A Phase 1, First-in-Human, Single Ascending Dose, Open-label, Non-randomized Study Evaluating the Pharmacokinetics, Pharmacodynamics, and Safety of ABBV-519 in Subjects With Systemic Lupus Erythematosus (SLE) or Rheumatoid Arthritis (RA)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 30
- 试验地点
- 13
- 主要终点
- Maximum Plasma Concentration (Cmax) of ABBV-519.
研究概览
简要总结
Systemic lupus erythematosus (SLE) is a chronic, systemic autoimmune disease characterized by B cell hyperactivity.
Rheumatoid Arthritis (RA) is a chronic inflammatory disease causing pain, stiffness, swelling and loss of joint function. The purpose of this study is to assess the pharmacokinetics, pharmacodynamics and safety of ABBV-519 in adult participants with SLE or RA.
This is a single ascending dose study in an estimated 30 adult participants with moderate SLE or RA. The total duration of the study will be approximately 425 days (60-day Screening Period, 1-day Treatment Period, and a 52 week Follow-up Period) at approximately 15 to 20 sites globally.
There may be higher treatment burden for participants in this trial compared to their standard of care (due to study procedures). Participants will attend regular visits during the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Basic Science
- 盲法
- None
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
- •Individuals between 18 and 75 years of age inclusive at the time of Screening.
- •Minimum baseline B-cell count of 50 cells/mcL.
- •Inclusion Criteria for SLE Participants:
- •Clinical diagnosis of SLE and fulfilling the 2019 EULAR/ACR classification criteria.
- •Positive ANA ≥ 1:80 and the presence of at least one of the following autoantibodies above the upper limit of normal (ULN): anti-double-stranded DNA (dsDNA), anti-Smith (Sm), anti-ribonucleoprotein (RNP), or anti-Sjogren's syndrome antigen A (SSA).
- •Hybrid Systemic Lupus Erythematosus Disease Activity Index (hSLEDAI) score of ≥ 4 (excluding anti-dsDNA and C3/C4). Lupus headache or organic brain syndrome do not count towards the hSLEDAI points required for eligibility.
- •Participants must have an inadequate response to ≥ 1 immunosuppressant therapies, used for at least 3 months.
- •Inclusion Criteria for RA Participants:
- •Clinical diagnosis of RA and fulfilling the 2010 ACR/EULAR classification criteria for RA.
- •Presence of rheumatoid factor (RF) or anti-citrullinated peptide antibodies (ACPA) above the ULN.
- •Presence of at least 6 swollen and 6 tender joints
- •High-sensitivity C-reactive protein (hs-CRP) ≥ 3 mg/L.
- •Failed at least 1 conventional synthetic disease-modifying antirheumatic drug (DMARD) and ≥ 1 biological or targeted DMARDs of different classes.
排除标准
- •Participants with a history of infection.
- •Participants with uncontrolled hypertension
- •Exclusion for SLE Participants:
- •Active neuropsychiatric SLE, or signs or symptoms of neuropsychiatric SLE within the 6 months prior to Screening (lupus headache permissible).
- •- Unstable or progressive glomerulonephritis (active class III or IV).
- •SLE overlap syndromes including, but not limited to RA, Sjogren's disease (SjD), SSc, polymyositis, dermatomyositis, or mixed connective tissue disease.
- •Exclusion for RA Participants:
- •-- History of RA overlap syndromes, including but not limited to SLE, SjD, scleroderma, mixed connective tissue disorder or polymyositis.
研究组 & 干预措施
Group 4: Dose D
Participants will receive a single subcutaneous (SC) dose of ABBV-519
干预措施: ABBV-519 (Drug)
Group 5: Dose E
Participants will receive a single subcutaneous (SC) dose of ABBV-519
干预措施: ABBV-519 (Drug)
Group 1: Dose A
Participants will receive a single intravenous (IV) dose of ABBV-519
干预措施: ABBV-519 (Drug)
Group 2: Dose B
Participants will receive a single intravenous (IV) dose of ABBV-519
干预措施: ABBV-519 (Drug)
Group 3: Dose C
Participants will receive a single intravenous (IV) dose of ABBV-519
干预措施: ABBV-519 (Drug)
结局指标
主要结局
Maximum Plasma Concentration (Cmax) of ABBV-519.
时间窗: Up to 85 Days
Cmax of ABBV-519
Change from Baseline in B Cells in Blood
时间窗: Up to 365 Days
Change from baseline in B cells in blood.
Time to Cmax (Tmax) of ABBV-519
时间窗: Up to 85 Days
Tmax of ABBV-519
Terminal Phase Elimination Half-Life (t1/2) of ABBV-519
时间窗: Up to 85 Days
t1/2 of ABBV-519
Area Under the Concentration-Time Curve From Time 0 to Last Measurable Concentration (AUCt) of ABBV-519
时间窗: Up to 85 Days
AUCt of ABBV-519
Percentage of Participants with Detection of Anti-Drug Antibodies (ADAs) for ABBV-519
时间窗: Up to 169 Days
Percentage of participants with detection of ADAs for ABBV-519
Number of Participants with Adverse Events (AEs)
时间窗: Up to 425 Days
An AE is defined as any untoward medical occurrence in a patient or clinical investigation in which a participant is administered a pharmaceutical product which does not necessarily have a causal relationship with this treatment.
次要结局
未报告次要终点