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)

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)

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.

Study Overview

• Status: Completed
• Conditions: Psoriasis
• Intervention / Treatment: Biological: tildrakizumab; Drug: Placebo

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 Type: Interventional
• Enrollment (Actual): 355
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

14

Arms and Interventions

Participant Group / 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: MK-3222; SCH 900222
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: MK-3222; SCH 900222
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: MK-3222; SCH 900222
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: MK-3222; SCH 900222
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: MK-3222; SCH 900222
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: MK-3222; SCH 900222
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: MK-3222; SCH 900222
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: MK-3222; SCH 900222
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With a Psoriasis Area and Severity Index (PASI)75 Response at 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.	Week 16
Number of Participants Experiencing Adverse Events	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.	Up to 72 weeks
Number of Particpants Discontinuing Study Treatment Due to Adverse Events	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.	Up to 52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With a PASI 75 Response at 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.	Week 12
Percentage of Participants With Physician's Global Assessment (PGA) of "Cleared" or "Minimal" at 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.	Week 16
Percentage of Participants With PASI 90 Response at 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.	Week 16
Percentage of Participants With PASI 100 Response at 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.	Week 16
PASI 75 Response Rate by Time	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.	Up to 16 Weeks
Mean Change From Baseline in PASI Score at 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).	Baseline and Weeks 12 and 16
Percentage of Participants With PASI 50 Response at 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.	Week 16
Mean Change From Baseline in Dermatology Life Quality Index (DLQI) at 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.	Week 16
Percentage of Participants Achieving DLQI Score of 0 or 1 at 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.	Week 16
Percentage of Participants Achieving a >=5 Point Reduction in DLQI at 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.	Week 16

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Kerbusch T, Li H, Wada R, Jauslin PM, Wenning L. Exposure-response characterisation of tildrakizumab in chronic plaque psoriasis: Pooled analysis of 3 randomised controlled trials. Br J Clin Pharmacol. 2020 Sep;86(9):1795-1806. doi: 10.1111/bcp.14280. Epub 2020 Mar 25.
• Jauslin P, Kulkarni P, Li H, Vatakuti S, Hussain A, Wenning L, Kerbusch T. Population-Pharmacokinetic Modeling of Tildrakizumab (MK-3222), an Anti-Interleukin-23-p19 Monoclonal Antibody, in Healthy Volunteers and Subjects with Psoriasis. Clin Pharmacokinet. 2019 Aug;58(8):1059-1068. doi: 10.1007/s40262-019-00743-7.
• Papp K, Thaci D, Reich K, Riedl E, Langley RG, Krueger JG, Gottlieb AB, Nakagawa H, Bowman EP, Mehta A, Li Q, Zhou Y, Shames R. Tildrakizumab (MK-3222), an anti-interleukin-23p19 monoclonal antibody, improves psoriasis in a phase IIb randomized placebo-controlled trial. Br J Dermatol. 2015 Oct;173(4):930-9. doi: 10.1111/bjd.13932. Epub 2015 Oct 15. Erratum In: Br J Dermatol. 2016 Jun;174(6):1426.

Study record dates

Study Major Dates

• Study Start (Actual): October 25, 2010
• Primary Completion (Actual): November 4, 2011
• Study Completion (Actual): October 24, 2012

Study Registration Dates

• First Submitted: October 7, 2010
• First Submitted That Met QC Criteria: October 20, 2010
• First Posted (Estimate): October 21, 2010

Study Record Updates

• Last Update Posted (Actual): February 5, 2019
• Last Update Submitted That Met QC Criteria: January 18, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Skin Diseases, Papulosquamous; Psoriasis
• Other Study ID Numbers: P05495; 2009-017272-24 (EudraCT Number); MK-3222-003 (Other Identifier: Merck Research Laboratories)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Study Data/Documents

1. CSR Synopsis