A Study to Evaluate the Efficacy and Safety/Tolerability of Subcutaneous Tildrakizumab (SCH 900222/MK-3222) in Participants With Moderate-to-Severe Chronic Plaque Psoriasis Followed by a Long-term Extension Study (MK-3222-011)

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.

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.

Eligibility Criteria:
Inclusion Criteria:

* 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

Exclusion Criteria:

* 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