A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase 2 Study Evaluating the Efficacy and Safety of Daxdilimab in Adult Participants With Active Proliferative Lupus Nephritis
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- Amgen
- 入组人数
- 19
- 试验地点
- 51
- 主要终点
- Percentage of Participants Who Achieved CRR at Week 48 Through Week 52
研究概览
简要总结
Phase 2, multicenter, double-blind, randomized, placebo-controlled, parallel-group trial to evaluate the efficacy and safety of daxdilimab in patients with active, proliferative lupus nephritis (LN).
详细描述
Approximately 210 participants will be randomized to receive daxdilimab or placebo administered subcutaneously through Week 52 in addition to their standard of care background therapy (mycophenolate mofetil (MMF) and corticosteroids). At Week 64, all participants will be assigned to a quarterly dosing maintenance regimen of either daxdilimab or placebo based upon pre-defined renal response observed by Week 52. The maximum trial duration per participant is approximately 116 weeks including a 4-week screening period, the 104 weeks for the treatment period where participants will receive daxdilimab or placebo, and approximately 8 weeks for the follow-up period. Safety evaluations will be performed regularly throughout the course of the study.
Acquired from Horizon in 2024.
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 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Willing and able to understand and provide written informed consent
- •Adult men or women 18 to 80 years of age
- •Willing and able to comply with the prescribed treatment protocol and evaluations for the duration of the trial
- •Fulfill the 2019 European League Against Rheumatism/American College of Rheumatology Classification Criteria for Systemic Lupus Erythematosus (SLE)
- •Have at least one of the following at Screening per central lab:
- •Antinuclear antibodies (ANA) ≥ 1:80
- •Anti-dsDNA antibodies elevated to above normal range as established by the central laboratory (ie, positive results)
- •Anti-Smith antibodies elevated to above normal (ie, positive results).
- •Diagnosis of proliferative LN based on a renal biopsy obtained within 6 months prior to signing the informed consent form (ICF) or during the Screening Period:
- •Class III (± class V) or class IV (± class V) LN according to the World Health Organization (WHO) or 2003 International Society of Nephrology (ISN)/Renal Pathology Society (RPS) classification (based on local evaluation of renal biopsy).
- •Urine protein to creatinine ratio ≥113.17 mg/mmol, obtained via a 24-hour urine collection at Screening.
- •Estimated glomerular filtration rate ≥35 mL/min/1.73 m2
- •Negative serum beta-human chorionic gonadotropin test at Screening (females of childbearing potential only).
排除标准
- •History of allergy, hypersensitivity reaction, or anaphylaxis to any component of the investigational product or to a previous monoclonal antibody or human immunoglobulin therapy.
- •Known intolerance to ≤1.0 gm/day of MMF or equivalent dose of mycophenolic acid (MPA).
- •A diagnosis of pure Class V membranous LN based on a renal biopsy obtained within 6 months prior to signing ICF or during the Screening Period.
- •History of dialysis within 12 months prior to signing the ICF or expected need for renal replacement therapy (dialysis or renal transplant) within a 12-month period after enrollment.
- •History of, or current renal diseases (other than LN) that in the opinion of the Investigator could interfere with the LN assessment and confound the disease activity assessment (eg, diabetic nephropathy).
- •Known history of a primary immunodeficiency or an underlying condition such as known human immunodeficiency virus (HIV) infection, a positive result for HIV infection per central laboratory, splenectomy, or any underlying condition that in the opinion of the Investigator significantly predisposes the participant to infection.
- •Hepatitis B, Hepatitis C, active tuberculosis (TB), any severe herpes infection, clinically active infection, or opportunistic infection.
- •Clinically significant cardiac disease including unstable angina, myocardial infarction, congestive heart failure within 6 months prior to Randomization.
- •History of cancer within the past 5 years, except in situ carcinoma of the cervix, cutaneous basal cell or squamous cell carcinoma with curative therapy.
- •Receipt of a live vaccine within 4 weeks prior to Day
- •The use of immunosuppressants, biologics, and DMARDS within the protocol defined washout periods.
研究组 & 干预措施
Placebo
Placebo injections over a total of 104 weeks
干预措施: Placebo (Normal Saline) (Drug)
Daxdilimab Arm 1
Daxdilimab injections over a total of 104 weeks
干预措施: Daxdilimab (Drug)
Daxdilimab Arm 2
Daxdilimab injections over a total of 104 weeks
干预措施: Daxdilimab (Drug)
结局指标
主要结局
Percentage of Participants Who Achieved CRR at Week 48 Through Week 52
时间窗: Week 48 to Week 52
CRR was defined as meeting all of the following: * Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m\^2 or no worse than 15% below Baseline * 24-hour urine protein to creatinine ratio (UPCR) ≤ 0.5 mg/mg * No discontinuation of trial intervention or use of restricted medication beyond the protocol-allowed threshold before assessment
次要结局
- Percentage of Participants Who Achieved Overall Renal Response (ORR) at Week 48 Through Week 52(Week 48 to Week 52)
- Change From Baseline in eGFR at Week 52(Baseline and Week 52)
- Proportion of Participants Achieving a Decrease in Daily Oral Corticosteroid (OCS) Dose of ≤ 2.5 mg Prednisone-Equivalent by Week 24 Maintained Through Week 52(Week 24 to Week 52)
- Serum Concentration of Daxdilimab(Week 0 pre-dose, and 6 hours post-dose; Week 2, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, and Week 36)
- Number of Participants With Detectable Anti-Drug Antibodies (ADA) Against Daxdilimab(Up to approximately 36 weeks)
- Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)(Up to approximately 36 weeks)