NCT04413617已完成2 期
A 24-WEEK RANDOMIZED, DOUBLE-BLIND, PARALLEL GROUP, ACTIVE COMPARATOR, MULTICENTER STUDY TO ASSESS THE EFFICACY AND SAFETY OF PF-06650833, PF-06651600 (RITLECITINIB) AND TOFACITINIB ALONE AND IN COMBINATION IN PARTICIPANTS WITH MODERATELY-SEVERELY ACTIVE RHEUMATOID ARTHRITIS WITH AN INADEQUATE RESPONSE TO METHOTREXATE
适应症
干预措施
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 460
- 试验地点
- 143
- 主要终点
- Change From Baseline (BL) in Disease Activity Score (DAS)28-C Reactive Protein (CRP) at Week 12
研究概览
简要总结
Dual objectives of increased efficacy compared to currently available SoC RA drugs and maintaining a favourable benefit - risk relationship.
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 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female participants between the ages of 18 and 70 years.
- •Participants who are willing and able to comply with all scheduled visits, treatment plan, laboratory tests, lifestyle considerations, and other study procedures.
- •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 participant has active disease at both Screening and Randomization, as defined by both: ≥6 joints tender or painful on motion, AND ≥6 joints swollen; and fulfills 1 of the following 2 criteria: High sensitivity C reactive protein (hsCRP) >7 mg/L at Screening (Visit 1) as performed by the central laboratory OR Erythrocyte sedimentation rate (ESR) (Westergren method) >28 mm h.
排除标准
- •Other acute or chronic medical or psychiatric condition including recent (within the past year) or active suicidal ideation or behavior or laboratory abnormality that may increase the risk associated with study participation or IP administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study.
- •Participants with a known immunodeficiency disorder or a first degree relative with a hereditary immunodeficiency.
- •Participants with any active or latent infections.
- •Participants with positive hepatitis B surface antigen (HBsAg).
- •Participants with positive HCV Ab tests will be reflex tested for HCV ribonucleic acid (HCV RNA).
- •Any history of either untreated or inadequately treated latent or active tuberculosis (TB) infection, current treatment for active or latent TB infection or evidence of currently active TB,
- •History of a major organ transplant (eg, heart, lung, kidney and liver) or hematopoietic stem cell/marrow transplant.
- •History of severe allergic or anaphylactoid reaction to kinase inhibitors, or corticosteroid preparations.
- •Known history of diverticulitis or symptomatic diverticulosis, perineal abscess or fistulae.
- •Participants with malignancy or history of malignancy (including lymphoma, leukemia, or lymphoproliferative disease).
- •Pre-existing chronic autoimmune disease (eg, inflammatory bowel disease, systemic lupus erythematosus, moderate-severe atopic dermatitis, dermatomyositis) other than RA. Secondary Sjogren's Syndrome (due to RA) may be included.
- •Participants with fibromyalgia will be excluded.
- •Previous treatment with total lymphoid irradiation.
- •Participants with an oral, tympanic, or temporal temperature of 38°C (100.4°F) or higher at baseline.
- •Participants may not receive any live/attenuated vaccine from 30 days prior to randomization during the course of the study, or for 30 days after the last dose of study medication. Participants who have current routine household contact with children who have received varicella or oral polio vaccine within 2 months of first study dose are also excluded.
- •History of any lymphoproliferative disorder.
- •Have hearing loss with progression over the previous 5 years, sudden hearing loss, or middle or inner ear disease.
- •History of any prior deep vein thrombosis (DVT) or pulmonary embolism [PE].
- •Recent (within 6 months of screening) myocardial infarction, coronary revascularization, or percutaneous angioplasty with or without placement of a coronary artery stent; acute coronary syndrome; chronic uncompensated heart failure or New York Heart Association Functional Class III or IV; left ventricular assist devices; implanted defibrillators.
- •Current severe chronic renal insufficiency or renal failure as defined by persistent (on repeated measurements) eGFR <60 mL/min per 1.73 m2 based on the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) calculation.
- •Any known coagulopathy or hypercoagulant syndrome.
- •Presence of any of the following laboratory abnormalities at screening or within the 3 months prior to first study dose:
- •Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels ≥1.5 x the upper limit of normal (ULN); Participants with a history of Gilbert's syndrome may have a direct bilirubin measured and would be eligible for this study provided the direct bilirubin is ≤ ULN and other liver function assessments are normal; Absolute neutrophil count of <1.5 x 109/L (<1500/mm3). Participants with cyclic (benign ethnic) neutropenia will be excluded; Absolute lymphocyte count of <0.5 x 109/L (<500/mm3); Absolute white blood cell (WBC) count of <3.0 x 109/L (<3000/mm3); Hemoglobin <9.0 g/dL (90 g/L); Platelet count ≤100 x 109/L (100,000 cells/mm3) or ≥1000 x 109/L (1,000,000 cells/mm3); Thrombocytopenia, as defined by a platelet count <100 x 109/L (<100,000/mm3) at screening visit or within the 3 months prior to first study dose. [Screening laboratory tests with abnormal results may be repeated once to confirm abnormal results. If results return to normal protocol acceptable limits within the 4-week screening period, the participant may enter the study].
- •Grade 3 or greater laboratory abnormality based on the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 toxicity scale, except for the following that are allowed: Grade 3 prothrombin time (PT) secondary to warfarin treatment; Grade 3 partial thromboplastin time (PTT) due to lupus anticoagulant and not related to liver disease or anti-coagulant therapy.
- •Participants previously treated with a biologic DMARD (except for up to 25% of participants who may have been treated with 1, and only 1 prior TNF inhibitor) or any other recent DMARD treatment (eg, a JAK inhibitor), or participants currently treated with any other prohibited medications will be excluded.
- •Prior use of tofacitinib or other JAK inhibitor in the context of a clinical trial is excluded. Concomitant use of tofacitinib (other than as prescribed by the randomization scheme) or other JAK inhibitor is prohibited.
- •Participants who have previously been treated with other, non-TNFa inhibiting biologic DMARDs [including, abatacept (Orencia®), tocilizumab (Actemra®), Sarilumab (Kevzara®), anakinra (Kineret®), rituximab (Rituxan®) or other selective B lymphocyte depleting agents, or other lymphocyte depleting agents/therapies (such as alemtuzab [CamPath®], natalizumab (Tysabri®), alkylating agents [eg, cyclophosphamide or chlorambucil], total lymphoid irradiation) are excluded from participation in the study.
- •Previous administration with an investigational drug within 30 days (or as determined by the local requirement) or 5 half-lives preceding the first dose of IP used in this study (whichever is longer).
- •Any 12-lead electrocardiogram (ECG) performed prior to randomization that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results.
研究组 & 干预措施
PF-06651600
Experimental
干预措施: PF-06651600 (Drug)
PF-06650833 + tofacitinib
Experimental
干预措施: PF-06650833 (Drug)
PF-06650833 + tofacitinib
Experimental
干预措施: Tofacitinib (Drug)
PF-06650833 + PF-06651600
Experimental
干预措施: PF-06650833 (Drug)
PF-06650833 + PF-06651600
Experimental
干预措施: PF-06651600 (Drug)
PF-06650833
Experimental
干预措施: PF-06650833 (Drug)
Tofacitinib
Experimental
干预措施: Tofacitinib (Drug)
结局指标
主要结局
Change From Baseline (BL) in Disease Activity Score (DAS)28-C Reactive Protein (CRP) at Week 12
时间窗: BL (defined as the last non-missing measurement collected prior to the first administration of study drug on Day 1), Week 12
DAS28 is a measure based on assessment of 28 joints for tenderness and swelling (tender and swollen joint counts). Disease Activity Score 28-C reactive protein (DAS28-CRP) is derived using differential weighting given to 4 components: tender joint count (range: 0-28), swollen joint count (range: 0-28), patient global assessment (recorded on a visual analog scale \[VAS\] scale of 0-100 mm), and CRP (milligram per liter). DAS28-CRP score ranges from 0 to 9.4. The lower the DAS28-CRP score is, the better the participant has response (remission = score\<2.6, low disease activity = score≤3.2). A negative value in change from BL indicates an improvement. Mixed Model Repeated Measures was used for statistical analysis, which used the change from BL of DAS28-CRP as an outcome and treatment, scheduled study visit, BL value of DAS28-CRP, treatment by visit interaction and BL by visit interaction as fixed effects. The model used the unstructured covariance matrix.
次要结局
- DAS28-CRP Remission (<2.6) Rates at Week 24(Week 24)
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs), and Withdrawals Due to TEAEs(From first dose of study intervention (Day 1) to Week 28)
- Number of Participants With Clinical Laboratory Abnormalities (Hematology and Chemistry, Without Regard to Baseline Abnormality)(From BL to Week 28)
- Number of Participants With Change From Baseline in Vital Signs Data Meeting the Pre-defined Categorical Summarization Criteria(From BL to Week 28)
- Number of Participants With Adverse Events of Special Interest(From first dose of study intervention (Day 1) to Week 28)
- Change From Baseline in DAS28-CRP at Week 24(BL (defined as the last non-missing measurement collected prior to the first administration of study drug on Day 1), Week 24)
- American College of Rheumatology (ACR)20, ACR 50, ACR 70, and ACR 90 Responder Rates at Week 12 and Week 24(BL (defined as the last non-missing measurement collected prior to the first administration of study drug on Day 1), Week 12, Week 24)
- Change From Baseline in the Tender/Painful and Swollen Joint Count at Week 12 and Week 24(BL (defined as the last non-missing measurement collected prior to the first administration of study drug on Day 1), Week 12, Week 24)
- Change From Baseline in the Physician's Global Assessment (PhGA) of Arthritis at Week 12 and Week 24(BL (defined as the last non-missing measurement collected prior to the first administration of study drug on Day 1), Week 12, Week 24)
研究者
研究点 (143)
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