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

Study Overview
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Brief Summary
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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).

Official Title
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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

Conditions
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Psoriasis

Intervention / Treatment
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* Drug: Ustekinumab
* Drug: Etanercept


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ustekinumab<br> | Drug: Ustekinumab<br>* 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<br>* Other names: Stelara;|
| Active Comparator: Etanercept<br> | Drug: Etanercept<br>* Etanercept 50 mg twice weekly by self-administered subcutaneous injection for 12 weeks, then once weekly for 4 weeks<br>* Other names: Enbrel;|
| No Intervention: No treatment<br> | |

What is the study measuring?
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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 | 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 | 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 | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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psoriasis, Ustekinumab, Stelara, Etanercept, Enbrel