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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)

Primary Purpose

Psoriasis

Status

Completed

Phase

Phase 2

Locations

Study Type

Interventional

Intervention

tildrakizumab

Placebo

About this trial

This is an interventional treatment trial for Psoriasis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm 7

Arm 8

Arm 9

Arm 10

Arm 11

Arm 12

Arm 13

Arm 14

Arm Type

Experimental

Placebo Comparator

Experimental

No Intervention

Arm Label

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

Part 3: Placebo Follow-up

Arm 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.

Outcomes

Primary Outcome Measures

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.

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.

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.

Secondary Outcome Measures

Percentage of Participants With a PASI 75 Response at 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.

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.

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.

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.

Mean Change From Baseline in PASI Score at 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.

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.

Percentage of Participants Achieving DLQI Score of 0 or 1 at Week 16

Percentage of Participants Achieving a >=5 Point Reduction in DLQI at Week 16

Full Information

NCT ID

NCT01225731

First Posted

October 7, 2010

Last Updated

January 18, 2019

Sponsor

Merck Sharp & Dohme LLC

1. Study Identification

Unique Protocol Identification Number

NCT01225731

Brief Title

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)

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)

Study Type

Interventional

2. Study Status

Record Verification Date

January 2019

Overall Recruitment Status

Completed

Study Start Date

October 25, 2010 (Actual)

Primary Completion Date

November 4, 2011 (Actual)

Study Completion Date

October 24, 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Merck Sharp & Dohme LLC

4. Oversight

Data Monitoring Committee

Yes

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Psoriasis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

355 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Part 1: Tildrakizumab 5 mg

Arm Type

Experimental

Arm Description

Participants receive tildrakizumab 5 mg, subcutaneously (SC) at Weeks 0 and 4

Arm Title

Part 1: Tildrakizumab 25 mg

Arm Type

Experimental

Arm Description

Participants receive tildrakizumab 25 mg, SC, at Weeks 0 and 4

Arm Title

Part 1: Tildrakizumab 100 mg

Arm Type

Experimental

Arm Description

Participants receive tildrakizumab 100 mg, SC, at Weeks 0 and 4

Arm Title

Part 1: Tildrakizumab 200 mg

Arm Type

Experimental

Arm Description

Participants receive tildrakizumab 200 mg, SC, at Weeks 0 and 4

Arm Title

Part 1: Placebo

Arm Type

Placebo Comparator

Arm Description

Participants receive placebo, SC, at Weeks 0 and 4

Arm Title

Part 2: Tildrakizumab 5 mg

Arm Type

Experimental

Arm Description

Participants receive tildrakizumab 5 mg, SC, every 12 weeks for up to 36 weeks

Arm Title

Part 2: Tildrakizumab 25 mg

Arm Type

Experimental

Arm Description

Participants receive tildrakizumab 25 mg, SC, every 12 weeks for up to 36 weeks

Arm Title

Part 2: Tildrakizumab 100 mg

Arm Type

Experimental

Arm Description

Participants receive tildrakizumab 100 mg, SC, every 12 weeks for up to 36 weeks

Arm Title

Part 2: Tildrakizumab 200 mg

Arm Type

Experimental

Arm Description

Participants receive tildrakizumab 200 mg, SC, every 12 weeks for up to 36 weeks

Arm Title

Part 3: Tildrakizumab 5 mg Follow-up

Arm Type

No Intervention

Arm Description

Participants are followed for up to 20 weeks after the last dose of study drug.

Arm Title

Part 3: Tildrakizumab 25 mg Follow-up

Arm Type

No Intervention

Arm Description

Participants are followed for up to 20 weeks after the last dose of study drug.

Arm Title

Part 3: Tildrakizumab 100 mg Follow-up

Arm Type

No Intervention

Arm Description

Participants are followed for up to 20 weeks after the last dose of study drug.

Arm Title

Part 3: Tildrakizumab 200 mg Follow-up

Arm Type

No Intervention

Arm Description

Participants are followed for up to 20 weeks after the last dose of study drug.

Arm Title

Part 3: Placebo Follow-up

Arm Type

No Intervention

Arm Description

Participants are followed for up to 20 weeks after the last dose of study drug.

Intervention Type

Biological

Intervention Name(s)

tildrakizumab

Other Intervention Name(s)

SCH 900222, MK-3222

Intervention Description

SC administration of tildrakizumab at assigned dose

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

SC administration of Placebo

Primary Outcome Measure Information:

Title

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

Description

Time Frame

Week 16

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

Title

Number of Particpants Discontinuing Study Treatment Due to Adverse Events

Description

Time Frame

Up to 52 weeks

Secondary Outcome Measure Information:

Title

Percentage of Participants With a PASI 75 Response at Week 12

Description

Time Frame

Week 12

Title

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

Description

Time Frame

Week 16

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

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

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

Title

Mean Change From Baseline in PASI Score at Weeks 12 and 16

Description

Time Frame

Baseline and Weeks 12 and 16

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

Title

Mean Change From Baseline in Dermatology Life Quality Index (DLQI) at Week 16

Description

Time Frame

Week 16

Title

Percentage of Participants Achieving DLQI Score of 0 or 1 at Week 16

Description

Time Frame

Week 16

Title

Percentage of Participants Achieving a >=5 Point Reduction in DLQI at Week 16

Description

Time Frame

Week 16

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Medical Director

Organizational Affiliation

Merck Sharp & Dohme LLC

Official's Role

Study Director

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

IPD Sharing URL

http://engagezone.msd.com/ds_documentation.php

Citations:

PubMed Identifier

26042589

Citation

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.

Results Reference

result

PubMed Identifier

32162721

Citation

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.

Results Reference

derived

PubMed Identifier

30915660

Citation

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.

Results Reference

derived

Available IPD and Supporting Information:

Available IPD/Information Type

CSR Synopsis

Available IPD/Information URL

http://www.merck.com/clinical-trials/study.html?id=P05495&kw=P05495&tab=access

Learn more about this trial

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)

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