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)

NCT01225731 | Completed Phase 2 Results DMC

• 3 other identifiers: P054952009-017272-24MK-3222-003
• Study Type: interventional
• Target: 355
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Psoriasis

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (10)

• Percentage of Participants With a PASI 75 Response at Week 12

  Week 12

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

  Week 16

• Percentage of Participants With PASI 90 Response at Week 16

  Week 16

• Percentage of Participants With PASI 100 Response at Week 16

  Week 16

• PASI 75 Response Rate by Time

  Up to 16 Weeks

Study Arms (14)

Part 1: Tildrakizumab 5 mg

EXPERIMENTAL

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

Biological: tildrakizumab

Part 1: Tildrakizumab 25 mg

EXPERIMENTAL

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

Biological: tildrakizumab

Part 1: Tildrakizumab 100 mg

EXPERIMENTAL

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

Biological: tildrakizumab

Part 1: Tildrakizumab 200 mg

EXPERIMENTAL

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

Biological: tildrakizumab

Part 1: Placebo

PLACEBO COMPARATOR

Participants receive placebo, SC, at Weeks 0 and 4

Drug: Placebo

Part 2: Tildrakizumab 5 mg

EXPERIMENTAL

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

Biological: tildrakizumab

Part 2: Tildrakizumab 25 mg

EXPERIMENTAL

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

Biological: tildrakizumab

Part 2: Tildrakizumab 100 mg

EXPERIMENTAL

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

Biological: tildrakizumab

Part 2: Tildrakizumab 200 mg

EXPERIMENTAL

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

Biological: tildrakizumab

Part 3: Tildrakizumab 5 mg Follow-up

NO INTERVENTION

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

Part 3: Tildrakizumab 25 mg Follow-up

NO INTERVENTION

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

Part 3: Tildrakizumab 100 mg Follow-up

NO INTERVENTION

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

Part 3: Tildrakizumab 200 mg Follow-up

NO INTERVENTION

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

Part 3: Placebo Follow-up

NO INTERVENTION

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

Interventions

tildrakizumab BIOLOGICAL

SC administration of tildrakizumab at assigned dose

Also known as: SCH 900222, MK-3222

Part 1: Tildrakizumab 100 mg; Part 1: Tildrakizumab 200 mg; Part 1: Tildrakizumab 25 mg; Part 1: Tildrakizumab 5 mg; Part 2: Tildrakizumab 100 mg; Part 2: Tildrakizumab 200 mg; Part 2: Tildrakizumab 25 mg; Part 2: Tildrakizumab 5 mg

Placebo DRUG

SC administration of Placebo

Part 1: Placebo

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (3)

• 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.

  PMID: 26042589 RESULT

• 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

• 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

Conditions

Psoriasis

Interventions

tildrakizumab

Condition Hierarchy (Ancestors)

Skin Diseases, Papulosquamous; Skin Diseases; Skin and Connective Tissue Diseases

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 7, 2010
• First Posted: October 21, 2010
• Study Start: October 25, 2010
• Primary Completion: November 4, 2011
• Study Completion: October 24, 2012
• Last Updated: February 5, 2019
• Results First Posted: March 30, 2015

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will share