A Phase II, Randomized, Double-blind, Placebo-controlled Study of the Safety and Efficacy of GDC-0853 in Patients With Moderate to Severe Active Systemic Lupus Erythematosus
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 260
- 试验地点
- 69
- 主要终点
- Systemic Lupus Erythematosus Responder Index (SRI)-4 Response at Week 48
研究概览
简要总结
This is a study to evaluate the safety and efficacy of GDC-0853 in combination with standard of care therapy in participants with moderate to severe active systemic lupus erythematosus (SLE).
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
- Double (Participant, Investigator)
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
- •Fulfillment of SLE classification criteria according to either American College of Rheumatology (ACR) or Systemic Lupus International Collaborating Clinics (SLICC) criteria at any time prior to or at screening
- •At least one serologic marker of SLE at screening as follows: positive antinuclear antibody (ANA) test by immunofluorescent assay with titer >/= 1:80; or positive anti-double-stranded DNA (anti-dsDNA) antibodies; or positive anti-Smith antibody
- •At both screening and Day 1, moderate to severe active SLE, defined as meeting all of the following unless indicated otherwise: Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score ≥ 8 (at screening only) with clinical SLEDAI-2K score >/= 4.0 (at both screening and Day 1), Physician's Global Assessment >/= 1.0 (out of 3), and currently receiving at least one standard oral treatment for SLE
- •If on oral corticosteroids (OCS), the dose must be </= 40 mg/day prednisone (or equivalent)
- •Stable doses of anti-malarial or immunosuppressive therapies
- •Participants must be willing to avoid pregnancy
排除标准
- •Proteinuria > 3.5 g/24 h or equivalent using urine protein-to-creatinine ratio (uPCR) in a first morning void urine sample
- •Active proliferative lupus nephritis (as assessed by the investigator) or histological evidence of active Class III or Class IV lupus nephritis on renal biopsy performed in the 6 months prior to screening (or during the screening period)
- •History of having required hemodialysis or high dose corticosteroids (>100 mg/d) prednisone or equivalent) for the management of lupus renal disease within 90 days of Day 1
- •Neuropsychiatric or central nervous system lupus manifestations
- •Serum creatinine > 2.5 mg/dL, or estimated glomerular-filtration rate < 30 milliliter per minute (mL/min) or on chronic renal replacement therapy
- •History of receiving a solid organ transplant
- •Evidence of active, latent, or inadequately treated infection with Mycobacterium tuberculosis (TB)
- •Significant and uncontrolled medical disease within the 12 weeks prior to screening in any organ system (e.g., cardiac, neurologic, pulmonary, renal, hepatic, endocrine, metabolic, gastrointestinal, or psychiatric) not related to SLE, which, in the investigator's or Sponsor's opinion, would preclude study participation
- •History of cancer, including hematological malignancy and solid tumors, within 10 years of screening
- •Need for systemic anticoagulation with warfarin, other oral or injectable anticoagulants, or anti-platelet agents
- •Evidence of chronic and/or active hepatitis B or C
研究组 & 干预措施
Placebo
Participants received matching placebo to GDC-0853 orally starting on Day 1 and ending at Week 48, in combination with background standard of care therapy.
干预措施: Placebo (Drug)
GDC-0853 (150mg) QD
Participants received GDC-0853 (150mg) orally once daily (QD) starting on Day 1 and ending at Week 48, in combination with background standard of care therapy.
干预措施: GDC-0853 (Drug)
GDC-0853 (200mg) BID
Participants received GDC-0853 (200mg) orally twice daily (BID) starting on Day 1 and ending at Week 48, in combination with background standard of care therapy.
干预措施: GDC-0853 (Drug)
结局指标
主要结局
Systemic Lupus Erythematosus Responder Index (SRI)-4 Response at Week 48
时间窗: Week 48
The Systemic Lupus Erythematosus Responder Index (SRI)-4 measures reduction in SLE disease activity and is a composite measure that includes the SLE Disease Activity Index (SLEDAI-2K), British Isles Lupus Activity Group (BILAG) 2004 and Physician Global Assessment. It is defined as: 1) Reduction of ≥4 points from baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score; 2) no new British Isles Lupus Assessment Group (BILAG) A or no more than 1 new BILAG B disease activity scores and 3) no worsening (defined as an increase of ≥0.3 points \[10 mm\] from baseline) in the Physician's Global Assessment of Disease Activity. The score range is from 0 to 100, with higher scores indicating greater disease activity.
次要结局
- SRI-4 Response at Week 24 With a Sustained Reduction of OCS Dose to < 10 mg/Day and </= Day 1 Dose During Week 12 Through Week 24(Week 24)
- SRI-4 Response at Week 24(Week 24)
- SRI-4 Response at Week 48 in Patients With High vs. Low Plasmablast Signature Levels(Week 48)
- SRI-4 Response at Week 48 With a Sustained Reduction of Oral Corticosteroids (OCS) Dose to Less Than (<)10 Milligrams Per Day (mg/Day) and Less Than or Equal to (</=) Day 1 Dose During Week 36 Through Week 48(Week 48)
- SRI-4 Response With a Sustained Reduction of OCS Dose to ≤ 10 mg/Day and ≤ Day 1 Dose During Week 36 Through 48 in Patients With High vs. Low Plasmablast Signature Levels(Week 48)
- Percentage of Participants With Adverse Events (AEs)(Baseline up to 8 weeks after the last dose of study drug (up to Week 56).)
- Plasma Concentrations of Fenebrutinib at Specified Timepoints(Baseline (Pre-dose), Week 24 (Pre-dose and Post-dose) and Week 48 (Pre-dose))
- BILAG-based Composite Lupus Assessment (BICLA) Response at Week 24 and 48(Week 24, 48)
- SRI-6 Response at Week 24 and 48(Week 24, 48)