Clinical trial NCT01276847: A Study to Assess the Effect of Ustekinumab (Stelara®) and Etanercept (Enbrel®) in Participants With Moderate to Severe Psoriasis (MK-0000-206)
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Psoriasis
Keywords: psoriasis
Ustekinumab
Stelara
Etanercept
Enbrel
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2011-01-13
Enrollment: 40
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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).


Eligibility criteria: 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

Primary outcomes:
measure: 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
timeFrame: Baseline and Weeks 1, 2, 4, and 16
Secondary outcomes:
measure: 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
timeFrame: Baseline and Weeks 1, 2, 4, and 16
measure: Change From Baseline in Gene Expression Score for Interleukin 17 (IL-17) in Psoriatic Lesions of Participants Treated With Etanercept
timeFrame: Baseline and Weeks 1, 2, 4, and 16
Other outcomes:
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