A Phase 1b/2a Open Label Dose Escalating Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Budoprutug in Adult Participants With Sys-temic Lupus Erythematosus (SLE)
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 发起方
- 入组人数
- 40
- 主要终点
- Number of participants with Adverse events (AEs) and Serious Adverse events (SAEs)
研究概览
简要总结
The purpose of the study is to determine the safety, tolerability, and pharmacokinetics of budoprutug in participants with SLE
详细描述
This is a Phase 1b/2a, multicenter, open-label study designed to evaluate the safety, tolerability, PK, and PD of budoprutug in adult participants with SLE.
In Phase 1b, participants who fulfill the 2012 Systemic Lupus International Collaborating Clinics(SLICC) classification criteria for SLE, and who have active SLE (as defined by a SLEDAI ≥ 4 at Screening and Day 1),have failed at least 1 line of treatment, and who are assessed as appropriate for the study by the Eligibility Adjudicator, will be enrolled in sequential escalating dose cohorts. Three dose cohorts are planned.
The Phase 2a expansion cohort will include approximately 16 to 20 participants with active SLE, at least one-half of whom will have renal involvement. Participants will continue to be followed through Week 52 for safety, PK, and PD assessmentsParticipants will also be monitored during this time for ongoing clinical response, safety parameters, and kinetics of re-population of B-cell subsets after the return of B cells to baseline values.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of SLE fulfilling SLICC criteria or 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) criteria at least 24 weeks prior to study entry, with one of the following at Screening
- •If taking a corticosteroid regimen prior to Screening, currently receiving ≤ 20 mg prednisone or equivalent by Day -
- •Exceptions for patients with active LN are detailed in Section XX (where we talk about CS use).
- •Female participants of non-childbearing potential must be either surgically sterile (hysterectomy, bilateral tubal ligation, salpingectomy, and/or bilateral oophorectomy at least 26 weeks before the Screening Visit) or postmenopausal, defined as spontaneous amenorrhea for at least 1 year, with follicle-stimulating hormone in the postmenopausal range at Screening, as per central laboratory reference range.
- •Additional criteria for Phase 2a participants only:
- •Hybrid SLEDAI ≥ 6 at Screening AND Day
- •Note: only the clinical aspects of hybrid SLEDAI must be confirmed on Day 1; laboratory values that contribute to hybrid SLEDAI do not need to be re-measured prior to dosing on Day
- •Additional criteria for contributions to hybrid SLEDAI are as follows:
- •Participants with neurological system contribution to hybrid SLEDAI will not be enrolled.
- •At least 6 points from the hybrid SLEDAI score must be derived from organ system involvement excluding points from oral ulcers, alopecia, or anti-dsDNA auto-antibododies
- •Additional criteria for Phase 2a participants with LN:
- •Diagnosis of International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 Class III or IV LN as evidenced by renal biopsy performed within 2 years prior to or during Screening, either with or without the presence of Class V LN.
- •Proteinuria (UPCR > 1.0 gram per gram [g/g]), based on a sample from a 24 hour urine collection during Screening.
- •Estimated glomerular filtration rate (eGFR) ≥ 30 mL/min/1.73 m2 (as calculated by the Chronic Kidney Disease Epidemiology Collaboration formula).
- •Currently receiving 1 or more immunosuppressive agents that has been stable for dose and route of administration for ≥ 8 weeks prior to baseline.
排除标准
- •Use of IV, intramuscular, intra-articular, or high-potency intralesional corticosteroids within 6 weeks prior to Screening or expectation of requiring parenteral corticosteroids during the study. Exceptions include protocol required pre-medication prior to infusion of budoprutug.
- •Use of high-potency topical corticosteroid and/or topical agents (immunosuppressant) for skin lesions within 7 days prior to Screening
- •The following laboratory values:
- •Absolute neutrophil count < 1.0 × 109/L.
- •White blood cell count < 2.0 × 109/L.
- •Cluster of differentiation (CD) 19 B-cell count <80 cells/µL.
- •Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 2 × ULN.
- •Total bilirubin > 1.5 × ULN, unless due to Gilbert's syndrome.
- •History of serious or significant infusion reaction associated with rituximab, belimumab, anifrolumab, or other monoclonal antibody therapy.
- •History of or current diagnosis of active tuberculosis, untreated latent tuberculosis infection (LTBI) or undergoing current treatment for untreated LTBI
- •History of chronic (i.e., chronic urinary tract infection), recurrent (3 or more of the same type of infection in a 52-week period), latent, or recent serious infection
- •Any previous use of CD19 targeted therapy (e.g., inebilizumab or cell therapy).
研究组 & 干预措施
Dose 1
Low dose
干预措施: budoprutug (Drug)
Dose 2
Middle dose
干预措施: budoprutug (Drug)
Dose 3
High Dose
干预措施: budoprutug (Drug)
结局指标
主要结局
Number of participants with Adverse events (AEs) and Serious Adverse events (SAEs)
时间窗: Day 1 through Week 24
Safety assessments of budoprutug include changes in vital signs, clinical findings on physicial exam, electrocardiogram and clinical laboratory findings
次要结局
- Immunogenicity(Day 1 through Week 24)
- PK parameters(Day 1 through Week 24)