A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Adding Methotrexate to Etanercept in Subjects With Moderate to Severe Plaque Psoriasis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 478
- 主要终点
- PASI 75 Response at Week 24
研究概览
简要总结
The purpose of this study is to evaluate the efficacy of adding methotrexate to etanercept compared with etanercept monotherapy as measured by the percentage of participants achieving a 75% improvement from baseline in the Psoriasis Area and Severity Index (PASI 75) at Week 24.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
- 另有 11 项未显示
研究组 & 干预措施
Etanercept Plus 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.
干预措施: Methotrexate (Drug)
Etanercept Plus 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.
干预措施: Etanercept (Drug)
Etanercept Plus 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.
干预措施: Etanercept (Drug)
Etanercept Plus 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.
干预措施: Placebo (Drug)
结局指标
主要结局
PASI 75 Response at Week 24
时间窗: Baseline and 24 Weeks
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.
次要结局
- PASI 90 Response at Week 24(Baseline and 24 Weeks)
- PASI 50 Response at Week 24(Baseline and 24 Weeks)
- PASI 90 Response at Week 12(Baseline and 12 Weeks)
- Static Physician Global Assessment (sPGA) Response at Week 24(Week 24)
- PASI 50 Response at Week 12(Baseline and 12 Weeks)
- PASI 75 Response at Week 12(Baseline and 12 Weeks)
- Static Physician Global Assessment (sPGA) Response at Week 12(Week 12)
- Change From Baseline in the Percentage of Body Surface Area Involved With Psoriasis at Week 12(Baseline and 12 Weeks)
- Change Form Baseline in Percentage of Body Surface Area Involved With Psoriasis at Week 24(Baseline and 24 Weeks)