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)
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| ClinicalTrials.gov Identifier: NCT01722331 |
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Recruitment Status :
Completed
First Posted : November 6, 2012
Results First Posted : June 13, 2018
Last Update Posted : March 23, 2022
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Sponsor:
Sun Pharmaceutical Industries Limited
Information provided by (Responsible Party):
Sun Pharmaceutical Industries Limited
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Brief Summary:
This study is being conducted to evaluate the efficacy and safety/tolerability of subcutaneous tildrakizumab (MK-3222), followed by an optional long-term safety extension study, in participants with moderate-to-severe chronic plaque psoriasis.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Plaque Psoriasis | Drug: Tildrakizumab 200 mg Drug: Tildrakizumab 100 mg Drug: Matching Placebo | Phase 3 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 772 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Triple (Participant, Care Provider, Investigator) |
| Primary Purpose: | Treatment |
| Official Title: | A 64-Week, Phase 3, Randomized, Placebo-Controlled, Parallel Design Study to Evaluate the Efficacy and Safety/Tolerability of Subcutaneous Tildrakizumab (SCH 900222/MK-3222), Followed by an Optional Long-Term Safety Extension Study, in Subjects With Moderate-to-Severe Chronic Plaque Psoriasis (Protocol No. MK-3222-010) |
| Actual Study Start Date : | December 6, 2012 |
| Actual Primary Completion Date : | October 28, 2015 |
| Actual Study Completion Date : | November 10, 2021 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Tildrakizumab 200 mg
Tildrakizumab 200 mg administered subcutaneously (SC) once a week at Weeks 0 and 4 and then every 12 weeks.
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Drug: Tildrakizumab 200 mg
Two tildrakizumab 100 mg/mL pre-filled syringes (PFS)
Other Name: MK-3222, SCH 900222 Drug: Matching Placebo Matching placebo to tildrakizumab PFS |
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Experimental: Tildrakizumab 100 mg
Tildrakizumab 100 mg administered SC once a week at Weeks 0 and 4 and then every 12 weeks.
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Drug: Tildrakizumab 100 mg
Tildrakizumab 100 mg/mL PFS
Other Name: MK-3222, SCH 900222 Drug: Matching Placebo Matching placebo to tildrakizumab PFS |
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Placebo Comparator: Placebo
Matching placebo administered SC once a week at Weeks 0 and 4.
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Drug: Tildrakizumab 200 mg
Two tildrakizumab 100 mg/mL pre-filled syringes (PFS)
Other Name: MK-3222, SCH 900222 Drug: Tildrakizumab 100 mg Tildrakizumab 100 mg/mL PFS
Other Name: MK-3222, SCH 900222 Drug: Matching Placebo Matching placebo to tildrakizumab PFS |
Primary Outcome Measures :
- Percentage of Participants With Psoriasis Area Sensitivity Index 75 (PASI-75) Response at Week 12 (Base Study) [ Time Frame: Week 12 (or end of trial if prior to Week 12) ]The PASI is a measure of the average redness, thickness, and scaliness of lesions (each graded on a 0-4 scale), weighed by the amount of body surface for each region involved (head=0.1; upper limbs=0.2; trunk= 0.3; and lower limbs=0.4) and the degree of involvement for each body region (0=no involvement to 6=90-100% involvement). Calculated PASI score ranges from 0 to 72, with higher score indicating more severe disease status. The PASI-75 response indicates the number of participants achieving a 75% reduction in PASI score compared to baseline.
- 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) [ Time Frame: Baseline and Week 12 (or end of trial if prior to Week 12) ]The PGA is used to determine the overall severity of a participant's psoriasis lesions at a given time point. Overall lesions will be graded for thickness, erythema, and scaling on a scale from 0 to 5. The sum of the 3 scales will be divided by 3 to obtain the PGA score. PGA is assessed as: 0= Cleared, except for residual discoloration. 1= Minimal, majority of lesions have individual scores that average 1. 2 =Mild, majority of lesions have individual scores that average 2. 3= Moderate, majority of lesions have individual scores that average 3. 4= Marked, majority of lesions have individual scores that average 4. 5= Severe, majority of lesions have individual scores that average 5.
- Number of Participants Experiencing an Adverse Event Up to Week 12 (Base Study) [ Time Frame: Up to 12 weeks ]An adverse event is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
- Number of Participants Discontinuing Study Drug Due to an Adverse Event Up to Week 12 (Base Study) [ Time Frame: Up to 12 weeks ]An adverse event is defined as any untoward medical occurrence in a participant or clinical investigation participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
- Number of Participants Discontinuing Study Drug Due to a Drug-Related Adverse Event (Base Study) [ Time Frame: Up to 12 weeks ]A drug-related adverse event is an adverse event that has been determined by the investigator to be related to the study drug.
Secondary Outcome Measures :
- Percentage of Participants With PASI-90 Response At Week 12 [ Time Frame: Week 12 (or end of trial if prior to Week 12) ]The PASI is a measure of the average redness, thickness, and scaliness of lesions (each graded on a 0-4 scale), weighed by the amount of body surface for each region involved (head=0.1; upper limbs=0.2; trunk= 0.3; and lower limbs=0.4) and the degree of involvement for each body region (0=no involvement to 6=90-100% involvement). Calculated PASI score ranges from 0 to 72, with higher score indicating more severe disease status. The PASI-90 response indicates the number of participants achieving a 90% reduction in PASI score compared to baseline.
- Percentage of Participants With PASI-100 Response at Week 12 [ Time Frame: Week 12 (or end of trial if prior to Week 12) ]The PASI is a measure of the average redness, thickness, and scaliness of lesions (each graded on a 0-4 scale), weighed by the amount of body surface for each region involved (head=0.1; upper limbs=0.2; trunk= 0.3; and lower limbs=0.4) and the degree of involvement for each body region (0=no involvement to 6=90-100% involvement). Calculated PASI score ranges from 0 to 72, with higher score indicating more severe disease status. The PASI-100 response indicates the number of participants achieving a 100% reduction in PASI score compared to baseline.
- Baseline Dermatology Life Quality Index (DLQI) Score [ Time Frame: Baseline ]The DLQI questionnaire consists of 10 questions, where each question is scored from 0 (not affected at all) to 3 (very much affected). The DLQI score is the sum of the 10 individual question scores and ranges from 0 to 30, with lower scores indicating better quality of life.
- Change From Baseline in the Participant DLQI Score at Week 12 [ Time Frame: Baseline and Week 12 (or end of trial if prior to Week 12) ]The DLQI questionnaire consists of 10 questions, where each question is scored from 0 (not affected at all) to 3 (very much affected). The DLQI score is the sum of the 10 individual question scores and ranges from 0 to 30, with lower scores indicating better quality of life. For a change from baseline, a larger negative number correlates with a greater improvement in the DLQI score.
- Percentage of Participants With DLQI Score of 0 or 1 at Week 12 [ Time Frame: Week 12 (or end of trial if prior to Week 12) ]The DLQI questionnaire consists of 10 questions, where each question is scored from 0 (not affected at all) to 3 (very much affected). The DLQI score is the sum of the 10 individual question scores and ranges from 0 to 30, with lower scores indicating better quality of life.
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| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
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.
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| Responsible Party: | Sun Pharmaceutical Industries Limited |
| ClinicalTrials.gov Identifier: | NCT01722331 |
| Other Study ID Numbers: |
3222-010 2012-002255-42 ( EudraCT Number ) P07770 ( Other Identifier: Merck Protocol Number ) 132284 ( Registry Identifier: JAPIC-CTI ) |
| First Posted: | November 6, 2012 Key Record Dates |
| Results First Posted: | June 13, 2018 |
| Last Update Posted: | March 23, 2022 |
| Last Verified: | February 2022 |
Additional relevant MeSH terms:
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Psoriasis Skin Diseases, Papulosquamous Skin Diseases |
Antibodies, Monoclonal Immunologic Factors Physiological Effects of Drugs |