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临床试验/NCT01285310
NCT01285310终止2 期

A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study, To Compare the Efficacy and Safety of Two Doses of Apremilast (CC-10004) in Subjects With Active Rheumatoid Arthritis Who Have Had an Inadequate Response to Methotrexate

Amgen48 个研究点 分布在 4 个国家目标入组 237 人开始时间: 2010年12月9日最近更新:
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适应症
干预措施
相关药物

试验速览

阶段
2 期
状态
终止
发起方
Amgen
入组人数
237
试验地点
48
主要终点
Percentage of Participants With an American College of Rheumatology 20% Improvement (ACR 20) Response at Week 16
研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

The purpose of this study is to determine whether Apremilast is safe and effective in the treatment of patients with rheumatoid arthritis, specifically in improving signs and symptoms of rheumatoid arthritis (tender and swollen joints, pain, physical function and structure) in treated patients who have had an inadequate response to Methotrexate.

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
Quadruple (Participant, Care Provider, 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

  • •Must have a documented diagnosis of Rheumatoid Arthritis (1987 American College of Rheumatology Criteria) with onset of signs/symptoms of disease ≥ 4 months of duration from randomization.
  • •Must be receiving treatment on an outpatient basis.
  • •Must have active disease despite current methotrexate treatment as defined below:
  • •≥ 6 swollen joints (66 swollen joint count) AND
  • •≥ 6 tender joints (68 tender joint count)
  • •. Must meet at least one of the four lab requirements below:
  • •High Sensitivity C-Reactive Protein (hsCRP) ≥ 10 mg/L
  • •Erythrocyte Sedimentation Rate (ESR) > 28 mm after the first 1 hour
  • •Positive for Rheumatoid Factor (RF)
  • •Positive for Anti-cyclic Citrullinated Peptide (anti-CCP) antibodies
  • •For participants participating in the Magnetic Resonance Imaging (MRI) assessment:
  • •Must have Rheumatoid Arthritis joint involvement, as assessed by swollen joint counts in: 1) at least two Metacarpophalangeal (MCP) swollen joints on the same hand, or 2) at least one swollen Metacarpophalangeal (MCP) joint and swollen wrist on the same hand.
  • •Must have been treated with methotrexate for at least 4 months prior to randomization, and must be on stable dose. Participants will be required to maintain their stable dose through Week 52 of the study. Oral folate (folic acid) supplementation is required with a minimum dose of 5 mg/week, or instead leucovorin may be used up to 10 mg/week orally.
  • •Non-steroidal anti-inflammatory drugs (NSAIDs) and pain medications are allowed, however, must be on stable regimen for at least 7 days prior to randomization and through Week 52 of the study.
  • •Oral corticosteroids (if taken) are allowed, however, must be on stable dose of prednisone ≤ 10 mg/day or equivalent for at least 28 days prior to randomization and through Week 52 of the study.
  • •Must meet the following laboratory criteria at screening:
  • •White blood cell count ≥ 3000/mm^3 (≥ 3.0 x 10^9/L) and < 14,000/mm^3 (< 14 x 10^9/L)
  • •Platelet count (≥ 100,000/μL ((≥ 100 x 10^9/L)
  • •Serum creatinine ≤ 1.5 mg/dL (≤ 132.6 μmol/L)
  • •Aspartate aminotransferase or serum glutamic oxaloacetic transaminase (AST/SGOT) and alanine aminotransferase or serum glutamic-pyruvic transaminase (ALT/ SGPT) ≤ 2 x upper limit of normal (ULN). If initial test shows Aspartate aminotransferase (AST) or alanine aminotransferase (SLT) or 2 times the upper limit of normal (ULN), one repeat test is allowed during the screening period.
  • •Total bilirubin ≤ 2 mg/dL (≤ 34 μmol/L). If initial test result is > 2 mg/dL, one repeat test is allowed during the screening period.
  • •Hemoglobin ≥ 9 g/dL (≥ 5.6 mmol/L)
  • •Hemoglobin A1c ≤ 9.0%
  • •Negative for hepatitis B surface antigen
  • •Negative for hepatitis C antibody
  • •Males who engage in activity in which conception is possible must use protocol described barrier contraception while on Investigational Product and for at least 28 days after the last dose of Investigational Product.
  • •Females of childbearing potential (FCBP) must have a negative pregnancy test at Screening and Baseline. FCBP who engage in activity in which conception is possible must use protocol described contraception while on Investigational Product and for at least 28 days after taking the last dose or Investigational Product.

排除标准

  • •Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following randomization.
  • •Rheumatic autoimmune disease other than Rheumatoid Arthritis, including systemic lupus erythematosus, mixed connective tissue disease, scleroderma, polymyositis or significant systemic involvement secondary to Rheumatoid Arthritis (eg, vasculitis, pulmonary fibrosis or Felty syndrome). Sjögren syndrome secondary to Rheumatoid Arthritis is allowable.
  • •Functional Class IV as defined by the American College of Rheumatology (ACR) Classification of Functional Status in Rheumatoid Arthritis.
  • •Prior history of, or current, inflammatory joint disease other than Rheumatoid Arthritis (eg, gout, reactive arthritis, psoriatic arthritis, ankylosing spondylitis, Lyme disease).
  • •Receiving treatment with Disease-modifying antirheumatic drugs (DMARDs) (other than methotrexate), including biologic Disease-modifying antirheumatic drugs (DMARDs)Previous use is only allowed after adequate washout prior to randomization.
  • •Inadequate response to treatment with an anti-tumor necrosis factor (anti-TNF) agent. Patients who terminated previous anti-tumor necrosis factor (anti-TNF) treatment due to cost or safety reason, such as discomfort with the subcutaneous injections, may participate in this study after adequate washout.
  • •Treatment with any investigational agent within four weeks (or five half-lives of the investigational drug, whichever is longer) of screening.
  • •Previous treatment with any cell depleting therapies, including investigational agents.
  • •Treatment with intravenous gamma globulin, plasmapheresis or Prosorba® column within 6 months of baseline.
  • •Intra-articular or parenteral corticosteroids are not allowed within 6 weeks prior to randomization.
  • •Any previous treatment with alkylating agents such as cyclophosphamide or chlorambucil, or with total lymphoid irradiation.
  • •Pregnant women or nursing (breast feeding) mothers.
  • •Evidence of serious uncontrolled concomitant cardiovascular, nervous system, pulmonary (including severe or very severe chronic obstructive pulmonary disease), renal, hepatic, endocrine (including uncontrolled diabetes mellitus as defined by Hemoglobin A1c > 9.0%) or gastrointestinal (GI) disease.
  • •Uncontrolled disease states, such as asthma, psoriasis or inflammatory bowel disease, where flares are commonly treated with oral or parenteral corticosteroids.
  • •Known active current or history of recurrent bacterial, viral, fungal, mycobacterial or other infections (including but not limited to tuberculosis and atypical mycobacterial disease, Hepatitis B and C, and herpes zoster, but excluding onychomycosis) or any major episode of infection requiring hospitalization or treatment with IV or oral antibiotics within 4 weeks of screening.
  • •History of positive Human Immunodeficiency Virus (HIV), or congenital or acquired immunodeficiency (eg, Common Variable Immunodeficiency Disease).
  • •History of malignancy, including solid tumors and hematologic malignancies (except basal cell carcinoma of the skin that has been excised and cured).
  • •History of alcohol, drug or chemical abuse within the 6 months prior to screening.
  • •Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study.
  • •Any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study.
  • •Any condition that in the investigator's opinion would interfere significantly with the efficacy evaluations, including the pain and joint assessments (eg, fibromyalgia).
  • •For Magnetic Resonance Imaging (MRI) Only:
  • •Receiving medication(s) or will require medication(s) during the study that impact on vascular flow (eg, nitrates, calcium channel blockers, ergot containing drugs) on the day of the Magnetic Resonance Imaging (MRI test and in the investigator's judgement the subject cannot hold back from taking these medications on the day of the Magnetic Resonance Imaging (MRI) prior to the Magnetic Resonance Imaging (MRI) test. The subject can continue taking the medication(s) at any time after the Magnetic Resonance Imaging (MRI) test is completed, as clinically indicated and scheduled. Exclusions of antihypertensive and migraine medications can be determined after discussion with the Sponsor.
  • •Unable to undergo an Magnetic Resonance Imaging (MRI) examination, including but not limited to the presence of a pacemaker, defibrillator, or other implanted device such as anterior interbody cages, aneurysm clip, pedicle screws, or any other metal contained in the body (eg, such as tattoos that contain metallic pigment, or metal in the eyes from metal grinding [eg, a metal worker, etc]), or severe claustrophobia, or any other contraindication to an Magnetic Resonance Imaging (MRI) as per local imaging center guidelines.
  • •Allergic or adverse reactions to gadolinium
  • •Estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73m2 (based on the Modification of Diet in Renal Disease [MDRD] formula).

研究组 & 干预措施

Apremilast 30 mg

Experimental

干预措施: Apremilast 30 mg (Drug)

Apremilast 20 mg

Experimental

干预措施: Apremilast 20 mg (Drug)

Apremilast 20 mg

Experimental

干预措施: Placebo (Drug)

Placebo

Placebo Comparator

干预措施: Placebo (Drug)

结局指标

主要结局

Percentage of Participants With an American College of Rheumatology 20% Improvement (ACR 20) Response at Week 16

时间窗: Baseline and Week 16

Percentage of participants with an American College of Rheumatology 20% Improvement (ACR 20) response. A participant was a responder if the following 3 criteria for improvement from Baseline were met: * ≥ 20% improvement in 68 tender joint count; * ≥ 20% improvement in 66 swollen joint count; and * ≥ 20% improvement in at least 3 of the 5 following parameters: Subject's assessment of pain (measured on a 100 mm visual analog scale \[VAS\]); Subject's global assessment of disease activity (measured on a 100 mm VAS); Physician's global assessment of disease activity (measured on a 100 mm VAS); Subject's self-assessment of physical function (Health Assessment Questionnaire - Disability Index (\[HAQ-DI\]); C-Reactive Protein.

次要结局

  • Percentage Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 16(Baseline and Week 16)
  • Percentage of Participants Who Achieve Low Disease Activity or Remission Based on the Clinical Disease Activity Index (CDAI) ≤ 10 at Week 16(Baseline and Week 16)
  • Change From Baseline in Disease Activity Score 28 (DAS28) (Using C-Reactive Protein) (CRP) at Week 16(Baseline and Week 16)
  • Percentage Change From Baseline in the Subject Assessment of Pain at Week 16(Baseline and Week 16)
  • Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 16(Baseline and Week 16)
  • Percentage of Participants With an American College of Rheumatology 20% Improvement (ACR 20) Response at Week 24(Baseline and Week 24)
  • Percentage Change From Baseline in the Subject Global Assessment of Disease Activity at Week 16(Baseline and Week 16)
  • Change From Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 16(Baseline and Week 16)
  • Percentage of Participants Who Achieve an Improvement of at Least 4 Units From Baseline in the Functional Assessment of Chronic Illness Therapy -Fatigue (FACIT-Fatigue) at Week 16(Baseline and Week 16)
  • Percentage Change From Baseline in the Subject Assessment of Pain at Week 24(Baseline and Week 24)
  • Change From Baseline in the Medical Outcome Study Short Form 36-item (SF-36) Physical Functioning Domain at Week 16(Baseline and Week 16)
  • Change From Baseline in the Clinical Disease Activity Index (CDAI) at Week 16(Baseline and Week 16)
  • Percentage Change From Baseline in the Tender Joint Count at Week 16(Baseline and Week 16)
  • Percentage Change From Baseline in the Physician Global Assessment of Disease Activity at Week 16(Baseline and Week 16)
  • Percentage Change From Baseline in the High Sensitivity C-Reactive Protein (CRP) at Week 16(Baseline and Week 16)
  • Change From Baseline in Disease Activity Score 28 (DAS28) Using CRP at Week 24(Baseline and Week 24)
  • Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Week 24(Baseline and Week 24)
  • Percentage Change From Baseline in the Swollen Joint Count at Week 16(Baseline and Week 16)
  • Percentage of Participants Who Achieve the European League Against Rheumatism (EULAR) Response Criteria Using CRP at Week 16(Baseline and Week 16)
  • Percentage of Participants With an American College of Rheumatology 50% Improvement (ACR 50) Response at Week 16(Baseline and Week 16)
  • Change From Baseline in the Medical Outcome Study Short Form 36-item (SF-36) Physical Functioning Domain at Week 24(Baseline and Week 24)
  • Percentage Change From Baseline in the Tender Joint Count at Week 24(Baseline and Week 24)
  • Percentage Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Week 16(Baseline and Week 16)
  • Percentage of Participants Who Achieve an Improvement of ≥ 0.22 Units From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 16(Baseline and Week 16)
  • Percentage Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Week 24(Baseline and Week 24)
  • Percentage of Participants Who Achieve the European League Against Rheumatism (EULAR) Response Criteria Using CRP at Week 24(Baseline and Week 24)
  • Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Week 52(Baseline and Week 52)
  • Change From Baseline in the Clinical Disease Activity Index (CDAI) at Week 52(Baseline and Week 52)
  • Percentage Change From Baseline in the Subject Global Assessment of Disease Activity at Week 52(Baseline and Week 52)
  • Percentage of Participants With an American College of Rheumatology 70% Improvement (ACR 70) Response at Week 16(Baseline and Week 16)
  • Percentage of Participants With an American College of Rheumatology 50% Improvement (ACR 50) Response at Week 24(Baseline and Week 24)
  • Percentage of Participants With an American College of Rheumatology 70% Improvement (ACR 70) Response at Week 24(Baseline and Week 24)
  • Change From Baseline in the Clinical Disease Activity Index (CDAI) at Week 24(Baseline and Week 24)
  • Percentage of Participants Who Achieve Low Disease Activity or Remission Based on the Clinical Disease Activity Index (CDAI) ≤ 10 at Week 24(Baseline and Week 24)
  • Percentage Change From Baseline in the Swollen Joint Count at Week 24(Baseline and Week 24)
  • Percentage Change From Baseline in the Physician Global Assessment of Disease Activity at Week 24(Baseline and Week 24)
  • Percentage Change From Baseline in the High Sensitivity C-Reactive Protein (CRP) at Week 24(Baseline and Week 24)
  • Percentage Change From Baseline in the Tender Joint Count at Week 52(Baseline and Week 52)
  • Percentage Change From Baseline in the Subject Assessment of Pain at Week 52(Baseline and Week 52)
  • Percentage of Participants Who Achieve an Improvement of ≥ 0.22 Units From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 52(Baseline and Week 52)
  • Percentage of Participants With an American College of Rheumatology 70% Improvement (ACR 70) Response at Week 52(Baseline and Week 52)
  • Percentage of Participants Who Achieve an Improvement of at Least 4 Units From Baseline in the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) at Week 52(Baseline and Week 52)
  • Percentage Change From Baseline in the Subject Global Assessment of Disease Activity at Week 24(Baseline and Week 24)
  • Change From Baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score at Week 24(Baseline and Week 24)
  • Percentage of Participants Who Achieve an Improvement of at Least 4 Units From Baseline in the Functional Assessment of Chronic Illness Therapy -Fatigue (FACIT-Fatigue) at Week 24(Baseline and Week 24)
  • Change From Baseline in the Medical Outcome Study Short Form 36-item (SF-36) Physical Functioning Domain at Week 52(Baseline and Week 52)
  • Percentage of Participants Who Achieve Low Disease Activity or Remission Based on the Clinical Disease Activity Index (CDAI) ≤ 10 at Week 52(Baseline and Week 52)
  • Percentage Change From Baseline in the Physician Global Assessment of Disease Activity at Week 52(Baseline and Week 52)
  • Percentage Change From Baseline in the Health Assessment Questionnaire - Disability Index (HAQ-DI) Score at Week 52(Baseline and Week 52)
  • Change From Baseline in the Clinical Disease Activity Index (CDAI) at Year 2(Baseline and Year 2)
  • Percentage Change From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) Score at Week 24(Baseline and Week 24)
  • Percentage Change From Baseline in the Swollen Joint Count at Week 52(Baseline and Week 52)
  • Change From Baseline in the FACIT-Fatigue Scale Score at Week 52(Baseline and Week 52)
  • Percentage of Participants Who Achieve the European League Against Rheumatism (EULAR) Response Criteria Using CRP at Week 52(Baseline and Week 52)
  • Percentage of Participants With an American College of Rheumatology 20% Improvement (ACR 20) Response at Year 2(Baseline and Year 2)
  • Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Year 2(Baseline and Year 2)
  • Percentage of Participants Who Achieve an Improvement of ≥ 0.22 Units From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 24(Baseline and Week 24)
  • Percentage of Participants With an American College of Rheumatology 20% Improvement (ACR 20) Response at Week 52(Baseline and Week 52)
  • Change From Baseline in the Disease Activity Score 28 (DAS 28) Using CRP at Week 52(Baseline and Week 52)
  • Percentage Change From Baseline in the High Sensitivity C-Reactive Protein (CRP) at Week 52(Baseline and Week 52)
  • Percentage Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Week 52(Baseline and Week 52)
  • Percentage of Participants With an American College of Rheumatology 50% Improvement (ACR 50) Response at Week 52(Baseline and Week 52)
  • Change From Baseline in the Medical Outcome Study Short Form 36-item (SF-36) Physical Functioning Domain at Year 2(Baseline and Year 2)
  • Change From Baseline in Disease Activity Score 28 (DAS28) (Using C-Reactive Protein) (CRP) at Year 2(Baseline and Year 2)
  • Percentage of Participants With an American College of Rheumatology 50% Improvement (ACR 50) Response at Year 2(Baseline and Year 2)
  • Percentage of Participants Who Achieve Low Disease Activity or Remission Based on the Clinical Disease Activity Index (CDAI) ≤ 10 at Year 2(Baseline and Year 2)
  • Percentage Change From Baseline in the Individual American College of Rheumatology Components at Year 2(Baseline and Year 2)
  • Change From Baseline in the Functional Assessment of Chronic Illness Therapy -Fatigue (FACIT-Fatigue) at Year 2(Baseline and Year 2)
  • Percentage of Participants Who Achieve the European League Against Rheumatism (EULAR) Response Criteria Using CRP at Year 2(Baseline and Year 2)
  • Percentage of Participants Who Achieve an Improvement of ≥ 0.22 Units From Baseline in the Health Assessment Questionnaire-Disability Index (HAQ-DI) at Year 2(Baseline and Year 2)
  • Percentage of Participants With an American College of Rheumatology 70% Improvement (ACR 70) Response at Year 2(Baseline and Year 2)
  • Percentage of Participants Who Achieve an Improvement of at Least 4 Units From Baseline in the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue) at Year 2(Baseline and Year 2)

研究者

发起方
Amgen
申办方类型
Industry
责任方
Sponsor

研究点 (48)

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