A Study to Evaluate the Efficacy and Safety of Subcutaneous MK-3222, Followed by an Optional Long-Term Safety Extension Study, in Participants With Moderate-to-Severe Chronic Plaque Psoriasis (MK-3222-010) (reSURFACE 1)
Primary Purpose
Plaque Psoriasis
Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Tildrakizumab 200 mg
Tildrakizumab 100 mg
Matching Placebo
Sponsored by

About this trial
This is an interventional treatment trial for Plaque Psoriasis
Eligibility Criteria
Inclusion Criteria:
- Clinical diagnosis of moderate-to-severe plaque psoriasis for at least 6 months prior to study enrollment
- A candidate for phototherapy or systemic therapy
- For the extension study: must have completed Part 3 of the base study
- For the extension study: must have achieved at least a PASI-50 response by the end of Part 3 of the base study
- For the extension study: must have received active tildrakizumab (MK-3222) treatment within 12 weeks prior to the end of Part 3 of the base study
- Premenopausal female participants must agree to abstain from heterosexual activity or use a medically accepted method of contraception or use appropriate effective contraception as per local regulations or guidelines
- If enrolled at a Japanese site, participants with psoriatic arthritis using non-steroidal anti-inflammatory drugs (NSAIDs) must be on a stable dose for at least 4 weeks prior to the first dose of study drug and must not be expected to require an increase in dose over the course of the study
Exclusion Criteria:
- Has erythrodermic psoriasis, predominantly pustular psoriasis, medication-induced or medication-exacerbated psoriasis, or new onset guttate psoriasis
- Current or history of severe psoriatic arthritis and is well-controlled on current treatment
- Women of child-bearing potential who are pregnant, intend to become pregnant within 6 months of completing the trial, or who are breast feeding
- Expected to require topical treatment, phototherapy, or systemic treatment during the trial
- Presence of any infection
- History of recurrent infection requiring treatment with systemic antibiotics within 2 weeks of screening
- Previous use of tildrakizumab (MK-3222) or other IL-23/Th-17 pathway inhibitors including P40, p19, and IL-17 antagonists
- Evidence of active or untreated latent tuberculosis (TB)
- Positive test for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV)
- At Japanese sites, positive test for HBs antibody and hepatitis B virus (HBV) deoxyribonucleic acid (DNA)
- At Japanese sites, positive test for the Hepatitis B core (HBc) antibody and HBV DNA
- For the extension study: women of child-bearing potential who are pregnant, intend to become pregnant within 6 months of completing the trial, or who are breast feeding
- For the extension study: active or uncontrolled significant organ dysfunction or clinically significant laboratory abnormalities
- For the extension study: expected to require topical treatment, phototherapy, or systemic treatment during the extension study
- At Japanese sites, abnormal for Beta D Glucan and/or KL-6 test result(s) at the screening visit.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
Tildrakizumab 200 mg
Tildrakizumab 100 mg
Placebo
Arm Description
Tildrakizumab 200 mg administered subcutaneously (SC) once a week at Weeks 0 and 4 and then every 12 weeks.
Tildrakizumab 100 mg administered SC once a week at Weeks 0 and 4 and then every 12 weeks.
Matching placebo administered SC once a week at Weeks 0 and 4.
Outcomes
Primary Outcome Measures
Percentage of Participants With Psoriasis Area Sensitivity Index 75 (PASI-75) Response at Week 12 (Base Study)
The PASI is a measure of the average redness, thickness, and scaliness of lesions (each graded on a 0-4 scale), weighed by the amount of body surface for each region involved (head=0.1; upper limbs=0.2; trunk= 0.3; and lower limbs=0.4) and the degree of involvement for each body region (0=no involvement to 6=90-100% involvement). Calculated PASI score ranges from 0 to 72, with higher score indicating more severe disease status. The PASI-75 response indicates the number of participants achieving a 75% reduction in PASI score compared to baseline.
Percentage of Participants With a Physician's Global Assessment (PGA) Score of Clear or Minimal With at Least a 2 Grade Reduction From Baseline at Week 12 (Base Study)
The PGA is used to determine the overall severity of a participant's psoriasis lesions at a given time point. Overall lesions will be graded for thickness, erythema, and scaling on a scale from 0 to 5. The sum of the 3 scales will be divided by 3 to obtain the PGA score. PGA is assessed as: 0= Cleared, except for residual discoloration. 1= Minimal, majority of lesions have individual scores that average 1. 2 =Mild, majority of lesions have individual scores that average 2. 3= Moderate, majority of lesions have individual scores that average 3. 4= Marked, majority of lesions have individual scores that average 4. 5= Severe, majority of lesions have individual scores that average 5.
Number of Participants Experiencing an Adverse Event Up to Week 12 (Base Study)
An adverse event is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Number of Participants Discontinuing Study Drug Due to an Adverse Event Up to Week 12 (Base Study)
An adverse event is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Number of Participants Discontinuing Study Drug Due to a Drug-Related Adverse Event (Base Study)
A drug-related adverse event is an adverse event that has been determined by the investigator to be related to the study drug.
Secondary Outcome Measures
Percentage of Participants With PASI-90 Response At Week 12
The PASI is a measure of the average redness, thickness, and scaliness of lesions (each graded on a 0-4 scale), weighed by the amount of body surface for each region involved (head=0.1; upper limbs=0.2; trunk= 0.3; and lower limbs=0.4) and the degree of involvement for each body region (0=no involvement to 6=90-100% involvement). Calculated PASI score ranges from 0 to 72, with higher score indicating more severe disease status. The PASI-90 response indicates the number of participants achieving a 90% reduction in PASI score compared to baseline.
Percentage of Participants With PASI-100 Response at Week 12
The PASI is a measure of the average redness, thickness, and scaliness of lesions (each graded on a 0-4 scale), weighed by the amount of body surface for each region involved (head=0.1; upper limbs=0.2; trunk= 0.3; and lower limbs=0.4) and the degree of involvement for each body region (0=no involvement to 6=90-100% involvement). Calculated PASI score ranges from 0 to 72, with higher score indicating more severe disease status. The PASI-100 response indicates the number of participants achieving a 100% reduction in PASI score compared to baseline.
Baseline Dermatology Life Quality Index (DLQI) Score
The DLQI questionnaire consists of 10 questions, where each question is scored from 0 (not affected at all) to 3 (very much affected). The DLQI score is the sum of the 10 individual question scores and ranges from 0 to 30, with lower scores indicating better quality of life.
Change From Baseline in the Participant DLQI Score at Week 12
The DLQI questionnaire consists of 10 questions, where each question is scored from 0 (not affected at all) to 3 (very much affected). The DLQI score is the sum of the 10 individual question scores and ranges from 0 to 30, with lower scores indicating better quality of life. For a change from baseline, a larger negative number correlates with a greater improvement in the DLQI score.
Percentage of Participants With DLQI Score of 0 or 1 at Week 12
The DLQI questionnaire consists of 10 questions, where each question is scored from 0 (not affected at all) to 3 (very much affected). The DLQI score is the sum of the 10 individual question scores and ranges from 0 to 30, with lower scores indicating better quality of life.
Full Information
NCT ID
NCT01722331
First Posted
November 2, 2012
Last Updated
February 23, 2022
Sponsor
Sun Pharmaceutical Industries Limited
1. Study Identification
Unique Protocol Identification Number
NCT01722331
Brief Title
A Study to Evaluate the Efficacy and Safety of Subcutaneous MK-3222, Followed by an Optional Long-Term Safety Extension Study, in Participants With Moderate-to-Severe Chronic Plaque Psoriasis (MK-3222-010)
Acronym
reSURFACE 1
Official Title
A 64-Week, Phase 3, Randomized, Placebo-Controlled, Parallel Design Study to Evaluate the Efficacy and Safety/Tolerability of Subcutaneous Tildrakizumab (SCH 900222/MK-3222), Followed by an Optional Long-Term Safety Extension Study, in Subjects With Moderate-to-Severe Chronic Plaque Psoriasis (Protocol No. MK-3222-010)
Study Type
Interventional
2. Study Status
Record Verification Date
February 2022
Overall Recruitment Status
Completed
Study Start Date
December 6, 2012 (Actual)
Primary Completion Date
October 28, 2015 (Actual)
Study Completion Date
November 10, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sun Pharmaceutical Industries Limited
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This study is being conducted to evaluate the efficacy and safety/tolerability of subcutaneous tildrakizumab (MK-3222), followed by an optional long-term safety extension study, in participants with moderate-to-severe chronic plaque psoriasis.
Detailed Description
Participants are initially randomized to receive tildrakizumab 200 or 100 mg once weekly at Weeks 0, 4, and every 12 weeks thereafter; or placebo at Weeks 0 and 4.
At Week 12, participants initially randomized to placebo will be re-randomized to receive either tildrakizumab 200 or 100 mg at Weeks 12 and 16.
At Week 28, all participants enrolled will be assessed for their improvement in PASI score from baseline.
RESPONDERS: Participants initially randomized to tildrakizumab who achieve at least a 75% improvement from baseline PASI will be re-randomized to either continue on their initial treatment or to receive placebo at Week 28.
Participants who are re-randomized to continue on their initial treatment will continue tildrakizumab 200 or 100 mg every 12 weeks through Week 64.
Participants who are re-randomized to placebo will receive placebo every 4 weeks until relapse (reduction in maximum PASI response by 50%). If relapse occurs, the tildrakizumab dose that the participants was originally randomized to at baseline will be re-initiated (tildrakizumab 200 or 100 mg). Participants will be dosed tildrakizumab at the visit when the relapse occurs, and subsequent dosing of tildrakizumab will be given 4 weeks after treatment re-initiation, and every 12 weeks thereafter through Week 64.
PARTIAL RESPONDERS: Participants initially randomized to tildrakizumab who achieved a PASI response of ≥50% but <75% improvement from baseline will be assigned a treatment regimen as described below, with their first dose started at Week 28.
Participants initially randomized to tildrakizumab 200 mg will remain on tildrakizumab 200 mg every 12 weeks.
Participants initially randomized to tildrakizumab 100 mg will be re-randomized to either remain on tildrakizumab 100 mg every 12 weeks or to receive tildrakizumab 200 mg every 12 weeks.
Participants initially randomized to placebo who achieved ≥50% improvement from baseline in PASI will receive tildrakizumab (200 or 100 mg) according to their re-randomized treatment assignment at Week 12 and continue on this treatment every 12 weeks through Week 64.
NON-RESPONDERS: Participants who did not achieve at least 50% improvement from baseline PASI at Week 28 will be discontinued from the study.
EXTENSION: Participants will receive tildrakizumab 200 mg or 100 mg every 12 weeks through Extension Week 192, depending on the treatment received at the time of completion of the base study.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Plaque Psoriasis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
772 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Tildrakizumab 200 mg
Arm Type
Experimental
Arm Description
Tildrakizumab 200 mg administered subcutaneously (SC) once a week at Weeks 0 and 4 and then every 12 weeks.
Arm Title
Tildrakizumab 100 mg
Arm Type
Experimental
Arm Description
Tildrakizumab 100 mg administered SC once a week at Weeks 0 and 4 and then every 12 weeks.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Matching placebo administered SC once a week at Weeks 0 and 4.
Intervention Type
Drug
Intervention Name(s)
Tildrakizumab 200 mg
Other Intervention Name(s)
MK-3222, SCH 900222
Intervention Description
Two tildrakizumab 100 mg/mL pre-filled syringes (PFS)
Intervention Type
Drug
Intervention Name(s)
Tildrakizumab 100 mg
Other Intervention Name(s)
MK-3222, SCH 900222
Intervention Description
Tildrakizumab 100 mg/mL PFS
Intervention Type
Drug
Intervention Name(s)
Matching Placebo
Intervention Description
Matching placebo to tildrakizumab PFS
Primary Outcome Measure Information:
Title
Percentage of Participants With Psoriasis Area Sensitivity Index 75 (PASI-75) Response at Week 12 (Base Study)
Description
The PASI is a measure of the average redness, thickness, and scaliness of lesions (each graded on a 0-4 scale), weighed by the amount of body surface for each region involved (head=0.1; upper limbs=0.2; trunk= 0.3; and lower limbs=0.4) and the degree of involvement for each body region (0=no involvement to 6=90-100% involvement). Calculated PASI score ranges from 0 to 72, with higher score indicating more severe disease status. The PASI-75 response indicates the number of participants achieving a 75% reduction in PASI score compared to baseline.
Time Frame
Week 12 (or end of trial if prior to Week 12)
Title
Percentage of Participants With a Physician's Global Assessment (PGA) Score of Clear or Minimal With at Least a 2 Grade Reduction From Baseline at Week 12 (Base Study)
Description
The PGA is used to determine the overall severity of a participant's psoriasis lesions at a given time point. Overall lesions will be graded for thickness, erythema, and scaling on a scale from 0 to 5. The sum of the 3 scales will be divided by 3 to obtain the PGA score. PGA is assessed as: 0= Cleared, except for residual discoloration. 1= Minimal, majority of lesions have individual scores that average 1. 2 =Mild, majority of lesions have individual scores that average 2. 3= Moderate, majority of lesions have individual scores that average 3. 4= Marked, majority of lesions have individual scores that average 4. 5= Severe, majority of lesions have individual scores that average 5.
Time Frame
Baseline and Week 12 (or end of trial if prior to Week 12)
Title
Number of Participants Experiencing an Adverse Event Up to Week 12 (Base Study)
Description
An adverse event is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Time Frame
Up to 12 weeks
Title
Number of Participants Discontinuing Study Drug Due to an Adverse Event Up to Week 12 (Base Study)
Description
An adverse event is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Time Frame
Up to 12 weeks
Title
Number of Participants Discontinuing Study Drug Due to a Drug-Related Adverse Event (Base Study)
Description
A drug-related adverse event is an adverse event that has been determined by the investigator to be related to the study drug.
Time Frame
Up to 12 weeks
Secondary Outcome Measure Information:
Title
Percentage of Participants With PASI-90 Response At Week 12
Description
The PASI is a measure of the average redness, thickness, and scaliness of lesions (each graded on a 0-4 scale), weighed by the amount of body surface for each region involved (head=0.1; upper limbs=0.2; trunk= 0.3; and lower limbs=0.4) and the degree of involvement for each body region (0=no involvement to 6=90-100% involvement). Calculated PASI score ranges from 0 to 72, with higher score indicating more severe disease status. The PASI-90 response indicates the number of participants achieving a 90% reduction in PASI score compared to baseline.
Time Frame
Week 12 (or end of trial if prior to Week 12)
Title
Percentage of Participants With PASI-100 Response at Week 12
Description
The PASI is a measure of the average redness, thickness, and scaliness of lesions (each graded on a 0-4 scale), weighed by the amount of body surface for each region involved (head=0.1; upper limbs=0.2; trunk= 0.3; and lower limbs=0.4) and the degree of involvement for each body region (0=no involvement to 6=90-100% involvement). Calculated PASI score ranges from 0 to 72, with higher score indicating more severe disease status. The PASI-100 response indicates the number of participants achieving a 100% reduction in PASI score compared to baseline.
Time Frame
Week 12 (or end of trial if prior to Week 12)
Title
Baseline Dermatology Life Quality Index (DLQI) Score
Description
The DLQI questionnaire consists of 10 questions, where each question is scored from 0 (not affected at all) to 3 (very much affected). The DLQI score is the sum of the 10 individual question scores and ranges from 0 to 30, with lower scores indicating better quality of life.
Time Frame
Baseline
Title
Change From Baseline in the Participant DLQI Score at Week 12
Description
The DLQI questionnaire consists of 10 questions, where each question is scored from 0 (not affected at all) to 3 (very much affected). The DLQI score is the sum of the 10 individual question scores and ranges from 0 to 30, with lower scores indicating better quality of life. For a change from baseline, a larger negative number correlates with a greater improvement in the DLQI score.
Time Frame
Baseline and Week 12 (or end of trial if prior to Week 12)
Title
Percentage of Participants With DLQI Score of 0 or 1 at Week 12
Description
The DLQI questionnaire consists of 10 questions, where each question is scored from 0 (not affected at all) to 3 (very much affected). The DLQI score is the sum of the 10 individual question scores and ranges from 0 to 30, with lower scores indicating better quality of life.
Time Frame
Week 12 (or end of trial if prior to Week 12)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Clinical diagnosis of moderate-to-severe plaque psoriasis for at least 6 months prior to study enrollment
A candidate for phototherapy or systemic therapy
For the extension study: must have completed Part 3 of the base study
For the extension study: must have achieved at least a PASI-50 response by the end of Part 3 of the base study
For the extension study: must have received active tildrakizumab (MK-3222) treatment within 12 weeks prior to the end of Part 3 of the base study
Premenopausal female participants must agree to abstain from heterosexual activity or use a medically accepted method of contraception or use appropriate effective contraception as per local regulations or guidelines
If enrolled at a Japanese site, participants with psoriatic arthritis using non-steroidal anti-inflammatory drugs (NSAIDs) must be on a stable dose for at least 4 weeks prior to the first dose of study drug and must not be expected to require an increase in dose over the course of the study
Exclusion Criteria:
Has erythrodermic psoriasis, predominantly pustular psoriasis, medication-induced or medication-exacerbated psoriasis, or new onset guttate psoriasis
Current or history of severe psoriatic arthritis and is well-controlled on current treatment
Women of child-bearing potential who are pregnant, intend to become pregnant within 6 months of completing the trial, or who are breast feeding
Expected to require topical treatment, phototherapy, or systemic treatment during the trial
Presence of any infection
History of recurrent infection requiring treatment with systemic antibiotics within 2 weeks of screening
Previous use of tildrakizumab (MK-3222) or other IL-23/Th-17 pathway inhibitors including P40, p19, and IL-17 antagonists
Evidence of active or untreated latent tuberculosis (TB)
Positive test for human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV)
At Japanese sites, positive test for HBs antibody and hepatitis B virus (HBV) deoxyribonucleic acid (DNA)
At Japanese sites, positive test for the Hepatitis B core (HBc) antibody and HBV DNA
For the extension study: women of child-bearing potential who are pregnant, intend to become pregnant within 6 months of completing the trial, or who are breast feeding
For the extension study: active or uncontrolled significant organ dysfunction or clinically significant laboratory abnormalities
For the extension study: expected to require topical treatment, phototherapy, or systemic treatment during the extension study
At Japanese sites, abnormal for Beta D Glucan and/or KL-6 test result(s) at the screening visit.
12. IPD Sharing Statement
Citations:
PubMed Identifier
28596043
Citation
Reich K, Papp KA, Blauvelt A, Tyring SK, Sinclair R, Thaci D, Nograles K, Mehta A, Cichanowitz N, Li Q, Liu K, La Rosa C, Green S, Kimball AB. Tildrakizumab versus placebo or etanercept for chronic plaque psoriasis (reSURFACE 1 and reSURFACE 2): results from two randomised controlled, phase 3 trials. Lancet. 2017 Jul 15;390(10091):276-288. doi: 10.1016/S0140-6736(17)31279-5. Epub 2017 Jun 6. Erratum In: Lancet. 2017 Jul 15;390(10091):230.
Results Reference
result
PubMed Identifier
36098877
Citation
Thaci D, Gerdes S, Du Jardin KG, Perrot JL, Puig L. Efficacy of Tildrakizumab Across Different Body Weights in Moderate-to-Severe Psoriasis Over 5 Years: Pooled Analyses from the reSURFACE Pivotal Studies. Dermatol Ther (Heidelb). 2022 Oct;12(10):2325-2341. doi: 10.1007/s13555-022-00793-z. Epub 2022 Sep 13.
Results Reference
derived
PubMed Identifier
33630387
Citation
Igarashi A, Nakagawa H, Morita A, Okubo Y, Sano S, Imafuku S, Tada Y, Honma M, Mendelsohn AM, Kawamura M, Ohtsuki M. Efficacy and safety of tildrakizumab in Japanese patients with moderate to severe plaque psoriasis: Results from a 64-week phase 3 study (reSURFACE 1). J Dermatol. 2021 Jun;48(6):853-863. doi: 10.1111/1346-8138.15789. Epub 2021 Feb 25.
Results Reference
derived
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
31268369
Citation
Elewski B, Menter A, Crowley J, Tyring S, Zhao Y, Lowry S, Rozzo S, Mendelsohn AM, Parno J, Gordon K. Sustained and continuously improved efficacy of tildrakizumab in patients with moderate-to-severe plaque psoriasis. J Dermatolog Treat. 2020 Dec;31(8):763-768. doi: 10.1080/09546634.2019.1640348. Epub 2019 Jul 22.
Results Reference
derived
PubMed Identifier
31218661
Citation
Reich K, Warren RB, Iversen L, Puig L, Pau-Charles I, Igarashi A, Ohtsuki M, Falques M, Harmut M, Rozzo S, Lebwohl MG, Cantrell W, Blauvelt A, Thaci D. Long-term efficacy and safety of tildrakizumab for moderate-to-severe psoriasis: pooled analyses of two randomized phase III clinical trials (reSURFACE 1 and reSURFACE 2) through 148 weeks. Br J Dermatol. 2020 Mar;182(3):605-617. doi: 10.1111/bjd.18232. Epub 2019 Jul 18. Erratum In: Br J Dermatol. 2022 Jul;187(1):131-132.
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
Learn more about this trial
A Study to Evaluate the Efficacy and Safety of Subcutaneous MK-3222, Followed by an Optional Long-Term Safety Extension Study, in Participants With Moderate-to-Severe Chronic Plaque Psoriasis (MK-3222-010)
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