A Study to Evaluate the Efficacy and Safety of Subcutaneous MK-3222, Followed by an Optional Long-Term Safety Extension Study, in Participants With Moderate-to-Severe Chronic Plaque Psoriasis (MK-3222-010)

This study is being conducted to evaluate the efficacy and safety/tolerability of subcutaneous tildrakizumab (MK-3222), followed by an optional long-term safety extension study, in participants with moderate-to-severe chronic plaque psoriasis.

Participants are initially randomized to receive tildrakizumab 200 or 100 mg once weekly at Weeks 0, 4, and every 12 weeks thereafter; or placebo at Weeks 0 and 4.

At Week 12, participants initially randomized to placebo will be re-randomized to receive either tildrakizumab 200 or 100 mg at Weeks 12 and 16.

At Week 28, all participants enrolled will be assessed for their improvement in PASI score from baseline.

RESPONDERS: Participants initially randomized to tildrakizumab who achieve at least a 75% improvement from baseline PASI will be re-randomized to either continue on their initial treatment or to receive placebo at Week 28.

* Participants who are re-randomized to continue on their initial treatment will continue tildrakizumab 200 or 100 mg every 12 weeks through Week 64.
* Participants who are re-randomized to placebo will receive placebo every 4 weeks until relapse (reduction in maximum PASI response by 50%). If relapse occurs, the tildrakizumab dose that the participants was originally randomized to at baseline will be re-initiated (tildrakizumab 200 or 100 mg). Participants will be dosed tildrakizumab at the visit when the relapse occurs, and subsequent dosing of tildrakizumab will be given 4 weeks after treatment re-initiation, and every 12 weeks thereafter through Week 64.

PARTIAL RESPONDERS: Participants initially randomized to tildrakizumab who achieved a PASI response of ≥50% but \<75% improvement from baseline will be assigned a treatment regimen as described below, with their first dose started at Week 28.

* Participants initially randomized to tildrakizumab 200 mg will remain on tildrakizumab 200 mg every 12 weeks.
* Participants initially randomized to tildrakizumab 100 mg will be re-randomized to either remain on tildrakizumab 100 mg every 12 weeks or to receive tildrakizumab 200 mg every 12 weeks.
* Participants initially randomized to placebo who achieved ≥50% improvement from baseline in PASI will receive tildrakizumab (200 or 100 mg) according to their re-randomized treatment assignment at Week 12 and continue on this treatment every 12 weeks through Week 64.

NON-RESPONDERS: Participants who did not achieve at least 50% improvement from baseline PASI at Week 28 will be discontinued from the study.

EXTENSION: Participants will receive tildrakizumab 200 mg or 100 mg every 12 weeks through Extension Week 192, depending on the treatment received at the time of completion of the base study.

Eligibility Criteria:
Inclusion Criteria:

* Clinical diagnosis of moderate-to-severe plaque psoriasis for at least 6 months prior to study enrollment
* A candidate for phototherapy or systemic therapy
* 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
* For the extension study: must have received active tildrakizumab (MK-3222) treatment within 12 weeks prior to the end of Part 3 of the base study
* Premenopausal female participants must agree to abstain from heterosexual activity or use a medically accepted method of contraception or use appropriate effective contraception as per local regulations or guidelines
* If enrolled at a Japanese site, participants with psoriatic arthritis using non-steroidal anti-inflammatory drugs (NSAIDs) must be on a stable dose for at least 4 weeks prior to the first dose of study drug and must not be expected to require an increase in dose over the course of the study

Exclusion Criteria:

* Has erythrodermic psoriasis, predominantly pustular psoriasis, medication-induced or medication-exacerbated psoriasis, or new onset guttate psoriasis
* Current or history of severe psoriatic arthritis and is well-controlled on current treatment
* Women of child-bearing potential who are pregnant, intend to become pregnant within 6 months of completing the trial, or who are breast feeding
* Expected to require topical treatment, phototherapy, or systemic treatment during the trial
* Presence of any infection
* History of recurrent infection requiring treatment with systemic antibiotics within 2 weeks of screening
* Previous use of tildrakizumab (MK-3222) or other IL-23/Th-17 pathway inhibitors including P40, p19, and IL-17 antagonists
* Evidence of active or untreated latent tuberculosis (TB)
* Positive test for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV)
* At Japanese sites, positive test for HBs antibody and hepatitis B virus (HBV) deoxyribonucleic acid (DNA)
* At Japanese sites, positive test for the Hepatitis B core (HBc) antibody and HBV DNA
* For the extension study: women of child-bearing potential who are pregnant, intend to become pregnant within 6 months of completing the trial, or who 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
* At Japanese sites, abnormal for Beta D Glucan and/or KL-6 test result(s) at the screening visit.