score - Inactive Disease (ASDAS-ID) at Week 12(Week 12)
- Number of Participants With Ankylosing Spondylitis Disease Activity Score-Major Improvement (ASDAS-MI) at Week 12(Baseline, Week 12)