A Study to Assess the Effect of Ustekinumab (Stelara®) and Etanercept (Enbrel®) in Participants With Moderate to Severe Psoriasis (MK-0000-206)

January 13, 2015 updated by: Merck Sharp & Dohme LLC

A Clinical Trial to Assess the Effects of Ustekinumab and Etanercept on Skin and Blood Biomarkers of Psoriasis in Patients With Moderate to Severe Disease

This is a two-part study. The purpose of the pilot study (Part 1) is to optimize the acquisition, handling and shipping procedure for skin biopsies obtained from participants with plaque psoriasis. No treatment will be administered. Part 2 will include 2 cohorts. In Cohort 1, the effects of 16 weeks of treatment with either ustekinumab or etanercept on biomarkers in lesional skin in participants with moderate to severe psoriasis will be evaluated. In Cohort 2, biomarkers of lesional skin from participants with moderate to severe psoriasis who are not treated with biologic therapy will be evaluated over 16 weeks. The primary hypothesis is that treatment with ustekinumab reduces messenger RNA (mRNA) expression of genes in the interleukin 12 (IL-12) pathway that are modulated by interferon gamma (IFN-γ).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

40

Phase

  • Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

17 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Is unlikely to conceive (for female participants of reproductive potential)- Part 2
  • Has a diagnosis of predominantly plaque psoriasis for ≥ 6 months-Parts 1 and 2
  • Has a plaque-type psoriatic lesion with a Target Lesion Score (TLS) score of ≥ 6 in a hidden area of the body such as the abdomen, thighs, lower back or buttock that is suitable for biopsy- Part 1
  • Is considered to be a candidate for phototherapy or systemic therapy - Part 2
  • Has a Psoriasis Area and Severity Index (PASI) score ≥ 12 at Baseline - Part 2
  • Has psoriasis body surface area (BSA) involvement ≥ 10% at Baseline - Part 2
  • Has a Physician's Global Assessment (PGA) of at least moderate disease (moderate, marked, or severe) at Baseline - Part 2
  • Is considered to be eligible according to the tuberculosis (TB) screening criteria - Part 2

Exclusion Criteria:

  • Has nonplaque forms of psoriasis specifically erythrodermic psoriasis, predominantly pustular psoriasis, medication-induced or medication-exacerbated psoriasis, or new onset guttate psoriasis - Parts 1 and 2
  • Women of childbearing potential who are pregnant, intend to become pregnant (within 6 months of completing the trial), or are lactating - Parts 1 and 2
  • Has a history of neoplastic disease or concurrent malignancy - Part 2
  • Requires oral or injectable corticosteroids during the trial - Part 2
  • Have any infection requiring treatment with antibiotics within 2 weeks prior to screening or serious infection requiring hospitalization or treatment with IV antibiotics within 8 weeks prior to screening - Part 2
  • Has a positive human immunodeficiency virus (HIV) test result, hepatitis B surface antigen, or hepatitis C test result - Part 2
  • Has received live virus vaccination within 4 weeks prior to screening or who intends to receive live virus vaccination during the trial - Part 2
  • Has previous exposure to any agents targeting IL-12 and/or IL-23 (e.g. ustekinumab) - Part 2
  • Has prior exposure tumor necrosis factor (TNF) antagonists (e.g. infliximab, etanercept, golimumab, adalimumab) and discontinued due to lack of efficacy or for adverse effects - Part 2
  • Has been treated with any medications that are associated with Progressive Multifocal Leukoencephalopathy (PML), such as efalizumab (Raptiva) or natalizumab (Tysabri) - Part 2
  • Has taken any immunosuppressive agents (e.g. corticosteroids, methotrexate, azathioprine, cyclosporine) for treatment of conditions other than for Psoriasis within 4 weeks of screening - Part 2
  • Is currently taking any of the prohibited medications and is unwilling to washout of the medication(s) for the indicated timeframe prior to screening and for the duration of the study - Part 2

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
No Intervention: No treatment
Experimental: Ustekinumab
Drug: Ustekinumab
Ustekinumab 45 mg per dose, administered subcutaneously for participants weighing ≤ 100 kg, and ustekinumab 90 mg per dose administered subcutaneously for participants weighing > 100 kg on Day 1, and Weeks 4 and 16
Other Names:
  • Stelara
Active Comparator: Etanercept
Drug: Etanercept
Etanercept 50 mg twice weekly by self-administered subcutaneous injection for 12 weeks, then once weekly for 4 weeks
Other Names:
  • Enbrel

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in Composite Gene Expression Score Based on IL-12 Pathway Related Interferon Gamma (IFN-γ)-Modulated Genes in Psoriatic Lesions of Participants Treated With Ustekinumab
Time Frame: Baseline and Weeks 1, 2, 4, and 16
Skin biopsies were collected from participants at baseline and after treatment with ustekinumab for 1,2,4 and 16 weeks. The expression of messenger RNA (mRNA) from three pre-defined IL-12 pathway related genes, modulated by interferon gamma (IFN-γ), namely IFN-γ, inducible nitric oxide synthase(iNOS) and CXC motif chemokine 10(CXCL10) was quantitated by real-time polymerase chain reaction (qPCR), with the data normalized by the delta-delta Ct method. The expression score for each gene, showing the percentage difference from baseline, was calculated as follows : [(baseline - post baseline)/baseline] x 100. Composite gene expression scores were derived for each individual by summing the expression scores of the individual genes. Positive composite scores denote a decrease from baseline in gene expression.
Baseline and Weeks 1, 2, 4, and 16

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change From Baseline in Composite Gene Expression Score Based on Interleukin 23 (IL-23) Pathway Related Genes in Psoriatic Lesions of Participants Treated With Ustekinumab
Time Frame: Baseline and Weeks 1, 2, 4, and 16
Skin biopsies were collected from participants at baseline and after treatment with ustekinumab for 1,2,4 and 16 weeks. The mRNA expression of eight pre-defined IL-23 pathway related genes, namely beta 4 defensin (DEFB4), CXC motif chemokine 8 (CXCL8), Interleukins 17A, 17F, 20, 22, 23A (IL-17, IL-17F, IL-20, IL-22, IL-23A) and cyclic AMP dependent protein kinase (CAMP) was quantitated by qPCR, with the data normalized by the delta-delta Ct method. The expression score for each gene, showing the percentage difference from baseline, was calculated as follows : [(baseline - post baseline)/baseline] x 100. Composite gene expression scores were derived for each individual by summing the expression scores of the individual genes. Positive composite scores denote a reduction from baseline in gene expression.
Baseline and Weeks 1, 2, 4, and 16
Change From Baseline in Gene Expression Score for Interleukin 17 (IL-17) in Psoriatic Lesions of Participants Treated With Etanercept
Time Frame: Baseline and Weeks 1, 2, 4, and 16
Participants had skin biopsies performed at baseline and after treatment with etanercept for 1,2,4 and 16 weeks. The expression of IL-17 mRNA was quantitated by qPCR, with the data normalized by the delta-delta Ct method. The expression score, showing the percentage difference from baseline, was calculated as follows : [(baseline - post baseline)/baseline] x 100.
Baseline and Weeks 1, 2, 4, and 16

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Merck Sharp & Dohme LLC

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

March 1, 2011

Primary Completion (Actual)

December 1, 2011

Study Completion (Actual)

December 1, 2011

Study Registration Dates

First Submitted

January 12, 2011

First Submitted That Met QC Criteria

January 12, 2011

First Posted (Estimate)

January 13, 2011

Study Record Updates

Last Update Posted (Estimate)

January 26, 2015

Last Update Submitted That Met QC Criteria

January 13, 2015

Last Verified

January 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 0000-206

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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