A Phase 2 Randomized, Double-blind, Placebo-controlled, Proof of Concept Study to Evaluate the Efficacy and Safety of VIB4920 in Subjects With Sjögren's Syndrome (SS)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- Amgen
- 入组人数
- 183
- 试验地点
- 2
- 主要终点
- Population 1: Change From Baseline in ESSDAI at Day 169
研究概览
简要总结
The purpose of the study is to evaluate the efficacy, safety, and tolerability of VIB4920 (formerly MEDI4920) in adult participants with Sjögren's Syndrome (SS).
详细描述
The study will enrol 2 SS populations: Population 1 will include participants with moderate to high systemic disease activity defined by European League Against Rheumatism (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI) >= 5; Population 2 will include participants with moderate to severe subjective symptoms defined by EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) score >= 5 and residual stimulated salivary flow but with mild systemic disease activity defined by ESSDAI score < 5. This study will include 3 periods: screening (4 weeks), treatment period (40 Weeks) and follow-up period (12 weeks). In the treatment period, participants from each of the populations will be randomized at 1:1 ratio to receive intravenous (IV) dose of VIB4920 or placebo (Stage I). After completion of Stage I, participants randomized to VIB4920 in Stage I will receive placebo and participants randomized to placebo in Stage I will receive VIB4920 (Stage II). Participants who had study drug discontinuation will not be eligible for treatment during Stage II. All participants will be followed for at least 12 weeks after their last dose of study drug administration.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Diagnosed with SS by meeting the 2016 American College of Rheumatology (ACR)/EULAR Classification Criteria.
- •Residual salivary gland function as defined by whole stimulated salivary flow > 0.1 mL/min (only for Population 2).
- •Have an ESSDAI score of >= 5 at screening; (not including the peripheral nervous system, central nervous system, and pulmonary domains) (only for Population 1).
- •Have an ESSPRI score of >= 5 at screening (only for Population 2).
- •Have an ESSDAI score of < 5 at screening (only for Population 2).
- •Positive for either anti-Ro autoantibodies or rheumatoid factor, or both at screening.
- •Male and female participants who agree to follow protocol defined contraceptive methods.
- •No active or untreated latent tuberculosis (TB).
排除标准
- •Medical history of confirmed deep venous thrombosis or arterial thromboembolism within 2 years of signing the informed consent form (ICF).
- •Risk factors for venous thromboembolism or arterial thrombosis, prothrombotic status.
- •Concomitant polymyositis or dermatomyositis or systemic sclerosis.
- •Active malignancy or history of malignancy, except in situ carcinoma of the cervix and cutaneous basal cell carcinoma.
- •Hepatitis B, hepatitis C, or human immunodeficiency virus infection.
- •More than one episode of herpes zoster and/or an opportunistic infection in the last 12 months.
- •Active viral, bacterial, or other infections or history of more than 2 infections requiring intravenous antibiotics within 12 months prior to signing the ICF.
- •Participants with corona virus disease 2019 (COVID-19) infection or who, in the judgment of the investigator, are at unacceptable risk of COVID-19 or its complications.
- •A documented positive severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) test within 2 weeks prior to randomization.
- •Received live (attenuated) vaccine within the 4 weeks prior to ICF signature.
- •Treated with any biologic B-cell-depleting therapy within 12 months or other B-cell targeting therapy < 3 months before randomization.
- •Injectable corticosteroids (including intraarticular) or treatment with > 10 mg/day dose oral prednisone or equivalent within 6 weeks prior to randomization (only for Population 1).
- •Treated with systemic corticosteroids for indications other than SS, rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE) for more than a total of 2 weeks within 24 weeks prior to screening visit (only for Population 1).
- •Received previous treatment with anti-CD40L compounds at any time before screening.
- •Pregnant or lactating or planning to get pregnant during the duration of the study.
研究组 & 干预措施
VIB4920 Dose 1 in Population 1
Participants in population 1 will receive IV VIB4920 Dose 1 in Stage I and placebo matched to VIB4920 in Stage II.
干预措施: VIB4920 (Drug)
VIB4920 Dose 1 in Population 1
Participants in population 1 will receive IV VIB4920 Dose 1 in Stage I and placebo matched to VIB4920 in Stage II.
干预措施: Placebo (Drug)
Placebo in Population 1
Participants in population 1 will receive IV placebo matched to VIB4920 in Stage I and IV VIB4920 Dose 1 in Stage II.
干预措施: VIB4920 (Drug)
Placebo in Population 1
Participants in population 1 will receive IV placebo matched to VIB4920 in Stage I and IV VIB4920 Dose 1 in Stage II.
干预措施: Placebo (Drug)
VIB4920 Dose 1 in Population 2
Participants in population 2 will receive IV VIB4920 Dose 1 in Stage I and placebo matched to VIB4920 in Stage II.
干预措施: VIB4920 (Drug)
VIB4920 Dose 1 in Population 2
Participants in population 2 will receive IV VIB4920 Dose 1 in Stage I and placebo matched to VIB4920 in Stage II.
干预措施: Placebo (Drug)
Placebo in Population 2
Participants in population 2 will receive IV placebo matched to VIB4920 in Stage I and IV VIB4920 Dose 1 in Stage II.
干预措施: VIB4920 (Drug)
Placebo in Population 2
Participants in population 2 will receive IV placebo matched to VIB4920 in Stage I and IV VIB4920 Dose 1 in Stage II.
干预措施: Placebo (Drug)
结局指标
主要结局
Population 1: Change From Baseline in ESSDAI at Day 169
时间窗: Baseline and Day 169
The ESSDAI is a systemic disease activity index for SS, assessing 12 domains (Constitutional, Salivary Glands, Lungs, Kidneys, Musculoskeletal, Peripheral Nervous System, Central Nervous System, Vascular, Gastrointestinal, Hematological, Ocular, and Extraglandular Manifestations). Each domain is graded for activity (0 = no activity to 3 = high activity) and weighted (1 for Biological to 6 for Muscular) based on its clinical significance, with the final score calculated as the sum of all weighted domain scores. The theoretical range is 0 to 123, with disease activity categorized as low (\<5), moderate (5-13), and high (≥14). A positive change form baseline represents an increase in symptoms.
Population 2: Change From Baseline in ESSPRI at Day 169
时间窗: Baseline and Day 169
The ESSPRI is a self-assessment tool for evaluating symptoms of dryness, fatigue, and pain (articular and/or muscular) in SS. Participants rate each of the three domains on a 0-10 numerical scale (0 = no; 10 maximal imaginable severity). All domains are equally weighted, and the total score is the mean of the three domain scores. The maximum total score for the ESSPRI assessment is 10. A positive change form baseline represents an increase in symptoms.
次要结局
- Population 1: Change From Baseline in ESSPRI at Day 169(Baseline and Day 169)
- Population 1: Number of Participants Who Achieved ESSDAI[3] and ESSDAI[4] Response at Day 169(Day 169)
- Change From Baseline in The Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score at Day 169(Baseline and Day 169)
- Change From Baseline in Ocular Surface Disease Index (OSDI) at Day 169(Baseline and Day 169)
- Patient Global Impression of Severity (PGIS) Score at Day 169(Baseline and Day 169)
- Population 2: Number of Participants Who Achieved ESSPRI Response at Day 169(Day 169)
- Number of Participants Who Experience Treatment-emergent Adverse Events (TEAEs)(Up to approximately 365 days)
- Serum Concentration of VIB4920(Day 1 pre-dose, Day 1 post-dose, Day 15, Day 29, Day 57, Day 85, Day 113, Day 141 pre-dose, Day 141 post-dose, Day 169 pre-dose, Day 169 post-dose, Day 197, Day 225, Day 253, Day 281, Day 309, Day 365)