A Phase II Open-Label Extension Study of Patients Previously Enrolled in Study GA29350 to Evaluate the Long-Term Safety and Efficacy of GDC-0853 in Patients With Moderate to Severe Rheumatoid Arthritis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 496
- 试验地点
- 104
- 主要终点
- Percentage of Participants With Adverse Events (AEs)
研究概览
简要总结
A study to evaluate the long-term safety and efficacy of GDC-0853 in participants with moderate to severe active Rheumatoid Arthritis (RA) who have completed 12 weeks of study treatment in Study GA29350. Eligible participants from Study GA29350 who elect to participate will receive treatment with GDC-0853 twice daily (BID) in an open-label fashion for 52 weeks, followed by a safety follow-up period of 8 weeks.
研究设计
- 研究类型
- Interventional
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 76 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Completion of treatment as specified in Study GA29350, including completion of the Day 84 study visit assessments
- •Acceptable safety and tolerability during Study GA29350 as determined by the investigator or Medical Monitor
- •Have not received any prohibited medications in Study GA29350
- •While taking methotrexate, must be willing to receive oral folic acid (at least 5 milligrams per week [mg/week])
- •If receiving oral corticosteroids (less than or equal to [</=] 10 milligrams per day [mg/day] prednisone or equivalent) and/or non-steroidal anti-inflammatory drugs, doses have remained stable for the duration of Study GA29350
排除标准
- •Met protocol defined treatment stopping criteria during Study GA29350
- •Treatment with any investigational agent (i.e., other than study drug) or live/attenuated vaccine or any other prohibited medication during Study GA29350 or since the last administration of study drug in Study GA29350
- •In the opinion of the investigator, any new (since initially enrolling in the Phase II Study GA29350), significant, uncontrolled comorbidity that would increase the risk to the participant in Study GA30067
- •Pregnant or lactating, or intending to become pregnant during the study
- •Participants who experienced a de novo or reactivated serious viral infection such as hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) during the Phase II Study GA29350
- •Any major episode of infection requiring hospitalization or treatment with intravenous antibiotics during the Phase II Study GA29350
- •Participants who developed a malignancy during the Phase II Study GA29350
- •12-lead electrocardiogram (ECG) on Day 84 in Study GA29350 that demonstrates clinically relevant abnormalities that may affect participant safety or interpretation of study results
- •Current treatment with medications that are well known to prolong the QT interval
研究组 & 干预措施
GDC-0853 (200mg BID) Cohort 1
Participants received GDC-0853 orally twice daily (BID) for 52 weeks, after completing 12 weeks in Cohort 1 of Study GA29350. Cohort 1 participants in GA29350 were enrolled with moderate to severe active Rheumatoid Arthritis (RA) and an inadequate response to previous methotrexate (MTX) therapy and then randomized to 12 weeks of GDC-0853 (50 mg daily, 150 mg daily, or 200 mg BID), adalimumab, or placebo.
干预措施: GDC-0853 (Drug)
GDC-0853 (200mg BID) Cohort 2
Participants received GDC-0853 orally twice daily (BID) for 52 weeks, after completing 12 weeks in Cohort 2 of Study GA29350. Cohort 2 participants in GA29350 were enrolled with moderate to severe active Rheumatoid Arthritis (RA) and an inadequate response to one or two tumor necrosis factor (TNF) inhibitors and methotrexate (MTX) therapy, and then randomized to 12 weeks of GDC-0853 (200 mg BID) or placebo.
干预措施: GDC-0853 (Drug)
结局指标
主要结局
Percentage of Participants With Adverse Events (AEs)
时间窗: Day 1 up until 8 weeks after the last dose of study drug (up to 1 year, 2 months)
An Adverse Event (AE) was considered any unfavorable and unintended sign, symptom, or disease associated with the use of the study drug, whether or not considered related to the study drug. Preexisting conditions that worsened during the study were reported as adverse events.
Percentage of Participants Achieving American College of Rheumatology 50% (ACR50) Response at Week 52
时间窗: Week 52
ACR50 response is defined as a ≥ 50% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant \[either C-reactive protein or Erythrocyte Sedimentation Rate\].
次要结局
- Percentage of Participants Achieving ACR50 Response up to Week 12(Weeks 4, 8 and 12)
- Percentage of Participants Achieving American College of Rheumatology 20% (ACR20) Response(Weeks 4, 8, 12, 24, 36 and 52)
- Percentage of Participants Achieving American College of Rheumatology 70% (ACR70) Response(Weeks 4, 8, 12, 24, 36 and 52)
- Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (3 Variables) (DAS28-3 CRP)(Baseline, Weeks 4, 8, 12, 24, 36 and 52)
- Disease Activity Score Based on 28-Joints Count and C-Reactive Protein (4 Variables) (DAS28-4 CRP)(Baseline, Weeks 4, 8, 12, 24, 36 and 52)
- Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (3 Variables) (DAS28-3 ESR)(Baseline, Weeks 4, 8, 12, 24, 36 and 52)
- Disease Activity Score Based on 28-Joints Count and Erythrocyte Sedimentation Rate (4 Variables) (DAS28-4 ESR)(Baseline, Weeks 4, 8, 12, 24, 36 and 52)
- Percentage of Participants With Remission Based on Disease Activity Score Based on 28-Joints Count (DAS28)(Weeks 4, 8, 12, 24, 36 and 52)
- Percentage of Participants With Low Disease Activity (LDA) Based on DAS28(Weeks 4, 8, 12, 24, 36 and 52)
- Percentage of Participants With ACR/EULAR Remission(Weeks 4, 8, 12, 24, 36 and 52)
- Change From Baseline in Simplified Disease Activity Index (SDAI)(Weeks 4, 8, 12, 24, 36 and 52)
- Change From Baseline in Clinical Disease Activity Index (CDAI)(Weeks 4, 8, 12, 24, 36 and 52)
- Change From Baseline in Tender/Painful Joint Count Based on 68 Joints(Weeks 4, 8, 12, 24, 36 and 52)
- Change From Baseline in Swollen Joint Count Based on 66 Joints(Weeks 4, 8, 12, 24, 36 and 52)
- Change From Baseline in Patient's Assessment of Arthritis Pain, Using Visual Analog Scale (VAS) Score(Weeks 4, 8, 12, 24, 36 and 52)
- Change From Baseline in Patient's Global Assessment of Arthritis, Using VAS Score(Weeks 4, 8, 12, 24, 36 and 52)
- Change From Baseline in Physician's Global Assessment of Arthritis, Using VAS Score(Weeks 4, 8, 12, 24, 36 and 52)
- Change From Baseline in C-Reactive Protein (CRP) Levels(Weeks 4, 8, 12, 24, 36 and 52)
- Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) Score(Weeks 4, 8, 12, 24, 36 and 52)
- Change From Baseline in 36-Item Short-Form Health Survey (SF-36) Version 2.0 (V2) Scores for Physical and Mental Components(Weeks 12, 24 and 52)
- Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score(Weeks 12, 24 and 52)
- Area Under the Concentration Time Curve (AUC) of GDC-0853 at Steady State (AUC,ss)(Pre-dose (0 hour) on Weeks 0 (Day 1), 4, 12, 24, 36, and 52/early termination)
- Minimum Plasma Concentration of GDC-0853 at Steady State (Ctrough,ss)(Pre-dose (0 hour) on Weeks 0 (Day 1), 4, 12, 24, 36, and 52/early termination)
- Plasma Decay Half-Life of GDC-0853 at Steady State (t1/2,ss)(Pre-dose (0 hour) on Weeks 0 (Day 1), 4, 12, 24, 36, and 52/early termination)
- Apparent Oral Clearance of GDC-0853 at Steady State (CL/F,ss)(Pre-dose (0 hour) on Weeks 0 (Day 1), 4, 12, 24, 36, and 52/early termination)