A 52-Week, Phase 3, Randomized, Active Comparator and Placebo-Controlled, Parallel Design Study to Evaluate the Efficacy and Safety/Tolerability of Subcutaneous Tildrakizumab (SCH 900222/MK-3222), Followed by an Optional Long-Term Safety Extension Study, in Subjects With Moderate-to-Severe Chronic Plaque Psoriasis (Protocol No. MK-3222-011)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,090
- 主要终点
- Percentage of Participants Achieving a Psoriasis Area Sensitivity Index 75% (PASI-75) Response at Week 12 (Part 1)
研究概览
简要总结
This study is being conducted to evaluate the efficacy and safety/tolerability of tildrakizumab (SCH 900222/MK-3222) in a population of participants with moderate-to-severe plaque psoriasis. The primary hypotheses of the study are that tildrakizumab is superior to placebo in the treatment of moderate-to-severe chronic plaque psoriasis as measured by the proportion of participants achieving >= Psoriasis Area Sensitivity Index of 75% (PASI-75) response and the proportion of participants with a Physician's Global Assessment (PGA) score of "clear" or "minimal" with at least a 2 grade reduction from baseline at Week 12.
详细描述
The base study consists of a screening phase of up to 4 weeks followed by a treatment period of 52 weeks, and a 20-week follow-up period. The base study treatment period is divided into 3 sequential parts.
In Part 1 of the base study (Week 0 to Week 12), participants will be randomized to one of 4 study arms (Arm A: tildrakizumab 200 mg + matching placebo to etanercept; Arm B: tildrakizumab 100 mg + matching placebo to etanercept; Arm C: matching placebo to tildrakizumab + matching placebo to etanercept; Arm D: matching placebo to tildrakizumab + etanercept 50 mg).
In Part 2 of the base study (Week 12 to Week 28), participants in Arm A and Arm B will receive matching placebo to tildrakizumab to maintain blinding at Week 12 and will receive either tildrakizumab 200 mg (Arm A) or tildrakizumab 100 mg (Arm B) at Weeks 12 and 16. Participants in Arm A and Arm B will also receive matching placebo to etanercept once weekly through study Week 28. At study Week 12, Arm C participants will be re-randomized to receive their first dose of tildrakizumab 200 mg or tildrakizumab 100 mg, and will receive additional doses of study medication according to their re-randomized treatment assignment at Week 16. Participants in Arm C will also receive matching placebo to etanercept through treatment Week 28. Participants in Arm D will continue with once weekly doses of etanercept through study Week 28 in combination with matching placebo to tildrakizumab.
In Part 3 of the base study (Week 28 to Week 52), participants in Arm A with >= PASI-75 response at Week 28 will be re-randomized to either continue tildrakizumab 200 mg or receive tildrakizumab 100 mg at study Weeks 28, 40, and 52. Participants with >= PASI-50 response but < PASI-75 response will continue to receive tildrakizumab 200 mg every 12 weeks and those participants with < PASI-50 response will be discontinued from the study. Participants in Arm B with >= PASI-75 response at Week 28 will continue to receive tildrakizumab 100 mg every 12 weeks. Those with >= PASI-50 response but < PASI-75 response will be re-randomized to receive continued tildrakizumab 100 mg or tildrakizumab 200 mg every 12 weeks. Participants in Arm B with < PASI-50 response will be discontinued from the study. Participants in Arm C will continue to receive treatment every 12 weeks according to their re-randomized treatment assignment. Participants in Arm D that achieve >= PASI-75 response at Week 28 will be discontinued from the study. Those participants with < PASI-75 response at Week 28 will be crossed over to tildrakizumab 200 mg to receive doses at Weeks 32, 36 and 48.
Eligible participants that choose to enroll in the extension study will have an additional treatment period of up to 192 weeks and will be monitored for an additional 20 weeks in the follow-up period. Each participant will receive tildrakizumab 200 mg or tildrakizumab 100 mg every 12 weeks up to study Week 244 according to their treatment assignment at the conclusion of Part 3 of the base study.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Clinical diagnosis of moderate-to-severe plaque psoriasis for at least 6 months prior to enrollment;
- •Candidate for phototherapy or systemic therapy;
- •Premenopausal female participants must agree to abstain from heterosexual activity or use a medically approved method of contraception or use appropriate effective contraception as per local regulations or guidelines
- •For the extension study: must have completed Part 3 of the base study
- •For the extension study: must have achieved at least a PASI-50 response by the end of Part 3 of the base study
排除标准
- •Non-plaque forms of psoriasis
- •Presence or history of severe psoriatic arthritis and is well-controlled on current treatment regimen
- •Women of childbearing potential who are pregnant, intend to become pregnant, or are lactating
- •Participant is expected to require topical therapy, phototherapy, or systemic therapy during the trial
- •Presence of any infection or history of recurrent infection requiring treatment with systemic antibiotics
- •Previous use of entanercept, tildrakizumab (MK-3222), or other interleukin-23 (IL-23)/T- helper cell 17 (Th-17) pathway inhibitors including p40, p19, and IL-17 antagonists
- •Latex allergy or sensitivity
- •Active or untreated latent tuberculosis (TB)
- •For the extension study: women of child-bearing potential who are pregnant, intend to become pregnant within 6 months of completing the trial, or are breast feeding
- •For the extension study: active or uncontrolled significant organ dysfunction or clinically significant laboratory abnormalities
- •For the extension study: expected to require topical treatment, phototherapy, or systemic treatment during the extension study
研究组 & 干预措施
Tildrakizumab 200 mg
Participants receive tildrakizumab 200 mg subcutaneously (SC) on Weeks 0, 4, 16, 28, 40 and 52 and, optionally, every 12 weeks thereafter until Week 244, plus etanercept placebo (PBO) twice weekly until Week 12 and once weekly from Week 12 to Week 28.
干预措施: Tildrakizumab 200 mg (Drug)
Tildrakizumab 200 mg
Participants receive tildrakizumab 200 mg subcutaneously (SC) on Weeks 0, 4, 16, 28, 40 and 52 and, optionally, every 12 weeks thereafter until Week 244, plus etanercept placebo (PBO) twice weekly until Week 12 and once weekly from Week 12 to Week 28.
干预措施: Etanercept Placebo (Drug)
Tildrakizumab 100 mg
Participants receive tildrakizumab 100 mg SC on Weeks 0, 4, 16, 28, 40 and 52 and, optionally, every 12 weeks thereafter until Week 244, plus etanercept placebo twice weekly until Week 12 and once weekly from Week 12 to Week 28.
干预措施: Tildrakizumab 100 mg (Drug)
Placebo
Participants receive matching placebo to tildrakizumab SC on Weeks 0 and 4 plus etanercept placebo twice weekly up to Week 12 and once weekly from Week 12 to Week 28. Participants will be re-randomized 1:1 at Week 12 to receive tildrakizumab 200 mg or tildrakizumab 100 mg on Weeks 12, 16, 28, 40 and 52 and, optionally, every 12 weeks thereafter until Week 244.
干预措施: Tildrakizumab Placebo (Drug)
Tildrakizumab 100 mg
Participants receive tildrakizumab 100 mg SC on Weeks 0, 4, 16, 28, 40 and 52 and, optionally, every 12 weeks thereafter until Week 244, plus etanercept placebo twice weekly until Week 12 and once weekly from Week 12 to Week 28.
干预措施: Etanercept Placebo (Drug)
Placebo
Participants receive matching placebo to tildrakizumab SC on Weeks 0 and 4 plus etanercept placebo twice weekly up to Week 12 and once weekly from Week 12 to Week 28. Participants will be re-randomized 1:1 at Week 12 to receive tildrakizumab 200 mg or tildrakizumab 100 mg on Weeks 12, 16, 28, 40 and 52 and, optionally, every 12 weeks thereafter until Week 244.
干预措施: Etanercept Placebo (Drug)
Etanercept 50 mg
Participants receive matching placebo to tildrakizumab SC on Weeks 0 and 4 and etanercept 50 mg twice weekly up to Week 12 and once weekly from Week 12 to Week 28. Participants who don't achieve PASI-75, receive tildrakizumab 200 mg after Week 28 (Weeks 32, 36 and 48) and, optionally, every 12 weeks thereafter until Week 244.
干预措施: Tildrakizumab Placebo (Drug)
Etanercept 50 mg
Participants receive matching placebo to tildrakizumab SC on Weeks 0 and 4 and etanercept 50 mg twice weekly up to Week 12 and once weekly from Week 12 to Week 28. Participants who don't achieve PASI-75, receive tildrakizumab 200 mg after Week 28 (Weeks 32, 36 and 48) and, optionally, every 12 weeks thereafter until Week 244.
干预措施: Etanercept 50 mg (Drug)
结局指标
主要结局
Percentage of Participants Achieving a Psoriasis Area Sensitivity Index 75% (PASI-75) Response at Week 12 (Part 1)
时间窗: Week 12
The PASI is a measure of the average redness, thickness, and scaliness of lesions (each graded on a 0-4 scale), weighed by the area of involvement. Calculated PASI score ranges from 0 to 72, with higher score indicating more severe disease status. The PASI-75 response indicates the number of participants achieving a 75% reduction in PASI score compared to baseline. Statistical analyses presented below compare tildrakizumab to placebo to support the primary hypothesis of the study.
Percentage of Participants With a Physician's Global Assessment (PGA) Score of Clear or Minimal With at Least a 2 Grade Reduction From Baseline at Week 12 (Part 1)
时间窗: Week 12
The PGA is used to determine the overall severity of a participant's psoriasis lesions at a given time point. Overall lesions will be graded for thickness, erythema, and scaling on a scale from 0 to 5. The sum of the 3 scales will be divided by 3 to obtain the PGA score. PGA is assessed as: 0= Cleared, except for residual discoloration. 1= Minimal, majority of lesions have individual scores that average 1. 2 =Mild, majority of lesions have individual scores that average 2. 3= Moderate, majority of lesions have individual scores that average 3. 4= Marked, majority of lesions have individual scores that average 4. 5= Severe, majority of lesions have individual scores that average 5. Statistical analyses presented below compare tildrakizumab to placebo to support the primary hypothesis of the study.
Percentage of Participants Experiencing an Adverse Event (AE) Up to Week 12 (Part 1)
时间窗: Up to Week 12
An adverse event is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Percentage of Participants Discontinuing Study Treatment Due to an AE Up to Week 12 (Part 1)
时间窗: Up to Week 12
An adverse event is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
次要结局
- Percentage of Participants Achieving a PASI-75 Response at Week 52 (Part 3)(Week 52)
- Percentage of Participants With a PGA Score of Clear or Minimal With at Least a 2 Grade Reduction From Baseline at Week 52 (Part 3)(Week 52)
- Percentage of Participants Achieving a PASI-90 Response at Week 12 (Part 1)(Week 12)
- Percentage of Participants Achieving a PASI-90 Response at Week 52 (Part 3)(Week 52)
- Percentage of Participants Achieving a PASI-75 Response at Week 28 (Part 2)(Week 28)
- Percentage of Participants Achieving a PASI-75 Response at Week 40 (Part 3)(Week 40)
- Percentage of Participants With a PGA Score of Clear or Minimal With at Least a 2 Grade Reduction From Baseline at Week 28 (Part 2)(Week 28)
- Percentage of Participants With a PGA Score of Clear or Minimal With at Least a 2 Grade Reduction From Baseline at Week 40 (Part 3)(Week 40)
- Percentage of Participants Achieving a PASI-100 Response at Week 12 (Part 1)(Week 12)
- Percentage of Participants Achieving a PASI-90 Response at Week 28 (Part 2)(Week 28)
- Percentage of Participants Achieving a PASI-90 Response at Week 40 (Part 3)(Week 40)
- Percentage of Participants Achieving a PASI-100 Response at Week 28 (Part 2)(Week 28)
- Change From Baseline in the DLQI at Week 28 (Part 2)(Baseline and Week 28)
- Change From Baseline in the DLQI at Week 40 (Part 3)(Baseline and Week 40)
- Percentage of Participants Achieving a PASI-100 Response at Week 40 (Part 3)(Week 40)
- Baseline Dermatology Life Quality Index (DLQI)(Baseline)
- Change From Baseline in the DLQI at Week 12 (Part 1)(Baseline and Week 12)
- Change From Baseline in the DLQI at Week 52 (Part 3)(Baseline and Week 52)
- Percentage of Participants Achieving a PASI-100 Response at Week 52 (Part 3)(Week 52)
- Percentage of Participants With a DLQI Score of 0 or 1 at Week 12 (Part 1)(Week 12)
- Percentage of Participants With a DLQI Score of 0 or 1 at Week 28 (Part 2)(Week 28)
- Percentage of Participants With a DLQI Score of 0 or 1 at Week 40 (Part 3)(Week 40)
- Percentage of Participants With a DLQI Score of 0 or 1 at Week 52 (Part 3)(Week 52)
- Mean Change From Baseline in PASI Score Over Time (Part 1)(Baseline and Week 4, Week 8 or Week 12)
- Mean Change From Baseline in PASI Score Over Time (Part 2)(Baseline and Week 16, Week 22 or Week 28)
- Mean Change From Baseline in PASI Score Over Time (Part 3)(Baseline and Week 32, Week 36, Week 40, Week 46 and Week 52)
- Mean Percent Change From Baseline in PASI Score Over Time (Part 1)(Baseline and Week 4, Week 8 or Week 12)
- Mean Percent Change From Baseline in PASI Score Over Time (Part 2)(Baseline and Week 16, Week 22 or Week 28)
- Mean Percent Change From Baseline in PASI Score Over Time (Part 3)(Baseline and Week 32, Week 36, Week 40, Week 46 and Week 52)