A Multicenter, Randomized, Double-blinded Study Evaluating the Pharmacokinetics, Efficacy and Safety of Multiple Switches Between Ustekinumab and ABP 654 Compared With Continued Use of Ustekinumab in Subjects With Moderate to Severe Plaque Psoriasis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 494
- 试验地点
- 88
- 主要终点
- Area Under the Plasma Concentration Time Curve (AUC) Over the Dosing Interval (AUCtau) Between Week 52 and Week 64
研究概览
简要总结
The purpose of the study is to evaluate pharmacokinetic similarity, efficacy, safety and immunogenicity of multiple switches between ustekinumab and ABP 654 compared with continued use of ustekinumab in participants with moderate to severe plaque psoriasis.
详细描述
This is a multi-center study and will enroll approximately 480 participants.
After eligibility confirmation, all participants will be randomized in a 1:1 ratio into 2 treatment arms: continued use of ustekinumab or multiple switches between ustekinumab and ABP 654 at Week 28. The randomization will be stratified by prior biologic use for psoriasis (yes versus [vs] no) at baseline (Week 0), geographic region, and baseline (Week 0) body weight.
All participants will receive an initial 3 doses of ustekinumab on Day 1 (Week 0), Week 4 and Week 16. At Week 28, participants will be randomized to continue on ustekinumab or switching between ABP 654 and ustekinumab every 12 weeks.
At Week 28, efficacy assessments will be conducted including evaluation of Psoriasis and Area Severity Index (PASI). Participants who do not achieve PASI 50 response or better improvement at Week 28 will be considered as run-in failures and will not be randomized at Week 28; these participants will complete End of Study procedures at Week 28. The run-in period will occur from Day 1 until randomization at Week 28. Those unable to complete the Week 28 visit or did not have a PASI assessment completed at Week 28 will be discontinued from the study.
The total duration of study participation for each participant will be 68 weeks, with up to 4 weeks for screening and 64 weeks after the first investigational product administration.
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
The investigators, study personnel (with the exception of the Data Monitoring Committee (DMC), and unblinded Parexel staff supporting DMC activities and randomization list activities) and the study participants will remain blinded to treatment allocation. ABP 654 and ustekinumab will be coded and labeled in a manner that protects blinding.
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant has stable moderate to severe plaque psoriasis for at least 6 months
- •Participant has a score of PASI ≥ 12, involvement of ≥ 10% body surface area and static Physician Global Assessment ≥ 3 at screening and at baseline
- •Participant is a candidate for phototherapy or systemic therapy
- •Participant has previous failure, inadequate response, intolerance, or contraindication to at least 1 conventional antipsoriatic systemic therapy
- •Female participant should have a negative serum pregnancy test during screening and a negative urine pregnancy test at baseline
- •Participant or legally acceptable representative is capable of giving signed Institutional Review Board (IRB)/Independent Ethics Committee (IEC) informed consent
- •Participant has no known history of latent or active tuberculosis
- •Participant with a positive purified protein derivative (PPD) test and a history of Bacillus Calmette-Guérin (BCG) vaccination is allowed with a negative Quantiferon/T-spot test
- •Participant with a positive PPD test or participant with a positive or indeterminate Quantiferon/T-spot test is allowed if he/she has all the following:
- •No symptoms per tuberculosis worksheet provided by the sponsor, Amgen Inc.
- •Documented history of adequate prophylaxis initiation prior to receiving investigational product in accordance with local recommendations
- •No known exposure to a case of active tuberculosis after most recent prophylaxis
- •No evidence of active tuberculosis on chest radiograph within 3 months prior to the first dose of investigational product
排除标准
- •Participant has erythrodermic psoriasis, pustular psoriasis, guttate psoriasis, medication induced psoriasis, or other skin conditions at the time of screening (eg, eczema) that would interfere with evaluations of the effect of investigational product of psoriasis
- •Participant has an active infection or history of infections
- •Participant has uncontrolled, clinically significant systemic disease, such as uncontrolled diabetes mellitus, cardiovascular disease, renal disease, liver disease, or hypertension
- •Participant has a mean QT internal or abnormal long QT syndrome corrected using Fridericia's formula (QTcF) of > 450 msec (for male participant) or > 470 msec (for female participant) at baseline that, in the opinion of the Investigator, is abnormal or clinically significant
- •Participant has moderate to severe heart failure (New York Heart Associate class III/IV)
- •Participant has known hypersensitivity to the investigational product or to any of the excipients
- •Participant has laboratory abnormalities at screening
- •Participant has had previous treatment with any agent specifically targeting interleukin (IL)-12 or IL-23 within 1 year prior to enrollment
- •Participant has received biologic treatment for psoriasis within the previous month or 5 drug half-lives (whichever is longer) prior to enrollment
- •Participant has received any investigational agents within the previous month or 5 half-lives (whichever is longer) prior to enrollment
- •Participant has received non-biologic systemic psoriasis therapy within 4 weeks prior to enrollment
- •Participant has received ultraviolet A phototherapy (with or without psoralen) or excimer laser within 4 weeks prior to enrollment, or ultraviolet B phototherapy within 2 weeks prior to enrollment
- •Participant has received topical psoriasis treatment within 2 weeks prior to enrollment
- •Participant has received other investigational procedures within 4 weeks prior to enrollment and during the course of the study
- •Female participant is pregnant or breastfeeding or planning to become pregnant while participating in the study and for at least 5 months after the last dose of investigational product
- •Sexually active participants and their partners who are of childbearing potential and not agreeing to use adequate protocol defined contraception methods while participating in the study and for 5 months after the last dose of investigational product
研究组 & 干预措施
Continued-use Group (Ustekinumab)
Participants will receive subcutaneous injection of ustekinumab up to Week 52.
干预措施: Ustekinumab (Drug)
Switching Group (Ustekinumab - ABP 654)
Participants will initially receive injection of ustekinumab up to Week 16. Thereafter, starting from Week 28, participants will switch between ABP 654 and ustekinumab every 12 weeks up to Week 52.
干预措施: Ustekinumab (Drug)
Switching Group (Ustekinumab - ABP 654)
Participants will initially receive injection of ustekinumab up to Week 16. Thereafter, starting from Week 28, participants will switch between ABP 654 and ustekinumab every 12 weeks up to Week 52.
干预措施: ABP 654 (Drug)
结局指标
主要结局
Area Under the Plasma Concentration Time Curve (AUC) Over the Dosing Interval (AUCtau) Between Week 52 and Week 64
时间窗: Blood samples were taken pre-dose week 52; and at 2 days, 7 days, 10 days, 2 weeks, 4 weeks, 8 weeks, and 12 weeks after the week 52 dose
AUCtau from time 0 (week 52) over the dosing interval up to week 64 is presented. Pharmacokinetic (PK) parameters are based on ABP 654 in the switching group and on ustekinumab in the continued-use group.
Maximum Observed Serum Concentration (Cmax) Between Week 52 and Week 64
时间窗: Blood samples were taken pre-dose week 52; and at 2 days, 7 days, 10 days, 2 weeks, 4 weeks, 8 weeks, and 12 weeks after the week 52 dose
Cmax between week 52 and week 64 is presented. PK parameters are based on ABP 654 in the switching group and on ustekinumab in the continued-use group.
次要结局
- Time of Maximum Serum Concentration (Tmax) Between Week 52 and Week 64(Blood samples were taken pre-dose week 52; and at 2 days, 7 days, 10 days, 2 weeks, 4 weeks, 8 weeks, and 12 weeks after the week 52 dose)
- PASI Percent Improvement From Baseline at Week 64(Baseline (day 1) and week 64)
- Number of Participants With Events of Interest (EOI): Post-randomization Period(Week 28 to week 64)
- Serum Trough Concentration at Steady-state (Ctrough,ss) at Week 28, Week 40, and Week 52(Blood samples were taken pre-dose week 28, week 40, and week 52)
- PASI 100 Response at Week 64(Baseline (day 1) and week 64)
- PASI 75 Response at Week 64(Baseline (day 1) and week 64)
- Number of Participants With Treatment-emergent Adverse Events (TEAEs): Post-randomization Period(Week 28 to week 64)
- Number of Participants With Antidrug Antibodies (ADAs): Post-randomization Period(Baseline (pre-dose day 1), week 4, week 16, week 28, week 40, week 52 and week 64)