A Phase 2, Randomized, Double-Blind, Placebo-Controlled, Mechanistic Insight and Dosage Optimization Study of the Efficacy and Safety of VIB4920 in Patients With Rheumatoid Arthritis (RA)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 78
- 试验地点
- 1
- 主要终点
- Change From Baseline to Day 113 in DAS28-CRP
研究概览
简要总结
The purpose of the study is to evaluate the efficacy, safety, and pharmacokinetics (PK) of VIB4920 (formerly MEDI4920) in adult participants with rheumatoid arthritis (RA).
详细描述
The overall study period will be approximately 337 days. After a screening period of up to 28 days, the participants will be randomized in a 1:1:1:1:1 ratio to receive intravenous dose of VIB4920 and/or placebo in 5 cohorts. Participants are to be followed on their stable background anti-RA therapy at least through 12 weeks (Day 85), at which time rescue therapy may be instituted. All participants will be followed at least through the primary (interim) analysis (Day 113), and those who have not instituted rescue therapy will be followed through Day 309 to determine the duration of clinical response. The primary analysis will be after all participants have completed Day 113, and the final analysis will be after all participants have completed follow-up.
Study with completed results 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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female adults, >= 18 years of age at time of informed consent.
- •Diagnosed with RA according to the European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) 2010 criteria >= 6 months prior to screening.
- •Disease Activity Score in 28 Joints (DAS 28) using C-reactive Protein (DAS28-CRP) > 3.2 at screening with >= 4 tender joint count (TJC) and >= 4 swollen joint count (SJC) out of the 28 joints assessed for DAS28 present at screening and confirmed present at visit 2 prior to randomization.
- •Positive for rheumatoid factor (RF) and/or anti-citrullinated protein antibodies (ACPA) at screening, in accordance with criteria at the central laboratory.
- •Treated with methotrexate (MTX), with or without a concomitant conventional disease-modifying anti-rheumatic drug (cDMARD).
- •Agreeing to use of protocol defined contraception methods.
排除标准
- •Prior or current inflammatory joint disease other than RA.
- •Severe interstitial lung disease.
- •Prior receipt of any biologic B-cell-depleting therapy.
- •Receipt of any anti - tumor necrosis factor alpha (TNF-α) biologic agent < 8 weeks prior to screening.
- •Receipt of any biologic disease-modifying anti-rheumatic drug (bDMARD) with a mechanism of action other than direct TNF-α blockade, < 12 weeks or < 5 half-lives of the drug prior to screening.
- •Injectable corticosteroids or treatment with > 10 mg/day dose of oral prednisolone or equivalent within 4 weeks prior to screening.
- •Previous treatment with anti-cluster of differentiation 40 ligand (CD40L) compounds at any time before randomization.
- •Hepatitis B, hepatitis C, or human immunodeficiency virus infection.
- •Pregnant or lactating or planning to get pregnant during the duration of the study.
- •Evidence of active tuberculosis (TB) or being at high risk for TB.
- •History of more than one episode of herpes zoster in the 12 months prior to screening or any opportunistic infection in the 12 months prior to screening, excluding localized mucocutaneous candidiasis.
- •Receipt of live vaccine or live therapeutic infectious agent within the 4 weeks prior to screening.
研究组 & 干预措施
VIB4920 3000 mg Once
Participants receive IV infusion of VIB4920 3000 mg on Day 1 and placebo on Days 15, 29, and 57.
干预措施: Placebo (Drug)
VIB4920 1500 mg 4 Times
Participants receive intravenous (IV) infusion of VIB4920 1500 mg on Days 1, 15, 29, and 57
干预措施: VIB4920 (Drug)
VIB4920 1500 mg Twice
Participants receive IV infusion of VIB4920 1500 mg on Days 1 and 57, placebo on Days 15 and 29.
干预措施: VIB4920 (Drug)
VIB4920 1500 mg Twice
Participants receive IV infusion of VIB4920 1500 mg on Days 1 and 57, placebo on Days 15 and 29.
干预措施: Placebo (Drug)
VIB4920 3000 mg Twice
Participants receive IV infusion of VIB4920 3000 mg on Days 1 and 57, placebo on Days 15 and 29.
干预措施: VIB4920 (Drug)
VIB4920 3000 mg Twice
Participants receive IV infusion of VIB4920 3000 mg on Days 1 and 57, placebo on Days 15 and 29.
干预措施: Placebo (Drug)
VIB4920 3000 mg Once
Participants receive IV infusion of VIB4920 3000 mg on Day 1 and placebo on Days 15, 29, and 57.
干预措施: VIB4920 (Drug)
Placebo
Participants receive IV infusion of placebo matched to VIB4920 on Days 1, 15, 29, and 57.
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline to Day 113 in DAS28-CRP
时间窗: Day 1 (Baseline), Day 113
The DAS28-CRP is a composite index used to assess rheumatoid arthritis disease activity, calculated based on the tender joint count (out of 28 evaluated joints), swollen joint count (out of 28 evaluated joints), Patient's Global Assessment of Disease Activity (0-100 mm), and high-sensitivity C-reactive protein (hsCRP; in mg/L). Scores on the DAS28-CRP range from 0 to approximately 10, where higher scores indicate more disease activity. A negative change from baseline indicates improvement in disease activity. Results are from a mixed-effect model for repeated measures (MMRM) analysis with treatment, visit, visit by treatment interaction, and baseline DAS28-CRP score included in the model.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Emergent Serious Adverse Events (TESAEs), and Treatment-emergent Adverse Events of Special Interest (TEAESIs)
时间窗: From first dose of study drug through Day 309 ± 7 days
Adverse event (AE): any untoward medical occurrence associated with the use of an intervention in humans, whether or not it is considered intervention-related. Serious adverse event (SAE): an AE that results in any of the following outcomes: death; life-threatening AE; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant incapacity; congenital anomaly/birth defect; other important medical event jeopardizing the participant's well-being. AEs of special interest (AESIs) include: thrombotic and embolic events; anaphylaxis and clinically significant (Common Terminology Criteria for Adverse Events \[CTCAE\] Grade 3 or higher) hypersensitivity reactions; severe infusion-related reactions (CTCAE Grade 3 or higher); immune complex disease; severe (CTCAE Grade 3 or higher) and/or opportunistic infections; hepatic function abnormality meeting the definition of Hy's Law; malignant neoplasm. (CTCAE Grade 3=Severe; Grade 4=Life-threatening; Grade 5=Fatal.)
次要结局
- PK of VIB4920: Area Under the Concentration-Time Curve From Time 0 to Day 56 (AUC0-56D)(Predose (within 30 minutes prior to start of infusion), and within 10 minutes of the end of infusion on Days 1 (Dose 1), 15 ± 1 day (d; Dose 2), 29 ± 3d (Dose 3), Day 56)
- PK of VIB4920: Total Body Clearance (CL) for Dose 1 and Total Body Clearance at Steady State (CLss) for Doses 2 to 4(Predose (within 30 minutes prior to start of infusion), and within 10 minutes of the end of infusion on Days 1 (Dose 1), 15 ± 1 day (d; Dose 2), 29 ± 3d (Dose 3), 57 ± 3d (Dose 4), and Days 85 ± 3d, 113 ± 5d, 141 ± 5d, 169 ± 5d, 197 ± 7d, 225 ± 7d)
- PK of VIB4920: Terminal Elimination Half-Life (t1/2)(Predose (within 30 minutes prior to start of infusion), and within 10 minutes of the end of infusion on Days 1 (Dose 1), 15 ± 1 day (d; Dose 2), 29 ± 3d (Dose 3), 57 ± 3d (Dose 4), and Days 85 ± 3d, 113 ± 5d, 141 ± 5d, 169 ± 5d, 197 ± 7d, 225 ± 7d)
- PK of VIB4920: Volume of Distribution at Steady State (Vss)(Predose (within 30 minutes prior to start of infusion), and within 10 minutes of the end of infusion on Days 1 (Dose 1), 15 ± 1 day (d; Dose 2), 29 ± 3d (Dose 3), 57 ± 3d (Dose 4), and Days 85 ± 3d, 113 ± 5d, 141 ± 5d, 169 ± 5d, 197 ± 7d, 225 ± 7d)
- Pharmacokinetics (PK) of VIB4920: Maximum Observed Concentration (Cmax)(Predose (within 30 minutes prior to start of infusion), and within 10 minutes of the end of infusion on Days 1 (Dose 1), 15 ± 1 day (d; Dose 2), 29 ± 3d (Dose 3), 57 ± 3d (Dose 4), and Days 85 ± 3d, 113 ± 5d, 141 ± 5d, 169 ± 5d, 197 ± 7d, 225 ± 7d)
- PK of VIB4920: Time to Cmax (Tmax)(Predose (within 30 minutes prior to start of infusion), and within 10 minutes of the end of infusion on Days 1 (Dose 1), 15 ± 1 day (d; Dose 2), 29 ± 3d (Dose 3), 57 ± 3d (Dose 4), and Days 85 ± 3d, 113 ± 5d, 141 ± 5d, 169 ± 5d, 197 ± 7d, 225 ± 7d)
- PK of VIB4920: Area Under the Concentration-Time Curve From Time 0 to the Last Quantifiable Concentration (AUClast)(Predose (within 30 minutes prior to start of infusion), and within 10 minutes of the end of infusion on Days 1 (Dose 1), 15 ± 1 day (d; Dose 2), 29 ± 3d (Dose 3), 57 ± 3d (Dose 4), and Days 85 ± 3d, 113 ± 5d, 141 ± 5d, 169 ± 5d, 197 ± 7d, 225 ± 7d)
- Total Soluble Cluster of Differentiation 40 Ligand (sCD40L) Plasma Concentration Over Time(Day 1 (Baseline), Days 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309)
- Percentage of Participants With Positive Anti-Drug Antibodies (ADA) to VIB4920(Day 1 (Baseline) to Day 309 Day 1 (Baseline) up to Day 309 (± 7 days))
- Change From Baseline to Day 113 in Anti-Citrullinated Protein Antibodies (ACPAs)(Day 1 (Baseline), Day 113)
- Change From Baseline to Day 113 in Rheumatoid Factor (RF)(Day 1 (Baseline), Day 113)
- Percentage of Participants With Clinical Remission at Day 113(Day 113)
- Time to Start of New Treatment for Rheumatoid Arthritis (Rescue Medication)(Day 1 (Baseline) up to Day 309 (± 7 days))