reSURFACE 1: A Study to Evaluate the Efficacy and Safety of Subcutaneous MK-3222, Followed by an Optional Long-Term Safety Extension Study, in Participants With Moderate-to-Severe Chronic Plaque Psoriasis (MK-3222-010)

• Sponsor: Sun Pharmaceutical Industries Limited (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01722331
• Collaborator: (none)
• Enrollment: 772
• Arms: 3
• Actual Duration (Months): 107.1

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Plaque Psoriasis	Drug: Tildrakizumab 200 mg; Drug: Tildrakizumab 100 mg; Drug: Matching Placebo	Phase 3

Detailed Description

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

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

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

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

• Participants who are re-randomized to continue on their initial treatment will continue tildrakizumab 200 or 100 mg every 12 weeks through Week 64.

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

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

• Participants initially randomized to tildrakizumab 200 mg will remain on tildrakizumab 200 mg every 12 weeks.

• Participants initially randomized to tildrakizumab 100 mg will be re-randomized to either remain on tildrakizumab 100 mg every 12 weeks or to receive tildrakizumab 200 mg every 12 weeks.

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

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

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 772 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A 64-Week, Phase 3, Randomized, 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-3222-010)
• Actual Study Start Date: Dec 6, 2012
• Actual Primary Completion Date: Oct 28, 2015
• Actual Study Completion Date: Nov 10, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Tildrakizumab 200 mg Tildrakizumab 200 mg administered subcutaneously (SC) once a week at Weeks 0 and 4 and then every 12 weeks.	Drug: Tildrakizumab 200 mg; Two tildrakizumab 100 mg/mL pre-filled syringes (PFS); Other Names: MK-3222, SCH 900222 ; Drug: Matching Placebo; Matching placebo to tildrakizumab PFS
Experimental: Tildrakizumab 100 mg Tildrakizumab 100 mg administered SC once a week at Weeks 0 and 4 and then every 12 weeks.	Drug: Tildrakizumab 100 mg; Tildrakizumab 100 mg/mL PFS; Other Names: MK-3222, SCH 900222 ; Drug: Matching Placebo; Matching placebo to tildrakizumab PFS
Placebo Comparator: Placebo Matching placebo administered SC once a week at Weeks 0 and 4.	Drug: Tildrakizumab 200 mg; Two tildrakizumab 100 mg/mL pre-filled syringes (PFS); Other Names: MK-3222, SCH 900222 ; Drug: Tildrakizumab 100 mg; Tildrakizumab 100 mg/mL PFS; Other Names: MK-3222, SCH 900222 ; Drug: Matching Placebo; Matching placebo to tildrakizumab PFS

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Psoriasis Area Sensitivity Index 75 (PASI-75) Response at Week 12 (Base Study) [Week 12 (or end of trial if prior to 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 amount of body surface for each region involved (head=0.1; upper limbs=0.2; trunk= 0.3; and lower limbs=0.4) and the degree of involvement for each body region (0=no involvement to 6=90-100% 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.

2. 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 (Base Study) [Baseline and Week 12 (or end of trial if prior to 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.

3. Number of Participants Experiencing an Adverse Event Up to Week 12 (Base Study) [Up to 12 weeks]

   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.

4. Number of Participants Discontinuing Study Drug Due to an Adverse Event Up to Week 12 (Base Study) [Up to 12 weeks]

   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.

5. Number of Participants Discontinuing Study Drug Due to a Drug-Related Adverse Event (Base Study) [Up to 12 weeks]

   A drug-related adverse event is an adverse event that has been determined by the investigator to be related to the study drug.

Secondary Outcome Measures

1. Percentage of Participants With PASI-90 Response At Week 12 [Week 12 (or end of trial if prior to 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 amount of body surface for each region involved (head=0.1; upper limbs=0.2; trunk= 0.3; and lower limbs=0.4) and the degree of involvement for each body region (0=no involvement to 6=90-100% 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.

2. Percentage of Participants With PASI-100 Response at Week 12 [Week 12 (or end of trial if prior to 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 amount of body surface for each region involved (head=0.1; upper limbs=0.2; trunk= 0.3; and lower limbs=0.4) and the degree of involvement for each body region (0=no involvement to 6=90-100% 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.

3. Baseline Dermatology Life Quality Index (DLQI) Score [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.

4. Change From Baseline in the Participant DLQI Score at Week 12 [Baseline and Week 12 (or end of trial if prior to 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. For a change from baseline, a larger negative number correlates with a greater improvement in the DLQI score.

5. Percentage of Participants With DLQI Score of 0 or 1 at Week 12 [Week 12 (or end of trial if prior to 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Clinical diagnosis of moderate-to-severe plaque psoriasis for at least 6 months prior to study enrollment

• A candidate for phototherapy or systemic therapy

• For the extension study: must have completed Part 3 of the base study

• For the extension study: must have achieved at least a PASI-50 response by the end of Part 3 of the base study

• For the extension study: must have received active tildrakizumab (MK-3222) treatment within 12 weeks prior to the end of Part 3 of the base study

• Premenopausal female participants must agree to abstain from heterosexual activity or use a medically accepted method of contraception or use appropriate effective contraception as per local regulations or guidelines

• If enrolled at a Japanese site, participants with psoriatic arthritis using non-steroidal anti-inflammatory drugs (NSAIDs) must be on a stable dose for at least 4 weeks prior to the first dose of study drug and must not be expected to require an increase in dose over the course of the study

Exclusion Criteria:

• Has erythrodermic psoriasis, predominantly pustular psoriasis, medication-induced or medication-exacerbated psoriasis, or new onset guttate psoriasis

• Current or history of severe psoriatic arthritis and is well-controlled on current treatment

• Women of child-bearing potential who are pregnant, intend to become pregnant within 6 months of completing the trial, or who are breast feeding

• Expected to require topical treatment, phototherapy, or systemic treatment during the trial

• Presence of any infection

• History of recurrent infection requiring treatment with systemic antibiotics within 2 weeks of screening

• Previous use of tildrakizumab (MK-3222) or other IL-23/Th-17 pathway inhibitors including P40, p19, and IL-17 antagonists

• Evidence of active or untreated latent tuberculosis (TB)

• Positive test for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV)

• At Japanese sites, positive test for HBs antibody and hepatitis B virus (HBV) deoxyribonucleic acid (DNA)

• At Japanese sites, positive test for the Hepatitis B core (HBc) antibody and HBV DNA

• For the extension study: women of child-bearing potential who are pregnant, intend to become pregnant within 6 months of completing the trial, or who are breast feeding

• For the extension study: active or uncontrolled significant organ dysfunction or clinically significant laboratory abnormalities

• For the extension study: expected to require topical treatment, phototherapy, or systemic treatment during the extension study

• At Japanese sites, abnormal for Beta D Glucan and/or KL-6 test result(s) at the screening visit.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Sun Pharmaceutical Industries Limited

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Sun Pharmaceutical Industries Limited
• ClinicalTrials.gov Identifier: NCT01722331
• Other Study ID Numbers: 3222-010; 2012-002255-42; P07770; 132284
• First Posted: Nov 6, 2012
• Last Update Posted: Mar 23, 2022
• Last Verified: Feb 1, 2022

• Additional relevant MeSH terms: Psoriasis; Antibodies, Monoclonal

Study Results

Participant Flow

Recruitment Details	The tables below present the Participant Flow for the Base Study only (Weeks 0 to 64: Part 1 for 12 weeks, Part 2 for 16 weeks, and Part 3 for 36 weeks).

Arm/Group Title	Tildrakizumab 200 mg (Parts 1, 2 & 3)	Tildrakizumab 100 mg (Parts 1, 2 & 3)	Tildrakizumab 100 mg (Parts 1 & 2)	Tildrakizumab 100 mg (Parts 1 & 2)/ 200 mg (Part 3)	Placebo (Part 1)	Placebo (Part 1)/ Tildrakizumab 200 mg (Parts 2 & 3)	Placebo (Part 1)/ Tildrakizumab 100 mg (Parts 2 & 3)
Arm/Group Description	Tildrakizumab 200 mg administered subcutaneously (SC) once a week at Weeks 0 and 4 (Part 1), Week 16 (Part 2), and Weeks 28, 40, 52 and 64 (Part 3).	Tildrakizumab 100 mg administered SC once a week at Weeks 0 and 4 (Part 1), Week 16 (Part 2), and Weeks 28, 40, 52 and 64 (Part 3).	Tildrakizumab 100 mg administered SC once a week at Weeks 0 and 4 (Part 1) and Week 16 (Part 2).	Tildrakizumab 100 mg administered SC once a week at Weeks 0 and 4 (Part 1) and Week 16 (Part 2). Tildrakizumab 200 mg administered SC once a week at Weeks 28, 40, 52, and 64 (Part 3).	Matching placebo administered SC once a week at Weeks 0 and 4 (Part 1).	Matching placebo administered SC once a week at Weeks 0 and 4 (Part 1). Tildrakizumab 200 mg administered SC once a week at Week 16 (Part 2) and Weeks 28, 40, 52 and 64 (Part 3).	Matching placebo administered SC once a week at Weeks 0 and 4. Tildrakizumab 200 mg administered SC once a week at Week 16 (Part 2) and Weeks 28, 40, 52 and 64 (Part 3).
Period Title: Part 1
STARTED	308	249	41	19	9	72	74
COMPLETED	298	249	32	19	0	72	74
NOT COMPLETED	10	0	9	0	9	0	0
Period Title: Part 1
STARTED	298	249	31	19	0	72	74
COMPLETED	279	249	0	19	0	62	67
NOT COMPLETED	19	0	31	0	0	10	7
Period Title: Part 1
STARTED	279	249	0	19	0	62	67
COMPLETED	264	232	0	18	0	59	65
NOT COMPLETED	15	17	0	1	0	3	2

Baseline Characteristics

Arm/Group Title	Tildrakizumab 200 mg (Part 1)	Tildrakizumab 100 mg (Part 1)	Placebo (Part 1)	Total
Arm/Group Description	Tildrakizumab 200 mg administered subcutaneously (SC) once a week at Weeks 0 and 4 and then every 12 weeks.	Tildrakizumab 100 mg administered SC once a week at Weeks 0 and 4 and then every 12 weeks.	Matching placebo administered SC once a week at Weeks 0 and 4.	Total of all reporting groups
Overall Participants	308	309	155	772
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	46.9 (13.16)	46.4 (13.09)	47.9 (13.55)	46.9 (13.21)
Sex: Female, Male (Count of Participants)
Female	82 26.6%	102 33%	55 35.5%	239 31%
Male	226 73.4%	207 67%	100 64.5%	533 69%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	37 12%	34 11%	19 12.3%	90 11.7%
Not Hispanic or Latino	271 88%	275 89%	135 87.1%	681 88.2%
Unknown or Not Reported	0 0%	0 0%	1 0.6%	1 0.1%
Physician's Global Assessment (PGA) score (Count of Participants)
<3	0 0%	1 0.3%	0 0%	1 0.1%
3	202 65.6%	206 66.7%	111 71.6%	519 67.2%
4	95 30.8%	95 30.7%	41 26.5%	231 29.9%
5	11 3.6%	7 2.3%	2 1.3%	20 2.6%
Body weight (Count of Participants)
<=90 kg	182 59.1%	183 59.2%	93 60%	458 59.3%
>90 kg	126 40.9%	126 40.8%	62 40%	314 40.7%
Prior exposure to biologics therapy for psoriasis (Count of Participants)
Yes	71 23.1%	71 23%	35 22.6%	177 22.9%
No	237 76.9%	238 77%	120 77.4%	595 77.1%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Psoriasis Area Sensitivity Index 75 (PASI-75) Response at Week 12 (Base Study)
Description	The PASI is a measure of the average redness, thickness, and scaliness of lesions (each graded on a 0-4 scale), weighed by the amount of body surface for each region involved (head=0.1; upper limbs=0.2; trunk= 0.3; and lower limbs=0.4) and the degree of involvement for each body region (0=no involvement to 6=90-100% 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.
Time Frame	Week 12 (or end of trial if prior to Week 12)

Outcome Measure Data

Analysis Population Description

Analysis population consists of all randomized participants who received at least one dose of assigned study drug between Weeks 0 and 12.

Arm/Group Title	Tildrakizumab 200 mg (Part 1)	Tildrakizumab 100 mg (Part 1)	Placebo (Part 1)
Arm/Group Description	Tildrakizumab 200 mg administered subcutaneously (SC) once a week at Weeks 0 and 4 and then every 12 weeks.	Tildrakizumab 100 mg administered SC once a week at Weeks 0 and 4 and then every 12 weeks.	Matching placebo administered SC once a week at Weeks 0 and 4.
Measure Participants	308	309	154
Number [Percentage of Participants]	62.3 20.2%	63.8 20.6%	5.8 3.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tildrakizumab 200 mg (Part 1), Placebo (Part 1)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by body weight (<=90kg, >90kg) and prior exposure to biologic therapy for psoriasis (yes/no). P-values are not adjusted for multiplicity.
Method of Estimation	Estimation Parameter	Difference in percentages
	Estimated Value	56.6
	Confidence Interval	(2-Sided) 95%; 49.6 to 62.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tildrakizumab 100 mg (Part 1), Placebo (Part 1)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by body weight (<=90kg, >90kg) and prior exposure to biologic therapy for psoriasis (yes/no). P-values are not adjusted for multiplicity.
Method of Estimation	Estimation Parameter	Difference in percentages
	Estimated Value	58.0
	Confidence Interval	(2-Sided) 95%; 51.0 to 64.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	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 (Base Study)
Description	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.
Time Frame	Baseline and Week 12 (or end of trial if prior to Week 12)

Outcome Measure Data

Analysis Population Description

Analysis population consists of all randomized participants who received at least one dose of assigned study drug between Weeks 0 and 12.

Arm/Group Title	Tildrakizumab 200 mg (Part 1)	Tildrakizumab 100 mg (Part 1)	Placebo (Part 1)
Arm/Group Description	Tildrakizumab 200 mg administered subcutaneously (SC) once a week at Weeks 0 and 4 and then every 12 weeks.	Tildrakizumab 100 mg administered SC once a week at Weeks 0 and 4 and then every 12 weeks.	Matching placebo administered SC once a week at Weeks 0 and 4.
Measure Participants	308	309	154
Number [Percentage of Participants]	59.1 19.2%	57.9 18.7%	7.1 4.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tildrakizumab 200 mg (Part 1), Placebo (Part 1)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by body weight (<=90kg, >90kg) and prior exposure to biologic therapy for psoriasis (yes/no). P-values are not adjusted for multiplicity.
Method of Estimation	Estimation Parameter	Difference in percentages
	Estimated Value	52.1
	Confidence Interval	(2-Sided) 95%; 44.8 to 58.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tildrakizumab 100 mg (Part 1), Placebo (Part 1)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by body weight (<=90kg, >90kg) and prior exposure to biologic therapy for psoriasis (yes/no). P-values are not adjusted for multiplicity.
Method of Estimation	Estimation Parameter	Difference in percentages
	Estimated Value	50.9
	Confidence Interval	(2-Sided) 95%; 43.6 to 57.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Primary Outcome

Title	Number of Participants Experiencing an Adverse Event Up to Week 12 (Base Study)
Description	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 12 weeks

Outcome Measure Data

Analysis Population Description

Analysis population included all randomized participants who received at least 1 dose of study medication during Weeks 0 to 12 based on the treatment actually received.

Arm/Group Title	Tildrakizumab 200 mg (Part 1)	Tildrakizumab 100 mg (Part 1)	Placebo (Part 1)
Arm/Group Description	Tildrakizumab 200 mg administered subcutaneously (SC) once a week at Weeks 0 and 4 and then every 12 weeks.	Tildrakizumab 100 mg administered SC once a week at Weeks 0 and 4 and then every 12 weeks.	Matching placebo administered SC once a week at Weeks 0 and 4.
Measure Participants	308	309	154
Count of Participants [Participants]	130 42.2%	146 47.2%	74 47.7%

4. Primary Outcome

Title	Number of Participants Discontinuing Study Drug Due to an Adverse Event Up to Week 12 (Base Study)
Description	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 12 weeks

Outcome Measure Data

Analysis Population Description

Analysis population included all randomized participants who received at least 1 dose of study medication during Weeks 0 to 12 based on the treatment actually received.

Arm/Group Title	Tildrakizumab 200 mg (Part 1)	Tildrakizumab 100 mg (Part 1)	Placebo (Part 1)
Arm/Group Description	Tildrakizumab 200 mg administered subcutaneously (SC) once a week at Weeks 0 and 4 and then every 12 weeks.	Tildrakizumab 100 mg administered SC once a week at Weeks 0 and 4 and then every 12 weeks.	Matching placebo administered SC once a week at Weeks 0 and 4.
Measure Participants	308	309	154
Count of Participants [Participants]	5 1.6%	0 0%	1 0.6%

5. Primary Outcome

Title	Number of Participants Discontinuing Study Drug Due to a Drug-Related Adverse Event (Base Study)
Description	A drug-related adverse event is an adverse event that has been determined by the investigator to be related to the study drug.
Time Frame	Up to 12 weeks

Outcome Measure Data

Analysis Population Description

Analysis population included all randomized participants who received at least 1 dose of study medication during Weeks 0 to 12 based on the treatment actually received.

Arm/Group Title	Tildrakizumab 200 mg (Part 1)	Tildrakizumab 100 mg (Part 1)	Placebo (Part 1)
Arm/Group Description	Tildrakizumab 200 mg administered subcutaneously (SC) once a week at Weeks 0 and 4 and then every 12 weeks.	Tildrakizumab 100 mg administered SC once a week at Weeks 0 and 4 and then every 12 weeks.	Matching placebo administered SC once a week at Weeks 0 and 4.
Measure Participants	308	309	154
Count of Participants [Participants]	2 0.6%	0 0%	0 0%

6. Secondary Outcome

Title	Percentage of Participants With PASI-90 Response At Week 12
Description	The PASI is a measure of the average redness, thickness, and scaliness of lesions (each graded on a 0-4 scale), weighed by the amount of body surface for each region involved (head=0.1; upper limbs=0.2; trunk= 0.3; and lower limbs=0.4) and the degree of involvement for each body region (0=no involvement to 6=90-100% 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.
Time Frame	Week 12 (or end of trial if prior to Week 12)

Outcome Measure Data

Analysis Population Description

Analysis population consists of all randomized participants who received at least one dose of assigned study drug between Weeks 0 and 12.

Arm/Group Title	Tildrakizumab 200 mg (Part 1)	Tildrakizumab 100 mg (Part 1)	Placebo (Part 1)
Arm/Group Description	Tildrakizumab 200 mg administered subcutaneously (SC) once a week at Weeks 0 and 4 and then every 12 weeks.	Tildrakizumab 100 mg administered SC once a week at Weeks 0 and 4 and then every 12 weeks.	Matching placebo administered SC once a week at Weeks 0 and 4.
Measure Participants	308	309	154
Number [Percentage of participants]	35.4 11.5%	34.6 11.2%	2.6 1.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tildrakizumab 200 mg (Part 1), Placebo (Part 1)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by body weight (<=90kg, >90kg) and prior exposure to biologic therapy for psoriasis (yes/no). P-values are not adjusted for multiplicity.
Method of Estimation	Estimation Parameter	Difference in percentages
	Estimated Value	32.9
	Confidence Interval	(2-Sided) 95%; 26.8 to 38.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tildrakizumab 100 mg (Part 1), Placebo (Part 1)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by body weight (<=90kg, >90kg) and prior exposure to biologic therapy for psoriasis (yes/no). P-values are not adjusted for multiplicity.
Method of Estimation	Estimation Parameter	Difference in percentages
	Estimated Value	32.1
	Confidence Interval	(2-Sided) 95%; 25.9 to 38.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Percentage of Participants With PASI-100 Response at Week 12
Description	The PASI is a measure of the average redness, thickness, and scaliness of lesions (each graded on a 0-4 scale), weighed by the amount of body surface for each region involved (head=0.1; upper limbs=0.2; trunk= 0.3; and lower limbs=0.4) and the degree of involvement for each body region (0=no involvement to 6=90-100% 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.
Time Frame	Week 12 (or end of trial if prior to Week 12)

Outcome Measure Data

Analysis Population Description

Analysis population consists of all randomized participants who received at least one dose of assigned study drug between Weeks 0 and 12.

Arm/Group Title	Tildrakizumab 200 mg (Part 1)	Tildrakizumab 100 mg (Part 1)	Placebo (Part 1)
Arm/Group Description	Tildrakizumab 200 mg administered subcutaneously (SC) once a week at Weeks 0 and 4 and then every 12 weeks.	Tildrakizumab 100 mg administered SC once a week at Weeks 0 and 4 and then every 12 weeks.	Matching placebo administered SC once a week at Weeks 0 and 4.
Measure Participants	308	309	154
Number [Percentage of participants]	14.0 4.5%	13.9 4.5%	1.3 0.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tildrakizumab 200 mg (Part 1), Placebo (Part 1)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by body weight (<=90kg, >90kg) and prior exposure to biologic therapy for psoriasis (yes/no). P-values are not adjusted for multiplicity.
Method of Estimation	Estimation Parameter	Difference in percentages
	Estimated Value	12.7
	Confidence Interval	(2-Sided) 95%; 8.3 to 17.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tildrakizumab 100 mg (Part 1), Placebo (Part 1)
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by body weight (<=90kg, >90kg) and prior exposure to biologic therapy for psoriasis (yes/no). P-values are not adjusted for multiplicity.
Method of Estimation	Estimation Parameter	Difference in percentages
	Estimated Value	12.7
	Confidence Interval	(2-Sided) 95%; 8.0 to 17.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Baseline Dermatology Life Quality Index (DLQI) Score
Description	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.
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Analysis population consists of all randomized participants who received at least one dose of assigned study drug between Weeks 0 and 12 and have baseline DLQI measurement

Arm/Group Title	Tildrakizumab 200 mg (Part 1)	Tildrakizumab 100 mg (Part 1)	Placebo (Part 1)
Arm/Group Description	Tildrakizumab 200 mg administered subcutaneously (SC) once a week at Weeks 0 and 4 and then every 12 weeks.	Tildrakizumab 100 mg administered SC once a week at Weeks 0 and 4 and then every 12 weeks.	Matching placebo administered SC once a week at Weeks 0 and 4.
Measure Participants	308	309	154
Mean (Standard Deviation) [Score on a scale]	13.2 (6.87)	13.9 (6.68)	13.2 (7.25)

9. Secondary Outcome

Title	Change From Baseline in the Participant DLQI Score at Week 12
Description	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. For a change from baseline, a larger negative number correlates with a greater improvement in the DLQI score.
Time Frame	Baseline and Week 12 (or end of trial if prior to Week 12)

Outcome Measure Data

Analysis Population Description

Analysis population consists of all randomized participants who received at least one dose of assigned study drug between Weeks 0 and 12 and have at least one DLQI measurement (post-baseline or baseline).

Arm/Group Title	Tildrakizumab 200 mg (Part 1)	Tildrakizumab 100 mg (Part 1)	Placebo (Part 1)
Arm/Group Description	Tildrakizumab 200 mg administered subcutaneously (SC) once a week at Weeks 0 and 4 and then every 12 weeks.	Tildrakizumab 100 mg administered SC once a week at Weeks 0 and 4 and then every 12 weeks.	Matching placebo administered SC once a week at Weeks 0 and 4.
Measure Participants	308	309	154
Least Squares Mean (95% Confidence Interval) [Score on a scale]	-10.0	-9.8	-2.3

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tildrakizumab 200 mg (Part 1), Placebo (Part 1)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Constrained Longitudinal Data Analysis
	Comments	Terms for time, the interaction of time by treatment, body weight (<=90 kg, >90 kg), and prior exposure to biologic therapy for psoriasis (yes/no).
Method of Estimation	Estimation Parameter	Difference in least squares means
	Estimated Value	-7.7
	Confidence Interval	(2-Sided) 95%; -8.6 to -6.8
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tildrakizumab 100 mg (Part 1), Placebo (Part 1)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Constrained Longitudinal Data Analysis
	Comments	Terms for time, the interaction of time by treatment, body weight (<=90 kg, >90 kg), and prior exposure to biologic therapy for psoriasis (yes/no).
Method of Estimation	Estimation Parameter	Difference in least squares means
	Estimated Value	-7.4
	Confidence Interval	(2-Sided) 95%; -8.3 to -6.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Percentage of Participants With DLQI Score of 0 or 1 at Week 12
Description	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.
Time Frame	Week 12 (or end of trial if prior to Week 12)

Outcome Measure Data

Analysis Population Description

Analysis population consists of all randomized participants who received at least one dose of assigned study drug between Weeks 0 and 12 and have a DLQI measurement at Week 12 (or end of trial if prior to Week 12).

Arm/Group Title	Tildrakizumab 200 mg (Part 1)	Tildrakizumab 100 mg (Part 1)	Placebo (Part 1)
Arm/Group Description	Tildrakizumab 200 mg administered subcutaneously (SC) once a week at Weeks 0 and 4 and then every 12 weeks.	Tildrakizumab 100 mg administered SC once a week at Weeks 0 and 4 and then every 12 weeks.	Matching placebo administered SC once a week at Weeks 0 and 4.
Measure Participants	299	304	150
Number [Percentage of participants]	44.2 14.4%	41.5 13.4%	5.3 3.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Tildrakizumab 200 mg (Part 1), Placebo (Part 1)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by body weight (<=90kg, >90kg) and prior exposure to biologic therapy for psoriasis (yes/no). P-values are not adjusted for multiplicity.
Method of Estimation	Estimation Parameter	Difference in percentages
	Estimated Value	38.9
	Confidence Interval	(2-Sided) 95%; 31.9 to 45.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Tildrakizumab 100 mg (Part 1), Placebo (Part 1)
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by body weight (<=90kg, >90kg) and prior exposure to biologic therapy for psoriasis (yes/no). P-values are not adjusted for multiplicity.
Method of Estimation	Estimation Parameter	Difference in percentages
	Estimated Value	36.1
	Confidence Interval	(2-Sided) 95%; 29.3 to 42.5
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Up to 84 weeks including a 20-week follow-up period (Part 1: Week 0 to Week 12; Part 2: Week 12 to Week 28; Part 3, Week 28 to Week 64)
Adverse Event Reporting Description	Part 1 includes all randomized participants who received at least 1 dose of Part 1 study drug, based on the treatment received. Part 2 includes all randomized participants who received at least 1 dose of Part 2 study drug, based on the treatment received, including those on placebo re-randomized at Week 12 to tildrakizumab. Part 3 includes all participants who received at least 1 dose of Part 3 study drug, based on the treatment received, including those re-randomized to placebo during Part 3.
Arm/Group Title	Tildrakizumab 200 mg (Part 1)		Tildrakizumab 100 mg (Part 1)		Placebo (Part 1)		Tildrakizumab 200 mg (Part 2)		Tildrakizumab 100 mg (Part 2)		Tildrakizumab 200 mg (Part 3)		Tildrakizumab 100 mg (Part 3)
Arm/Group Description	Tildrakizumab 200 mg administered once a week at Weeks 0 and 4.		Tildrakizumab 100 mg administered once a week at Weeks 0 and 4.		Placebo administered once a week at Weeks 0 and 4.		Tildrakizumab 200 mg administered once a week at Week 16 (includes placebo participants re-randomized at Week 12 to receive tildrakizumab 200 mg).		Tildrakizumab 100 mg administered once a week at Week 16 (includes placebo participants re-randomized at Week 12 to receive tildrakizumab 100 mg). Includes 1 participant who did not enter Part 2, but received an unscheduled dose at Week 12.		Participants received tildrakizumab 200 mg (depending on their PASI response) at Weeks 28, 40, 52, and 64 (includes participants re-randomized to placebo during Part 3).		Participants received tildrakizumab 100 mg (depending on their PASI response) at Weeks 28, 40, 52, and 64 (includes participants re-randomized to placebo during Part 3).
All Cause Mortality
	Tildrakizumab 200 mg (Part 1)		Tildrakizumab 100 mg (Part 1)		Placebo (Part 1)		Tildrakizumab 200 mg (Part 2)		Tildrakizumab 100 mg (Part 2)		Tildrakizumab 200 mg (Part 3)		Tildrakizumab 100 mg (Part 3)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/308 (0%)		0/309 (0%)		0/155 (0%)		0/298 (0%)		0/299 (0%)		0/279 (0%)		1/19 (5.3%)
Serious Adverse Events
	Tildrakizumab 200 mg (Part 1)		Tildrakizumab 100 mg (Part 1)		Placebo (Part 1)		Tildrakizumab 200 mg (Part 2)		Tildrakizumab 100 mg (Part 2)		Tildrakizumab 200 mg (Part 3)		Tildrakizumab 100 mg (Part 3)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/308 (2.6%)		5/309 (1.6%)		1/154 (0.6%)		8/370 (2.2%)		7/374 (1.9%)		21/360 (5.8%)		14/316 (4.4%)
Blood and lymphatic system disorders
Anaemia	0/308 (0%)	0	0/309 (0%)	0	0/154 (0%)	0	0/370 (0%)	0	0/374 (0%)	0	0/360 (0%)	0	1/316 (0.3%)	1
Cardiac disorders
Acute myocardial infarction	0/308 (0%)	0	1/309 (0.3%)	1	0/154 (0%)	0	0/370 (0%)	0	0/374 (0%)	0	0/360 (0%)	0	0/316 (0%)	0
Coronary artery disease	1/308 (0.3%)	1	0/309 (0%)	0	0/154 (0%)	0	1/370 (0.3%)	1	0/374 (0%)	0	1/360 (0.3%)	1	0/316 (0%)	0
Tachycardia	1/308 (0.3%)	1	0/309 (0%)	0	0/154 (0%)	0	0/370 (0%)	0	0/374 (0%)	0	0/360 (0%)	0	0/316 (0%)	0
Angina pectoris	0/308 (0%)	0	0/309 (0%)	0	0/154 (0%)	0	0/370 (0%)	0	0/374 (0%)	0	1/360 (0.3%)	1	0/316 (0%)	0
Eye disorders
Cataract	0/308 (0%)	0	0/309 (0%)	0	0/154 (0%)	0	0/370 (0%)	0	0/374 (0%)	0	1/360 (0.3%)	1	0/316 (0%)	0
Macular fibrosis	0/308 (0%)	0	0/309 (0%)	0	0/154 (0%)	0	0/370 (0%)	0	0/374 (0%)	0	1/360 (0.3%)	1	0/316 (0%)	0
Gastrointestinal disorders
Pancreatitis acute	1/308 (0.3%)	1	0/309 (0%)	0	0/154 (0%)	0	0/370 (0%)	0	0/374 (0%)	0	0/360 (0%)	0	0/316 (0%)	0
Salivary gland enlargement	1/308 (0.3%)	1	0/309 (0%)	0	0/154 (0%)	0	0/370 (0%)	0	0/374 (0%)	0	0/360 (0%)	0	0/316 (0%)	0
Constipation	0/308 (0%)	0	0/309 (0%)	0	0/154 (0%)	0	0/370 (0%)	0	1/374 (0.3%)	1	0/360 (0%)	0	0/316 (0%)	0
Diverticulum	0/308 (0%)	0	0/309 (0%)	0	0/154 (0%)	0	0/370 (0%)	0	1/374 (0.3%)	1	0/360 (0%)	0	0/316 (0%)	0
Pancreatitis	0/308 (0%)	0	0/309 (0%)	0	0/154 (0%)	0	0/370 (0%)	0	1/374 (0.3%)	1	0/360 (0%)	0	0/316 (0%)	0
Food poisoning	0/308 (0%)	0	0/309 (0%)	0	0/154 (0%)	0	0/370 (0%)	0	0/374 (0%)	0	0/360 (0%)	0	1/316 (0.3%)	1
General disorders
Non-cardiac chest pain	0/308 (0%)	0	0/309 (0%)	0	0/154 (0%)	0	0/370 (0%)	0	0/374 (0%)	0	2/360 (0.6%)	2	1/316 (0.3%)	1
Hepatobiliary disorders
Cholecystitis	0/308 (0%)	0	0/309 (0%)	0	0/154 (0%)	0	0/370 (0%)	0	0/374 (0%)	0	1/360 (0.3%)	1	0/316 (0%)	0
Cholelithiasis	0/308 (0%)	0	0/309 (0%)	0	0/154 (0%)	0	0/370 (0%)	0	0/374 (0%)	0	0/360 (0%)	0	1/316 (0.3%)	1
Immune system disorders
Anaphylactic reaction	0/308 (0%)	0	0/309 (0%)	0	0/154 (0%)	0	0/370 (0%)	0	0/374 (0%)	0	1/360 (0.3%)	1	0/316 (0%)	0
Infections and infestations
Cellulitis	0/308 (0%)	0	1/309 (0.3%)	1	0/154 (0%)	0	0/370 (0%)	0	0/374 (0%)	0	2/360 (0.6%)	2	0/316 (0%)	0
Epiglottitis	1/308 (0.3%)	1	0/309 (0%)	0	0/154 (0%)	0	0/370 (0%)	0	0/374 (0%)	0	0/360 (0%)	0	0/316 (0%)	0
Bone tuberculosis	0/308 (0%)	0	0/309 (0%)	0	0/154 (0%)	0	1/370 (0.3%)	1	0/374 (0%)	0	0/360 (0%)	0	0/316 (0%)	0
Diverticulitis	0/308 (0%)	0	0/309 (0%)	0	0/154 (0%)	0	0/370 (0%)	0	1/374 (0.3%)	1	1/360 (0.3%)	1	0/316 (0%)	0
Gastroenteritis	0/308 (0%)	0	0/309 (0%)	0	0/154 (0%)	0	0/370 (0%)	0	1/374 (0.3%)	1	1/360 (0.3%)	1	0/316 (0%)	0
Gastroenteritis salmonella	0/308 (0%)	0	0/309 (0%)	0	0/154 (0%)	0	0/370 (0%)	0	0/374 (0%)	0	1/360 (0.3%)	1	0/316 (0%)	0
Sinusitis	0/308 (0%)	0	0/309 (0%)	0	0/154 (0%)	0	0/370 (0%)	0	0/374 (0%)	0	0/360 (0%)	0	1/316 (0.3%)	1
Injury, poisoning and procedural complications
Lower limb fracture	0/308 (0%)	0	0/309 (0%)	0	0/154 (0%)	0	0/370 (0%)	0	0/374 (0%)	0	0/360 (0%)	0	1/316 (0.3%)	1
Musculoskeletal and connective tissue disorders
Rotator cuff syndrome	0/308 (0%)	0	0/309 (0%)	0	0/154 (0%)	0	0/370 (0%)	0	0/374 (0%)	0	1/360 (0.3%)	1	0/316 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	0/308 (0%)	0	0/309 (0%)	0	0/154 (0%)	0	1/370 (0.3%)	1	1/374 (0.3%)	1	0/360 (0%)	0	2/316 (0.6%)	3
Pancreatic carcinoma	0/308 (0%)	0	0/309 (0%)	0	0/154 (0%)	0	1/370 (0.3%)	1	0/374 (0%)	0	1/360 (0.3%)	1	0/316 (0%)	0
Squamous cell carcinoma of skin	0/308 (0%)	0	0/309 (0%)	0	0/154 (0%)	0	0/370 (0%)	0	1/374 (0.3%)	1	2/360 (0.6%)	2	2/316 (0.6%)	2
Benign biliary neoplasm	0/308 (0%)	0	0/309 (0%)	0	0/154 (0%)	0	0/370 (0%)	0	0/374 (0%)	0	0/360 (0%)	0	1/316 (0.3%)	1
Bowen's disease	0/308 (0%)	0	0/309 (0%)	0	0/154 (0%)	0	0/370 (0%)	0	0/374 (0%)	0	1/360 (0.3%)	1	1/316 (0.3%)	1
Carcinoma in situ of skin	0/308 (0%)	0	0/309 (0%)	0	0/154 (0%)	0	0/370 (0%)	0	0/374 (0%)	0	0/360 (0%)	0	1/316 (0.3%)	1
Nervous system disorders
Presyncope	0/308 (0%)	0	0/309 (0%)	0	1/154 (0.6%)	1	0/370 (0%)	0	0/374 (0%)	0	0/360 (0%)	0	0/316 (0%)	0
Lacunar infarction	0/308 (0%)	0	0/309 (0%)	0	0/154 (0%)	0	1/370 (0.3%)	1	0/374 (0%)	0	0/360 (0%)	0	0/316 (0%)	0
Cerebellar infarction	0/308 (0%)	0	0/309 (0%)	0	0/154 (0%)	0	0/370 (0%)	0	0/374 (0%)	0	0/360 (0%)	0	1/316 (0.3%)	1
Sciatica	0/308 (0%)	0	0/309 (0%)	0	0/154 (0%)	0	0/370 (0%)	0	0/374 (0%)	0	1/360 (0.3%)	1	0/316 (0%)	0
Transient ischaemic attack	0/308 (0%)	0	0/309 (0%)	0	0/154 (0%)	0	0/370 (0%)	0	0/374 (0%)	0	1/360 (0.3%)	1	0/316 (0%)	0
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous	1/308 (0.3%)	1	0/309 (0%)	0	0/154 (0%)	0	1/370 (0.3%)	1	0/374 (0%)	0	0/360 (0%)	0	0/316 (0%)	0
Psychiatric disorders
Suicide attempt	1/308 (0.3%)	1	0/309 (0%)	0	0/154 (0%)	0	0/370 (0%)	0	0/374 (0%)	0	0/360 (0%)	0	0/316 (0%)	0
Renal and urinary disorders
Nephrolithiasis	0/308 (0%)	0	1/309 (0.3%)	1	0/154 (0%)	0	0/370 (0%)	0	0/374 (0%)	0	0/360 (0%)	0	0/316 (0%)	0
Reproductive system and breast disorders
Uterine haemorrhage	0/308 (0%)	0	0/309 (0%)	0	0/154 (0%)	0	0/370 (0%)	0	0/374 (0%)	0	1/360 (0.3%)	1	0/316 (0%)	0
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	1/308 (0.3%)	1	0/309 (0%)	0	0/154 (0%)	0	0/370 (0%)	0	0/374 (0%)	0	0/360 (0%)	0	0/316 (0%)	0
Pneumothorax	0/308 (0%)	0	1/309 (0.3%)	1	0/154 (0%)	0	0/370 (0%)	0	0/374 (0%)	0	0/360 (0%)	0	0/316 (0%)	0
Pulmonary embolism	0/308 (0%)	0	0/309 (0%)	0	0/154 (0%)	0	1/370 (0.3%)	1	0/374 (0%)	0	1/360 (0.3%)	1	0/316 (0%)	0
Sleep apnoea syndrome	0/308 (0%)	0	0/309 (0%)	0	0/154 (0%)	0	0/370 (0%)	0	0/374 (0%)	0	0/360 (0%)	0	1/316 (0.3%)	1
Skin and subcutaneous tissue disorders
Psoriasis	0/308 (0%)	0	1/309 (0.3%)	1	0/154 (0%)	0	1/370 (0.3%)	1	0/374 (0%)	0	0/360 (0%)	0	0/316 (0%)	0
Vascular disorders
Deep vein thrombosis	0/308 (0%)	0	0/309 (0%)	0	0/154 (0%)	0	1/370 (0.3%)	1	0/374 (0%)	0	0/360 (0%)	0	0/316 (0%)	0
Aneurysm	0/308 (0%)	0	0/309 (0%)	0	0/154 (0%)	0	0/370 (0%)	0	0/374 (0%)	0	1/360 (0.3%)	1	0/316 (0%)	0
Other (Not Including Serious) Adverse Events
	Tildrakizumab 200 mg (Part 1)		Tildrakizumab 100 mg (Part 1)		Placebo (Part 1)		Tildrakizumab 200 mg (Part 2)		Tildrakizumab 100 mg (Part 2)		Tildrakizumab 200 mg (Part 3)		Tildrakizumab 100 mg (Part 3)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	35/308 (11.4%)		36/309 (11.7%)		23/154 (14.9%)		38/370 (10.3%)		42/374 (11.2%)		86/360 (23.9%)		78/316 (24.7%)
Infections and infestations
Nasopharyngitis	20/308 (6.5%)	20	24/309 (7.8%)	26	8/154 (5.2%)	8	17/370 (4.6%)	18	24/374 (6.4%)	24	44/360 (12.2%)	55	48/316 (15.2%)	66
Upper respiratory tract infection	15/308 (4.9%)	15	10/309 (3.2%)	10	9/154 (5.8%)	10	20/370 (5.4%)	21	16/374 (4.3%)	17	37/360 (10.3%)	43	26/316 (8.2%)	32
Skin and subcutaneous tissue disorders
Psoriasis	0/308 (0%)	0	2/309 (0.6%)	2	8/154 (5.2%)	8	3/370 (0.8%)	4	2/374 (0.5%)	2	9/360 (2.5%)	9	9/316 (2.8%)	9

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The investigator agrees not to publish or publicly present any interim results of the trial without the prior written consent of the sponsor. The investigator further agrees to provide to the sponsor 45 days prior to submission for publication or presentation, review copies of abstracts or manuscripts for publication that report any results of the trial.