A Phase 3, Multicenter, Randomized, Double-Blind Study Evaluating the Efficacy and Safety of ABP 654 Compared With 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
- 563
- 试验地点
- 84
- 主要终点
- PASI Percent Change From Baseline to Week 12
研究概览
简要总结
The purpose of the study is to evaluate the efficacy, safety, and immunogenicity of ABP 654 compared with ustekinumab in participants with moderate to severe plaque psoriasis.
详细描述
This is a multicenter study and will enroll approximately 542 participants.
The total duration of study participation for each participant will be 56 weeks, with up to 4 weeks for screening, and for 52 weeks after the first administration of either ABP 654 or ustekinumab.
After confirmation of eligibility, all participants will be randomized in a 1:1 ratio into 2 treatment groups (Group A will receive ABP 654, and Group B will receive ustekinumab) stratified by prior biologic use for psoriasis (yes versus [vs] no), geographic region, and baseline body weight (BW).
Based on the psoriasis area and severity index (PASI) score (to determine better improvement or partial improvement) at week 28, the participants in the study will proceed as follows:
- Participants who do not achieve PASI 50 response or better improvement at Week 28 will be considered to have completed the study and will complete end of study procedures (ie, week 52 procedures), and those unable to complete week 28 visit, or did not have a PASI assessment completed, will be discontinued from the study.
- Participants who achieve PASI 75 response or better improvement will continue on the study and will be re-randomized in a blinded fashion such that participants initially randomized to Group A (ABP 654) will continue to receive ABP 654 and those in Group B (ustekinumab) will re-randomized, to either continue on ustekinumab (Treatment Group B1) or switch to ABP 654 (Treatment Group B2).
- Participants with PASI 50 response or better but less than PASI 75 response and on the Investigator's decision, participants will continue on the originally assigned treatment with dose intensification and will not be re-randomized. However, participants that do not dose intensify will be re-randomized.
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
The Investigators, study personnel with the exception of the clinical research organization's unblinded biostatistician and unblinded programmers; and the data monitoring committee, and the study participants will remain blinded to treatment allocation.
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
- •Participants are eligible to be included in the study only if all of the following criteria apply:
- •Stable moderate to severe plaque psoriasis for at least 6 months
- •Baseline score of PASI >= 12, involvement of >= 10% BSA, and sPGA >= 3 at screening and at baseline
- •Candidate for phototherapy or systemic therapy
- •Previous failure, inadequate response, intolerance, or contraindication to at least 1 conventional anti-psoriatic systemic therapy
- •Female participants should have negative serum pregnancy test during screening and a negative urine pregnancy test at baseline
- •No known history of latent or active tuberculosis (TB), and has a negative test for TB during screening (with negative purified protein derivative (PPD), and Negative Quantiferon®/T-spot test)
- •Participants with a positive purified protein derivative and a history of Bacillus Calmette-Guérin (BCG) vaccination are allowed with a negative Quantiferon®/T-spot®
- •Participants with a positive PPD test (without history of BCG vaccination) or participants with a positive or indeterminate Quantiferon®/T-spot test are allowed if they have all of the following:
- •No symptoms per TB worksheet provided by the sponsor
- •Documented history of adequate prophylaxis initiation prior to receiving investigational product (IP) in accordance with local recommendations
- •No known exposure to a case of active TB after most recent prophylaxis
- •No evidence of active TB on chest radiograph within 3 months prior to the first dose of IP
排除标准
- •Participants are excluded from the study if any of the following criteria apply:
- •Skin disease related conditions such as, Erythrodermic psoriasis (PsO), pustular PsO, guttate PsO, medication induced PsO, or other skin conditions at the time of the screening visit (eg, eczema) that would interfere with evaluations of the effect of IP on PsO
- •Participant has an active infection, recurrent or chronic infections, serious infection or history of infections
- •Known history of human immunodeficiency virus
- •Hepatitis B surface antigen or hepatitis C virus antibody positivity at screening
- •Uncontrolled, clinically significant systemic disease such as uncontrolled diabetes mellitus, cardiovascular disease, renal disease, liver disease, or hypertension
- •Moderate to severe heart failure (New York Heart Associate class III/IV)
- •Known hypersensitivity to the IP or to any of the excipients
- •Any abnormal laboratory parameters at screening, as defined in protocol
- •Previous treatment with any agent specifically targeting interleukin (IL)-12 or IL-23
- •Received biologic treatment for psoriasis within the previous month or 5 drug half-lives prior to randomization
- •Received non-biologic systemic psoriasis therapy within 4 weeks prior to randomization
- •Received Ultra-violet A (UVA) phototherapy (with or without psoralen) or excimer laser within 4 weeks prior to randomization, or ultra-violet B (UVB) phototherapy within 2 weeks prior to randomization
- •Received topical psoriasis treatment within 2 weeks prior to randomization (exception: upper mid-strength to least potent [class III to VII] topical steroids permitted on the palms, soles, face, and intertriginous areas; bland emollients)
- •Received live viral or live bacterial vaccination within 2 weeks prior to randomization
- •Received BCG vaccination within 1 year prior to randomization
- •Other investigational procedures within 4 weeks prior to randomization and during the study
- •Participants not agreeing to follow protocol defined contraceptives procedures
- •Participants likely not to be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures
研究组 & 干预措施
Treatment Group B (Ustekinumab - ABP 654)
Participants will receive SC injection of ustekinumab,45 mg (baseline BW <= 100 kg) or 90 mg (baseline BW > 100 kg) at weeks 0, 4, and 16. At week 28, participants will be re-randomized to continue on ustekinumab (Treatment group B1), or to receive ABP 654 (Treatment group B2) on weeks 28 and 40. Depending on PASI score, some participants may not be re-randomized and may receive dose intensification with ustekinumab Q8W at weeks 28, 36, and 44.
干预措施: Ustekinumab (Drug)
Treatment Group B (Ustekinumab - ABP 654)
Participants will receive SC injection of ustekinumab,45 mg (baseline BW <= 100 kg) or 90 mg (baseline BW > 100 kg) at weeks 0, 4, and 16. At week 28, participants will be re-randomized to continue on ustekinumab (Treatment group B1), or to receive ABP 654 (Treatment group B2) on weeks 28 and 40. Depending on PASI score, some participants may not be re-randomized and may receive dose intensification with ustekinumab Q8W at weeks 28, 36, and 44.
干预措施: ABP 654 (Drug)
Treatment Group A (ABP 654)
Participants will receive subcutaneous (SC) injection of ABP 654, 45 mg (baseline BW less than equal to [<=] 100 kg) or 90 mg (baseline BW greater than [>] 100 kg) at weeks 0, 4, and 16. Further from week 28 participants will receive ABP 654 (same dose) every 12 weeks (Q12W) at weeks 28 and 40 or may receive dose intensification Q8W at weeks 28, 36, and 44, depending on PASI score.
干预措施: ABP 654 (Drug)
结局指标
主要结局
PASI Percent Change From Baseline to Week 12
时间窗: Baseline (Day 1 [Week 0]) and Week 12
The PASI is a measure of the average redness (erythema), thickness (induration), and scaliness (scaling; each graded on a 0-4 scale \[0 = clear; 1-4 = increasing severity\]) of the lesions, weighted by the area of involvement in the four main body areas (i.e., head, arms, trunk to groin, and legs to top of buttocks). The PASI score ranges from 0 to 72. Higher scores represent worse symptom severity.
次要结局
- PASI Percent Change at Other Timepoints(Baseline (Day 1 [Week 0]), Weeks 4, 16, 28, 36 (dose intensification only), 40 (re-randomized FAS only), 44 (dose intensification only) and Week 52 (End of Study [EOS]))
- Percentage of Participants With PASI 75 Response Throughout the Study(Baseline (Day 1 [Week 0]), Weeks 4, 16, 28, 36 (dose intensification only), 40 (re-randomized FAS only), 44 (dose intensification only) and Week 52 (EOS))
- Number of Participants Developing Anti-drug Antibodies (ADAs) to ABP 654(Baseline; Day 1 (Week 0) to Week 28; Week 28 to Week 52 (EOS))
- Change From Baseline in Percentage of BSA Affected With Psoriasis at Week 12 and Week 52(Baseline (Day 1 [Week 0]), Week 12 and Week 52 (EOS))
- Number of Participants With Events of Interests (EOIs)(Day 1 (Week 0) to Week 28; Week 28 to Week 52 (EOS))
- Percentage of Participants With PASI 100 Response Throughout the Study(Baseline (Day 1 [Week 0]), Weeks 4, 16, 28, 36 (dose intensification only), 40 (re-randomized FAS only), 44 (dose intensification only) and Week 52 (EOS))
- Percentage of Participants With sPGA Responses (0/1) at Week 12 and Week 52(Week 12 and Week 52 (EOS))
- Number of Participants With Treatment Emergent Adverse Events (TEAEs)(Day 1 (Week 0) to Week 28; Week 28 to Week 52 (EOS))