A Randomized, Placebo-controlled, Double-blind, Multicenter Study to Assess the Efficacy and Safety of Nipocalimab in Adults With Primary Sjogren's Syndrome (pSS)
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 163
- 试验地点
- 69
- 主要终点
- Change from Baseline in Clinical European League Against Rheumatism Sjogren's Syndrome Disease Activity Index (clinESSDAI) Score at Week 24
研究概览
简要总结
The purpose of this study is to evaluate the efficacy and safety of nipocalimab in participants with primary Sjogren's syndrome (pSS) versus placebo.
详细描述
Sjogren's syndrome is a chronic, progressive autoimmune disease of unclear etiology typically originating in exocrine glands and capable of affecting the function of almost any organ system in the body. Nipocalimab is a fully human aglycosylated immunoglobulin (Ig)G1 monoclonal antibody designed to selectively bind, saturate, and block the IgG binding site on the endogenous neonatal fragment crystallizable receptor (FcRn). Nipocalimab blocks the binding site for IgG on FcRn, leads directly to increased IgG catabolism and a decrease in circulating IgG antibody concentrations, including pathogenic IgG antibody concentrations, and directly inhibits inflammatory cellular responses to these pathogenic IgG. Therefore, Nipocalimab may successfully treat pSS and improve disease manifestations. The study will consist of Screening Period (less than or equal to [<=] 6 Weeks), Double-blind Treatment Period (24 Weeks), and a Follow-up Period (6 Weeks). Key safety assessments will include adverse events (AEs), serious adverse events (SAEs), adverse events of special interests (AESIs), clinical laboratory safety tests (hematology, chemistry, urinalysis, and lipid profile) and vital signs. The total duration of the study is up to 36 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Double (Participant, Investigator)
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
- •Meets classification criteria for primary Sjogren's syndrome (pSS) by the 2016 American College of Rheumatology (ACR) / European League Against Rheumatism (EULAR) at the time of screening (results either obtained during screening or documented in the participant's medical history are acceptable to fulfill these criteria for Schirmer's test, unstimulated salivary flow test, ocular staining score, or labial salivary gland biopsy), and was diagnosed with pSS no less than 26 weeks prior to screening
- •At screening is seropositive for antibodies to pSS-associated antigen A (Ro/Sjogren's syndrome-related antigen A [SSA])
- •Total Clinical European League Against Rheumatism Sjogren's Syndrome Disease Activity Index (clinESSDAI) score greater than or equal to (>=) 6
- •At least one abnormal laboratory marker of pSS-related inflammatory disease activity, and at least low activity in one or more specified European League Against Rheumatism Sjogren's Syndrome Disease Activity Index (ESSDAI) domains
- •It is recommended to be up to date on all age-appropriate vaccinations prior to screening per routine local medical guidelines. It is strongly recommended that participants will have completed a locally-approved (or emergency use-authorized) coronavirus disease 2019 (COVID-19) vaccination regimen at least 2 weeks prior to study related visits or procedures. Study participants should, follow applicable local vaccine labelling, guidelines, and standards-of-care for participants receiving immune-targeted therapy will be followed when determining an appropriate interval between vaccination and study enrollment
排除标准
- •Has any confirmed or suspected clinical immunodeficiency syndrome not related to treatment of his/her pSS or has a family history of congenital or hereditary immunodeficiency unless confirmed absent in the participant
- •Comorbidities (for example, asthma, chronic obstructive pulmonary disease) which have required 3 or more courses of systemic glucocorticoids within the previous 12 months
- •Has any unstable or progressive manifestation of pSS that is likely to warrant escalation in therapy beyond permitted background medications and/or has severely active pSS
- •Has received oral cyclophosphamide within 3 months or intravenous (IV) cyclophosphamide within 6 months prior to first administration of study intervention
- •Has Sjogren's syndrome overlap syndromes where another confirmed autoimmune rheumatic or systemic inflammatory condition (for example, rheumatoid arthritis [RA], systemic lupus erythematosus [SLE], scleroderma, inflammatory bowel disease [IBD]) is the primary diagnosis or has clinical manifestations that, in the opinion of the investigator, or the sponsor or sponsor's representative, are likely to interfere with the investigator's ability to assess pSS manifestations
研究组 & 干预措施
Group 1: Placebo
Participants will receive placebo intravenously (IV) every 2 weeks (q2w) through Week 22 along with standard of care treatments ([including ophthalmic drops, artificial tears and saliva, punctum plugs, and secretagogues], and/or one immunomodulator with or without low-dose glucocorticosteroids).
干预措施: Placebo (Other)
Group 1: Placebo
Participants will receive placebo intravenously (IV) every 2 weeks (q2w) through Week 22 along with standard of care treatments ([including ophthalmic drops, artificial tears and saliva, punctum plugs, and secretagogues], and/or one immunomodulator with or without low-dose glucocorticosteroids).
干预措施: Standard of Care Treatment (Drug)
Group 2: Nipocalimab Dose 1
Participants will receive nipocalimab dose 1 IV q2w through Week 22 along with standard of care treatments ([including ophthalmic drops, artificial tears and saliva, punctum plugs, and secretagogues], and/or one immunomodulator with or without low-dose glucocorticosteroids).
干预措施: Nipocalimab (Drug)
Group 2: Nipocalimab Dose 1
Participants will receive nipocalimab dose 1 IV q2w through Week 22 along with standard of care treatments ([including ophthalmic drops, artificial tears and saliva, punctum plugs, and secretagogues], and/or one immunomodulator with or without low-dose glucocorticosteroids).
干预措施: Standard of Care Treatment (Drug)
Group 3: Nipocalimab Dose 2
Participants will receive nipocalimab dose 2 IV q2w through Week 22 along with standard of care treatments ([including ophthalmic drops, artificial tears and saliva, punctum plugs, and secretagogues], and/or one immunomodulator with or without low-dose glucocorticosteroids).
干预措施: Nipocalimab (Drug)
Group 3: Nipocalimab Dose 2
Participants will receive nipocalimab dose 2 IV q2w through Week 22 along with standard of care treatments ([including ophthalmic drops, artificial tears and saliva, punctum plugs, and secretagogues], and/or one immunomodulator with or without low-dose glucocorticosteroids).
干预措施: Standard of Care Treatment (Drug)
结局指标
主要结局
Change from Baseline in Clinical European League Against Rheumatism Sjogren's Syndrome Disease Activity Index (clinESSDAI) Score at Week 24
时间窗: Baseline to Week 24
The clinESSDAI is a validated tool used in clinical studies to measure the systemic disease activity in participants with primary Sjogren's syndrome. The clinESSDAI includes 11 domains divided into 3-4 activity levels, where zero represents no activity and low, medium, and high scores can vary in numerical value depending on the domain.
次要结局
- Improvement of Greater than or Equal to (>=) 4 Points from Baseline in ESSDAI Score (Minimal Clinically Important Improvement) at Week 24(Baseline to Week 24)
- Improvement of >= 4 Points from Baseline in clinESSDAI Score (Minimal Clinically Important Improvement) at Week 24(Baseline to Week 24)
- ESSPRI Response at Week 24(Week 24)
- Improvement in Disease Activity Level by >= 1 Level in at Least One clinESSDAI or ESSDAI Domain at Week 24(Week 24)
- Percentage of Participants with Clinically Significant Abnormalities in Laboratory Parameters(Up to 36 weeks)
- Serum Concentration of Nipocalimab Over Time(Up to Week 30)
- Number of Participants with Antibodies to Nipocalimab (Anti-drug Antibodies [ADAs] and Neutralizing Antibodies [NAbs])(Up to Week 36)
- Number of Participants with Change from Baseline in Autoantibodies(Baseline to Week 36)
- Change from Baseline in European League Against Rheumatism (EULAR) Sjogren Syndrome Patient Reported Index (ESSPRI) Score at Week 24(Baseline to Week 24)
- Percentage of Participants with Adverse Events of Special interests (AESIs)(Up to 36 weeks)
- Percentage of Participants with TEAEs Leading to Treatment Discontinuation(Up to 30 weeks)
- Percentage of Participants with Clinically Significant Abnormalities in Vital Signs(Up to 36 weeks)
- Number of Participants with Change from Baseline in Biomarkers(Baseline to Week 36)
- Disease Response as Assessed by Sjögren's Tool for Assessing Response (STAR) Composite Score at Week 24(Week 24)
- Improvement from Baseline in >= 3 of 5 Composite of Relevant Endpoints for Sjogren's Syndrome (CRESS) Categories at Week 24(Baseline to Week 24)
- Percentage of Participants with Treatment-emergent Serious Adverse Events (SAEs)(Up to 30 weeks)
- Percentage of Participants with Treatment-emergent Adverse Events (TEAEs)(Up to 30 weeks)