A Study to Evaluate the Efficacy and Safety/Tolerability of Subcutaneous Tildrakizumab (SCH 900222/MK-3222) in Participants With Moderate-to-Severe Chronic Plaque Psoriasis Followed by a Long-term Extension Study (MK-3222-011)

NCT01729754 | Completed Phase 3 Results DMC

• 3 other identifiers: 3222-0112012-001377-88P07771
• Study Type: interventional
• Target: 1,090
• Locations: 0 countries
• Sites: N/A

Brief Summary

This study is being conducted to evaluate the efficacy and safety/tolerability of tildrakizumab (SCH 900222/MK-3222) in a population of participants with moderate-to-severe plaque psoriasis. The primary hypotheses of the study are that tildrakizumab is superior to placebo in the treatment of moderate-to-severe chronic plaque psoriasis as measured by the proportion of participants achieving \>= Psoriasis Area Sensitivity Index of 75% (PASI-75) response and the proportion 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.

Conditions

Plaque Psoriasis

Outcome Measures

Primary Outcomes (4)

• Percentage of Participants Achieving a Psoriasis Area Sensitivity Index 75% (PASI-75) Response at Week 12 (Part 1)

  The PASI is a measure of the average redness, thickness, and scaliness of lesions (each graded on a 0-4 scale), weighed by the area of 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. Statistical analyses presented below compare tildrakizumab to placebo to support the primary hypothesis of the study.

  Week 12

• 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 (Part 1)

  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. Statistical analyses presented below compare tildrakizumab to placebo to support the primary hypothesis of the study.

  Week 12

• Percentage of Participants Experiencing an Adverse Event (AE) Up to Week 12 (Part 1)

  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.

  Up to Week 12

• Percentage of Participants Discontinuing Study Treatment Due to an AE Up to Week 12 (Part 1)

  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.

  Up to Week 12

Secondary Outcomes (29)

• Percentage of Participants Achieving a PASI-75 Response at Week 28 (Part 2)

  Week 28

• Percentage of Participants Achieving a PASI-75 Response at Week 40 (Part 3)

  Week 40

• Percentage of Participants Achieving a PASI-75 Response at Week 52 (Part 3)

  Week 52

• Percentage of Participants With a PGA Score of Clear or Minimal With at Least a 2 Grade Reduction From Baseline at Week 28 (Part 2)

  Week 28

• Percentage of Participants With a PGA Score of Clear or Minimal With at Least a 2 Grade Reduction From Baseline at Week 40 (Part 3)

  Week 40

Study Arms (4)

Tildrakizumab 200 mg

EXPERIMENTAL

Participants receive tildrakizumab 200 mg subcutaneously (SC) on Weeks 0, 4, 16, 28, 40 and 52 and, optionally, every 12 weeks thereafter until Week 244, plus etanercept placebo (PBO) twice weekly until Week 12 and once weekly from Week 12 to Week 28.

Drug: Tildrakizumab 200 mg; Drug: Etanercept Placebo

Tildrakizumab 100 mg

EXPERIMENTAL

Participants receive tildrakizumab 100 mg SC on Weeks 0, 4, 16, 28, 40 and 52 and, optionally, every 12 weeks thereafter until Week 244, plus etanercept placebo twice weekly until Week 12 and once weekly from Week 12 to Week 28.

Drug: Tildrakizumab 100 mg; Drug: Etanercept Placebo

Placebo

PLACEBO COMPARATOR

Participants receive matching placebo to tildrakizumab SC on Weeks 0 and 4 plus etanercept placebo twice weekly up to Week 12 and once weekly from Week 12 to Week 28. Participants will be re-randomized 1:1 at Week 12 to receive tildrakizumab 200 mg or tildrakizumab 100 mg on Weeks 12, 16, 28, 40 and 52 and, optionally, every 12 weeks thereafter until Week 244.

Drug: Tildrakizumab Placebo; Drug: Etanercept Placebo

Etanercept 50 mg

ACTIVE COMPARATOR

Participants receive matching placebo to tildrakizumab SC on Weeks 0 and 4 and etanercept 50 mg twice weekly up to Week 12 and once weekly from Week 12 to Week 28. Participants who don't achieve PASI-75, receive tildrakizumab 200 mg after Week 28 (Weeks 32, 36 and 48) and, optionally, every 12 weeks thereafter until Week 244.

Drug: Tildrakizumab Placebo; Drug: Etanercept 50 mg

Interventions

Tildrakizumab 200 mg DRUG

Tildrakizumab 200 mg administered SC. Each pre-filled syringe (PFS) or autoinjector (AI) contains 1 mL of solution, tildrakizumab 100 mg/mL.

Also known as: SCH 900222, MK-3222

Tildrakizumab 200 mg

Tildrakizumab 100 mg DRUG

Tildrakizumab 100 mg administered SC. Each PFS or AI contains 1 mL of solution, tildrakizumab 100 mg/mL.

Also known as: SCH 900222, MK-3222

Tildrakizumab 100 mg

Tildrakizumab Placebo DRUG

Matching placebo to tildrakizumab administered SC

Etanercept 50 mg; Placebo

Etanercept Placebo DRUG

Matching placebo to etanercept administered SC

Placebo; Tildrakizumab 100 mg; Tildrakizumab 200 mg

Etanercept 50 mg DRUG

Etanercept 50 mg administered SC

Also known as: Embrel

Etanercept 50 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Clinical diagnosis of moderate-to-severe plaque psoriasis for at least 6 months prior to enrollment;
• Candidate for phototherapy or systemic therapy;
• Premenopausal female participants must agree to abstain from heterosexual activity or use a medically approved method of contraception or use appropriate effective contraception as per local regulations or guidelines
• 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

You may not qualify if:

• Non-plaque forms of psoriasis
• Presence or history of severe psoriatic arthritis and is well-controlled on current treatment regimen
• Women of childbearing potential who are pregnant, intend to become pregnant, or are lactating
• Participant is expected to require topical therapy, phototherapy, or systemic therapy during the trial
• Presence of any infection or history of recurrent infection requiring treatment with systemic antibiotics
• Previous use of entanercept, tildrakizumab (MK-3222), or other interleukin-23 (IL-23)/T- helper cell 17 (Th-17) pathway inhibitors including p40, p19, and IL-17 antagonists
• Latex allergy or sensitivity
• Active or untreated latent tuberculosis (TB)
• For the extension study: women of child-bearing potential who are pregnant, intend to become pregnant within 6 months of completing the trial, or 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

Sponsors & Collaborators

• Sun Pharmaceutical Industries Limited: lead

Related Publications (8)

• 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.

  PMID: 28596043 RESULT

• Armstrong AW, Blauvelt A, Lebwohl M, Asahina A, Gogineni R, Griffiths CEM. Efficacy and safety of tildrakizumab in patients with early- vs. late-onset psoriasis. Br J Dermatol. 2025 Aug 18;193(3):442-450. doi: 10.1093/bjd/ljaf171.

  PMID: 40365708 DERIVED

• 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.

  PMID: 36098877 DERIVED

• Thaci D, Piaserico S, Warren RB, Gupta AK, Cantrell W, Draelos Z, Foley P, Igarashi A, Langley RG, Asahina A, Young M, Falques M, Pau-Charles I, Mendelsohn AM, Rozzo SJ, Reich K. Five-year efficacy and safety of tildrakizumab in patients with moderate-to-severe psoriasis who respond at week 28: pooled analyses of two randomized phase III clinical trials (reSURFACE 1 and reSURFACE 2). Br J Dermatol. 2021 Aug;185(2):323-334. doi: 10.1111/bjd.19866. Epub 2021 May 4.

  PMID: 33544883 DERIVED

• 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.

  PMID: 32162721 DERIVED

• 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.

  PMID: 31268369 DERIVED

• 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.

  PMID: 31218661 DERIVED

• 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.

  PMID: 30915660 DERIVED

MeSH Terms

Interventions

tildrakizumab; Etanercept

Intervention Hierarchy (Ancestors)

Immunoglobulin Fc Fragments; Immunoglobulin Fragments; Peptide Fragments; Peptides; Amino Acids, Peptides, and Proteins; Immunoglobulin Constant Regions; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Receptors, Tumor Necrosis Factor; Receptors, Cytokine; Receptors, Immunologic; Receptors, Cell Surface; Membrane Proteins

Results Point of Contact

• Title: Head-Clinical Development
• Organization: Sun Pharma Advanced Research Company Limited

clinical.trials@sparcmail.com

912266455645

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 13, 2012
• First Posted: November 20, 2012
• Study Start: February 5, 2013
• Primary Completion: September 28, 2015
• Study Completion: October 26, 2021
• Last Updated: March 8, 2022
• Results First Posted: June 27, 2018

Record last verified: 2022-02