The Efficacy and Safety of Adding Methotrexate to Etanerc... | NCT01001208

NCT01001208

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

Sponsor/Collaborators Module

Name	Class
Immunex Corporation	INDUSTRY

Oversight Module

No data available

No data is available for this block.

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Etanercept Plus Methotrexate	Experimental	Participants received 50 mg etanercept twice weekly (BIW) for the first 12 weeks and then 50 mg etanercept once weekly (QW) for the second 12 weeks. Participants also received active methotrexate titrated as follows: 7.5 mg per week (3 capsules) for weeks 1 and 2, 10 mg per week (4 capsules) for weeks 3 and 4, and then up to 15 mg per week (6 capsules) or the maximum tolerated dose for the remainder of the 24-week treatment period.	Drug: Methotrexate Drug: Etanercept
Etanercept Plus Placebo	Active Comparator	Participants received 50 mg etanercept twice weekly (BIW) for the first 12 weeks and then 50 mg etanercept once weekly (QW) for the second 12 weeks. Participants also received oral placebo that was the same number of capsules per week as the methotrexate dosing regimen.	Drug: Etanercept Drug: Placebo

Name	Type	Description	Arm Group Labels	Other Names
Methotrexate	Drug	Methotrexate tablets over-encapsulated for blinding	Etanercept Plus Methotrexate

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
PASI 75 Response at Week 24	Percentage of participants achieving at least a 75% decrease (improvement) from Baseline in the Psoriasis Area and Severity Index (PASI) at Week 24. PASI Score incorporates measures of erythema, desquamation, infiltration, and affected body surface area. Involvement and severity of psoriasis was scored by a blinded assessor using a scale of 0 to 72, where 0 = no psoriasis and 72 = severe disease.	Baseline and 24 Weeks

Secondary Outcomes

Measure	Description	Time Frame
PASI 50 Response at Week 24	Percentage of participants achieving at least a 50% decrease (improvement) from Baseline in the Psoriasis Area and Severity Index (PASI) at Week 24. PASI Score incorporates measures of erythema, desquamation, infiltration, and affected body surface area. Involvement and severity of psoriasis was scored by a blinded assessor using a scale of 0 to 72, where 0 = no psoriasis and 72 = severe disease.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Is capable of understanding and giving written, voluntary informed consent before study screening
Male or female ≥18 years of age at time of screening
Has had stable moderate to severe plaque psoriasis for at least 6 months (eg, no morphology changes or significant flares of disease activity)
Has involved body surface area (BSA) ≥ 10% and Psoriasis Area and Severity Index (PASI) ≥ 10 at screening and at baseline
Is a candidate for systemic therapy or phototherapy in the opinion of the investigator
Has a negative test for hepatitis B surface antigen and hepatitis C antibody
Has a negative purified protein derivative test within 30 days prior to the first IP dose. Tuberculin skin tests should be considered positive when they have greater than or equal to 5 mm of induration at 48-72 hours after test is placed. Patients with a positive tuberculin skin test (if less than or equal to 14 mm of induration) are allowed if they have a history of Bacillus Calmette-Guerin vaccination with a negative Quantiferon test in the past year, no symptoms per tuberculosis worksheet, and a negative chest X ray.
Has a negative serum pregnancy test within 28 days before initiating Investigational Product (IP) and negative urine pregnancy test at baseline for females (except those at least 3 years post menopausal or surgically sterile)
Females are willing to use highly effective form of birth control (decided upon with the investigator) during the study and for 3 months after the end of treatment (except women at least 3 years post menopausal or surgically sterile)
Males are willing to use highly effective form of birth control (decided upon with the investigator) during the study and for 5 months after the end of treatment (except for men who are surgically sterile or whose female partners are at least 3 years post menopausal, surgically sterile, or are using a highly effective form of birth control)
Men with a pregnant female partner are willing to use effective methods (decided upon with the investigator) to ensure that an unborn child is not exposed to IP via semen
Patient or designee must have the ability to inject etanercept subcutaneously

Exclusion Criteria:

Skin-disease related

Has active guttate, erythrodermic, or pustular psoriasis at the time of the screening visit.
Has evidence of skin conditions at the time of the screening visit (eg, eczema) that would interfere with evaluations of the effect of IP on psoriasis.

Medical conditions

Has significant concurrent medical conditions, including:
Type 1 diabetes
Poorly controlled type 2 diabetes (hemoglobin A1c > 8.5)
Symptomatic heart failure (New York Heart Association [NYHA] class II, III, or IV)
Myocardial infarction within the last year
Current or history of unstable angina pectoris within the last year
Uncontrolled hypertension as defined by a resting blood pressure ≥ 160/95 mmHg prior to randomization (confirmed by a repeat assessment)
Severe chronic pulmonary disease (eg, requiring oxygen therapy)
No major chronic inflammatory disease or connective tissue disease other than psoriasis and/or psoriatic arthritis
Multiple sclerosis or any other demyelinating disease
Active malignancy, including evidence of cutaneous basal or squamous cell carcinoma or melanoma, or history of cancer (other than fully resected and surgically cured cutaneous basal cell and squamous cell carcinoma) within 5 years before the first IP dose. If malignancy occurred more than 5 years ago, documentation of disease-free state since treatment is required.
Known immunodeficiency syndromes including human immunodeficiency virus (HIV)
Uncontrolled, clinically significant history of renal disease
Alcoholic hepatitis
Any condition that, in the opinion of the investigator, might cause this study to be detrimental to the patient
Has any active CTC grade 2 or higher infection (including chronic or localized infections) within 30 days prior to screening, at screening, or during screening period prior to first investigational product (IP) dose
Is pregnant or breast feeding
Has any condition that could, in the opinion of the investigator, compromise the patient's ability to give written consent and/or comply with the study procedures, such as a history of substance abuse or a psychiatric condition Methotrexate contraindications or precautions
Has a family history of heritable liver disease (eg, hemachromatosis, Wilson's disease)
Has a history of or evidence at screening or baseline of alcohol abuse, alcoholic liver disease, or other clinically significant liver disease
Is unwilling or unable to limit alcohol consumption during the 24-week trial period (allowable limits are: not more than 4 drinks a week, not more than 2 drinks in a single day. 1 drink = 1 (5 oz) glass of wine = 1.5 oz liquor = 12 oz of beer or hard cider)
Has an estimated total cumulative methotrexate exposure (by medical history) exceeding 1000 mg, unless a subsequent liver biopsy has demonstrated no grade IIIb or greater injury
Has a history of significant methotrexate toxicity including pneumonitis or significant cytopenias

Laboratory abnormalities

Has laboratory abnormalities at screening, including:
Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > the upper limit of normal (if screen fail for abnormal AST/ALT, 1 repeat measurement is allowed)
Serum total bilirubin ≥ 1.5 mg/dL
Abnormal serum albumin (< 3.5 g/dL)
Hemoglobin < 11 g/dL
Platelet count < 125,000 /mm^3
White blood cell count < 3,500 cells/mm^3
Absolute neutrophil count < 1500/mm^3
Estimated creatinine clearance < 50 mL/min (Cockroft-Gault formula, calculated value to be provided to sites)
Any other laboratory abnormality, which, in the opinion of the investigator, will prevent the patient from completing the study or will interfere with the interpretation of the study results

Washouts and disallowed medications

Has used any of the following therapies within 14 days of IP initiation:
Ultraviolet light B therapy
Topical cyclosporine or calcineurin inhibitors
Topical vitamin A or D analog preparations
Class III through VII topical steroids (exception: permitted on the scalp, axillae, and groin)
Has used any of the following therapies within 28 days of IP initiation:
Intravenous or oral calcineurin inhibitors
Ultraviolet light A therapy
Psoralen and ultraviolet light A therapy
Oral retinoids
Class I or II topical steroids
Anthralin
Any other systemic psoriasis therapy (eg, cyclosporine), including oral or parenteral corticosteroids
Cyclophosphamide
Sulfasalazine
Has used methotrexate within 28 days of IP initiation. Patients with prior use of methotrexate must be excluded if subject discontinued because of a clinically significant adverse event (eg, severe skin reactions, methotrexate-induced lung disease, or any other adverse event that the investigator feels might cause this study to be detrimental to the patient)
Has used biologic therapies (other than interleukin (IL)12/IL23 inhibitors or anti-timor necrosis factor (TNF) agents) within 3 months of IP initiation
Has used an IL12/23 inhibitor within 6 months of IP initiation (eg, CNTO 1275, ABT 874)
Has used one or more anti-TNF agents (eg, etanercept, adalimumab, infliximab) within 3 months of IP initiation. Patients with prior use of an anti-TNF agent must be excluded if the subject discontinued for lack of efficacy or a clinically significant adverse event (eg, serious infection, neurologic event, malignancy, hematologic event, or any other adverse event that the investigator feels might cause this study to be detrimental to the patient).
Has previously used efalizumab (Raptiva®).
Other investigational procedures are excluded.
currently enrolled in or has not yet completed at least 30 days or 5 half-lives (if applicable; whichever is longer) since ending other investigational device or drug study(s), or is receiving other investigational agent(s).

Contacts/Locations Module

Name	Affiliation	Role
MD	Amgen	Study Director

References Module

Label	URL
AmgenTrials clinical trials website	View source

IPD Sharing Statement Module

No data available

No data is available for this block.

Arm/Group Information

ID	Title	Description
FG000	Etanercept + Methotrexate	Participants received 50 mg etanercept twice weekly (BIW) for the first 12 weeks and then 50 mg etanercept once weekly (QW) for the second 12 weeks. Participants also received active methotrexate titrated as follows: 7.5 mg per week (3 capsules) for weeks 1 and 2, 10 mg per week (4 capsules) for weeks 3 and 4, and then up to 15 mg per week (6 capsules) or the maximum tolerated dose for the remainder of the 24-week treatment period.
FG001	Etanercept + Placebo	Participants received 50 mg etanercept twice weekly (BIW) for the first 12 weeks and then 50 mg etanercept once weekly (QW) for the second 12 weeks. Participants also received oral placebo that was the same number of capsules per week as the methotrexate dosing regimen.

Periods

Title

Milestones

Reasons Not Completed

Overall Study

Type	Comment	Milestone Data
STARTED		FG000239 subjects FG001239 subjects
COMPLETED		FG000211 subjects FG001206 subjects
NOT COMPLETED		FG00028 subjects FG00133 subjects

Type	Comment	Reasons
Adverse Event		FG00010 subjects FG0015 subjects
Lost to Follow-up		FG0005 subjects FG001

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Etanercept + Methotrexate	Participants received 50 mg etanercept twice weekly (BIW) for the first 12 weeks and then 50 mg etanercept once weekly (QW) for the second 12 weeks. Participants also received active methotrexate titrated as follows: 7.5 mg per week (3 capsules) for weeks 1 and 2, 10 mg per week (4 capsules) for weeks 3 and 4, and then up to 15 mg per week (6 capsules) or the maximum tolerated dose for the remainder of the 24-week treatment period.

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

PASI 75 Response at Week 24

Percentage of participants achieving at least a 75% decrease (improvement) from Baseline in the Psoriasis Area and Severity Index (PASI) at Week 24. PASI Score incorporates measures of erythema, desquamation, infiltration, and affected body surface area. Involvement and severity of psoriasis was scored by a blinded assessor using a scale of 0 to 72, where 0 = no psoriasis and 72 = severe disease.

Intention-to-Treat with available data; last observation carried forward (LOCF) imputation was used.

Posted

Number

Percentage of participants

Baseline and 24 Weeks

ID	Title	Description
OG000	Etanercept + Methotrexate	Participants received 50 mg etanercept twice weekly (BIW) for the first 12 weeks and then 50 mg etanercept once weekly (QW) for the second 12 weeks. Participants also received active methotrexate titrated as follows: 7.5 mg per week (3 capsules) for weeks 1 and 2, 10 mg per week (4 capsules) for weeks 3 and 4, and then up to 15 mg per week (6 capsules) or the maximum tolerated dose for the remainder of the 24-week treatment period.

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 + Placebo	Participants received 50 mg etanercept twice weekly (BIW) for the first 12 weeks and then 50 mg etanercept once weekly (QW) for the second 12 weeks. Participants also received oral placebo that was the same number of capsules per week as the methotrexate dosing regimen.

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Myocardial Infarction	Cardiac disorders	MedDRA 13.1	Systematic Assessment

Term	Organ System	Source Vocabulary	Assessment Type	Notes	Statistical Information
Nausea	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment

More Info Module

Certain Agreements

Title	Organization	Phone	Extension	Email
Study Director	Amgen Inc.	866-572-6436

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

ID	Term
D011565	Psoriasis

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

Intervention Browse Module

ID	Term
D008727	Methotrexate
D000068800	Etanercept

ID	Term
D000630	Aminopterin
D011622	Pterins
D011621	Pteridines
D006574	Heterocyclic Compounds, 2-Ring

Masking Info

EG0001 affected239 at risk

EG0010 affected239 at risk

EG0007 affected239 at risk

EG00113 affected239 at risk