A Study to Assess the Effect of Ustekinumab (Stelara®) an... | NCT01276847

NCT01276847

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Status Module

Description Module

Label	Type	Intervention Names
Ustekinumab	Experimental	Drug: Ustekinumab
Etanercept	Active Comparator	Drug: Etanercept
No treatment	No Intervention

Name	Type	Description	Arm Group Labels	Other Names
Ustekinumab	Drug	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

Outcomes Module

Primary Outcomes

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 Outcomes

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.

Eligibility Module

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

ID	Title	Description
FG000	Etanercept	Etanercept : Etanercept 50 mg twice weekly by self-administered subcutaneous injection for 12 weeks, then once weekly for 4 weeks
FG001	No Treatment	No treatment administered
FG002	Ustekinumab	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

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Etanercept	Etanercept : Etanercept 50 mg twice weekly by self-administered subcutaneous injection for 12 weeks, then once weekly for 4 weeks
BG001	No Treatment	No treatment administered

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type	Title	Description	Population Description	Reporting Status	Anticipated Posting Date	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Time Frame	Units Analyzed	Denominator Units Selected	Arm/Group Information	Denominators	Classes	Analyses
Primary	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.	Pre-specified to be collected only in participants treated with Ustekinumab. One participant treated with Ustekinumab with extreme outlying data, likely due to mislabeling of lesional and nonlesional tissues, was excluded from the analysis.	Posted		Median	90% Confidence Interval	Gene expression score		Baseline and Weeks 1, 2, 4, and 16

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Etanercept	Etanercept : Etanercept 50 mg twice weekly by self-administered subcutaneous injection for 12 weeks, then once weekly for 4 weeks

ID	Term
D017444	Skin Diseases, Papulosquamous
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases

ID	Term
D061067	Antibodies, Monoclonal, Humanized
D000911	Antibodies, Monoclonal
D000906	Antibodies
D007136	Immunoglobulins