A Study to Determine the Optimal Dose of Tildrakizumab (SCH 900222/MK-3222) for the Treatment of Moderate-to-severe Chronic Plaque Psoriasis (P05495) (MK-3222-003)

• Sponsor: Merck Sharp & Dohme LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01225731
• Collaborator: (none)
• Enrollment: 355
• Arms: 14
• Actual Duration (Months): 24

Study Details

Study Description

Brief Summary

This is a response-driven study of tildrakuzumab for the treatment of moderate to severe chronic plaque psoriasis. The primary study hypothesis is that one or more doses of tildrakizumab will be superior to placebo for the treatment of psoriasis.

Condition or Disease	Intervention/Treatment	Phase
Psoriasis	Biological: tildrakizumab; Drug: Placebo	Phase 2

Detailed Description

Each participant will be enrolled in the trial for approximately 72-76 weeks. Each participant will receive assigned treatment at Weeks 0 and 4 in Part I. At Week 16, the dosage of treatment the patient is assigned to may be adjusted based on the Psoriasis Area and Severity Index (PASI) 75 response (responder vs non-responder). Participants will receive study medication once every 12 weeks during Part 2 (Weeks 16 to 52); no participants will receive placebo in Part 2. Part 3 is an observational period and each subject will continue to be monitored on a monthly basis through Week 72. Subjects will not receive any study medication during Part 3.

Study Design

• Study Type: Interventional
• Actual Enrollment: 355 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Randomized, Double-Blinded, Placebo-Controlled, Parallel-Design, Dose-Range Finding Study of Subcutaneous Tildrakizumab (SCH 900222/MK-3222) in Subjects With Moderate-to-Severe Chronic Plaque Psoriasis (Study P05495)
• Actual Study Start Date: Oct 25, 2010
• Actual Primary Completion Date: Nov 4, 2011
• Actual Study Completion Date: Oct 24, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Part 1: Tildrakizumab 5 mg Participants receive tildrakizumab 5 mg, subcutaneously (SC) at Weeks 0 and 4	Biological: tildrakizumab; SC administration of tildrakizumab at assigned dose; Other Names: SCH 900222 MK-3222
Experimental: Part 1: Tildrakizumab 25 mg Participants receive tildrakizumab 25 mg, SC, at Weeks 0 and 4	Biological: tildrakizumab; SC administration of tildrakizumab at assigned dose; Other Names: SCH 900222 MK-3222
Experimental: Part 1: Tildrakizumab 100 mg Participants receive tildrakizumab 100 mg, SC, at Weeks 0 and 4	Biological: tildrakizumab; SC administration of tildrakizumab at assigned dose; Other Names: SCH 900222 MK-3222
Experimental: Part 1: Tildrakizumab 200 mg Participants receive tildrakizumab 200 mg, SC, at Weeks 0 and 4	Biological: tildrakizumab; SC administration of tildrakizumab at assigned dose; Other Names: SCH 900222 MK-3222
Placebo Comparator: Part 1: Placebo Participants receive placebo, SC, at Weeks 0 and 4	Drug: Placebo; SC administration of Placebo
Experimental: Part 2: Tildrakizumab 5 mg Participants receive tildrakizumab 5 mg, SC, every 12 weeks for up to 36 weeks	Biological: tildrakizumab; SC administration of tildrakizumab at assigned dose; Other Names: SCH 900222 MK-3222
Experimental: Part 2: Tildrakizumab 25 mg Participants receive tildrakizumab 25 mg, SC, every 12 weeks for up to 36 weeks	Biological: tildrakizumab; SC administration of tildrakizumab at assigned dose; Other Names: SCH 900222 MK-3222
Experimental: Part 2: Tildrakizumab 100 mg Participants receive tildrakizumab 100 mg, SC, every 12 weeks for up to 36 weeks	Biological: tildrakizumab; SC administration of tildrakizumab at assigned dose; Other Names: SCH 900222 MK-3222
Experimental: Part 2: Tildrakizumab 200 mg Participants receive tildrakizumab 200 mg, SC, every 12 weeks for up to 36 weeks	Biological: tildrakizumab; SC administration of tildrakizumab at assigned dose; Other Names: SCH 900222 MK-3222
No Intervention: Part 3: Tildrakizumab 5 mg Follow-up Participants are followed for up to 20 weeks after the last dose of study drug.
No Intervention: Part 3: Tildrakizumab 25 mg Follow-up Participants are followed for up to 20 weeks after the last dose of study drug.
No Intervention: Part 3: Tildrakizumab 100 mg Follow-up Participants are followed for up to 20 weeks after the last dose of study drug.
No Intervention: Part 3: Tildrakizumab 200 mg Follow-up Participants are followed for up to 20 weeks after the last dose of study drug.
No Intervention: Part 3: Placebo Follow-up Participants are followed for up to 20 weeks after the last dose of study drug.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With a Psoriasis Area and Severity Index (PASI)75 Response at Week 16 [Week 16]

   The PASI score measures the severity and extent of psoriasis. Using a scale of 0=none to 4= very severe, each body region (head, trunk, arms, and legs) is rated for redness, thickness, and scaling of the largest psoriatic area in that region producing a Lesion Score. The percentage of the area affected by disease is then estimated, ranging from 0 = no lesions to 6 = 90-100% of the region is covered providing an Area Score. Then, the Lesion Score and Area Score for each region are multiplied, producing 4 subtotals. The 4 region subtotals are multiplied by a standardized percentage of body surface area for that region (head = 0.1, trunk = 0.3, arms=0.2, and legs = 0.4); these four region calculations are added to provide the final PASI score, ranging from 0 = no disease to 72 = maximal disease). PASI 75 response was defined as >=75% improvement in PASI score when compared to the baseline score.

2. Number of Participants Experiencing Adverse Events [Up to 72 weeks]

   An adverse event is any unfavorable and unintended change in the structure, function, or chemistry of the body whether or not considered related to the study treatment.

3. Number of Particpants Discontinuing Study Treatment Due to Adverse Events [Up to 52 weeks]

   An adverse event is any unfavorable and unintended change in the structure, function, or chemistry of the body whether or not considered related to the study treatment. Participants may be discontinued from study drug due to adverse events, but remain on the study.

Secondary Outcome Measures

1. Percentage of Participants With a PASI 75 Response at Week 12 [Week 12]

   The PASI score measures the severity and extent of psoriasis. Using a scale of 0=none to 4= very severe, each body region (head, trunk, arms, and legs) is rated for redness, thickness, and scaling of the largest psoriatic area in that region producing a Lesion Score. The percentage of the area affected by disease is then estimated, ranging from 0 = no lesions to 6 = 90-100% of the region is covered providing an Area Score. Then, the Lesion Score and Area Score for each region are multiplied, producing 4 subtotals. The 4 region subtotals are multiplied by a standardized percentage of body surface area for that region (head = 0.1, trunk = 0.3, arms=0.2, and legs = 0.4); these four region calculations are added to provide the final PASI score, ranging from 0 = no disease to 72 = maximal disease). PASI 75 response was defined as >=75% improvement in PASI score when compared to the baseline score.

2. Percentage of Participants With Physician's Global Assessment (PGA) of "Cleared" or "Minimal" at Week 16 [Week 16]

   The PGA is used to determine the overall severity of a subject's psoriasis lesions at a given time point. Overall lesions will be graded for induration, 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 . 2 =Mild, majority of lesions have individual scores that average 2. 3= Modreate, 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. Percentage of Participants With PASI 90 Response at Week 16 [Week 16]

   The PASI score measures the severity and extent of psoriasis. Using a scale of 0=none to 4= very severe, each body region (head, trunk, arms, and legs) is rated for redness, thickness, and scaling of the largest psoriatic area in that region producing a Lesion Score. The percentage of the area affected by disease is then estimated, ranging from 0 = no lesions to 6 = 90-100% of the region is covered providing an Area Score. Then, the Lesion Score and Area Score for each region are multiplied, producing 4 subtotals. The 4 region subtotals are multiplied by a standardized percentage of body surface area for that region (head = 0.1, trunk = 0.3, arms=0.2, and legs = 0.4); these four region calculations are added to provide the final PASI score, ranging from 0 = no disease to 72 = maximal disease). PASI 90 response was defined as >=90 % improvement in PASI score when compared to the baseline score.

4. Percentage of Participants With PASI 100 Response at Week 16 [Week 16]

   The PASI score measures the severity and extent of psoriasis. Using a scale of 0=none to 4= very severe, each body region (head, trunk, arms, and legs) is rated for redness, thickness, and scaling of the largest psoriatic area in that region producing a Lesion Score. The percentage of the area affected by disease is then estimated, ranging from 0 = no lesions to 6 = 90-100% of the region is covered providing an Area Score. Then, the Lesion Score and Area Score for each region are multiplied, producing 4 subtotals. The 4 region subtotals are multiplied by a standardized percentage of body surface area for that region (head = 0.1, trunk = 0.3, arms=0.2, and legs = 0.4); these four region calculations are added to provide the final PASI score, ranging from 0 = no disease to 72 = maximal disease). PASI 100 response was defined as 100 % improvement in PASI score when compared to the baseline score.

5. PASI 75 Response Rate by Time [Up to 16 Weeks]

   The PASI score measures the severity and extent of psoriasis. Using a scale of 0=none to 4= very severe, each body region (head, trunk, arms, and legs) is rated for redness, thickness, and scaling of the largest psoriatic area in that region producing a Lesion Score. The percentage of the area affected by disease is then estimated, ranging from 0 = no lesions to 6 = 90-100% of the region is covered providing an Area Score. Then, the Lesion Score and Area Score for each region are multiplied, producing 4 subtotals. The 4 region subtotals are multiplied by a standardized percentage of body surface area for that region (head = 0.1, trunk = 0.3, arms=0.2, and legs = 0.4); these four region calculations are added to provide the final PASI score, ranging from 0 = no disease to 72 = maximal disease).PASI 75 response was defined as >=75% improvement in PASI score when compared to the baseline score at Week 2, 4, 6, 8, 12, or 16.

6. Mean Change From Baseline in PASI Score at Weeks 12 and 16 [Baseline and Weeks 12 and 16]

   The PASI score measures the severity and extent of psoriasis. Using a scale of 0=none to 4= very severe, each body region (head, trunk, arms, and legs) is rated for redness, thickness, and scaling of the largest psoriatic area in that region producing a Lesion Score. The percentage of the area affected by disease is then estimated, ranging from 0 = no lesions to 6 = 90-100% of the region is covered providing an Area Score. Then, the Lesion Score and Area Score for each region are multiplied, producing 4 subtotals. The 4 region subtotals are multiplied by a standardized percentage of body surface area for that region (head = 0.1, trunk = 0.3, arms=0.2, and legs = 0.4); these four region calculations are added to provide the final PASI score, ranging from 0 = no disease to 72 = maximal disease).

7. Percentage of Participants With PASI 50 Response at Week 16 [Week 16]

   The PASI score measures the severity and extent of psoriasis. Using a scale of 0=none to 4= very severe, each body region (head, trunk, arms, and legs) is rated for redness, thickness, and scaling of the largest psoriatic area in that region producing a Lesion Score. The percentage of the area affected by disease is then estimated, ranging from 0 = no lesions to 6 = 90-100% of the region is covered providing an Area Score. Then, the Lesion Score and Area Score for each region are multiplied, producing 4 subtotals. The 4 region subtotals are multiplied by a standardized percentage of body surface area for that region (head = 0.1, trunk = 0.3, arms=0.2, and legs = 0.4); these four region calculations are added to provide the final PASI score, ranging from 0 = no disease to 72 = maximal disease). PASI 50 response was defined as >=50 % improvement in PASI score when compared to the baseline score.

8. Mean Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 16 [Week 16]

   The DLQI is a 10-item questionnaire that measures how much participant skin problems have affected their life. Responses range from 0=Not at all to 3=Very much. The DLQI is broken down into 6 subscales: Symptoms and feelings (range 0-6), Daily activities (range 0-6), Leisure (range 0-6), Work and school (range 0-3), Personal relationships (range 0-6), and Treatment (range 0-3). DLQI subscales were summed to yield the DLQI total score, which could range from 0 to 30. For both DLQI subscales and DLQI total score, a higher score indicated a greater negative impact on life.

9. Percentage of Participants Achieving DLQI Score of 0 or 1 at Week 16 [Week 16]

   The DLQI is a 10-item questionnaire that measures how much participant skin problems have affected their life. Responses range from 0=Not at all to 3=Very much. The DLQI is broken down into 6 subscales: Symptoms and feelings (range 0-6), Daily activities (range 0-6), Leisure (range 0-6), Work and school (range 0-3), Personal relationships (range 0-6), and Treatment (range 0-3). DLQI subscales were summed to yield the DLQI total score, which could range from 0 to 30. For both DLQI subscales and DLQI total score, a higher score indicated a greater negative impact on life.

10. Percentage of Participants Achieving a >=5 Point Reduction in DLQI at Week 16 [Week 16]

    The DLQI is a 10-item questionnaire that measures how much participant skin problems have affected their life. Responses range from 0=Not at all to 3=Very much. The DLQI is broken down into 6 subscales: Symptoms and feelings (range 0-6), Daily activities (range 0-6), Leisure (range 0-6), Work and school (range 0-3), Personal relationships (range 0-6), and Treatment (range 0-3). DLQI subscales were summed to yield the DLQI total score, which could range from 0 to 30. For both DLQI subscales and DLQI total score, a higher score indicated a greater negative impact on life.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Adult participants (≥18 years of age) with a diagnosis of moderate-to-severe chronic plaque psoriasis (defined by ≥10% body surface area [BSA] involvement, "moderate" or greater score on the Physician's Global Assessment [PGA] scale, and PASI score ≥12 at Baseline)

• Participants must have a diagnosis of predominantly plaque psoriasis for ≥6 months (as determined by interview and confirmation of diagnosis through physical examination by investigator) and be considered candidates for phototherapy or systemic therapy. Participants with psoriatic arthritis may be included in the study

Exclusion Criteria:

• Nonplaque forms of psoriasis specifically erythrodermic psoriasis, predominantly pustular psoriasis, medication-induced or medication-exacerbated psoriasis, or new onset guttate psoriasis

• Participants who will require oral or injectable corticosteroids during the trial

• Presence of any infection requiring treatment with systemic antibiotics within 2 weeks prior to Screening, or serious infection (eg, pneumonia, cellulitis, bone or joint infections) requiring hospitalization or treatment with intravenous antibiotics within 8 weeks prior to Screening

• Participants with evidence of active or untreated latent tuberculosis (TB) according to Screening criteria specified in the protocol. (Prophylactic treatment for latent TB as per local guidelines must be initiated at least 4 weeks prior to treatment with study medication)

• Previous exposure to any agents targeting interleukin-12 (IL-12) and/or Interleukin-23 (IL-23)

• Participants with prior exposure to two or more tumor necrosis factor (TNF) antagonists with discontinuation due to lack of efficacy.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Merck Sharp & Dohme LLC

Investigators

• Study Director: Medical Director, Merck Sharp & Dohme LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT01225731
• Other Study ID Numbers: P05495; 2009-017272-24; MK-3222-003
• First Posted: Oct 21, 2010
• Last Update Posted: Feb 5, 2019
• Last Verified: Jan 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Additional relevant MeSH terms: Psoriasis

Study Results

Participant Flow

Arm/Group Title	Part 1: Tildrakizumab 5 mg	Part 1: Tildrakizumab 25 mg	Part 1: Tildrakizumab 100 mg	Part 1: Tildrakizumab 200 mg	Part 1: Placebo	Part 2: Tildrakizumab 5 mg	Part 2: Tildrakizumab 25 mg	Part 2: Tildrakizumab 100 mg	Part 2: Tildrakizumab 200 mg	Part 3: Tildrakizumab 5 mg Follow-up	Part 3: Tildrakizumab 25 mg Follow-up	Part 3: Tildrakizumab 100 mg Follow-up	Part 3: Tildrakizumab 200 mg Follow-up
Arm/Group Description	Participants receive tildrakizumab 5 mg, subcutaneously (SC) at Weeks 0 and 4	Participants receive tildrakizumab 25 mg, SC, at Weeks 0 and 4	Participants receive tildrakizumab 100 mg, SC, at Weeks 0 and 4	Participants receive tildrakizumab 200 mg, SC, at Weeks 0 and 4	Participants receive placebo, SC, at Weeks 0 and 4	Participants receive tildrakizumab 5 mg, SC, every 12 weeks for up to 36 weeks	Participants receive tildrakizumab 25 mg, SC, every 12 weeks for up to 36 weeks	Participants receive tildrakizumab 100 mg, SC, every 12 weeks for up to 36 weeks	Participants receive tildrakizumab 200 mg, SC, every 12 weeks for up to 36 weeks	Participants are followed for up to 20 weeks after the last dose of study drug.	Participants are followed for up to 20 weeks after the last dose of study drug.	Participants are followed for up to 20 weeks after the last dose of study drug.	Participants are followed for up to 20 weeks after the last dose of study drug.
Period Title: Part 1
STARTED	42	92	89	86	46	0	0	0	0	0	0	0	0
COMPLETED	40	87	88	84	40	0	0	0	0	0	0	0	0
NOT COMPLETED	2	5	1	2	6	0	0	0	0	0	0	0	0
Period Title: Part 1
STARTED	0	0	0	0	0	13	94	153	79	0	0	0	0
COMPLETED	0	0	0	0	0	10	86	128	68	0	0	0	0
NOT COMPLETED	0	0	0	0	0	3	8	25	11	0	0	0	0
Period Title: Part 1
STARTED	0	0	0	0	0	0	0	0	0	10	86	126	67
COMPLETED	0	0	0	0	0	0	0	0	0	10	80	116	60
NOT COMPLETED	0	0	0	0	0	0	0	0	0	0	6	10	7

Baseline Characteristics

Arm/Group Title	Part 1: Tildrakizumab 5 mg	Part 1: Tildrakizumab 25 mg	Part 1: Tildrakizumab 100 mg	Part 1: Tildrakizumab 200 mg	Part 1: Placebo	Total
Arm/Group Description	Participants receive tildrakizumab 5 mg, subcutaneously (SC) at Weeks 0 and 4	Participants receive tildrakizumab 25 mg, SC, at Weeks 0 and 4	Participants receive tildrakizumab 100 mg, SC, at Weeks 0 and 4	Participants receive tildrakizumab 200 mg, SC, at Weeks 0 and 4	Participants receive placebo, SC, at Weeks 0 and 4	Total of all reporting groups
Overall Participants	42	92	89	86	46	355
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	43.2 (12.9)	46.3 (13.7)	45.5 (12.8)	43.2 (12.6)	45.9 (11.7)	44.9 (12.9)
Sex: Female, Male (Count of Participants)
Female	11 26.2%	32 34.8%	13 14.6%	21 24.4%	8 17.4%	85 23.9%
Male	31 73.8%	60 65.2%	76 85.4%	65 75.6%	38 82.6%	270 76.1%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With a Psoriasis Area and Severity Index (PASI)75 Response at Week 16
Description	The PASI score measures the severity and extent of psoriasis. Using a scale of 0=none to 4= very severe, each body region (head, trunk, arms, and legs) is rated for redness, thickness, and scaling of the largest psoriatic area in that region producing a Lesion Score. The percentage of the area affected by disease is then estimated, ranging from 0 = no lesions to 6 = 90-100% of the region is covered providing an Area Score. Then, the Lesion Score and Area Score for each region are multiplied, producing 4 subtotals. The 4 region subtotals are multiplied by a standardized percentage of body surface area for that region (head = 0.1, trunk = 0.3, arms=0.2, and legs = 0.4); these four region calculations are added to provide the final PASI score, ranging from 0 = no disease to 72 = maximal disease). PASI 75 response was defined as >=75% improvement in PASI score when compared to the baseline score.
Time Frame	Week 16

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS), all randomized participants who received >=1 dose of study drug and had a baseline and >=1 post-treatment efficacy measurement. The last non-missing post-baseline PASI score was carried forward (LOCF) unless the participant discontinued drug due to lack of efficacy, loss of response, or use of prohibited medications.

Arm/Group Title	Part 1: Tildrakizumab 5 mg	Part 1: Tildrakizumab 25 mg	Part 1: Tildrakizumab 100 mg	Part 1: Tildrakizumab 200 mg	Part 1: Placebo
Arm/Group Description	Participants receive tildrakizumab 5 mg, subcutaneously (SC) at Weeks 0 and 4	Participants receive tildrakizumab 25 mg, SC, at Weeks 0 and 4	Participants receive tildrakizumab 100 mg, SC, at Weeks 0 and 4	Participants receive tildrakizumab 200 mg, SC, at Weeks 0 and 4	Participants receive placebo, SC, at Weeks 0 and 4
Measure Participants	42	90	89	86	45
Number [Percentage of participants]	33.33 79.4%	64.44 70%	66.29 74.5%	74.42 86.5%	4.44 9.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: Tildrakizumab 5 mg, Part 1: Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by baseline weight (≤90 kg or >90 kg) and prior use of biologics for psoriasis (Yes/No).
Method of Estimation	Estimation Parameter	% Difference in Response Rate
	Estimated Value	28.89
	Confidence Interval	(2-Sided) 95%; 13.41 to 44.36
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Part 1: Tildrakizumab 25 mg, Part 1: Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by baseline weight (≤90 kg or >90 kg) and prior use of biologics for psoriasis (Yes/No).
Method of Estimation	Estimation Parameter	% Difference in Response Rate
	Estimated Value	60.00
	Confidence Interval	(2-Sided) 95%; 48.42 to 71.58
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Part 1: Tildrakizumab 100 mg, Part 1: Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by baseline weight (≤90 kg or >90 kg) and prior use of biologics for psoriasis (Yes/No).
Method of Estimation	Estimation Parameter	% Difference in Response Rate
	Estimated Value	61.85
	Confidence Interval	(2-Sided) 95%; 50.33 to 73.37
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Part 1: Tildrakizumab 200 mg, Part 1: Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by baseline weight (≤90 kg or >90 kg) and prior use of biologics for psoriasis (Yes/No).
Method of Estimation	Estimation Parameter	% Difference in Response Rate
	Estimated Value	69.97
	Confidence Interval	(2-Sided) 95%; 58.96 to 80.99
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percentage of Participants With a PASI 75 Response at Week 12
Description	The PASI score measures the severity and extent of psoriasis. Using a scale of 0=none to 4= very severe, each body region (head, trunk, arms, and legs) is rated for redness, thickness, and scaling of the largest psoriatic area in that region producing a Lesion Score. The percentage of the area affected by disease is then estimated, ranging from 0 = no lesions to 6 = 90-100% of the region is covered providing an Area Score. Then, the Lesion Score and Area Score for each region are multiplied, producing 4 subtotals. The 4 region subtotals are multiplied by a standardized percentage of body surface area for that region (head = 0.1, trunk = 0.3, arms=0.2, and legs = 0.4); these four region calculations are added to provide the final PASI score, ranging from 0 = no disease to 72 = maximal disease). PASI 75 response was defined as >=75% improvement in PASI score when compared to the baseline score.
Time Frame	Week 12

Outcome Measure Data

Analysis Population Description

The FAS, all randomized participants who received >=1 dose of study drug and had a baseline and >=1 post-treatment efficacy measurement. The last non-missing post-baseline PASI score was carried forward (LOCF) unless the participant discontinued drug due to lack of efficacy, loss of response, or use of prohibited medications.

Arm/Group Title	Part 1: Tildrakizumab 5 mg	Part 1: Tildrakizumab 25 mg	Part 1: Tildrakizumab 100 mg	Part 1: Tildrakizumab 200 mg	Part 1: Placebo
Arm/Group Description	Participants receive tildrakizumab 5 mg, subcutaneously (SC) at Weeks 0 and 4	Participants receive tildrakizumab 25 mg, SC, at Weeks 0 and 4	Participants receive tildrakizumab 100 mg, SC, at Weeks 0 and 4	Participants receive tildrakizumab 200 mg, SC, at Weeks 0 and 4	Participants receive placebo, SC, at Weeks 0 and 4
Measure Participants	42	90	89	86	45
Number [Percentage of participants]	23.81 56.7%	58.89 64%	60.67 68.2%	72.09 83.8%	4.44 9.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: Tildrakizumab 5 mg, Part 1: Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.009
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by baseline weight (≤90 kg or >90 kg) and prior use of biologics for psoriasis (Yes/No).
Method of Estimation	Estimation Parameter	% Difference in Response Rate
	Estimated Value	19.37
	Confidence Interval	(2-Sided) 95%; 5.15 to 33.58
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Part 1: Tildrakizumab 25 mg, Part 1: Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by baseline weight (≤90 kg or >90 kg) and prior use of biologics for psoriasis (Yes/No).
Method of Estimation	Estimation Parameter	% Difference in Response Rate
	Estimated Value	54.44
	Confidence Interval	(2-Sided) 95%; 42.63 to 66.26
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Part 1: Tildrakizumab 100 mg, Part 1: Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by baseline weight (≤90 kg or >90 kg) and prior use of biologics for psoriasis (Yes/No).
Method of Estimation	Estimation Parameter	% Difference in Response Rate
	Estimated Value	56.23
	Confidence Interval	(2-Sided) 95%; 44.43 to 68.03
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Part 1: Tildrakizumab 200 mg, Part 1: Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by baseline weight (≤90 kg or >90 kg) and prior use of biologics for psoriasis (Yes/No).
Method of Estimation	Estimation Parameter	% Difference in Response Rate
	Estimated Value	67.65
	Confidence Interval	(2-Sided) 95%; 56.42 to 78.88
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Percentage of Participants With Physician's Global Assessment (PGA) of "Cleared" or "Minimal" at Week 16
Description	The PGA is used to determine the overall severity of a subject's psoriasis lesions at a given time point. Overall lesions will be graded for induration, 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 . 2 =Mild, majority of lesions have individual scores that average 2. 3= Modreate, 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	Week 16

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS), all randomized participants who received >=1 dose of study drug and had a baseline and >=1 post-treatment efficacy measurement. The last non-missing post-baseline PGA value was carried forward (LOCF) unless the participant discontinued drug due to lack of efficacy, loss of response, or use of prohibited medications.

Arm/Group Title	Part 1: Tildrakizumab 5 mg	Part 1: Tildrakizumab 25 mg	Part 1: Tildrakizumab 100 mg	Part 1: Tildrakizumab 200 mg	Part 1: Placebo
Arm/Group Description	Participants receive tildrakizumab 5 mg, subcutaneously (SC) at Weeks 0 and 4	Participants receive tildrakizumab 25 mg, SC, at Weeks 0 and 4	Participants receive tildrakizumab 100 mg, SC, at Weeks 0 and 4	Participants receive tildrakizumab 200 mg, SC, at Weeks 0 and 4	Participants receive placebo, SC, at Weeks 0 and 4
Measure Participants	42	90	89	86	45
Number [Percentage of participants]	33.33 79.4%	57.78 62.8%	61.80 69.4%	74.42 86.5%	2.22 4.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Part 1: Tildrakizumab 5 mg, Part 1: Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by baseline weight (≤90 kg or >90 kg) and prior use of biologics for psoriasis (Yes/No).
Method of Estimation	Estimation Parameter	% Difference in Response Rate
	Estimated Value	31.11
	Confidence Interval	(2-Sided) 95%; 16.22 to 46.0
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Part 1: Tildrakizumab 25 mg, Part 1: Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by baseline weight (≤90 kg or >90 kg) and prior use of biologics for psoriasis (Yes/No).
Method of Estimation	Estimation Parameter	% Difference in Response Rate
	Estimated Value	55.56
	Confidence Interval	(2-Sided) 95%; 44.48 to 66.63
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Part 1: Tildrakizumab 100 mg, Part 1: Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by baseline weight (≤90 kg or >90 kg) and prior use of biologics for psoriasis (Yes/No).
Method of Estimation	Estimation Parameter	% Difference in Response Rate
	Estimated Value	59.58
	Confidence Interval	(2-Sided) 95%; 48.60 to 70.55
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Part 1: Tildrakizumab 200 mg, Part 1: Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments	Stratified by baseline weight (≤90 kg or >90 kg) and prior use of biologics for psoriasis (Yes/No).
Method of Estimation	Estimation Parameter	% Difference in Response Rate
	Estimated Value	72.20
	Confidence Interval	(2-Sided) 95%; 62.02 to 82.37
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Percentage of Participants With PASI 90 Response at Week 16
Description	The PASI score measures the severity and extent of psoriasis. Using a scale of 0=none to 4= very severe, each body region (head, trunk, arms, and legs) is rated for redness, thickness, and scaling of the largest psoriatic area in that region producing a Lesion Score. The percentage of the area affected by disease is then estimated, ranging from 0 = no lesions to 6 = 90-100% of the region is covered providing an Area Score. Then, the Lesion Score and Area Score for each region are multiplied, producing 4 subtotals. The 4 region subtotals are multiplied by a standardized percentage of body surface area for that region (head = 0.1, trunk = 0.3, arms=0.2, and legs = 0.4); these four region calculations are added to provide the final PASI score, ranging from 0 = no disease to 72 = maximal disease). PASI 90 response was defined as >=90 % improvement in PASI score when compared to the baseline score.
Time Frame	Week 16

Outcome Measure Data

Analysis Population Description

The FAS, all randomized participants who received >=1 dose of study drug and had a baseline and >=1 post-treatment efficacy measurement, and data for this endpoint.

Arm/Group Title	Part 1: Tildrakizumab 5 mg	Part 1: Tildrakizumab 25 mg	Part 1: Tildrakizumab 100 mg	Part 1: Tildrakizumab 200 mg	Part 1: Placebo
Arm/Group Description	Participants receive tildrakizumab 5 mg, subcutaneously (SC) at Weeks 0 and 4	Participants receive tildrakizumab 25 mg, SC, at Weeks 0 and 4	Participants receive tildrakizumab 100 mg, SC, at Weeks 0 and 4	Participants receive tildrakizumab 200 mg, SC, at Weeks 0 and 4	Participants receive placebo, SC, at Weeks 0 and 4
Measure Participants	40	87	88	84	41
Number [Percentage of participants]	12.50 29.8%	25.29 27.5%	38.64 43.4%	52.38 60.9%	2.44 5.3%

5. Secondary Outcome

Title	Percentage of Participants With PASI 100 Response at Week 16
Description	The PASI score measures the severity and extent of psoriasis. Using a scale of 0=none to 4= very severe, each body region (head, trunk, arms, and legs) is rated for redness, thickness, and scaling of the largest psoriatic area in that region producing a Lesion Score. The percentage of the area affected by disease is then estimated, ranging from 0 = no lesions to 6 = 90-100% of the region is covered providing an Area Score. Then, the Lesion Score and Area Score for each region are multiplied, producing 4 subtotals. The 4 region subtotals are multiplied by a standardized percentage of body surface area for that region (head = 0.1, trunk = 0.3, arms=0.2, and legs = 0.4); these four region calculations are added to provide the final PASI score, ranging from 0 = no disease to 72 = maximal disease). PASI 100 response was defined as 100 % improvement in PASI score when compared to the baseline score.
Time Frame	Week 16

Outcome Measure Data

Analysis Population Description

The FAS, all randomized participants who received >=1 dose of study drug and had a baseline and >=1 post-treatment efficacy measurement, and data fior this endpoint

Arm/Group Title	Part 1: Tildrakizumab 5 mg	Part 1: Tildrakizumab 25 mg	Part 1: Tildrakizumab 100 mg	Part 1: Tildrakizumab 200 mg	Part 1: Placebo
Arm/Group Description	Participants receive tildrakizumab 5 mg, subcutaneously (SC) at Weeks 0 and 4	Participants receive tildrakizumab 25 mg, SC, at Weeks 0 and 4	Participants receive tildrakizumab 100 mg, SC, at Weeks 0 and 4	Participants receive tildrakizumab 200 mg, SC, at Weeks 0 and 4	Participants receive placebo, SC, at Weeks 0 and 4
Measure Participants	40	87	88	84	41
Number [Percentage of participants]	5.0 11.9%	9.20 10%	14.77 16.6%	16.67 19.4%	0.00 0%

6. Secondary Outcome

Title	PASI 75 Response Rate by Time
Description	The PASI score measures the severity and extent of psoriasis. Using a scale of 0=none to 4= very severe, each body region (head, trunk, arms, and legs) is rated for redness, thickness, and scaling of the largest psoriatic area in that region producing a Lesion Score. The percentage of the area affected by disease is then estimated, ranging from 0 = no lesions to 6 = 90-100% of the region is covered providing an Area Score. Then, the Lesion Score and Area Score for each region are multiplied, producing 4 subtotals. The 4 region subtotals are multiplied by a standardized percentage of body surface area for that region (head = 0.1, trunk = 0.3, arms=0.2, and legs = 0.4); these four region calculations are added to provide the final PASI score, ranging from 0 = no disease to 72 = maximal disease).PASI 75 response was defined as >=75% improvement in PASI score when compared to the baseline score at Week 2, 4, 6, 8, 12, or 16.
Time Frame	Up to 16 Weeks

Outcome Measure Data

Analysis Population Description

The FAS, all randomized participants who received >=1 dose of study drug and had a baseline and >=1 post-treatment efficacy measurement. and data for the specific Week.

Arm/Group Title	Part 1: Tildrakizumab 5 mg	Part 1: Tildrakizumab 25 mg	Part 1: Tildrakizumab 100 mg	Part 1: Tildrakizumab 200 mg	Part 1: Placebo
Arm/Group Description	Participants receive tildrakizumab 5 mg, subcutaneously (SC) at Weeks 0 and 4	Participants receive tildrakizumab 25 mg, SC, at Weeks 0 and 4	Participants receive tildrakizumab 100 mg, SC, at Weeks 0 and 4	Participants receive tildrakizumab 200 mg, SC, at Weeks 0 and 4	Participants receive placebo, SC, at Weeks 0 and 4
Measure Participants	42	90	89	86	45
Week 2 (n=42, 89, 89, 85, 45)	0.00 0%	1.12 1.2%	1.12 1.3%	0.00 0%	0.00 0%
Week 4 (n=42, 89, 89, 85, 45)	0.00 0%	11.24 12.2%	11.24 12.6%	3.53 4.1%	0.00 0%
Week 6 (n=40, 86, 88, 84,44)	12.50 29.8%	20.93 22.8%	25.00 28.1%	30.95 36%	2.27 4.9%
Week 8 (n=40, 88, 87, 83, 43)	12.50 29.8%	35.23 38.3%	47.13 53%	61.45 71.5%	4.65 10.1%
Week 12 (n=40, 87, 88, 83, 42)	25.00 59.5%	59.77 65%	61.36 68.9%	73.49 85.5%	4.76 10.3%
Week 16 (n=40, 87, 88, 84, 41)	35.00 83.3%	65.52 71.2%	67.05 75.3%	76.19 88.6%	4.88 10.6%

7. Secondary Outcome

Title	Mean Change From Baseline in PASI Score at Weeks 12 and 16
Description	The PASI score measures the severity and extent of psoriasis. Using a scale of 0=none to 4= very severe, each body region (head, trunk, arms, and legs) is rated for redness, thickness, and scaling of the largest psoriatic area in that region producing a Lesion Score. The percentage of the area affected by disease is then estimated, ranging from 0 = no lesions to 6 = 90-100% of the region is covered providing an Area Score. Then, the Lesion Score and Area Score for each region are multiplied, producing 4 subtotals. The 4 region subtotals are multiplied by a standardized percentage of body surface area for that region (head = 0.1, trunk = 0.3, arms=0.2, and legs = 0.4); these four region calculations are added to provide the final PASI score, ranging from 0 = no disease to 72 = maximal disease).
Time Frame	Baseline and Weeks 12 and 16

Outcome Measure Data

Analysis Population Description

The FAS, all randomized participants who received >=1 dose of study drug and had a baseline and >=1 post-treatment efficacy measurement, and data for Week 12 and Week 16.

Arm/Group Title	Part 1: Tildrakizumab 5 mg	Part 1: Tildrakizumab 25 mg	Part 1: Tildrakizumab 100 mg	Part 1: Tildrakizumab 200 mg	Part 1: Placebo
Arm/Group Description	Participants receive tildrakizumab 5 mg, subcutaneously (SC) at Weeks 0 and 4	Participants receive tildrakizumab 25 mg, SC, at Weeks 0 and 4	Participants receive tildrakizumab 100 mg, SC, at Weeks 0 and 4	Participants receive tildrakizumab 200 mg, SC, at Weeks 0 and 4	Participants receive placebo, SC, at Weeks 0 and 4
Measure Participants	42	90	89	86	45
Week 12	-10.2	-14.4	-14.1	-14.9	-2.2
Week 16	-10.0	-14.6	-14.9	-15.6	-2.4

8. Secondary Outcome

Title	Percentage of Participants With PASI 50 Response at Week 16
Description	The PASI score measures the severity and extent of psoriasis. Using a scale of 0=none to 4= very severe, each body region (head, trunk, arms, and legs) is rated for redness, thickness, and scaling of the largest psoriatic area in that region producing a Lesion Score. The percentage of the area affected by disease is then estimated, ranging from 0 = no lesions to 6 = 90-100% of the region is covered providing an Area Score. Then, the Lesion Score and Area Score for each region are multiplied, producing 4 subtotals. The 4 region subtotals are multiplied by a standardized percentage of body surface area for that region (head = 0.1, trunk = 0.3, arms=0.2, and legs = 0.4); these four region calculations are added to provide the final PASI score, ranging from 0 = no disease to 72 = maximal disease). PASI 50 response was defined as >=50 % improvement in PASI score when compared to the baseline score.
Time Frame	Week 16

Outcome Measure Data

Analysis Population Description

The FAS, all randomized participants who received >=1 dose of study drug and had a baseline and >=1 post-treatment efficacy measurement. The last non-missing post-baseline PASI score was carried forward (LOCF) unless the participant discontinued drug due to lack of efficacy, loss of response, or use of prohibited medications.

Arm/Group Title	Part 1: Tildrakizumab 5 mg	Part 1: Tildrakizumab 25 mg	Part 1: Tildrakizumab 100 mg	Part 1: Tildrakizumab 200 mg	Part 1: Placebo
Arm/Group Description	Participants receive tildrakizumab 5 mg, subcutaneously (SC) at Weeks 0 and 4	Participants receive tildrakizumab 25 mg, SC, at Weeks 0 and 4	Participants receive tildrakizumab 100 mg, SC, at Weeks 0 and 4	Participants receive tildrakizumab 200 mg, SC, at Weeks 0 and 4	Participants receive placebo, SC, at Weeks 0 and 4
Measure Participants	42	90	89	86	45
Number [Percentage of participants]	57.14 136%	82.22 89.4%	82.02 92.2%	91.86 106.8%	8.89 19.3%

9. Secondary Outcome

Title	Mean Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 16
Description	The DLQI is a 10-item questionnaire that measures how much participant skin problems have affected their life. Responses range from 0=Not at all to 3=Very much. The DLQI is broken down into 6 subscales: Symptoms and feelings (range 0-6), Daily activities (range 0-6), Leisure (range 0-6), Work and school (range 0-3), Personal relationships (range 0-6), and Treatment (range 0-3). DLQI subscales were summed to yield the DLQI total score, which could range from 0 to 30. For both DLQI subscales and DLQI total score, a higher score indicated a greater negative impact on life.
Time Frame	Week 16

Outcome Measure Data

Analysis Population Description

The FAS, all randomized participants who received >=1 dose of study drug and had a baseline and >=1 post-treatment efficacy measurement, and had data for this endpoint.

Arm/Group Title	Part 1: Tildrakizumab 5 mg	Part 1: Tildrakizumab 25 mg	Part 1: Tildrakizumab 100 mg	Part 1: Tildrakizumab 200 mg	Part 1: Placebo
Arm/Group Description	Participants receive tildrakizumab 5 mg, subcutaneously (SC) at Weeks 0 and 4	Participants receive tildrakizumab 25 mg, SC, at Weeks 0 and 4	Participants receive tildrakizumab 100 mg, SC, at Weeks 0 and 4	Participants receive tildrakizumab 200 mg, SC, at Weeks 0 and 4	Participants receive placebo, SC, at Weeks 0 and 4
Measure Participants	40	87	88	83	42
Mean (95% Confidence Interval) [Score on a scale]	-4.9	-9.2	-8.5	-8.8	1.0

10. Secondary Outcome

Title	Percentage of Participants Achieving DLQI Score of 0 or 1 at Week 16
Description	The DLQI is a 10-item questionnaire that measures how much participant skin problems have affected their life. Responses range from 0=Not at all to 3=Very much. The DLQI is broken down into 6 subscales: Symptoms and feelings (range 0-6), Daily activities (range 0-6), Leisure (range 0-6), Work and school (range 0-3), Personal relationships (range 0-6), and Treatment (range 0-3). DLQI subscales were summed to yield the DLQI total score, which could range from 0 to 30. For both DLQI subscales and DLQI total score, a higher score indicated a greater negative impact on life.
Time Frame	Week 16

Outcome Measure Data

Analysis Population Description

The FAS, all randomized participants who received >=1 dose of study drug and had a baseline and >=1 post-treatment efficacy measurement, and data for this endpoint, excluding all participants on the placebo arm.

Arm/Group Title	Part 1: Tildrakizumab 5 mg	Part 1: Tildrakizumab 25 mg	Part 1: Tildrakizumab 100 mg	Part 1: Tildrakizumab 200 mg
Arm/Group Description	Participants receive tildrakizumab 5 mg, subcutaneously (SC) at Weeks 0 and 4	Participants receive tildrakizumab 25 mg, SC, at Weeks 0 and 4	Participants receive tildrakizumab 100 mg, SC, at Weeks 0 and 4	Participants receive tildrakizumab 200 mg, SC, at Weeks 0 and 4
Measure Participants	40	87	88	83
Number [Percentage of participants]	32.5 77.4%	57.47 62.5%	52.27 58.7%	57.83 67.2%

11. Secondary Outcome

Title	Percentage of Participants Achieving a >=5 Point Reduction in DLQI at Week 16
Description	The DLQI is a 10-item questionnaire that measures how much participant skin problems have affected their life. Responses range from 0=Not at all to 3=Very much. The DLQI is broken down into 6 subscales: Symptoms and feelings (range 0-6), Daily activities (range 0-6), Leisure (range 0-6), Work and school (range 0-3), Personal relationships (range 0-6), and Treatment (range 0-3). DLQI subscales were summed to yield the DLQI total score, which could range from 0 to 30. For both DLQI subscales and DLQI total score, a higher score indicated a greater negative impact on life.
Time Frame	Week 16

Outcome Measure Data

Analysis Population Description

The FAS, all randomized participants who received >=1 dose of study drug and had a baseline and >=1 post-treatment efficacy measurement, and had data for this endpoint.

Arm/Group Title	Part 1: Tildrakizumab 5 mg	Part 1: Tildrakizumab 25 mg	Part 1: Tildrakizumab 100 mg	Part 1: Tildrakizumab 200 mg	Part 1: Placebo
Arm/Group Description	Participants receive tildrakizumab 5 mg, subcutaneously (SC) at Weeks 0 and 4	Participants receive tildrakizumab 25 mg, SC, at Weeks 0 and 4	Participants receive tildrakizumab 100 mg, SC, at Weeks 0 and 4	Participants receive tildrakizumab 200 mg, SC, at Weeks 0 and 4	Participants receive placebo, SC, at Weeks 0 and 4
Measure Participants	40	87	88	83	42
Number [Percentage of participants]	52.50 125%	70.11 76.2%	64.77 72.8%	73.49 85.5%	19.05 41.4%

12. Primary Outcome

Title	Number of Participants Experiencing Adverse Events
Description	An adverse event is any unfavorable and unintended change in the structure, function, or chemistry of the body whether or not considered related to the study treatment.
Time Frame	Up to 72 weeks

Outcome Measure Data

Analysis Population Description

All participants receiving at least one dose of study drug.

Arm/Group Title	Part 1: Tildrakizumab 5 mg	Part 1: Tildrakizumab 25 mg	Part 1: Tildrakizumab 100 mg	Part 1: Tildrakizumab 200 mg	Part 1: Placebo	Part 2: Tildrakizumab 5 mg	Part 2: Tildrakizumab 25 mg	Part 2: Tildrakizumab 100 mg	Part 2: Tildrakizumab 200 mg	Part 3: Tildrakizumab 5 mg Follow-up	Part 3: Tildrakizumab 25 mg Follow-up	Part 3: Tildrakizumab 100 mg Follow-up	Part 3: Tildrakizumab 200 mg Follow-up
Arm/Group Description	Participants receive tildrakizumab 5 mg, subcutaneously (SC) at Weeks 0 and 4	Participants receive tildrakizumab 25 mg, SC, at Weeks 0 and 4	Participants receive tildrakizumab 100 mg, SC, at Weeks 0 and 4	Participants receive tildrakizumab 200 mg, SC, at Weeks 0 and 4	Participants receive placebo, SC, at Weeks 0 and 4	Participants receive tildrakizumab 5 mg, SC, every 12 weeks for up to 36 weeks	Participants receive tildrakizumab 25 mg, SC, every 12 weeks for up to 36 weeks	Participants receive tildrakizumab 100 mg, SC, every 12 weeks for up to 36 weeks	Participants receive tildrakizumab 200 mg, SC, every 12 weeks for up to 36 weeks	Participants are followed for up to 20 weeks after the last dose of study drug	Participants are followed for up to 20 weeks after the last dose of study drug	Participants are followed for up to 20 weeks after the last dose of study drug	Participants are followed for up to 20 weeks after the last dose of study drug
Measure Participants	42	91	89	86	45	13	94	153	79	10	86	126	67
Number [Participants]	30 71.4%	56 60.9%	58 65.2%	54 62.8%	31 67.4%	7 2%	60 NaN	105 NaN	52 NaN	3 NaN	32 NaN	53 NaN	28 NaN

13. Primary Outcome

Title	Number of Particpants Discontinuing Study Treatment Due to Adverse Events
Description	An adverse event is any unfavorable and unintended change in the structure, function, or chemistry of the body whether or not considered related to the study treatment. Participants may be discontinued from study drug due to adverse events, but remain on the study.
Time Frame	Up to 52 weeks

Outcome Measure Data

Analysis Population Description

All particpants receiving at least one dose of study drug during the treatment period.

Arm/Group Title	Part 1: Tildrakizumab 5 mg	Part 1: Tildrakizumab 25 mg	Part 1: Tildrakizumab 100 mg	Part 1: Tildrakizumab 200 mg	Part 1: Placebo	Part 2: Tildrakizumab 5 mg	Part 2: Tildrakizumab 25 mg	Part 2: Tildrakizumab 100 mg	Part 2: Tildrakizumab 200 mg
Arm/Group Description	Participants receive tildrakizumab 5 mg, subcutaneously (SC) at Weeks 0 and 4	Participants receive tildrakizumab 25 mg, SC, at Weeks 0 and 4	Participants receive tildrakizumab 100 mg, SC, at Weeks 0 and 4	Participants receive tildrakizumab 200 mg, SC, at Weeks 0 and 4	Participants receive placebo, SC, at Weeks 0 and 4	Participants receive tildrakizumab 5 mg, SC, every 12 weeks for up to 36 weeks	Participants receive tildrakizumab 25 mg, SC, every 12 weeks for up to 36 weeks	Participants receive tildrakizumab 100 mg, SC, every 12 weeks for up to 36 weeks	Participants receive tildrakizumab 200 mg, SC, every 12 weeks for up to 36 weeks
Measure Participants	42	91	89	86	45	13	94	153	79
Number [Participants]	1 2.4%	2 2.2%	1 1.1%	1 1.2%	1 2.2%	0 0%	5 NaN	5 NaN	3 NaN

Adverse Events

Time Frame	Up to 72 weeks
Adverse Event Reporting Description	All participants who received at least one dose of tildrakizumab or placebo.
Arm/Group Title	Part 1: Tildrakizumab 5 mg		Part 1: Tildrakizumab 25 mg		Part 1: Tildrakizumab 100 mg		Part 1: Tildrakizumab 200 mg		Part 1: Placebo		Part 2: Tildrakizumab 5 mg		Part 2: Tildrakizumab 25 mg		Part 2: Tildrakizumab 100 mg		Part 2: Tildrakizumab 200 mg		Part 3: Tildrakizumab 5 mg Follow-up		Part 3: Tildrakizumab 25 mg Follow-up		Part 3: Tildrakizumab 100 mg Follow-up		Part 3: Tildrakizumab 200 mg Follow-up		Placebo Follow-up
Arm/Group Description	Participants receive tildrakizumab 5 mg, subcutaneously (SC) at Weeks 0 and 4		Participants receive tildrakizumab 25 mg, SC, at Weeks 0 and 4		Participants receive tildrakizumab 100 mg, SC, at Weeks 0 and 4		Participants receive tildrakizumab 200 mg, SC, at Weeks 0 and 4		Participants receive placebo, SC, at Weeks 0 and 4		Participants receive tildrakizumab 5 mg, SC, every 12 weeks for up to 36 weeks		Participants receive tildrakizumab 25 mg, SC, every 12 weeks for up to 36 weeks		Participants receive tildrakizumab 100 mg, SC, every 12 weeks for up to 36 weeks		Participants receive tildrakizumab 200 mg, SC, every 12 weeks for up to 36 weeks		Participants are followed for up to 20 weeks after the last dose of study drug.		Participants are followed for up to 20 weeks after the last dose of study drug.		Participants are followed for up to 20 weeks after the last dose of study drug.		Participants are followed for up to 20 weeks after the last dose of study drug.		Participants who received placebo in Part 1 and did not receive additional therapy.
All Cause Mortality
	Part 1: Tildrakizumab 5 mg		Part 1: Tildrakizumab 25 mg		Part 1: Tildrakizumab 100 mg		Part 1: Tildrakizumab 200 mg		Part 1: Placebo		Part 2: Tildrakizumab 5 mg		Part 2: Tildrakizumab 25 mg		Part 2: Tildrakizumab 100 mg		Part 2: Tildrakizumab 200 mg		Part 3: Tildrakizumab 5 mg Follow-up		Part 3: Tildrakizumab 25 mg Follow-up		Part 3: Tildrakizumab 100 mg Follow-up		Part 3: Tildrakizumab 200 mg Follow-up		Placebo Follow-up
	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	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	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Part 1: Tildrakizumab 5 mg		Part 1: Tildrakizumab 25 mg		Part 1: Tildrakizumab 100 mg		Part 1: Tildrakizumab 200 mg		Part 1: Placebo		Part 2: Tildrakizumab 5 mg		Part 2: Tildrakizumab 25 mg		Part 2: Tildrakizumab 100 mg		Part 2: Tildrakizumab 200 mg		Part 3: Tildrakizumab 5 mg Follow-up		Part 3: Tildrakizumab 25 mg Follow-up		Part 3: Tildrakizumab 100 mg Follow-up		Part 3: Tildrakizumab 200 mg Follow-up		Placebo Follow-up
	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	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	0/42 (0%)		1/91 (1.1%)		1/89 (1.1%)		2/86 (2.3%)		0/45 (0%)		0/13 (0%)		5/94 (5.3%)		6/153 (3.9%)		3/79 (3.8%)		0/12 (0%)		1/87 (1.1%)		2/137 (1.5%)		2/75 (2.7%)		1/2 (50%)
General disorders
Death	0/42 (0%)	0	0/91 (0%)	0	1/89 (1.1%)	1	0/86 (0%)	0	0/45 (0%)	0	0/13 (0%)	0	0/94 (0%)	0	0/153 (0%)	0	0/79 (0%)	0	0/12 (0%)	0	0/87 (0%)	0	0/137 (0%)	0	0/75 (0%)	0	0/2 (0%)	0
Hernia	0/42 (0%)	0	0/91 (0%)	0	0/89 (0%)	0	0/86 (0%)	0	0/45 (0%)	0	0/13 (0%)	0	0/94 (0%)	0	0/153 (0%)	0	0/79 (0%)	0	0/12 (0%)	0	1/87 (1.1%)	1	0/137 (0%)	0	0/75 (0%)	0	0/2 (0%)	0
Infections and infestations
Arthritis bacterial	0/42 (0%)	0	1/91 (1.1%)	1	0/89 (0%)	0	0/86 (0%)	0	0/45 (0%)	0	0/13 (0%)	0	0/94 (0%)	0	0/153 (0%)	0	0/79 (0%)	0	0/12 (0%)	0	0/87 (0%)	0	0/137 (0%)	0	0/75 (0%)	0	0/2 (0%)	0
Appendicitis	0/42 (0%)	0	0/91 (0%)	0	0/89 (0%)	0	0/86 (0%)	0	0/45 (0%)	0	0/13 (0%)	0	0/94 (0%)	0	1/153 (0.7%)	1	0/79 (0%)	0	0/12 (0%)	0	0/87 (0%)	0	0/137 (0%)	0	0/75 (0%)	0	0/2 (0%)	0
Cellulitis	0/42 (0%)	0	0/91 (0%)	0	0/89 (0%)	0	0/86 (0%)	0	0/45 (0%)	0	0/13 (0%)	0	0/94 (0%)	0	0/153 (0%)	0	1/79 (1.3%)	1	0/12 (0%)	0	0/87 (0%)	0	0/137 (0%)	0	0/75 (0%)	0	0/2 (0%)	0
Epiglottitis	0/42 (0%)	0	0/91 (0%)	0	0/89 (0%)	0	0/86 (0%)	0	0/45 (0%)	0	0/13 (0%)	0	0/94 (0%)	0	1/153 (0.7%)	1	0/79 (0%)	0	0/12 (0%)	0	0/87 (0%)	0	0/137 (0%)	0	0/75 (0%)	0	0/2 (0%)	0
Sinusitis	0/42 (0%)	0	0/91 (0%)	0	0/89 (0%)	0	0/86 (0%)	0	0/45 (0%)	0	0/13 (0%)	0	1/94 (1.1%)	1	1/153 (0.7%)	1	0/79 (0%)	0	0/12 (0%)	0	0/87 (0%)	0	0/137 (0%)	0	0/75 (0%)	0	0/2 (0%)	0
Soft tissue infection	0/42 (0%)	0	0/91 (0%)	0	0/89 (0%)	0	0/86 (0%)	0	0/45 (0%)	0	0/13 (0%)	0	0/94 (0%)	0	0/153 (0%)	0	0/79 (0%)	0	0/12 (0%)	0	0/87 (0%)	0	0/137 (0%)	0	1/75 (1.3%)	1	0/2 (0%)	0
Injury, poisoning and procedural complications
Contusion	0/42 (0%)	0	0/91 (0%)	0	0/89 (0%)	0	0/86 (0%)	0	0/45 (0%)	0	0/13 (0%)	0	0/94 (0%)	0	1/153 (0.7%)	2	0/79 (0%)	0	0/12 (0%)	0	0/87 (0%)	0	0/137 (0%)	0	0/75 (0%)	0	0/2 (0%)	0
Lower limb fracture	0/42 (0%)	0	0/91 (0%)	0	0/89 (0%)	0	0/86 (0%)	0	0/45 (0%)	0	0/13 (0%)	0	0/94 (0%)	0	0/153 (0%)	0	1/79 (1.3%)	1	0/12 (0%)	0	0/87 (0%)	0	0/137 (0%)	0	0/75 (0%)	0	0/2 (0%)	0
Tendonn rupture	0/42 (0%)	0	0/91 (0%)	0	0/89 (0%)	0	0/86 (0%)	0	0/45 (0%)	0	0/13 (0%)	0	0/94 (0%)	0	1/153 (0.7%)	1	0/79 (0%)	0	0/12 (0%)	0	0/87 (0%)	0	0/137 (0%)	0	0/75 (0%)	0	0/2 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	0/42 (0%)	0	0/91 (0%)	0	0/89 (0%)	0	0/86 (0%)	0	0/45 (0%)	0	0/13 (0%)	0	1/94 (1.1%)	1	0/153 (0%)	0	0/79 (0%)	0	0/12 (0%)	0	0/87 (0%)	0	0/137 (0%)	0	0/75 (0%)	0	0/2 (0%)	0
Back pain	0/42 (0%)	0	0/91 (0%)	0	0/89 (0%)	0	0/86 (0%)	0	0/45 (0%)	0	0/13 (0%)	0	0/94 (0%)	0	0/153 (0%)	0	1/79 (1.3%)	1	0/12 (0%)	0	0/87 (0%)	0	0/137 (0%)	0	0/75 (0%)	0	0/2 (0%)	0
Bursitis	0/42 (0%)	0	0/91 (0%)	0	0/89 (0%)	0	0/86 (0%)	0	0/45 (0%)	0	0/13 (0%)	0	0/94 (0%)	0	0/153 (0%)	0	1/79 (1.3%)	1	0/12 (0%)	0	0/87 (0%)	0	0/137 (0%)	0	0/75 (0%)	0	0/2 (0%)	0
Psoriatic arthropathy	0/42 (0%)	0	0/91 (0%)	0	0/89 (0%)	0	0/86 (0%)	0	0/45 (0%)	0	0/13 (0%)	0	1/94 (1.1%)	1	0/153 (0%)	0	0/79 (0%)	0	0/12 (0%)	0	0/87 (0%)	0	0/137 (0%)	0	1/75 (1.3%)	1	0/2 (0%)	0
Arthropathy	0/42 (0%)	0	0/91 (0%)	0	0/89 (0%)	0	0/86 (0%)	0	0/45 (0%)	0	0/13 (0%)	0	0/94 (0%)	0	0/153 (0%)	0	0/79 (0%)	0	0/12 (0%)	0	0/87 (0%)	0	1/137 (0.7%)	1	0/75 (0%)	0	0/2 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant melanoma	0/42 (0%)	0	0/91 (0%)	0	0/89 (0%)	0	0/86 (0%)	0	0/45 (0%)	0	0/13 (0%)	0	1/94 (1.1%)	1	0/153 (0%)	0	0/79 (0%)	0	0/12 (0%)	0	0/87 (0%)	0	0/137 (0%)	0	0/75 (0%)	0	0/2 (0%)	0
Malignant melanoma in situ	0/42 (0%)	0	0/91 (0%)	0	0/89 (0%)	0	0/86 (0%)	0	0/45 (0%)	0	0/13 (0%)	0	0/94 (0%)	0	1/153 (0.7%)	2	0/79 (0%)	0	0/12 (0%)	0	0/87 (0%)	0	0/137 (0%)	0	0/75 (0%)	0	0/2 (0%)	0
Rectal cancer	0/42 (0%)	0	0/91 (0%)	0	0/89 (0%)	0	0/86 (0%)	0	0/45 (0%)	0	0/13 (0%)	0	0/94 (0%)	0	1/153 (0.7%)	1	0/79 (0%)	0	0/12 (0%)	0	0/87 (0%)	0	0/137 (0%)	0	0/75 (0%)	0	0/2 (0%)	0
Nervous system disorders
Ischaemic stroke	0/42 (0%)	0	0/91 (0%)	0	0/89 (0%)	0	0/86 (0%)	0	0/45 (0%)	0	0/13 (0%)	0	1/94 (1.1%)	1	0/153 (0%)	0	0/79 (0%)	0	0/12 (0%)	0	0/87 (0%)	0	0/137 (0%)	0	0/75 (0%)	0	0/2 (0%)	0
Thrombotic cerebral infarction	0/42 (0%)	0	0/91 (0%)	0	0/89 (0%)	0	0/86 (0%)	0	0/45 (0%)	0	0/13 (0%)	0	0/94 (0%)	0	0/153 (0%)	0	0/79 (0%)	0	0/12 (0%)	0	0/87 (0%)	0	1/137 (0.7%)	1	0/75 (0%)	0	0/2 (0%)	0
Reproductive system and breast disorders
Ovarian cyst	0/42 (0%)	0	0/91 (0%)	0	0/89 (0%)	0	1/86 (1.2%)	1	0/45 (0%)	0	0/13 (0%)	0	0/94 (0%)	0	0/153 (0%)	0	0/79 (0%)	0	0/12 (0%)	0	0/87 (0%)	0	0/137 (0%)	0	0/75 (0%)	0	0/2 (0%)	0
Skin and subcutaneous tissue disorders
Psoriasis	0/42 (0%)	0	0/91 (0%)	0	0/89 (0%)	0	0/86 (0%)	0	0/45 (0%)	0	0/13 (0%)	0	0/94 (0%)	0	0/153 (0%)	0	0/79 (0%)	0	0/12 (0%)	0	0/87 (0%)	0	0/137 (0%)	0	0/75 (0%)	0	1/2 (50%)	1
Vascular disorders
Lymphoedema	0/42 (0%)	0	0/91 (0%)	0	0/89 (0%)	0	1/86 (1.2%)	1	0/45 (0%)	0	0/13 (0%)	0	0/94 (0%)	0	0/153 (0%)	0	0/79 (0%)	0	0/12 (0%)	0	0/87 (0%)	0	0/137 (0%)	0	0/75 (0%)	0	0/2 (0%)	0
Other (Not Including Serious) Adverse Events
	Part 1: Tildrakizumab 5 mg		Part 1: Tildrakizumab 25 mg		Part 1: Tildrakizumab 100 mg		Part 1: Tildrakizumab 200 mg		Part 1: Placebo		Part 2: Tildrakizumab 5 mg		Part 2: Tildrakizumab 25 mg		Part 2: Tildrakizumab 100 mg		Part 2: Tildrakizumab 200 mg		Part 3: Tildrakizumab 5 mg Follow-up		Part 3: Tildrakizumab 25 mg Follow-up		Part 3: Tildrakizumab 100 mg Follow-up		Part 3: Tildrakizumab 200 mg Follow-up		Placebo Follow-up
	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	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	20/42 (47.6%)		35/91 (38.5%)		33/89 (37.1%)		30/86 (34.9%)		21/45 (46.7%)		7/13 (53.8%)		38/94 (40.4%)		64/153 (41.8%)		32/79 (40.5%)		3/12 (25%)		14/87 (16.1%)		29/137 (21.2%)		17/75 (22.7%)		1/2 (50%)
Congenital, familial and genetic disorders
Odontogenic cyst	0/42 (0%)	0	0/91 (0%)	0	0/89 (0%)	0	0/86 (0%)	0	0/45 (0%)	0	1/13 (7.7%)	1	1/94 (1.1%)	1	0/153 (0%)	0	0/79 (0%)	0	0/12 (0%)	0	0/87 (0%)	0	0/137 (0%)	0	0/75 (0%)	0	0/2 (0%)	0
Gastrointestinal disorders
Abdominal pain upper	0/42 (0%)	0	0/91 (0%)	0	0/89 (0%)	0	0/86 (0%)	0	0/45 (0%)	0	0/13 (0%)	0	1/94 (1.1%)	1	1/153 (0.7%)	1	1/79 (1.3%)	1	1/12 (8.3%)	1	0/87 (0%)	0	0/137 (0%)	0	0/75 (0%)	0	0/2 (0%)	0
Diarrhoea	1/42 (2.4%)	1	5/91 (5.5%)	5	6/89 (6.7%)	7	3/86 (3.5%)	4	3/45 (6.7%)	3	0/13 (0%)	0	0/94 (0%)	0	5/153 (3.3%)	6	3/79 (3.8%)	4	0/12 (0%)	0	1/87 (1.1%)	1	1/137 (0.7%)	1	1/75 (1.3%)	1	0/2 (0%)	0
Gastric ulcer	0/42 (0%)	0	0/91 (0%)	0	0/89 (0%)	0	0/86 (0%)	0	0/45 (0%)	0	1/13 (7.7%)	1	0/94 (0%)	0	0/153 (0%)	0	0/79 (0%)	0	0/12 (0%)	0	0/87 (0%)	0	0/137 (0%)	0	0/75 (0%)	0	0/2 (0%)	0
Gastrooesophageal reflux disease	0/42 (0%)	0	0/91 (0%)	0	1/89 (1.1%)	1	0/86 (0%)	0	0/45 (0%)	0	1/13 (7.7%)	1	3/94 (3.2%)	3	2/153 (1.3%)	2	0/79 (0%)	0	0/12 (0%)	0	0/87 (0%)	0	1/137 (0.7%)	1	0/75 (0%)	0	0/2 (0%)	0
Hiatus hernia	1/42 (2.4%)	1	0/91 (0%)	0	0/89 (0%)	0	0/86 (0%)	0	0/45 (0%)	0	1/13 (7.7%)	1	0/94 (0%)	0	0/153 (0%)	0	0/79 (0%)	0	0/12 (0%)	0	0/87 (0%)	0	0/137 (0%)	0	0/75 (0%)	0	0/2 (0%)	0
General disorders
Pyrexia	0/42 (0%)	0	1/91 (1.1%)	1	3/89 (3.4%)	4	0/86 (0%)	0	1/45 (2.2%)	1	0/13 (0%)	0	0/94 (0%)	0	3/153 (2%)	4	2/79 (2.5%)	2	0/12 (0%)	0	0/87 (0%)	0	1/137 (0.7%)	1	0/75 (0%)	0	1/2 (50%)	1
Infections and infestations
Acute tonsilitis	0/42 (0%)	0	0/91 (0%)	0	0/89 (0%)	0	0/86 (0%)	0	0/45 (0%)	0	1/13 (7.7%)	1	1/94 (1.1%)	1	0/153 (0%)	0	0/79 (0%)	0	0/12 (0%)	0	0/87 (0%)	0	0/137 (0%)	0	0/75 (0%)	0	0/2 (0%)	0
Bronchiitis	3/42 (7.1%)	3	3/91 (3.3%)	3	1/89 (1.1%)	1	0/86 (0%)	0	2/45 (4.4%)	2	1/13 (7.7%)	2	0/94 (0%)	0	3/153 (2%)	6	2/79 (2.5%)	3	0/12 (0%)	0	2/87 (2.3%)	2	0/137 (0%)	0	2/75 (2.7%)	2	0/2 (0%)	0
Diverticulitis	0/42 (0%)	0	0/91 (0%)	0	0/89 (0%)	0	0/86 (0%)	0	0/45 (0%)	0	1/13 (7.7%)	1	0/94 (0%)	0	0/153 (0%)	0	0/79 (0%)	0	0/12 (0%)	0	0/87 (0%)	0	0/137 (0%)	0	0/75 (0%)	0	0/2 (0%)	0
Ear infection	0/42 (0%)	0	1/91 (1.1%)	1	0/89 (0%)	0	1/86 (1.2%)	1	0/45 (0%)	0	1/13 (7.7%)	1	0/94 (0%)	0	0/153 (0%)	0	0/79 (0%)	0	0/12 (0%)	0	1/87 (1.1%)	1	0/137 (0%)	0	0/75 (0%)	0	0/2 (0%)	0
Folliculitis	0/42 (0%)	0	1/91 (1.1%)	1	1/89 (1.1%)	1	2/86 (2.3%)	4	1/45 (2.2%)	1	1/13 (7.7%)	1	0/94 (0%)	0	1/153 (0.7%)	1	1/79 (1.3%)	1	0/12 (0%)	0	0/87 (0%)	0	0/137 (0%)	0	2/75 (2.7%)	2	0/2 (0%)	0
Gastroenteritis	2/42 (4.8%)	2	0/91 (0%)	0	3/89 (3.4%)	3	3/86 (3.5%)	3	1/45 (2.2%)	1	1/13 (7.7%)	1	5/94 (5.3%)	5	4/153 (2.6%)	5	5/79 (6.3%)	5	0/12 (0%)	0	1/87 (1.1%)	1	1/137 (0.7%)	1	1/75 (1.3%)	1	0/2 (0%)	0
Nasopharyngitis	7/42 (16.7%)	9	12/91 (13.2%)	14	13/89 (14.6%)	15	11/86 (12.8%)	11	9/45 (20%)	10	3/13 (23.1%)	4	24/94 (25.5%)	32	34/153 (22.2%)	42	13/79 (16.5%)	21	0/12 (0%)	0	6/87 (6.9%)	9	12/137 (8.8%)	13	5/75 (6.7%)	6	0/2 (0%)	0
Rhinitis	1/42 (2.4%)	1	1/91 (1.1%)	1	2/89 (2.2%)	2	2/86 (2.3%)	2	0/45 (0%)	0	1/13 (7.7%)	1	0/94 (0%)	0	2/153 (1.3%)	2	3/79 (3.8%)	3	0/12 (0%)	0	1/87 (1.1%)	1	1/137 (0.7%)	1	2/75 (2.7%)	2	0/2 (0%)	0
Upper Respiratory Tract Infection	2/42 (4.8%)	3	0/91 (0%)	0	3/89 (3.4%)	3	2/86 (2.3%)	2	0/45 (0%)	0	0/13 (0%)	0	3/94 (3.2%)	5	6/153 (3.9%)	7	4/79 (5.1%)	5	0/12 (0%)	0	2/87 (2.3%)	2	3/137 (2.2%)	3	3/75 (4%)	3	0/2 (0%)	0
Injury, poisoning and procedural complications
Contusion	0/42 (0%)	0	2/91 (2.2%)	2	0/89 (0%)	0	0/86 (0%)	0	0/45 (0%)	0	1/13 (7.7%)	1	1/94 (1.1%)	1	0/153 (0%)	0	2/79 (2.5%)	2	0/12 (0%)	0	0/87 (0%)	0	1/137 (0.7%)	1	0/75 (0%)	0	0/2 (0%)	0
Injury	0/42 (0%)	0	0/91 (0%)	0	0/89 (0%)	0	0/86 (0%)	0	0/45 (0%)	0	1/13 (7.7%)	1	0/94 (0%)	0	0/153 (0%)	0	0/79 (0%)	0	0/12 (0%)	0	0/87 (0%)	0	0/137 (0%)	0	0/75 (0%)	0	0/2 (0%)	0
Investigations
Blood pressure systolic increased	0/42 (0%)	0	0/91 (0%)	0	0/89 (0%)	0	0/86 (0%)	0	0/45 (0%)	0	1/13 (7.7%)	1	0/94 (0%)	0	0/153 (0%)	0	0/79 (0%)	0	0/12 (0%)	0	0/87 (0%)	0	0/137 (0%)	0	0/75 (0%)	0	0/2 (0%)	0
Hypercholesterolaemia	0/42 (0%)	0	0/91 (0%)	0	0/89 (0%)	0	1/86 (1.2%)	1	0/45 (0%)	0	1/13 (7.7%)	1	1/94 (1.1%)	1	0/153 (0%)	0	0/79 (0%)	0	0/12 (0%)	0	0/87 (0%)	0	0/137 (0%)	0	0/75 (0%)	0	0/2 (0%)	0
Musculoskeletal and connective tissue disorders
Back pain	1/42 (2.4%)	1	4/91 (4.4%)	4	3/89 (3.4%)	4	3/86 (3.5%)	4	0/45 (0%)	0	0/13 (0%)	0	4/94 (4.3%)	5	8/153 (5.2%)	8	3/79 (3.8%)	3	1/12 (8.3%)	1	3/87 (3.4%)	4	5/137 (3.6%)	5	1/75 (1.3%)	1	0/2 (0%)	0
Nervous system disorders
Headache	3/42 (7.1%)	3	5/91 (5.5%)	8	6/89 (6.7%)	8	7/86 (8.1%)	8	4/45 (8.9%)	6	0/13 (0%)	0	3/94 (3.2%)	3	13/153 (8.5%)	17	3/79 (3.8%)	6	0/12 (0%)	0	1/87 (1.1%)	1	5/137 (3.6%)	7	2/75 (2.7%)	3	0/2 (0%)	0
Psychiatric disorders
Sleep disorder	0/42 (0%)	0	0/91 (0%)	0	0/89 (0%)	0	0/86 (0%)	0	0/45 (0%)	0	1/13 (7.7%)	1	0/94 (0%)	0	0/153 (0%)	0	0/79 (0%)	0	0/12 (0%)	0	0/87 (0%)	0	0/137 (0%)	0	0/75 (0%)	0	0/2 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	3/42 (7.1%)	3	2/91 (2.2%)	2	2/89 (2.2%)	2	1/86 (1.2%)	1	2/45 (4.4%)	2	0/13 (0%)	0	2/94 (2.1%)	2	5/153 (3.3%)	5	0/79 (0%)	0	0/12 (0%)	0	1/87 (1.1%)	1	1/137 (0.7%)	1	0/75 (0%)	0	0/2 (0%)	0
Dyspnoea	0/42 (0%)	0	0/91 (0%)	0	0/89 (0%)	0	0/86 (0%)	0	0/45 (0%)	0	0/13 (0%)	0	0/94 (0%)	0	2/153 (1.3%)	3	0/79 (0%)	0	1/12 (8.3%)	1	0/87 (0%)	0	0/137 (0%)	0	0/75 (0%)	0	0/2 (0%)	0
Skin and subcutaneous tissue disorders
Pruritus	1/42 (2.4%)	1	4/91 (4.4%)	5	0/89 (0%)	0	4/86 (4.7%)	6	4/45 (8.9%)	4	0/13 (0%)	0	1/94 (1.1%)	1	2/153 (1.3%)	2	3/79 (3.8%)	3	0/12 (0%)	0	0/87 (0%)	0	1/137 (0.7%)	1	1/75 (1.3%)	1	0/2 (0%)	0

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 in any media that report any results of the trial. The Sponsor shall have the right to review and comment on the data analysis and presentation.