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临床试验/NCT02996500
NCT02996500已完成2 期

A 12 WEEK RANDOMIZED, DOUBLE-BLIND, DOUBLE DUMMY, PARALLEL GROUP, ACTIVE AND PLACEBO-CONTROLLED, MULTICENTER STUDY TO ASSESS THE EFFICACY AND SAFETY PROFILE OF PF-06650833 IN SUBJECTS WITH ACTIVE RHEUMATOID ARTHRITIS WITH AN INADEQUATE RESPONSE TO METHOTREXATE

Pfizer99 个研究点 分布在 11 个国家目标入组 269 人开始时间: 2016年11月10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
已完成
发起方
Pfizer
入组人数
269
试验地点
99
主要终点
Change From Baseline in the Simplified Disease Activity Index (SDAI) at Week 12
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

This is a Phase 2, multicenter, randomized, double blind, double dummy, placebo and active-controlled, parallel group study to assess the efficacy and safety of PF 06650833 at Week 12 in subjects with moderate-severe, active, RA who have had an inadequate response to MTX. PF-06650833 or matching placebo tablets will be administered orally QD under fasting conditions, and tofacitinib or matching tofacitinib placebo tablets will be administered orally BID for 12 weeks in a blinded fashion.

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 75 Years（Adult, Older Adult）
性别
All
接受健康志愿者
否

入选标准

  • •Male and female (including WOCBP) subjects between the ages of 18 and 75 years, inclusive.
  • •Diagnosis of RA and meeting the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria for RA with a Total Score ≥6/
  • •The subject has active disease at both Screening and Baseline, as defined by both:
  • •6 joints tender or painful on motion, AND
  • •6 joints swollen; and fulfills 1 of the following 2 criteria at Screening:
  • •High sensitivity C reactive protein (hsCRP) >7 mg/L at screening
  • •Erythrocyte sedimentation rate (ESR) (Westergren method) >28 mm/hr;
  • •Meets Class I, II or III of the ACR 1991 Revised Criteria for Global Functional Status in RA.
  • •Subjects must be ACPA positive between screening and randomization.
  • •Subjects must have been taking oral MTX for at least 3 months at an adequate dose to determine that the subject had an inadequate response to MTX
  • •Up to 50 % of subjects may have received one (and only one) approved TNF-inhibiting biologic agent administered that was inadequately effective and/or not tolerated. The anti-TNF biologic could also have been discontinued due to lack of continued access.

排除标准

  • •Subjects with a known immunodeficiency disorder or a first degree relative with a hereditary immunodeficiency.
  • •Subjects with any of the following infections or infections history:
  • •Any infection requiring treatment within 2 weeks prior to screening (Visit 1).
  • •Any infection requiring hospitalization, parenteral antimicrobial therapy within 60 days, or as otherwise judged to be an opportunistic infection or clinically significant by the investigator, within the past 6 months.
  • •Infected joint prosthesis at any time with the prosthesis still in situ.
  • •Recurrent (more than one episode) herpes zoster or disseminated (a single episode) herpes zoster or disseminated (a single episode) herpes simplex.
  • •Subjects will be screened for HIV. Subjects who test positive for HIV will be excluded from the study.
  • •Subjects will be screened for hepatitis B virus infection and will be excluded if positive for hepatitis B surface antigen (HBsAg). Subjects with HBsAg negative testing but who test positive for hepatitis B core antibody (HBcAb) must have further testing for hepatitis B surface antibody (HBsAb). If HBsAb is negative, the subject will be excluded from the study.
  • •Subjects with clinically significant active hepatic disease or hepatic impairment by laboratory assessment.
  • •Subjects will be screened for hepatitis C virus (HCV Ab). Subjects with positive HCV Ab tests will be reflex tested for HCV ribonucleic acid (HCV RNA). Only subjects with negative HCV Ab or HCV RNA will be allowed to enroll in the study.
  • •Evidence of active or latent, untreated or inadequately treated infection with Mycobacterium tuberculosis (TB)
  • •Pre-existing chronic autoimmune disease.

研究组 & 干预措施

Arm 1: 20 mg QD

Experimental

PF-06650833 , 20 mg QD

干预措施: PF-06650833 (Drug)

Arm 2: 60 mg QD

Experimental

PF-06650833, 60 mg QD

干预措施: PF-06650833 (Drug)

Arm 3: 200 mg QD

Experimental

Pf-06650833, 200 mg QD

干预措施: PF-06650833 (Drug)

Arm 4: 400 mg QD

Experimental

PF-06650833, 400 mg QD

干预措施: PF-06650833 (Drug)

Placebo

Placebo Comparator

Placebo, 0 mg BID

干预措施: Placebo (Drug)

Arm 5: Tofacitinib

Active Comparator

Tofacitinib 5 mg BID

干预措施: Tofacitinib (Drug)

结局指标

主要结局

Change From Baseline in the Simplified Disease Activity Index (SDAI) at Week 12

时间窗: Baseline and Week 12

The SDAI is a continuous composite measure derived from components of the American College of Rheumatology (ACR) Core Dataset.The SDAI was calculated using the following formula: SDAI = Tender / Painful Joint Count(TJC) (using 28 joints) + Swollen Joint Count (SJC) (using 28 joints) + Patient Global Assessment of Arthritis (PtGA) (0-10 cm scale) + Physician's Global Assessment of Arthritis (PhGA) (0-10 cm scale) + high sensitivity C-reactive protein (hsCRP) (mg/dL). SDAI total score= 0-86. SDAI \<=3.3 indicates disease remission, \>3.4 to 11 = low disease activity, \>11 to 26 = moderate disease activity, and \>26 = high disease activity. The primary analysis utilized a Bayesian ANCOVA model with an informative placebo prior distribution with borrowing from tofacitinib historical placebo data. The confidence interval was credible interval in this statistical analysis. The efficacy endpoint for the tofatinicib arm was an exploratory endpoint and neither primary nor secondary endpoints.

次要结局

  • Change From Baseline in SDAI at Weeks 4 and 8(Baseline, Weeks 4 and 8)
  • Percentage of Participants With SDAI Low Disease Activity Score (LDAS) (SDAI <=11) at 4, 8, and 12 Weeks(Weeks 4, 8 and 12)
  • Percentage of Participants With SDAI Remission (SDAI <=3.3) at 4, 8, and 12 Weeks(Weeks 4, 8 and 12)
  • Percentage of Participants With DAS28-3 (CRP) LDAS (DAS28 <3.2) at 4, 8, and 12 Weeks(Weeks 4, 8 and 12)
  • Percentage of Participants With DAS28-4 (CRP) Remission (DAS28 <2.6) at 4, 8 and 12 Weeks(Weeks 4, 8 and 12)
  • Change From Baseline in DAS28-4 (ESR) at 4, 8 and 12 Weeks(Baseline, Weeks 4, 8 and 12)
  • Change From Baseline in DAS28-3 (ESR) at 4, 8 and 12 Weeks(Baseline, Weeks 4, 8 and 12)
  • Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response at 4, 8 and 12 Weeks(Weeks 4, 8 and 12)
  • Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response at 4, 8 and 12 Weeks(Weeks 4, 8 and 12)
  • Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response at 4, 8 and 12 Weeks(Weeks 4, 8 and 12)
  • Change From Baseline in the Tender/Painful and Swollen Joint Counts at 4, 8 and 12 Weeks(Baseline, Weeks 4, 8 and 12)
  • Percentage of Participants With Disease Activity Score-28 (4 Components Based on Erythrocyte Sedimentation Rate) (DAS28-4 [ESR]) LDAS (DAS28 <3.2) at 4, 8, and 12 Weeks(Weeks 4, 8 and 12)
  • Percentage of Participants With DAS28-3 (ESR) Remission (DAS28 <2.6) at 4, 8 and 12 Weeks(Weeks 4, 8 and 12)
  • Percentage of Participants With DAS28-3 (ESR) LDAS (DAS28 <3.2) at 4, 8, and 12 Weeks(Weeks 4, 8 and 12)
  • Percentage of Participants With Disease Activity Score-28 (4 Components Based on High-Sensitivity C-Reactive Protein) (DAS28-4 [CRP]) LDAS (DAS28 <3.2) at 4, 8, and 12 Weeks(Weeks 4, 8 and 12)
  • Percentage of Participants With DAS28-4 (ESR) Remission (DAS28 <2.6) at 4, 8 and 12 Weeks(Weeks 4, 8 and 12)
  • Percentage of Participants With DAS28-3 (CRP) Remission (DAS28 <2.6) at 4, 8 and 12 Weeks(Weeks 4, 8 and 12)
  • Change From Baseline in DAS28-4 (CRP) at 4, 8 and 12 Weeks(Baseline, Weeks 4, 8 and 12)
  • Change From Baseline in DAS28-3 (CRP) at 4, 8 and 12 Weeks(Baseline, Weeks 4, 8 and 12)
  • Change From Baseline in High-Sensitivity C-Reactive Protein (Hs-CRP) at 4, 8 and 12 Weeks(Baseline, Weeks 4, 8 and 12)
  • Change From Baseline in the Physician's Global Assessment of Arthritis (PhGA) at 4, 8, and 12 Weeks(Baseline, Weeks 4, 8 and 12)
  • Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Treatment-Related TEAEs(Baseline up to 28 calendar days after the last administration of the investigational product (about 21 months))
  • Number of Participants With Vital Signs Data Meeting Pre-sepcified Criteria(Baseline up to 28 calendar days after the last administration of the investigational product (about 21 months))
  • Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-sepcified Criteria(Baseline up to 28 calendar days after the last administration of the investigational product (about 21 months))
  • Change From Baseline in the Health Assessment Questionnaire - Disability Index (HAQ-DI) at Weeks 4, 8, and 12(Baseline, Weeks 4, 8 and 12)
  • Number of Participants With Laboratory Abnormalities (Without Regard to Baseline Abnormality)(Baseline up to 28 calendar days after the last administration of the investigational product (about 21 months))
  • Change From Baseline in the Patient Global Assessment of Arthritis (PtGA) VAS at Weeks 4, 8, 12(Baseline, Weeks 4, 8 and 12)
  • Number of Participants With Urinalysis Data Meeting Pre-specified Criteria(Baseline up to 28 calendar days after the last administration of the investigational product (about 21 months))
  • Change From Baseline in the Patient's Assessment of Arthritis Pain (PAAP) Visual Analogue Scale (VAS) at Weeks 4, 8, 12(Baseline, Weeks 4, 8 and 12)
  • Change From Baseline in the 36 Item Short Form Health Survey (SF-36) Version 2 (Acute) 8 Domain Scores at Week 12(Baseline and Week 12)
  • Change From Baseline in the Physical Component Score (PCS) and Mental Component Score (MCS) at Week 12(Baseline and Week 12)
  • Change From Baseline in the European Quality of Life 5 Dimensions-3 Level (EQ-5D-3L) Score at Week 12(Baseline and Week 12)
  • Change From Baseline in the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Total Score at Week 12(Baseline and Week 12)

研究者

发起方
Pfizer
申办方类型
Industry
责任方
Sponsor

研究点 (99)

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