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)

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)

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01729754

Acronym

reSURFACE 2

Enrollment

1090

Registered

2012-11-20

Start date

2013-02-05

Completion date

2021-10-26

Last updated

2022-03-08

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Plaque Psoriasis

Brief summary

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.

Detailed description

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.

Interventions

DRUGTildrakizumab 200 mg

Tildrakizumab 200 mg administered SC. Each pre-filled syringe (PFS) or autoinjector (AI) contains 1 mL of solution, tildrakizumab 100 mg/mL.

DRUGTildrakizumab 100 mg

Tildrakizumab 100 mg administered SC. Each PFS or AI contains 1 mL of solution, tildrakizumab 100 mg/mL.

DRUGTildrakizumab Placebo

Matching placebo to tildrakizumab administered SC

DRUGEtanercept Placebo

Matching placebo to etanercept administered SC

DRUGEtanercept 50 mg

Etanercept 50 mg administered SC

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Participants Achieving a Psoriasis Area Sensitivity Index 75% (PASI-75) Response at Week 12 (Part 1)	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)	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)	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)	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.

Secondary

Measure	Time frame	Description
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	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. Week-28 responder (Wk-28 R) is a participant who achieved ≥ 75% improvement in PASI from baseline at Week 28. Week-28 partial responder (Wk-28 PR) is a participant who achieved ≥50% and \<75% improvement in PASI response from baseline at Week 28.
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	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. Week-28 responder (Wk-28 R) is a participant who achieved ≥ 75% improvement in PASI from baseline at Week 28. Week-28 partial responder (Wk-28 PR) is a participant who achieved ≥50% and \<75% improvement in PASI response from baseline at Week 28.
Percentage of Participants Achieving a PASI-90 Response at Week 12 (Part 1)	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-90 response indicates the number of participants achieving a 90% reduction in PASI score compared to baseline.
Percentage of Participants Achieving a PASI-90 Response at Week 28 (Part 2)	Week 28	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-90 response indicates the number of participants achieving a 90% reduction in PASI score compared to baseline.
Percentage of Participants Achieving a PASI-90 Response at Week 40 (Part 3)	Week 40	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-90 response indicates the number of participants achieving a 90% reduction in PASI score compared to baseline. Week-28 responder (Wk-28 R) is a participant who achieved ≥ 75% improvement in PASI from baseline at Week 28. Week-28 partial responder (Wk-28 PR) is a participant who achieved ≥50% and \<75% improvement in PASI response from baseline at Week 28.
Percentage of Participants Achieving a PASI-90 Response at Week 52 (Part 3)	Week 52	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-90 response indicates the number of participants achieving a 90% reduction in PASI score compared to baseline. Week-28 responder (Wk-28 R) is a participant who achieved ≥ 75% improvement in PASI from baseline at Week 28. Week-28 partial responder (Wk-28 PR) is a participant who achieved ≥50% and \<75% improvement in PASI response from baseline at Week 28.
Percentage of Participants Achieving a PASI-100 Response at Week 12 (Part 1)	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-100 response indicates the number of participants achieving a 100% reduction in PASI score compared to baseline.
Percentage of Participants Achieving a PASI-100 Response at Week 28 (Part 2)	Week 28	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-100 response indicates the number of participants achieving a 100% reduction in PASI score compared to baseline.
Percentage of Participants Achieving a PASI-100 Response at Week 40 (Part 3)	Week 40	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-100 response indicates the number of participants achieving a 100% reduction in PASI score compared to baseline. Week-28 responder (Wk-28 R) is a participant who achieved ≥ 75% improvement in PASI from baseline at Week 28. Week-28 partial responder (Wk-28 PR) is a participant who achieved ≥50% and \<75% improvement in PASI response from baseline at Week 28.
Percentage of Participants Achieving a PASI-100 Response at Week 52 (Part 3)	Week 52	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-100 response indicates the number of participants achieving a 90% reduction in PASI score compared to baseline. Week-28 responder (Wk-28 R) is a participant who achieved ≥ 75% improvement in PASI from baseline at Week 28. Week-28 partial responder (Wk-28 PR) is a participant who achieved ≥50% and \<75% improvement in PASI response from baseline at Week 28.
Baseline Dermatology Life Quality Index (DLQI)	Baseline	The DLQI questionnaire consists of 10 questions, where each question is scored from 0 (not affected at all) to 3 (very much affected). The DLQI score is the sum of the 10 individual question scores and ranges from 0 to 30, with lower scores indicating better quality of life.
Change From Baseline in the DLQI at Week 12 (Part 1)	Baseline and Week 12	The DLQI questionnaire consists of 10 questions, where each question is scored from 0 (not affected at all) to 3 (very much affected). The DLQI score is the sum of the 10 individual question scores and ranges from 0 to 30, with lower scores indicating better quality of life.
Percentage of Participants Achieving a PASI-75 Response at Week 28 (Part 2)	Week 28	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. Primary analysis for this endpoint is for participants randomized to tildrakizumab 200 mg, tildrakizumab 100 mg, or etanercept in Part 1.
Change From Baseline in the DLQI at Week 40 (Part 3)	Baseline and Week 40	The DLQI questionnaire consists of 10 questions, where each question is scored from 0 (not affected at all) to 3 (very much affected). The DLQI score is the sum of the 10 individual question scores and ranges from 0 to 30, with lower scores indicating better quality of life. Week-28 responder (Wk-28 R) is a participant who achieved ≥ 75% improvement in PASI from baseline at Week 28. Week-28 partial responder (Wk-28 PR) is a participant who achieved ≥50% and \<75% improvement in PASI response from baseline at Week 28.
Change From Baseline in the DLQI at Week 52 (Part 3)	Baseline and Week 52	The DLQI questionnaire consists of 10 questions, where each question is scored from 0 (not affected at all) to 3 (very much affected). The DLQI score is the sum of the 10 individual question scores and ranges from 0 to 30, with lower scores indicating better quality of life. Week-28 responder (Wk-28 R) is a participant who achieved ≥ 75% improvement in PASI from baseline at Week 28. Week-28 partial responder (Wk-28 PR) is a participant who achieved ≥50% and \<75% improvement in PASI response from baseline at Week 28.
Percentage of Participants With a DLQI Score of 0 or 1 at Week 12 (Part 1)	Week 12	The DLQI questionnaire consists of 10 questions, where each question is scored from 0 (not affected at all) to 3 (very much affected). The DLQI score is the sum of the 10 individual question scores and ranges from 0 to 30, with lower scores indicating better quality of life.
Percentage of Participants With a DLQI Score of 0 or 1 at Week 28 (Part 2)	Week 28	The DLQI questionnaire consists of 10 questions, where each question is scored from 0 (not affected at all) to 3 (very much affected). The DLQI score is the sum of the 10 individual question scores and ranges from 0 to 30, with lower scores indicating better quality of life.
Percentage of Participants With a DLQI Score of 0 or 1 at Week 40 (Part 3)	Week 40	The DLQI questionnaire consists of 10 questions, where each question is scored from 0 (not affected at all) to 3 (very much affected). The DLQI score is the sum of the 10 individual question scores and ranges from 0 to 30, with lower scores indicating better quality of life. Week-28 responder (Wk-28 R) is a participant who achieved ≥ 75% improvement in PASI from baseline at Week 28. Week-28 partial responder (Wk-28 PR) is a participant who achieved ≥50% and \<75% improvement in PASI response from baseline at Week 28.
Percentage of Participants With a DLQI Score of 0 or 1 at Week 52 (Part 3)	Week 52	The DLQI questionnaire consists of 10 questions, where each question is scored from 0 (not affected at all) to 3 (very much affected). The DLQI score is the sum of the 10 individual question scores and ranges from 0 to 30, with lower scores indicating better quality of life. Week-28 responder (Wk-28 R) is a participant who achieved ≥ 75% improvement in PASI from baseline at Week 28. Week-28 partial responder (Wk-28 PR) is a participant who achieved ≥50% and \<75% improvement in PASI response from baseline at Week 28.
Mean Change From Baseline in PASI Score Over Time (Part 1)	Baseline and Week 4, Week 8 or 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.
Mean Change From Baseline in PASI Score Over Time (Part 2)	Baseline and Week 16, Week 22 or Week 28	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.
Mean Change From Baseline in PASI Score Over Time (Part 3)	Baseline and Week 32, Week 36, Week 40, Week 46 and Week 52	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. Week-28 responder (Wk-28 R) is a participant who achieved ≥ 75% improvement in PASI from baseline at Week 28. Week-28 partial responder (Wk-28 PR) is a participant who achieved ≥50% and \<75% improvement in PASI response from baseline at Week 28.
Mean Percent Change From Baseline in PASI Score Over Time (Part 1)	Baseline and Week 4, Week 8 or 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.
Mean Percent Change From Baseline in PASI Score Over Time (Part 2)	Baseline and Week 16, Week 22 or Week 28	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.
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	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. Week-28 responder (Wk-28 R) is a participant who achieved ≥ 75% improvement in PASI from baseline at Week 28. Week-28 partial responder (Wk-28 PR) is a participant who achieved ≥50% and \<75% improvement in PASI response from baseline at Week 28.
Change From Baseline in the DLQI at Week 28 (Part 2)	Baseline and Week 28	The DLQI questionnaire consists of 10 questions, where each question is scored from 0 (not affected at all) to 3 (very much affected). The DLQI score is the sum of the 10 individual question scores and ranges from 0 to 30, with lower scores indicating better quality of life.
Percentage of Participants Achieving a PASI-75 Response at Week 40 (Part 3)	Week 40	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. Week-28 responder (Wk-28 R) is a participant who achieved ≥ 75% improvement in PASI from baseline at Week 28. Week-28 partial responder (Wk-28 PR) is a participant who achieved ≥50% and \<75% improvement in PASI response from baseline at Week 28.
Percentage of Participants Achieving a PASI-75 Response at Week 52 (Part 3)	Week 52	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. Week-28 responder (Wk-28 R) is a participant who achieved ≥ 75% improvement in PASI from baseline at Week 28. Week-28 partial responder (Wk-28 PR) is a participant who achieved ≥50% and \<75% improvement in PASI response from baseline at Week 28.
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	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.

Participant flow

Pre-assignment details

The tables below present the Participant Flow for the Base Study only (Weeks 0 to 52: Part 1 for 12 weeks, Part 2 for 16 weeks, and Part 3 for 24 weeks).

Participants by arm

Arm	Count
Tildrakizumab 200 mg (Part 1) Participants received tildrakizumab 200 mg SC on Weeks 0 and 4 plus etanercept placebo twice weekly until Week 12 (Part 1).	314
Tildrakizumab 100 mg (Part 1) Participants received tildrakizumab 100 mg SC on Weeks 0 and 4 plus etanercept placebo twice weekly until Week 12 (Part 1).	307
Placebo (Part 1) Participants received tildrakizumab placebo SC at Weeks 0 and 4 and etanercept placebo SC twice weekly until Week 12 (Part 1).	156
Etanercept 50 mg (Part 1) Participants received matching placebo to tildrakizumab SC on Weeks 0 and 4 and etanercept 50 mg twice weekly until Week 12.	313
Total	1,090

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004	FG005	FG006	FG007	FG008	FG009
Part 1	Adverse Event	2	0	0	1	0	0	2	0	0	5
Part 1	Lack of Efficacy	1	0	0	0	0	0	2	0	0	0
Part 1	Lost to Follow-up	1	0	0	2	0	0	3	0	0	3
Part 1	Non-compliance with Study Drug	1	0	0	0	0	0	0	0	0	0
Part 1	Other Protocol Specified Criteria	2	0	0	0	0	0	1	0	0	4
Part 1	Physician Decision	0	0	0	0	0	0	0	0	0	4
Part 1	Pregnancy	0	0	0	1	0	0	0	0	0	1
Part 1	Progressive Disease	0	0	0	0	0	0	0	0	0	1
Part 1	Protocol Violation	2	0	0	1	0	0	1	0	0	0
Part 1	Withdrawal by Subject	5	0	0	7	0	0	5	0	0	6
Part 2	Adverse Event	2	0	0	0	0	0	0	0	1	2
Part 2	Lack of Efficacy	0	0	0	0	0	0	0	0	2	2
Part 2	Lost to Follow-up	0	0	0	2	0	0	0	1	0	2
Part 2	Non-Compliance with Study Drug	0	0	0	0	0	0	0	0	0	1
Part 2	Other Protocol Specified Criteria	1	0	0	0	0	0	0	1	0	0
Part 2	Pregnancy	0	0	0	1	0	0	0	0	0	1
Part 2	Withdrawal by Subject	3	0	0	2	0	0	0	1	1	4
Part 3	Adverse Event	0	0	1	0	0	5	0	0	0	3
Part 3	Death	0	0	0	0	0	2	0	0	0	0
Part 3	Lack of Efficacy	0	0	0	0	2	0	0	0	0	4
Part 3	Lost to Follow-up	0	1	2	0	0	3	0	0	1	0
Part 3	Other Protocol Specified Criteria	0	0	0	0	0	2	0	1	0	0
Part 3	Physician Decision	0	0	1	0	0	0	0	0	0	0
Part 3	Withdrawal by Subject	0	4	1	0	2	1	0	2	0	0

Baseline characteristics

Characteristic	Total	Tildrakizumab 200 mg (Part 1)	Etanercept 50 mg (Part 1)	Placebo (Part 1)	Tildrakizumab 100 mg (Part 1)
Age, Continuous	45.2 Years STANDARD_DEVIATION 13.52	44.6 Years STANDARD_DEVIATION 13.62	45.8 Years STANDARD_DEVIATION 13.97	46.4 Years STANDARD_DEVIATION 12.2	44.6 Years STANDARD_DEVIATION 13.59
Body weight <=90 kg	626 Participants	180 Participants	180 Participants	90 Participants	176 Participants
Body weight >90 kg	464 Participants	134 Participants	133 Participants	66 Participants	131 Participants
Prior exposure to biologic therapy for psoriasis No	956 Participants	276 Participants	276 Participants	136 Participants	268 Participants
Prior exposure to biologic therapy for psoriasis Yes	134 Participants	38 Participants	37 Participants	20 Participants	39 Participants
Psoriasis Area Sensitivity Index (PASI)	20.1 Score on a scale STANDARD_DEVIATION 7.51	19.8 Score on a scale STANDARD_DEVIATION 7.52	20.2 Score on a scale STANDARD_DEVIATION 7.36	20.0 Score on a scale STANDARD_DEVIATION 7.57	20.5 Score on a scale STANDARD_DEVIATION 7.63
Race (NIH/OMB) American Indian or Alaska Native	2 Participants	0 Participants	1 Participants	0 Participants	1 Participants
Race (NIH/OMB) Asian	36 Participants	14 Participants	10 Participants	3 Participants	9 Participants
Race (NIH/OMB) Black or African American	24 Participants	8 Participants	8 Participants	1 Participants	7 Participants
Race (NIH/OMB) More than one race	15 Participants	2 Participants	3 Participants	3 Participants	7 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants	0 Participants	0 Participants	1 Participants	0 Participants
Race (NIH/OMB) Unknown or Not Reported	16 Participants	6 Participants	2 Participants	4 Participants	4 Participants
Race (NIH/OMB) White	996 Participants	284 Participants	289 Participants	144 Participants	279 Participants
Sex: Female, Male Female	311 Participants	89 Participants	91 Participants	44 Participants	87 Participants
Sex: Female, Male Male	779 Participants	225 Participants	222 Participants	112 Participants	220 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	0 / 527	3 / 487	0 / 156	0 / 313
other Total, other adverse events	167 / 527	151 / 487	23 / 156	118 / 313
serious Total, serious adverse events	26 / 527	30 / 487	4 / 156	20 / 313

Outcome results

Primary

Percentage of Participants Achieving a Psoriasis Area Sensitivity Index 75% (PASI-75) Response at Week 12 (Part 1)

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.

Time frame: Week 12

Population: Analysis population includes all randomized participants who received at least 1 dose of Part 1 study treatment based on the treatment assigned.

Arm	Measure	Value (NUMBER)
Tildrakizumab 200 mg	Percentage of Participants Achieving a Psoriasis Area Sensitivity Index 75% (PASI-75) Response at Week 12 (Part 1)	65.6 Percentage of participants
Tildrakizumab 100 mg	Percentage of Participants Achieving a Psoriasis Area Sensitivity Index 75% (PASI-75) Response at Week 12 (Part 1)	61.2 Percentage of participants
Placebo	Percentage of Participants Achieving a Psoriasis Area Sensitivity Index 75% (PASI-75) Response at Week 12 (Part 1)	5.8 Percentage of participants
Etanercept 50 mg	Percentage of Participants Achieving a Psoriasis Area Sensitivity Index 75% (PASI-75) Response at Week 12 (Part 1)	48.2 Percentage of participants

p-value: <0.00195% CI: [52.9, 65.9]Cochran-Mantel-Haenszel

p-value: <0.00195% CI: [48.3, 61.8]Cochran-Mantel-Haenszel

Primary

Percentage of Participants Discontinuing Study Treatment Due to an AE Up to Week 12 (Part 1)

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.

Time frame: Up to Week 12

Population: Analysis population includes participants who took at least one dose of Part 1 study medication based on the treatment actually received.

Arm	Measure	Value (NUMBER)
Tildrakizumab 200 mg	Percentage of Participants Discontinuing Study Treatment Due to an AE Up to Week 12 (Part 1)	1.0 Percentage of participants
Tildrakizumab 100 mg	Percentage of Participants Discontinuing Study Treatment Due to an AE Up to Week 12 (Part 1)	1.0 Percentage of participants
Placebo	Percentage of Participants Discontinuing Study Treatment Due to an AE Up to Week 12 (Part 1)	1.3 Percentage of participants
Etanercept 50 mg	Percentage of Participants Discontinuing Study Treatment Due to an AE Up to Week 12 (Part 1)	1.9 Percentage of participants

Primary

Percentage of Participants Experiencing an Adverse Event (AE) Up to Week 12 (Part 1)

Time frame: Up to Week 12

Population: Analysis population includes participants who took at least one dose of Part 1 study drug based on the treatment actually received.

Arm	Measure	Value (NUMBER)
Tildrakizumab 200 mg	Percentage of Participants Experiencing an Adverse Event (AE) Up to Week 12 (Part 1)	49.4 Percentage of participants
Tildrakizumab 100 mg	Percentage of Participants Experiencing an Adverse Event (AE) Up to Week 12 (Part 1)	44.3 Percentage of participants
Placebo	Percentage of Participants Experiencing an Adverse Event (AE) Up to Week 12 (Part 1)	55.1 Percentage of participants
Etanercept 50 mg	Percentage of Participants Experiencing an Adverse Event (AE) Up to Week 12 (Part 1)	54.0 Percentage of participants

Primary

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)

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.

Time frame: Week 12

Population: Analysis population includes all randomized participants who received at least 1 dose of Part 1 study treatment based on the treatment assigned.

Arm	Measure	Value (NUMBER)
Tildrakizumab 200 mg	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)	59.2 Percentage of participants
Tildrakizumab 100 mg	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)	54.7 Percentage of participants
Placebo	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)	4.5 Percentage of participants
Etanercept 50 mg	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)	47.6 Percentage of participants

p-value: <0.00195% CI: [47.9, 60.8]Cochran-Mantel-Haenszel

p-value: <0.00195% CI: [43.2, 56.5]Cochran-Mantel-Haenszel

Secondary

Baseline Dermatology Life Quality Index (DLQI)

Time frame: Baseline

Population: Analysis population includes randomized participants who received at least one dose of study medication with baseline and post-baseline DLQI values in Part 1.

Arm	Measure	Value (MEAN)	Dispersion
Tildrakizumab 200 mg	Baseline Dermatology Life Quality Index (DLQI)	13.2 Score on a scale	Standard Deviation 7.03
Tildrakizumab 100 mg	Baseline Dermatology Life Quality Index (DLQI)	14.8 Score on a scale	Standard Deviation 7.24
Placebo	Baseline Dermatology Life Quality Index (DLQI)	13.7 Score on a scale	Standard Deviation 6.98
Etanercept 50 mg	Baseline Dermatology Life Quality Index (DLQI)	14.5 Score on a scale	Standard Deviation 7.2

Secondary

Change From Baseline in the DLQI at Week 12 (Part 1)

Time frame: Baseline and Week 12

Population: Analysis population includes randomized participants who received at least one dose of study medication with baseline or post-baseline DLQI values in Part 1.

Arm	Measure	Value (LEAST_SQUARES_MEAN)
Tildrakizumab 200 mg	Change From Baseline in the DLQI at Week 12 (Part 1)	-10.3 Score on a scale
Tildrakizumab 100 mg	Change From Baseline in the DLQI at Week 12 (Part 1)	-10.2 Score on a scale
Placebo	Change From Baseline in the DLQI at Week 12 (Part 1)	-2.0 Score on a scale
Etanercept 50 mg	Change From Baseline in the DLQI at Week 12 (Part 1)	-8.9 Score on a scale

p-value: <0.00195% CI: [-9.3, -7.2]cLDA

p-value: <0.00195% CI: [-9.3, -7.3]cLDA

p-value: 0.00295% CI: [-2.1, -0.5]cLDA

p-value: 0.00195% CI: [-2.2, -0.6]cLDA

Secondary

Change From Baseline in the DLQI at Week 28 (Part 2)

Time frame: Baseline and Week 28

Population: Analysis population includes randomized participants who received at least one dose of study medication and with baseline or post-baseline DLQI values in Part 1 or Part 2.

Arm	Measure	Value (LEAST_SQUARES_MEAN)
Tildrakizumab 200 mg	Change From Baseline in the DLQI at Week 28 (Part 2)	-11.7 Score on a scale
Tildrakizumab 100 mg	Change From Baseline in the DLQI at Week 28 (Part 2)	-11.2 Score on a scale
Placebo	Change From Baseline in the DLQI at Week 28 (Part 2)	-9.5 Score on a scale

p-value: <0.00195% CI: [-2.4, -1]cLDA

p-value: <0.00195% CI: [-2.9, -1.5]cLDA

Secondary

Change From Baseline in the DLQI at Week 40 (Part 3)

The DLQI questionnaire consists of 10 questions, where each question is scored from 0 (not affected at all) to 3 (very much affected). The DLQI score is the sum of the 10 individual question scores and ranges from 0 to 30, with lower scores indicating better quality of life. Week-28 responder (Wk-28 R) is a participant who achieved ≥ 75% improvement in PASI from baseline at Week 28. Week-28 partial responder (Wk-28 PR) is a participant who achieved ≥50% and \<75% improvement in PASI response from baseline at Week 28.

Time frame: Baseline and Week 40

Population: Participants who received at least one dose of study medication in Part 3 and with valid DLQI value at baseline and Week 40.

Arm	Measure	Value (MEAN)	Dispersion
Tildrakizumab 200 mg	Change From Baseline in the DLQI at Week 40 (Part 3)	-11.6 Score on a scale	Standard Deviation 6.61
Tildrakizumab 100 mg	Change From Baseline in the DLQI at Week 40 (Part 3)	-12.0 Score on a scale	Standard Deviation 7.11
Placebo	Change From Baseline in the DLQI at Week 40 (Part 3)	-13.2 Score on a scale	Standard Deviation 6.92
Etanercept 50 mg	Change From Baseline in the DLQI at Week 40 (Part 3)	-9.7 Score on a scale	Standard Deviation 5.62
Tildrakizumab 100 mg (Parts 1 & 2)/ 200 mg (Part 3) Wk-28 PR	Change From Baseline in the DLQI at Week 40 (Part 3)	-9.0 Score on a scale	Standard Deviation 7.76
Tildrakizumab 100 mg (Parts 1, 2, & 3) Wk-28 PR	Change From Baseline in the DLQI at Week 40 (Part 3)	-9.8 Score on a scale	Standard Deviation 7.25
Placebo (Part 1)/ Tildrakizumab 200 mg (Parts 2 & 3)	Change From Baseline in the DLQI at Week 40 (Part 3)	-10.4 Score on a scale	Standard Deviation 6.66
Placebo (Part 1)/ Tildrakizumab 100 mg (Parts 2 & 3)	Change From Baseline in the DLQI at Week 40 (Part 3)	-10.1 Score on a scale	Standard Deviation 6.08
Etanercept 50 mg (Parts 1 & 2)/ Tildrakizumab 200 mg (Part 3)	Change From Baseline in the DLQI at Week 40 (Part 3)	-10.8 Score on a scale	Standard Deviation 6.81

Secondary

Change From Baseline in the DLQI at Week 52 (Part 3)

Time frame: Baseline and Week 52

Population: Participants who received at least one dose of study medication in Part 3 and with valid DLQI value at baseline and Week 52.

Arm	Measure	Value (MEAN)	Dispersion
Tildrakizumab 200 mg	Change From Baseline in the DLQI at Week 52 (Part 3)	-11.3 Score on a scale	Standard Deviation 6.16
Tildrakizumab 100 mg	Change From Baseline in the DLQI at Week 52 (Part 3)	-11.5 Score on a scale	Standard Deviation 7.26
Placebo	Change From Baseline in the DLQI at Week 52 (Part 3)	-13.1 Score on a scale	Standard Deviation 6.8
Etanercept 50 mg	Change From Baseline in the DLQI at Week 52 (Part 3)	-9.2 Score on a scale	Standard Deviation 6.18
Tildrakizumab 100 mg (Parts 1 & 2)/ 200 mg (Part 3) Wk-28 PR	Change From Baseline in the DLQI at Week 52 (Part 3)	-9.4 Score on a scale	Standard Deviation 8.47
Tildrakizumab 100 mg (Parts 1, 2, & 3) Wk-28 PR	Change From Baseline in the DLQI at Week 52 (Part 3)	-9.3 Score on a scale	Standard Deviation 7.22
Placebo (Part 1)/ Tildrakizumab 200 mg (Parts 2 & 3)	Change From Baseline in the DLQI at Week 52 (Part 3)	-11.1 Score on a scale	Standard Deviation 6.45
Placebo (Part 1)/ Tildrakizumab 100 mg (Parts 2 & 3)	Change From Baseline in the DLQI at Week 52 (Part 3)	-10.4 Score on a scale	Standard Deviation 6.38
Etanercept 50 mg (Parts 1 & 2)/ Tildrakizumab 200 mg (Part 3)	Change From Baseline in the DLQI at Week 52 (Part 3)	-11.5 Score on a scale	Standard Deviation 6.97

Secondary

Mean Change From Baseline in PASI Score Over Time (Part 1)

Time frame: Baseline and Week 4, Week 8 or Week 12

Population: Analysis population includes randomized participants who received at least one dose of study medication in Part 1 and with valid PASI value at baseline and at the time point for endpoint (ie, Weeks 4, 8 and 12).

Arm	Measure	Group	Value (MEAN)	Dispersion
Tildrakizumab 200 mg	Mean Change From Baseline in PASI Score Over Time (Part 1)	Week 4	-8.1 Scores on a scale	Standard Deviation 6.54
Tildrakizumab 200 mg	Mean Change From Baseline in PASI Score Over Time (Part 1)	Week 12	-15.4 Scores on a scale	Standard Deviation 7.77
Tildrakizumab 200 mg	Mean Change From Baseline in PASI Score Over Time (Part 1)	Week 8	-13.1 Scores on a scale	Standard Deviation 7.71
Tildrakizumab 100 mg	Mean Change From Baseline in PASI Score Over Time (Part 1)	Week 4	-7.9 Scores on a scale	Standard Deviation 6.83
Tildrakizumab 100 mg	Mean Change From Baseline in PASI Score Over Time (Part 1)	Week 12	-15.1 Scores on a scale	Standard Deviation 7.94
Tildrakizumab 100 mg	Mean Change From Baseline in PASI Score Over Time (Part 1)	Week 8	-12.8 Scores on a scale	Standard Deviation 7.57
Placebo	Mean Change From Baseline in PASI Score Over Time (Part 1)	Week 8	-3.1 Scores on a scale	Standard Deviation 7.18
Placebo	Mean Change From Baseline in PASI Score Over Time (Part 1)	Week 4	-2.3 Scores on a scale	Standard Deviation 6.18
Placebo	Mean Change From Baseline in PASI Score Over Time (Part 1)	Week 12	-3.4 Scores on a scale	Standard Deviation 6.77
Etanercept 50 mg	Mean Change From Baseline in PASI Score Over Time (Part 1)	Week 4	-7.0 Scores on a scale	Standard Deviation 7.15
Etanercept 50 mg	Mean Change From Baseline in PASI Score Over Time (Part 1)	Week 12	-13.5 Scores on a scale	Standard Deviation 8.29
Etanercept 50 mg	Mean Change From Baseline in PASI Score Over Time (Part 1)	Week 8	-11.4 Scores on a scale	Standard Deviation 8.77

Secondary

Mean Change From Baseline in PASI Score Over Time (Part 2)

Time frame: Baseline and Week 16, Week 22 or Week 28

Population: Analysis population includes randomized participants who received at least one dose of study medication in Part 2 and with valid PASI value at baseline and at the time point for endpoint (ie, Weeks 16, 22 and 28).

Arm	Measure	Group	Value (MEAN)	Dispersion
Tildrakizumab 200 mg	Mean Change From Baseline in PASI Score Over Time (Part 2)	Week 16	-16.2 Scores on a scale	Standard Deviation 7.7
Tildrakizumab 200 mg	Mean Change From Baseline in PASI Score Over Time (Part 2)	Week 28	-17.0 Scores on a scale	Standard Deviation 7.81
Tildrakizumab 200 mg	Mean Change From Baseline in PASI Score Over Time (Part 2)	Week 22	-17.1 Scores on a scale	Standard Deviation 7.66
Tildrakizumab 100 mg	Mean Change From Baseline in PASI Score Over Time (Part 2)	Week 22	-16.7 Scores on a scale	Standard Deviation 7.88
Tildrakizumab 100 mg	Mean Change From Baseline in PASI Score Over Time (Part 2)	Week 16	-15.9 Scores on a scale	Standard Deviation 7.87
Tildrakizumab 100 mg	Mean Change From Baseline in PASI Score Over Time (Part 2)	Week 28	-16.5 Scores on a scale	Standard Deviation 7.71
Placebo	Mean Change From Baseline in PASI Score Over Time (Part 2)	Week 22	-14.5 Scores on a scale	Standard Deviation 8.32
Placebo	Mean Change From Baseline in PASI Score Over Time (Part 2)	Week 16	-14.2 Scores on a scale	Standard Deviation 8.2
Placebo	Mean Change From Baseline in PASI Score Over Time (Part 2)	Week 28	-14.8 Scores on a scale	Standard Deviation 7.85
Etanercept 50 mg	Mean Change From Baseline in PASI Score Over Time (Part 2)	Week 16	-11.6 Scores on a scale	Standard Deviation 6.97
Etanercept 50 mg	Mean Change From Baseline in PASI Score Over Time (Part 2)	Week 28	-17.3 Scores on a scale	Standard Deviation 7.62
Etanercept 50 mg	Mean Change From Baseline in PASI Score Over Time (Part 2)	Week 22	-15.1 Scores on a scale	Standard Deviation 6.55
Tildrakizumab 100 mg (Parts 1 & 2)/ 200 mg (Part 3) Wk-28 PR	Mean Change From Baseline in PASI Score Over Time (Part 2)	Week 22	-13.7 Scores on a scale	Standard Deviation 7.18
Tildrakizumab 100 mg (Parts 1 & 2)/ 200 mg (Part 3) Wk-28 PR	Mean Change From Baseline in PASI Score Over Time (Part 2)	Week 16	-9.6 Scores on a scale	Standard Deviation 6.71
Tildrakizumab 100 mg (Parts 1 & 2)/ 200 mg (Part 3) Wk-28 PR	Mean Change From Baseline in PASI Score Over Time (Part 2)	Week 28	-14.5 Scores on a scale	Standard Deviation 8.46

Secondary

Mean Change From Baseline in PASI Score Over Time (Part 3)

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. Week-28 responder (Wk-28 R) is a participant who achieved ≥ 75% improvement in PASI from baseline at Week 28. Week-28 partial responder (Wk-28 PR) is a participant who achieved ≥50% and \<75% improvement in PASI response from baseline at Week 28.

Time frame: Baseline and Week 32, Week 36, Week 40, Week 46 and Week 52

Population: Analysis population includes randomized participants who received at least one dose of study medication in Part 3 and with valid PASI value at baseline and at the time point for endpoint (ie, Weeks 32, 36, 40, 46 and 52).

Arm	Measure	Group	Value (MEAN)	Dispersion
Tildrakizumab 200 mg	Mean Change From Baseline in PASI Score Over Time (Part 3)	Week 36	-18.9 Scores on a scale	Standard Deviation 7.11
Tildrakizumab 200 mg	Mean Change From Baseline in PASI Score Over Time (Part 3)	Week 52	-18.9 Scores on a scale	Standard Deviation 7.13
Tildrakizumab 200 mg	Mean Change From Baseline in PASI Score Over Time (Part 3)	Week 32	-19.0 Scores on a scale	Standard Deviation 7.13
Tildrakizumab 200 mg	Mean Change From Baseline in PASI Score Over Time (Part 3)	Week 46	-19.0 Scores on a scale	Standard Deviation 7.13
Tildrakizumab 200 mg	Mean Change From Baseline in PASI Score Over Time (Part 3)	Week 40	-18.8 Scores on a scale	Standard Deviation 7.04
Tildrakizumab 100 mg	Mean Change From Baseline in PASI Score Over Time (Part 3)	Week 40	-18.5 Scores on a scale	Standard Deviation 7.56
Tildrakizumab 100 mg	Mean Change From Baseline in PASI Score Over Time (Part 3)	Week 32	-19.0 Scores on a scale	Standard Deviation 8.03
Tildrakizumab 100 mg	Mean Change From Baseline in PASI Score Over Time (Part 3)	Week 52	-18.4 Scores on a scale	Standard Deviation 7.66
Tildrakizumab 100 mg	Mean Change From Baseline in PASI Score Over Time (Part 3)	Week 36	-19.0 Scores on a scale	Standard Deviation 8.17
Tildrakizumab 100 mg	Mean Change From Baseline in PASI Score Over Time (Part 3)	Week 46	-18.1 Scores on a scale	Standard Deviation 7.45
Placebo	Mean Change From Baseline in PASI Score Over Time (Part 3)	Week 46	-18.7 Scores on a scale	Standard Deviation 6.76
Placebo	Mean Change From Baseline in PASI Score Over Time (Part 3)	Week 40	-18.7 Scores on a scale	Standard Deviation 6.95
Placebo	Mean Change From Baseline in PASI Score Over Time (Part 3)	Week 32	-18.7 Scores on a scale	Standard Deviation 6.83
Placebo	Mean Change From Baseline in PASI Score Over Time (Part 3)	Week 52	-18.4 Scores on a scale	Standard Deviation 6.65
Placebo	Mean Change From Baseline in PASI Score Over Time (Part 3)	Week 36	-18.9 Scores on a scale	Standard Deviation 7.18
Etanercept 50 mg	Mean Change From Baseline in PASI Score Over Time (Part 3)	Week 52	-14.6 Scores on a scale	Standard Deviation 5.72
Etanercept 50 mg	Mean Change From Baseline in PASI Score Over Time (Part 3)	Week 36	-14.5 Scores on a scale	Standard Deviation 5.92
Etanercept 50 mg	Mean Change From Baseline in PASI Score Over Time (Part 3)	Week 46	-14.5 Scores on a scale	Standard Deviation 5.99
Etanercept 50 mg	Mean Change From Baseline in PASI Score Over Time (Part 3)	Week 32	-14.0 Scores on a scale	Standard Deviation 5.72
Etanercept 50 mg	Mean Change From Baseline in PASI Score Over Time (Part 3)	Week 40	-14.4 Scores on a scale	Standard Deviation 6
Tildrakizumab 100 mg (Parts 1 & 2)/ 200 mg (Part 3) Wk-28 PR	Mean Change From Baseline in PASI Score Over Time (Part 3)	Week 40	-16.0 Scores on a scale	Standard Deviation 8.73
Tildrakizumab 100 mg (Parts 1 & 2)/ 200 mg (Part 3) Wk-28 PR	Mean Change From Baseline in PASI Score Over Time (Part 3)	Week 32	-15.0 Scores on a scale	Standard Deviation 6.69
Tildrakizumab 100 mg (Parts 1 & 2)/ 200 mg (Part 3) Wk-28 PR	Mean Change From Baseline in PASI Score Over Time (Part 3)	Week 36	-15.7 Scores on a scale	Standard Deviation 8.09
Tildrakizumab 100 mg (Parts 1 & 2)/ 200 mg (Part 3) Wk-28 PR	Mean Change From Baseline in PASI Score Over Time (Part 3)	Week 46	-16.2 Scores on a scale	Standard Deviation 8.76
Tildrakizumab 100 mg (Parts 1 & 2)/ 200 mg (Part 3) Wk-28 PR	Mean Change From Baseline in PASI Score Over Time (Part 3)	Week 52	-15.5 Scores on a scale	Standard Deviation 9
Tildrakizumab 100 mg (Parts 1, 2, & 3) Wk-28 PR	Mean Change From Baseline in PASI Score Over Time (Part 3)	Week 36	-16.0 Scores on a scale	Standard Deviation 8.13
Tildrakizumab 100 mg (Parts 1, 2, & 3) Wk-28 PR	Mean Change From Baseline in PASI Score Over Time (Part 3)	Week 40	-16.5 Scores on a scale	Standard Deviation 8.59
Tildrakizumab 100 mg (Parts 1, 2, & 3) Wk-28 PR	Mean Change From Baseline in PASI Score Over Time (Part 3)	Week 46	-15.8 Scores on a scale	Standard Deviation 9.72
Tildrakizumab 100 mg (Parts 1, 2, & 3) Wk-28 PR	Mean Change From Baseline in PASI Score Over Time (Part 3)	Week 52	-16.3 Scores on a scale	Standard Deviation 9.55
Tildrakizumab 100 mg (Parts 1, 2, & 3) Wk-28 PR	Mean Change From Baseline in PASI Score Over Time (Part 3)	Week 32	-15.5 Scores on a scale	Standard Deviation 7.08
Placebo (Part 1)/ Tildrakizumab 200 mg (Parts 2 & 3)	Mean Change From Baseline in PASI Score Over Time (Part 3)	Week 40	-17.9 Scores on a scale	Standard Deviation 7.03
Placebo (Part 1)/ Tildrakizumab 200 mg (Parts 2 & 3)	Mean Change From Baseline in PASI Score Over Time (Part 3)	Week 36	-17.6 Scores on a scale	Standard Deviation 6.8
Placebo (Part 1)/ Tildrakizumab 200 mg (Parts 2 & 3)	Mean Change From Baseline in PASI Score Over Time (Part 3)	Week 32	-16.9 Scores on a scale	Standard Deviation 7.68
Placebo (Part 1)/ Tildrakizumab 200 mg (Parts 2 & 3)	Mean Change From Baseline in PASI Score Over Time (Part 3)	Week 46	-17.9 Scores on a scale	Standard Deviation 6.24
Placebo (Part 1)/ Tildrakizumab 200 mg (Parts 2 & 3)	Mean Change From Baseline in PASI Score Over Time (Part 3)	Week 52	-18.1 Scores on a scale	Standard Deviation 7
Placebo (Part 1)/ Tildrakizumab 100 mg (Parts 2 & 3)	Mean Change From Baseline in PASI Score Over Time (Part 3)	Week 40	-16.9 Scores on a scale	Standard Deviation 7.99
Placebo (Part 1)/ Tildrakizumab 100 mg (Parts 2 & 3)	Mean Change From Baseline in PASI Score Over Time (Part 3)	Week 36	-16.7 Scores on a scale	Standard Deviation 8.19
Placebo (Part 1)/ Tildrakizumab 100 mg (Parts 2 & 3)	Mean Change From Baseline in PASI Score Over Time (Part 3)	Week 52	-17.0 Scores on a scale	Standard Deviation 7.3
Placebo (Part 1)/ Tildrakizumab 100 mg (Parts 2 & 3)	Mean Change From Baseline in PASI Score Over Time (Part 3)	Week 46	-17.1 Scores on a scale	Standard Deviation 7.3
Placebo (Part 1)/ Tildrakizumab 100 mg (Parts 2 & 3)	Mean Change From Baseline in PASI Score Over Time (Part 3)	Week 32	-16.4 Scores on a scale	Standard Deviation 8.02
Etanercept 50 mg (Parts 1 & 2)/ Tildrakizumab 200 mg (Part 3)	Mean Change From Baseline in PASI Score Over Time (Part 3)	Week 52	-16.2 Scores on a scale	Standard Deviation 6.83
Etanercept 50 mg (Parts 1 & 2)/ Tildrakizumab 200 mg (Part 3)	Mean Change From Baseline in PASI Score Over Time (Part 3)	Week 32	-10.5 Scores on a scale	Standard Deviation 6.25
Etanercept 50 mg (Parts 1 & 2)/ Tildrakizumab 200 mg (Part 3)	Mean Change From Baseline in PASI Score Over Time (Part 3)	Week 46	-15.6 Scores on a scale	Standard Deviation 7.16
Etanercept 50 mg (Parts 1 & 2)/ Tildrakizumab 200 mg (Part 3)	Mean Change From Baseline in PASI Score Over Time (Part 3)	Week 36	-12.9 Scores on a scale	Standard Deviation 6.64
Etanercept 50 mg (Parts 1 & 2)/ Tildrakizumab 200 mg (Part 3)	Mean Change From Baseline in PASI Score Over Time (Part 3)	Week 40	-14.6 Scores on a scale	Standard Deviation 6.42

Secondary

Mean Percent Change From Baseline in PASI Score Over Time (Part 1)

Time frame: Baseline and Week 4, Week 8 or Week 12

Arm	Measure	Group	Value (MEAN)	Dispersion
Tildrakizumab 200 mg	Mean Percent Change From Baseline in PASI Score Over Time (Part 1)	Week 4	-40.2 Percent change	Standard Deviation 27.86
Tildrakizumab 200 mg	Mean Percent Change From Baseline in PASI Score Over Time (Part 1)	Week 12	-78.0 Percent change	Standard Deviation 22.31
Tildrakizumab 200 mg	Mean Percent Change From Baseline in PASI Score Over Time (Part 1)	Week 8	-65.7 Percent change	Standard Deviation 26.58
Tildrakizumab 100 mg	Mean Percent Change From Baseline in PASI Score Over Time (Part 1)	Week 4	-39.3 Percent change	Standard Deviation 30.02
Tildrakizumab 100 mg	Mean Percent Change From Baseline in PASI Score Over Time (Part 1)	Week 12	-74.8 Percent change	Standard Deviation 28.11
Tildrakizumab 100 mg	Mean Percent Change From Baseline in PASI Score Over Time (Part 1)	Week 8	-63.8 Percent change	Standard Deviation 29.65
Placebo	Mean Percent Change From Baseline in PASI Score Over Time (Part 1)	Week 8	-15.3 Percent change	Standard Deviation 35.95
Placebo	Mean Percent Change From Baseline in PASI Score Over Time (Part 1)	Week 4	-11.7 Percent change	Standard Deviation 30.37
Placebo	Mean Percent Change From Baseline in PASI Score Over Time (Part 1)	Week 12	-17.4 Percent change	Standard Deviation 32.95
Etanercept 50 mg	Mean Percent Change From Baseline in PASI Score Over Time (Part 1)	Week 4	-33.9 Percent change	Standard Deviation 33.55
Etanercept 50 mg	Mean Percent Change From Baseline in PASI Score Over Time (Part 1)	Week 12	-66.7 Percent change	Standard Deviation 30.78
Etanercept 50 mg	Mean Percent Change From Baseline in PASI Score Over Time (Part 1)	Week 8	-55.7 Percent change	Standard Deviation 35.1

Secondary

Mean Percent Change From Baseline in PASI Score Over Time (Part 2)

Time frame: Baseline and Week 16, Week 22 or Week 28

Arm	Measure	Group	Value (MEAN)	Dispersion
Tildrakizumab 200 mg	Mean Percent Change From Baseline in PASI Score Over Time (Part 2)	Week 16	-82.0 Percent change	Standard Deviation 21.26
Tildrakizumab 200 mg	Mean Percent Change From Baseline in PASI Score Over Time (Part 2)	Week 28	-85.7 Percent change	Standard Deviation 17.44
Tildrakizumab 200 mg	Mean Percent Change From Baseline in PASI Score Over Time (Part 2)	Week 22	-86.6 Percent change	Standard Deviation 17.58
Tildrakizumab 100 mg	Mean Percent Change From Baseline in PASI Score Over Time (Part 2)	Week 22	-82.9 Percent change	Standard Deviation 23.16
Tildrakizumab 100 mg	Mean Percent Change From Baseline in PASI Score Over Time (Part 2)	Week 16	-79.3 Percent change	Standard Deviation 25.27
Tildrakizumab 100 mg	Mean Percent Change From Baseline in PASI Score Over Time (Part 2)	Week 28	-82.5 Percent change	Standard Deviation 22.33
Placebo	Mean Percent Change From Baseline in PASI Score Over Time (Part 2)	Week 22	-71.9 Percent change	Standard Deviation 29.4
Placebo	Mean Percent Change From Baseline in PASI Score Over Time (Part 2)	Week 16	-70.3 Percent change	Standard Deviation 27.55
Placebo	Mean Percent Change From Baseline in PASI Score Over Time (Part 2)	Week 28	-73.5 Percent change	Standard Deviation 24.4
Etanercept 50 mg	Mean Percent Change From Baseline in PASI Score Over Time (Part 2)	Week 16	-59.2 Percent change	Standard Deviation 28.34
Etanercept 50 mg	Mean Percent Change From Baseline in PASI Score Over Time (Part 2)	Week 28	-84.0 Percent change	Standard Deviation 16.89
Etanercept 50 mg	Mean Percent Change From Baseline in PASI Score Over Time (Part 2)	Week 22	-77.9 Percent change	Standard Deviation 20.25
Tildrakizumab 100 mg (Parts 1 & 2)/ 200 mg (Part 3) Wk-28 PR	Mean Percent Change From Baseline in PASI Score Over Time (Part 2)	Week 22	-70.1 Percent change	Standard Deviation 25.24
Tildrakizumab 100 mg (Parts 1 & 2)/ 200 mg (Part 3) Wk-28 PR	Mean Percent Change From Baseline in PASI Score Over Time (Part 2)	Week 16	-49.4 Percent change	Standard Deviation 28.95
Tildrakizumab 100 mg (Parts 1 & 2)/ 200 mg (Part 3) Wk-28 PR	Mean Percent Change From Baseline in PASI Score Over Time (Part 2)	Week 28	-72.9 Percent change	Standard Deviation 30.05

Secondary

Mean Percent Change From Baseline in PASI Score Over Time (Part 3)

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. Week-28 responder (Wk-28 R) is a participant who achieved ≥ 75% improvement in PASI from baseline at Week 28. Week-28 partial responder (Wk-28 PR) is a participant who achieved ≥50% and \<75% improvement in PASI response from baseline at Week 28.

Time frame: Baseline and Week 32, Week 36, Week 40, Week 46 and Week 52

Arm	Measure	Group	Value (MEAN)	Dispersion
Tildrakizumab 200 mg	Mean Percent Change From Baseline in PASI Score Over Time (Part 3)	Week 36	-94.5 Percent change	Standard Deviation 7.47
Tildrakizumab 200 mg	Mean Percent Change From Baseline in PASI Score Over Time (Part 3)	Week 52	-94.7 Percent change	Standard Deviation 8.06
Tildrakizumab 200 mg	Mean Percent Change From Baseline in PASI Score Over Time (Part 3)	Week 32	-94.9 Percent change	Standard Deviation 6.19
Tildrakizumab 200 mg	Mean Percent Change From Baseline in PASI Score Over Time (Part 3)	Week 46	-94.8 Percent change	Standard Deviation 7.77
Tildrakizumab 200 mg	Mean Percent Change From Baseline in PASI Score Over Time (Part 3)	Week 40	-94.2 Percent change	Standard Deviation 7.69
Tildrakizumab 100 mg	Mean Percent Change From Baseline in PASI Score Over Time (Part 3)	Week 40	-92.6 Percent change	Standard Deviation 10.25
Tildrakizumab 100 mg	Mean Percent Change From Baseline in PASI Score Over Time (Part 3)	Week 32	-94.0 Percent change	Standard Deviation 7.02
Tildrakizumab 100 mg	Mean Percent Change From Baseline in PASI Score Over Time (Part 3)	Week 52	-92.2 Percent change	Standard Deviation 10.57
Tildrakizumab 100 mg	Mean Percent Change From Baseline in PASI Score Over Time (Part 3)	Week 36	-94.0 Percent change	Standard Deviation 6.93
Tildrakizumab 100 mg	Mean Percent Change From Baseline in PASI Score Over Time (Part 3)	Week 46	-91.4 Percent change	Standard Deviation 12.09
Placebo	Mean Percent Change From Baseline in PASI Score Over Time (Part 3)	Week 46	-94.3 Percent change	Standard Deviation 7.64
Placebo	Mean Percent Change From Baseline in PASI Score Over Time (Part 3)	Week 40	-94.3 Percent change	Standard Deviation 7.4
Placebo	Mean Percent Change From Baseline in PASI Score Over Time (Part 3)	Week 32	-94.3 Percent change	Standard Deviation 7.33
Placebo	Mean Percent Change From Baseline in PASI Score Over Time (Part 3)	Week 52	-93.4 Percent change	Standard Deviation 9.81
Placebo	Mean Percent Change From Baseline in PASI Score Over Time (Part 3)	Week 36	-94.4 Percent change	Standard Deviation 7.06
Etanercept 50 mg	Mean Percent Change From Baseline in PASI Score Over Time (Part 3)	Week 52	-80.4 Percent change	Standard Deviation 15.68
Etanercept 50 mg	Mean Percent Change From Baseline in PASI Score Over Time (Part 3)	Week 36	-79.9 Percent change	Standard Deviation 15.94
Etanercept 50 mg	Mean Percent Change From Baseline in PASI Score Over Time (Part 3)	Week 46	-79.3 Percent change	Standard Deviation 17.77
Etanercept 50 mg	Mean Percent Change From Baseline in PASI Score Over Time (Part 3)	Week 32	-77.1 Percent change	Standard Deviation 16.73
Etanercept 50 mg	Mean Percent Change From Baseline in PASI Score Over Time (Part 3)	Week 40	-79.1 Percent change	Standard Deviation 17.1
Tildrakizumab 100 mg (Parts 1 & 2)/ 200 mg (Part 3) Wk-28 PR	Mean Percent Change From Baseline in PASI Score Over Time (Part 3)	Week 40	-75.7 Percent change	Standard Deviation 19.24
Tildrakizumab 100 mg (Parts 1 & 2)/ 200 mg (Part 3) Wk-28 PR	Mean Percent Change From Baseline in PASI Score Over Time (Part 3)	Week 32	-71.1 Percent change	Standard Deviation 13.21
Tildrakizumab 100 mg (Parts 1 & 2)/ 200 mg (Part 3) Wk-28 PR	Mean Percent Change From Baseline in PASI Score Over Time (Part 3)	Week 36	-74.4 Percent change	Standard Deviation 15.69
Tildrakizumab 100 mg (Parts 1 & 2)/ 200 mg (Part 3) Wk-28 PR	Mean Percent Change From Baseline in PASI Score Over Time (Part 3)	Week 46	-77.1 Percent change	Standard Deviation 19.67
Tildrakizumab 100 mg (Parts 1 & 2)/ 200 mg (Part 3) Wk-28 PR	Mean Percent Change From Baseline in PASI Score Over Time (Part 3)	Week 52	-75.7 Percent change	Standard Deviation 36
Tildrakizumab 100 mg (Parts 1, 2, & 3) Wk-28 PR	Mean Percent Change From Baseline in PASI Score Over Time (Part 3)	Week 36	-77.9 Percent change	Standard Deviation 15.47
Tildrakizumab 100 mg (Parts 1, 2, & 3) Wk-28 PR	Mean Percent Change From Baseline in PASI Score Over Time (Part 3)	Week 40	-80.6 Percent change	Standard Deviation 17.57
Tildrakizumab 100 mg (Parts 1, 2, & 3) Wk-28 PR	Mean Percent Change From Baseline in PASI Score Over Time (Part 3)	Week 46	-75.3 Percent change	Standard Deviation 23.35
Tildrakizumab 100 mg (Parts 1, 2, & 3) Wk-28 PR	Mean Percent Change From Baseline in PASI Score Over Time (Part 3)	Week 52	-79.6 Percent change	Standard Deviation 21.46
Tildrakizumab 100 mg (Parts 1, 2, & 3) Wk-28 PR	Mean Percent Change From Baseline in PASI Score Over Time (Part 3)	Week 32	-75.3 Percent change	Standard Deviation 16.9
Placebo (Part 1)/ Tildrakizumab 200 mg (Parts 2 & 3)	Mean Percent Change From Baseline in PASI Score Over Time (Part 3)	Week 40	-88.2 Percent change	Standard Deviation 14.55
Placebo (Part 1)/ Tildrakizumab 200 mg (Parts 2 & 3)	Mean Percent Change From Baseline in PASI Score Over Time (Part 3)	Week 36	-87.7 Percent change	Standard Deviation 15.2
Placebo (Part 1)/ Tildrakizumab 200 mg (Parts 2 & 3)	Mean Percent Change From Baseline in PASI Score Over Time (Part 3)	Week 32	-84.4 Percent change	Standard Deviation 24.18
Placebo (Part 1)/ Tildrakizumab 200 mg (Parts 2 & 3)	Mean Percent Change From Baseline in PASI Score Over Time (Part 3)	Week 46	-90.3 Percent change	Standard Deviation 12.32
Placebo (Part 1)/ Tildrakizumab 200 mg (Parts 2 & 3)	Mean Percent Change From Baseline in PASI Score Over Time (Part 3)	Week 52	-91.0 Percent change	Standard Deviation 12.16
Placebo (Part 1)/ Tildrakizumab 100 mg (Parts 2 & 3)	Mean Percent Change From Baseline in PASI Score Over Time (Part 3)	Week 40	-84.1 Percent change	Standard Deviation 17.08
Placebo (Part 1)/ Tildrakizumab 100 mg (Parts 2 & 3)	Mean Percent Change From Baseline in PASI Score Over Time (Part 3)	Week 36	-83.1 Percent change	Standard Deviation 19.83
Placebo (Part 1)/ Tildrakizumab 100 mg (Parts 2 & 3)	Mean Percent Change From Baseline in PASI Score Over Time (Part 3)	Week 52	-87.1 Percent change	Standard Deviation 12.9
Placebo (Part 1)/ Tildrakizumab 100 mg (Parts 2 & 3)	Mean Percent Change From Baseline in PASI Score Over Time (Part 3)	Week 46	-86.9 Percent change	Standard Deviation 13.08
Placebo (Part 1)/ Tildrakizumab 100 mg (Parts 2 & 3)	Mean Percent Change From Baseline in PASI Score Over Time (Part 3)	Week 32	-81.6 Percent change	Standard Deviation 21.69
Etanercept 50 mg (Parts 1 & 2)/ Tildrakizumab 200 mg (Part 3)	Mean Percent Change From Baseline in PASI Score Over Time (Part 3)	Week 52	-84.2 Percent change	Standard Deviation 16.07
Etanercept 50 mg (Parts 1 & 2)/ Tildrakizumab 200 mg (Part 3)	Mean Percent Change From Baseline in PASI Score Over Time (Part 3)	Week 32	-54.7 Percent change	Standard Deviation 24.05
Etanercept 50 mg (Parts 1 & 2)/ Tildrakizumab 200 mg (Part 3)	Mean Percent Change From Baseline in PASI Score Over Time (Part 3)	Week 46	-80.3 Percent change	Standard Deviation 17.92
Etanercept 50 mg (Parts 1 & 2)/ Tildrakizumab 200 mg (Part 3)	Mean Percent Change From Baseline in PASI Score Over Time (Part 3)	Week 36	-65.9 Percent change	Standard Deviation 21.35
Etanercept 50 mg (Parts 1 & 2)/ Tildrakizumab 200 mg (Part 3)	Mean Percent Change From Baseline in PASI Score Over Time (Part 3)	Week 40	-76.5 Percent change	Standard Deviation 17.98

Secondary

Percentage of Participants Achieving a PASI-100 Response at Week 12 (Part 1)

Time frame: Week 12

Population: Analysis population includes randomized participants who received at least one dose of study medication in study Part 1 and with valid PASI value at baseline and Week 12.

Arm	Measure	Value (NUMBER)
Tildrakizumab 200 mg	Percentage of Participants Achieving a PASI-100 Response at Week 12 (Part 1)	11.8 Perentage of participants
Tildrakizumab 100 mg	Percentage of Participants Achieving a PASI-100 Response at Week 12 (Part 1)	12.4 Perentage of participants
Placebo	Percentage of Participants Achieving a PASI-100 Response at Week 12 (Part 1)	0 Perentage of participants
Etanercept 50 mg	Percentage of Participants Achieving a PASI-100 Response at Week 12 (Part 1)	4.8 Perentage of participants

p-value: <0.00195% CI: [7.8, 16]Cochran-Mantel-Haenszel

p-value: <0.00195% CI: [8.5, 16.6]Cochran-Mantel-Haenszel

p-value: 0.00195% CI: [2.8, 11.6]Cochran-Mantel-Haenszel

p-value: <0.00195% CI: [3.3, 12.3]Cochran-Mantel-Haenszel

Secondary

Percentage of Participants Achieving a PASI-100 Response at Week 28 (Part 2)

Time frame: Week 28

Population: Analysis population includes participants randomized to tildrakizumab 100 mg, tildrakizumab 200 mg, or etanercept in Part 1 who received at least one dose of study medication in study Part 2.

Arm	Measure	Value (NUMBER)
Tildrakizumab 200 mg	Percentage of Participants Achieving a PASI-100 Response at Week 28 (Part 2)	27.0 Percentage of participants
Tildrakizumab 100 mg	Percentage of Participants Achieving a PASI-100 Response at Week 28 (Part 2)	22.8 Percentage of participants
Placebo	Percentage of Participants Achieving a PASI-100 Response at Week 28 (Part 2)	11.2 Percentage of participants

p-value: <0.00195% CI: [9.4, 22.1]Cochran-Mantel-Haenszel

p-value: <0.00195% CI: [5.6, 17.9]Cochran-Mantel-Haenszel

Secondary

Percentage of Participants Achieving a PASI-100 Response at Week 40 (Part 3)

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-100 response indicates the number of participants achieving a 100% reduction in PASI score compared to baseline. Week-28 responder (Wk-28 R) is a participant who achieved ≥ 75% improvement in PASI from baseline at Week 28. Week-28 partial responder (Wk-28 PR) is a participant who achieved ≥50% and \<75% improvement in PASI response from baseline at Week 28.

Time frame: Week 40

Population: Participants who received at least one dose of study medication in Part 3 and with valid PASI value at baseline and at Week 40.

Arm	Measure	Value (NUMBER)
Tildrakizumab 200 mg	Percentage of Participants Achieving a PASI-100 Response at Week 40 (Part 3)	39.3 Percentage of participants
Tildrakizumab 100 mg	Percentage of Participants Achieving a PASI-100 Response at Week 40 (Part 3)	38.9 Percentage of participants
Placebo	Percentage of Participants Achieving a PASI-100 Response at Week 40 (Part 3)	33.5 Percentage of participants
Etanercept 50 mg	Percentage of Participants Achieving a PASI-100 Response at Week 40 (Part 3)	11.7 Percentage of participants
Tildrakizumab 100 mg (Parts 1 & 2)/ 200 mg (Part 3) Wk-28 PR	Percentage of Participants Achieving a PASI-100 Response at Week 40 (Part 3)	0 Percentage of participants
Tildrakizumab 100 mg (Parts 1, 2, & 3) Wk-28 PR	Percentage of Participants Achieving a PASI-100 Response at Week 40 (Part 3)	14.3 Percentage of participants
Placebo (Part 1)/ Tildrakizumab 200 mg (Parts 2 & 3)	Percentage of Participants Achieving a PASI-100 Response at Week 40 (Part 3)	29.9 Percentage of participants
Placebo (Part 1)/ Tildrakizumab 100 mg (Parts 2 & 3)	Percentage of Participants Achieving a PASI-100 Response at Week 40 (Part 3)	28.1 Percentage of participants
Etanercept 50 mg (Parts 1 & 2)/ Tildrakizumab 200 mg (Part 3)	Percentage of Participants Achieving a PASI-100 Response at Week 40 (Part 3)	5.3 Percentage of participants

Secondary

Percentage of Participants Achieving a PASI-100 Response at Week 52 (Part 3)

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-100 response indicates the number of participants achieving a 90% reduction in PASI score compared to baseline. Week-28 responder (Wk-28 R) is a participant who achieved ≥ 75% improvement in PASI from baseline at Week 28. Week-28 partial responder (Wk-28 PR) is a participant who achieved ≥50% and \<75% improvement in PASI response from baseline at Week 28.

Time frame: Week 52

Population: Participants who received at least one dose of study medication in Part 3 and with valid PASI value at baseline and at Week 52.

Arm	Measure	Value (NUMBER)
Tildrakizumab 200 mg	Percentage of Participants Achieving a PASI-100 Response at Week 52 (Part 3)	46.7 Percentage of participants
Tildrakizumab 100 mg	Percentage of Participants Achieving a PASI-100 Response at Week 52 (Part 3)	37.5 Percentage of participants
Placebo	Percentage of Participants Achieving a PASI-100 Response at Week 52 (Part 3)	35.3 Percentage of participants
Etanercept 50 mg	Percentage of Participants Achieving a PASI-100 Response at Week 52 (Part 3)	10.0 Percentage of participants
Tildrakizumab 100 mg (Parts 1 & 2)/ 200 mg (Part 3) Wk-28 PR	Percentage of Participants Achieving a PASI-100 Response at Week 52 (Part 3)	5.3 Percentage of participants
Tildrakizumab 100 mg (Parts 1, 2, & 3) Wk-28 PR	Percentage of Participants Achieving a PASI-100 Response at Week 52 (Part 3)	31.6 Percentage of participants
Placebo (Part 1)/ Tildrakizumab 200 mg (Parts 2 & 3)	Percentage of Participants Achieving a PASI-100 Response at Week 52 (Part 3)	39.4 Percentage of participants
Placebo (Part 1)/ Tildrakizumab 100 mg (Parts 2 & 3)	Percentage of Participants Achieving a PASI-100 Response at Week 52 (Part 3)	23.8 Percentage of participants
Etanercept 50 mg (Parts 1 & 2)/ Tildrakizumab 200 mg (Part 3)	Percentage of Participants Achieving a PASI-100 Response at Week 52 (Part 3)	15.9 Percentage of participants

Secondary

Percentage of Participants Achieving a PASI-75 Response at Week 28 (Part 2)

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. Primary analysis for this endpoint is for participants randomized to tildrakizumab 200 mg, tildrakizumab 100 mg, or etanercept in Part 1.

Time frame: Week 28

Population: Analysis population includes all participants randomized to tildrakizumab or etanercept in Part 1 who received at least one dose of study medication in Part 2.

Arm	Measure	Value (NUMBER)
Tildrakizumab 200 mg	Percentage of Participants Achieving a PASI-75 Response at Week 28 (Part 2)	72.6 Percentage of participants
Tildrakizumab 100 mg	Percentage of Participants Achieving a PASI-75 Response at Week 28 (Part 2)	73.5 Percentage of participants
Placebo	Percentage of Participants Achieving a PASI-75 Response at Week 28 (Part 2)	53.6 Percentage of participants

p-value: <0.00195% CI: [11.5, 26.7]Cochran-Mantel-Haenszel

p-value: <0.00195% CI: [12.4, 27.6]Cochran-Mantel-Haenszel

Secondary

Percentage of Participants Achieving a PASI-75 Response at Week 40 (Part 3)

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. Week-28 responder (Wk-28 R) is a participant who achieved ≥ 75% improvement in PASI from baseline at Week 28. Week-28 partial responder (Wk-28 PR) is a participant who achieved ≥50% and \<75% improvement in PASI response from baseline at Week 28.

Time frame: Week 40

Population: Participants who received at least one dose of study medication in Part 3 and with valid PASI value at baseline and at Week 40.

Arm	Measure	Value (NUMBER)
Tildrakizumab 200 mg	Percentage of Participants Achieving a PASI-75 Response at Week 40 (Part 3)	96.3 Percentage of participants
Tildrakizumab 100 mg	Percentage of Participants Achieving a PASI-75 Response at Week 40 (Part 3)	92.6 Percentage of participants
Placebo	Percentage of Participants Achieving a PASI-75 Response at Week 40 (Part 3)	97.6 Percentage of participants
Etanercept 50 mg	Percentage of Participants Achieving a PASI-75 Response at Week 40 (Part 3)	63.3 Percentage of participants
Tildrakizumab 100 mg (Parts 1 & 2)/ 200 mg (Part 3) Wk-28 PR	Percentage of Participants Achieving a PASI-75 Response at Week 40 (Part 3)	66.7 Percentage of participants
Tildrakizumab 100 mg (Parts 1, 2, & 3) Wk-28 PR	Percentage of Participants Achieving a PASI-75 Response at Week 40 (Part 3)	61.9 Percentage of participants
Placebo (Part 1)/ Tildrakizumab 200 mg (Parts 2 & 3)	Percentage of Participants Achieving a PASI-75 Response at Week 40 (Part 3)	82.1 Percentage of participants
Placebo (Part 1)/ Tildrakizumab 100 mg (Parts 2 & 3)	Percentage of Participants Achieving a PASI-75 Response at Week 40 (Part 3)	68.8 Percentage of participants
Etanercept 50 mg (Parts 1 & 2)/ Tildrakizumab 200 mg (Part 3)	Percentage of Participants Achieving a PASI-75 Response at Week 40 (Part 3)	57.0 Percentage of participants

Secondary

Percentage of Participants Achieving a PASI-75 Response at Week 52 (Part 3)

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. Week-28 responder (Wk-28 R) is a participant who achieved ≥ 75% improvement in PASI from baseline at Week 28. Week-28 partial responder (Wk-28 PR) is a participant who achieved ≥50% and \<75% improvement in PASI response from baseline at Week 28.

Time frame: Week 52

Population: Participants who received at least one dose of study medication in Part 3 and with valid PASI value at baseline and at Week 52.

Arm	Measure	Value (NUMBER)
Tildrakizumab 200 mg	Percentage of Participants Achieving a PASI-75 Response at Week 52 (Part 3)	97.1 Percentage of participants
Tildrakizumab 100 mg	Percentage of Participants Achieving a PASI-75 Response at Week 52 (Part 3)	94.2 Percentage of participants
Placebo	Percentage of Participants Achieving a PASI-75 Response at Week 52 (Part 3)	93.6 Percentage of participants
Etanercept 50 mg	Percentage of Participants Achieving a PASI-75 Response at Week 52 (Part 3)	66.7 Percentage of participants
Tildrakizumab 100 mg (Parts 1 & 2)/ 200 mg (Part 3) Wk-28 PR	Percentage of Participants Achieving a PASI-75 Response at Week 52 (Part 3)	78.9 Percentage of participants
Tildrakizumab 100 mg (Parts 1, 2, & 3) Wk-28 PR	Percentage of Participants Achieving a PASI-75 Response at Week 52 (Part 3)	68.4 Percentage of participants
Placebo (Part 1)/ Tildrakizumab 200 mg (Parts 2 & 3)	Percentage of Participants Achieving a PASI-75 Response at Week 52 (Part 3)	92.4 Percentage of participants
Placebo (Part 1)/ Tildrakizumab 100 mg (Parts 2 & 3)	Percentage of Participants Achieving a PASI-75 Response at Week 52 (Part 3)	85.7 Percentage of participants
Etanercept 50 mg (Parts 1 & 2)/ Tildrakizumab 200 mg (Part 3)	Percentage of Participants Achieving a PASI-75 Response at Week 52 (Part 3)	81.4 Percentage of participants

Secondary

Percentage of Participants Achieving a PASI-90 Response at Week 12 (Part 1)

Time frame: Week 12

Population: Analysis population includes randomized participants who received at least one dose of study medication in study Part 1.

Arm	Measure	Value (NUMBER)
Tildrakizumab 200 mg	Percentage of Participants Achieving a PASI-90 Response at Week 12 (Part 1)	36.6 Percentage of participants
Tildrakizumab 100 mg	Percentage of Participants Achieving a PASI-90 Response at Week 12 (Part 1)	38.8 Percentage of participants
Placebo	Percentage of Participants Achieving a PASI-90 Response at Week 12 (Part 1)	1.3 Percentage of participants
Etanercept 50 mg	Percentage of Participants Achieving a PASI-90 Response at Week 12 (Part 1)	21.4 Percentage of participants

p-value: <0.00195% CI: [29.2, 41.1]Cochran-Mantel-Haenszel

p-value: <0.00195% CI: [31.1, 43.4]Cochran-Mantel-Haenszel

p-value: <0.00195% CI: [8.3, 22.1]Cochran-Mantel-Haenszel

p-value: <0.00195% CI: [10.3, 24.4]Cochran-Mantel-Haenszel

Secondary

Percentage of Participants Achieving a PASI-90 Response at Week 28 (Part 2)

Time frame: Week 28

Arm	Measure	Value (NUMBER)
Tildrakizumab 200 mg	Percentage of Participants Achieving a PASI-90 Response at Week 28 (Part 2)	57.7 Percentage of participants
Tildrakizumab 100 mg	Percentage of Participants Achieving a PASI-90 Response at Week 28 (Part 2)	55.5 Percentage of participants
Placebo	Percentage of Participants Achieving a PASI-90 Response at Week 28 (Part 2)	30.7 Percentage of participants

p-value: <0.00195% CI: [19.1, 34.7]Cochran-Mantel-Haenszel

p-value: <0.00195% CI: [17, 32.6]Cochran-Mantel-Haenszel

Secondary

Percentage of Participants Achieving a PASI-90 Response at Week 40 (Part 3)

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-90 response indicates the number of participants achieving a 90% reduction in PASI score compared to baseline. Week-28 responder (Wk-28 R) is a participant who achieved ≥ 75% improvement in PASI from baseline at Week 28. Week-28 partial responder (Wk-28 PR) is a participant who achieved ≥50% and \<75% improvement in PASI response from baseline at Week 28.

Time frame: Week 40

Population: Participants who received at least one dose of study medication in Part 3 and with valid PASI value at baseline and at Week 40.

Arm	Measure	Value (NUMBER)
Tildrakizumab 200 mg	Percentage of Participants Achieving a PASI-90 Response at Week 40 (Part 3)	76.6 Percentage of participants
Tildrakizumab 100 mg	Percentage of Participants Achieving a PASI-90 Response at Week 40 (Part 3)	73.1 Percentage of participants
Placebo	Percentage of Participants Achieving a PASI-90 Response at Week 40 (Part 3)	78.8 Percentage of participants
Etanercept 50 mg	Percentage of Participants Achieving a PASI-90 Response at Week 40 (Part 3)	28.3 Percentage of participants
Tildrakizumab 100 mg (Parts 1 & 2)/ 200 mg (Part 3) Wk-28 PR	Percentage of Participants Achieving a PASI-90 Response at Week 40 (Part 3)	23.8 Percentage of participants
Tildrakizumab 100 mg (Parts 1, 2, & 3) Wk-28 PR	Percentage of Participants Achieving a PASI-90 Response at Week 40 (Part 3)	42.9 Percentage of participants
Placebo (Part 1)/ Tildrakizumab 200 mg (Parts 2 & 3)	Percentage of Participants Achieving a PASI-90 Response at Week 40 (Part 3)	64.2 Percentage of participants
Placebo (Part 1)/ Tildrakizumab 100 mg (Parts 2 & 3)	Percentage of Participants Achieving a PASI-90 Response at Week 40 (Part 3)	48.4 Percentage of participants
Etanercept 50 mg (Parts 1 & 2)/ Tildrakizumab 200 mg (Part 3)	Percentage of Participants Achieving a PASI-90 Response at Week 40 (Part 3)	24.6 Percentage of participants

Secondary

Percentage of Participants Achieving a PASI-90 Response at Week 52 (Part 3)

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-90 response indicates the number of participants achieving a 90% reduction in PASI score compared to baseline. Week-28 responder (Wk-28 R) is a participant who achieved ≥ 75% improvement in PASI from baseline at Week 28. Week-28 partial responder (Wk-28 PR) is a participant who achieved ≥50% and \<75% improvement in PASI response from baseline at Week 28.

Time frame: Week 52

Population: Participants who received at least one dose of study medication in Part 3 and with valid PASI value at baseline and at Week 52.

Arm	Measure	Value (NUMBER)
Tildrakizumab 200 mg	Percentage of Participants Achieving a PASI-90 Response at Week 52 (Part 3)	81.9 Percentage of participants
Tildrakizumab 100 mg	Percentage of Participants Achieving a PASI-90 Response at Week 52 (Part 3)	68.3 Percentage of participants
Placebo	Percentage of Participants Achieving a PASI-90 Response at Week 52 (Part 3)	78.4 Percentage of participants
Etanercept 50 mg	Percentage of Participants Achieving a PASI-90 Response at Week 52 (Part 3)	31.7 Percentage of participants
Tildrakizumab 100 mg (Parts 1 & 2)/ 200 mg (Part 3) Wk-28 PR	Percentage of Participants Achieving a PASI-90 Response at Week 52 (Part 3)	26.3 Percentage of participants
Tildrakizumab 100 mg (Parts 1, 2, & 3) Wk-28 PR	Percentage of Participants Achieving a PASI-90 Response at Week 52 (Part 3)	42.1 Percentage of participants
Placebo (Part 1)/ Tildrakizumab 200 mg (Parts 2 & 3)	Percentage of Participants Achieving a PASI-90 Response at Week 52 (Part 3)	63.6 Percentage of participants
Placebo (Part 1)/ Tildrakizumab 100 mg (Parts 2 & 3)	Percentage of Participants Achieving a PASI-90 Response at Week 52 (Part 3)	47.6 Percentage of participants
Etanercept 50 mg (Parts 1 & 2)/ Tildrakizumab 200 mg (Part 3)	Percentage of Participants Achieving a PASI-90 Response at Week 52 (Part 3)	41.6 Percentage of participants

Secondary

Percentage of Participants With a DLQI Score of 0 or 1 at Week 12 (Part 1)

Time frame: Week 12

Population: Analysis population includes randomized participants who received at least one dose of study medication in Part 1 and with a valid DLQI value at Week 12.

Arm	Measure	Value (NUMBER)
Tildrakizumab 200 mg	Percentage of Participants With a DLQI Score of 0 or 1 at Week 12 (Part 1)	47.4 Percentage of participants
Tildrakizumab 100 mg	Percentage of Participants With a DLQI Score of 0 or 1 at Week 12 (Part 1)	40.2 Percentage of participants
Placebo	Percentage of Participants With a DLQI Score of 0 or 1 at Week 12 (Part 1)	8.0 Percentage of participants
Etanercept 50 mg	Percentage of Participants With a DLQI Score of 0 or 1 at Week 12 (Part 1)	35.5 Percentage of participants

p-value: <0.00195% CI: [31.8, 46.1]Cochran-Mantel-Haenszel

p-value: <0.00195% CI: [24.5, 39.1]Cochran-Mantel-Haenszel

p-value: 0.00395% CI: [4.1, 19.5]Cochran-Mantel-Haenszel

p-value: 0.22195% CI: [-2.9, 12.5]Cochran-Mantel-Haenszel

Secondary

Percentage of Participants With a DLQI Score of 0 or 1 at Week 28 (Part 2)

Time frame: Week 28

Population: Analysis population includes randomized participants to tildrakizumab 200 mg, tildrakizumab 100 mg or etanercept in Part 1, who received at least one dose of study medication in Part 2 and with a valid DLQI value at Week 28.

Arm	Measure	Value (NUMBER)
Tildrakizumab 200 mg	Percentage of Participants With a DLQI Score of 0 or 1 at Week 28 (Part 2)	65.0 Percentage of participants
Tildrakizumab 100 mg	Percentage of Participants With a DLQI Score of 0 or 1 at Week 28 (Part 2)	54.1 Percentage of participants
Placebo	Percentage of Participants With a DLQI Score of 0 or 1 at Week 28 (Part 2)	39.4 Percentage of participants

p-value: <0.00195% CI: [17.7, 33.4]Cochran-Mantel-Haenszel

p-value: <0.00195% CI: [6.9, 22.9]Cochran-Mantel-Haenszel

Secondary

Percentage of Participants With a DLQI Score of 0 or 1 at Week 40 (Part 3)

Time frame: Week 40

Population: Participants who received at least one dose of study medication in Part 3 and with valid DLQI value at Week 40.

Arm	Measure	Value (NUMBER)
Tildrakizumab 200 mg	Percentage of Participants With a DLQI Score of 0 or 1 at Week 40 (Part 3)	72.2 Percentage of participants
Tildrakizumab 100 mg	Percentage of Participants With a DLQI Score of 0 or 1 at Week 40 (Part 3)	68.5 Percentage of participants
Placebo	Percentage of Participants With a DLQI Score of 0 or 1 at Week 40 (Part 3)	71.2 Percentage of participants
Etanercept 50 mg	Percentage of Participants With a DLQI Score of 0 or 1 at Week 40 (Part 3)	41.7 Percentage of participants
Tildrakizumab 100 mg (Parts 1 & 2)/ 200 mg (Part 3) Wk-28 PR	Percentage of Participants With a DLQI Score of 0 or 1 at Week 40 (Part 3)	9.5 Percentage of participants
Tildrakizumab 100 mg (Parts 1, 2, & 3) Wk-28 PR	Percentage of Participants With a DLQI Score of 0 or 1 at Week 40 (Part 3)	19.0 Percentage of participants
Placebo (Part 1)/ Tildrakizumab 200 mg (Parts 2 & 3)	Percentage of Participants With a DLQI Score of 0 or 1 at Week 40 (Part 3)	50.7 Percentage of participants
Placebo (Part 1)/ Tildrakizumab 100 mg (Parts 2 & 3)	Percentage of Participants With a DLQI Score of 0 or 1 at Week 40 (Part 3)	51.5 Percentage of participants
Etanercept 50 mg (Parts 1 & 2)/ Tildrakizumab 200 mg (Part 3)	Percentage of Participants With a DLQI Score of 0 or 1 at Week 40 (Part 3)	38.8 Percentage of participants

Secondary

Percentage of Participants With a DLQI Score of 0 or 1 at Week 52 (Part 3)

Time frame: Week 52

Population: Participants who received at least one dose of study medication in Part 3 and with valid DLQI value at Week 52.

Arm	Measure	Value (NUMBER)
Tildrakizumab 200 mg	Percentage of Participants With a DLQI Score of 0 or 1 at Week 52 (Part 3)	72.4 Percentage of participants
Tildrakizumab 100 mg	Percentage of Participants With a DLQI Score of 0 or 1 at Week 52 (Part 3)	71.4 Percentage of participants
Placebo	Percentage of Participants With a DLQI Score of 0 or 1 at Week 52 (Part 3)	68.8 Percentage of participants
Etanercept 50 mg	Percentage of Participants With a DLQI Score of 0 or 1 at Week 52 (Part 3)	40.0 Percentage of participants
Tildrakizumab 100 mg (Parts 1 & 2)/ 200 mg (Part 3) Wk-28 PR	Percentage of Participants With a DLQI Score of 0 or 1 at Week 52 (Part 3)	10.5 Percentage of participants
Tildrakizumab 100 mg (Parts 1, 2, & 3) Wk-28 PR	Percentage of Participants With a DLQI Score of 0 or 1 at Week 52 (Part 3)	42.1 Percentage of participants
Placebo (Part 1)/ Tildrakizumab 200 mg (Parts 2 & 3)	Percentage of Participants With a DLQI Score of 0 or 1 at Week 52 (Part 3)	60.0 Percentage of participants
Placebo (Part 1)/ Tildrakizumab 100 mg (Parts 2 & 3)	Percentage of Participants With a DLQI Score of 0 or 1 at Week 52 (Part 3)	57.8 Percentage of participants
Etanercept 50 mg (Parts 1 & 2)/ Tildrakizumab 200 mg (Part 3)	Percentage of Participants With a DLQI Score of 0 or 1 at Week 52 (Part 3)	48.3 Percentage of participants

Secondary

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)

Time frame: Week 28

Population: Analysis population includes participants randomized to tildrakizumab 100 mg, tildrakizumab 200 mg, or etanercept in Part 1 who received at least one dose of study medication in Part 2.

Arm	Measure	Value (NUMBER)
Tildrakizumab 200 mg	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)	69.2 Percentage of participants
Tildrakizumab 100 mg	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)	64.6 Percentage of participants
Placebo	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)	45.3 Percentage of participants

p-value: <0.00195% CI: [16.2, 31.7]Cochran-Mantel-Haenszel

p-value: <0.00195% CI: [11.7, 27.3]Cochran-Mantel-Haenszel

Secondary

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)

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. Week-28 responder (Wk-28 R) is a participant who achieved ≥ 75% improvement in PASI from baseline at Week 28. Week-28 partial responder (Wk-28 PR) is a participant who achieved ≥50% and \<75% improvement in PASI response from baseline at Week 28.

Time frame: Week 40

Population: Participants who received at least one dose of study medication in Part 3 and with valid PGA value at baseline and at Week 40.

Arm	Measure	Value (NUMBER)
Tildrakizumab 200 mg	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)	83.2 Percentage of participants
Tildrakizumab 100 mg	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)	79.2 Percentage of participants
Placebo	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)	84.9 Percentage of participants
Etanercept 50 mg	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)	57.6 Percentage of participants
Tildrakizumab 100 mg (Parts 1 & 2)/ 200 mg (Part 3) Wk-28 PR	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)	38.1 Percentage of participants
Tildrakizumab 100 mg (Parts 1, 2, & 3) Wk-28 PR	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)	57.1 Percentage of participants
Placebo (Part 1)/ Tildrakizumab 200 mg (Parts 2 & 3)	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)	75.8 Percentage of participants
Placebo (Part 1)/ Tildrakizumab 100 mg (Parts 2 & 3)	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)	62.5 Percentage of participants
Etanercept 50 mg (Parts 1 & 2)/ Tildrakizumab 200 mg (Part 3)	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)	50.9 Percentage of participants

Secondary

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)

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. Week-28 responder (Wk-28 R) is a participant who achieved ≥ 75% improvement in PASI from baseline at Week 28. Week-28 partial responder (Wk-28 PR) is a participant who achieved ≥50% and \<75% improvement in PASI response from baseline at Week 28.

Time frame: Week 52

Population: Participants who received at least one dose of study medication in Part 3 and with valid PGA value at baseline and at Week 52.

Arm	Measure	Value (NUMBER)
Tildrakizumab 200 mg	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)	84.8 Percentage of participants
Tildrakizumab 100 mg	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)	77.7 Percentage of participants
Placebo	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)	79.4 Percentage of participants
Etanercept 50 mg	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)	50.8 Percentage of participants
Tildrakizumab 100 mg (Parts 1 & 2)/ 200 mg (Part 3) Wk-28 PR	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)	42.1 Percentage of participants
Tildrakizumab 100 mg (Parts 1, 2, & 3) Wk-28 PR	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)	57.9 Percentage of participants
Placebo (Part 1)/ Tildrakizumab 200 mg (Parts 2 & 3)	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)	77.3 Percentage of participants
Placebo (Part 1)/ Tildrakizumab 100 mg (Parts 2 & 3)	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)	55.6 Percentage of participants
Etanercept 50 mg (Parts 1 & 2)/ Tildrakizumab 200 mg (Part 3)	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)	68.5 Percentage of participants

Source: ClinicalTrials.gov · Data processed: Mar 18, 2026

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)

Conditions

Brief summary

Detailed description

Related papers

Interventions

Sponsors

Study design

Eligibility

Inclusion criteria

Exclusion criteria

Design outcomes

Primary

Secondary

Participant flow

Pre-assignment details

Participants by arm

Withdrawals & dropouts

Baseline characteristics

Adverse events

Outcome results

Percentage of Participants Achieving a Psoriasis Area Sensitivity Index 75% (PASI-75) Response at Week 12 (Part 1)

Percentage of Participants Discontinuing Study Treatment Due to an AE Up to Week 12 (Part 1)

Percentage of Participants Experiencing an Adverse Event (AE) Up to Week 12 (Part 1)

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)

Baseline Dermatology Life Quality Index (DLQI)

Change From Baseline in the DLQI at Week 12 (Part 1)

Change From Baseline in the DLQI at Week 28 (Part 2)

Change From Baseline in the DLQI at Week 40 (Part 3)

Change From Baseline in the DLQI at Week 52 (Part 3)

Mean Change From Baseline in PASI Score Over Time (Part 1)

Mean Change From Baseline in PASI Score Over Time (Part 2)

Mean Change From Baseline in PASI Score Over Time (Part 3)

Mean Percent Change From Baseline in PASI Score Over Time (Part 1)

Mean Percent Change From Baseline in PASI Score Over Time (Part 2)

Mean Percent Change From Baseline in PASI Score Over Time (Part 3)

Percentage of Participants Achieving a PASI-100 Response at Week 12 (Part 1)

Percentage of Participants Achieving a PASI-100 Response at Week 28 (Part 2)

Percentage of Participants Achieving a PASI-100 Response at Week 40 (Part 3)

Percentage of Participants Achieving a PASI-100 Response at Week 52 (Part 3)

Percentage of Participants Achieving a PASI-75 Response at Week 28 (Part 2)

Percentage of Participants Achieving a PASI-75 Response at Week 40 (Part 3)

Percentage of Participants Achieving a PASI-75 Response at Week 52 (Part 3)

Percentage of Participants Achieving a PASI-90 Response at Week 12 (Part 1)

Percentage of Participants Achieving a PASI-90 Response at Week 28 (Part 2)

Percentage of Participants Achieving a PASI-90 Response at Week 40 (Part 3)

Percentage of Participants Achieving a PASI-90 Response at Week 52 (Part 3)

Percentage of Participants With a DLQI Score of 0 or 1 at Week 12 (Part 1)

Percentage of Participants With a DLQI Score of 0 or 1 at Week 28 (Part 2)

Percentage of Participants With a DLQI Score of 0 or 1 at Week 40 (Part 3)

Percentage of Participants With a DLQI Score of 0 or 1 at Week 52 (Part 3)

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)

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)

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)