NCT04908865已完成4 期
A Multi-Center, Open-Label Study to Evaluate Safety, Efficacy and Pharmacokinetics of Belimumab Plus Standard Therapy in Chinese Paediatric Patients With Active Systemic Lupus Erythematosus (SLE)
适应症
干预措施
相关药物
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 67
- 试验地点
- 9
- 主要终点
- Number of Participants With Adverse Events of Special Interest (AESIs) Through Week 52
研究概览
简要总结
This study will be conducted to evaluate the safety, efficacy and pharmacokinetics of belimumab administered in combination with background standard therapy in pediatric participants with active SLE.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 5 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants have or have had in series, 4 or more of the American College of Rheumatology (ACR) 11 criteria for the classification of SLE.
- •Participant's age is 5 to 17 years at the time of informed consent.
- •Have active SLE disease defined as a SELENA SLEDAI score >= 8 at screening (SELENA SLEDAI scoring).
- •Have unequivocally positive autoantibody test results defined as an anti-nuclear antibody (ANA) titer >=1:80 and/or a positive anti-Double stranded deoxyribonucleic acid (dsDNA) serum antibody test.
- •Are on a stable SLE therapy at Baseline. The stable treatment at Baseline consists of corticosteroids, anti-malarials, immunosuppressive/immunomodulatory agents and Non-steroidal anti-inflammatory drugs (NSAIDs), alone or in combination, at a fixed dose for a period of at least 30 days prior to Day
- •No gender restriction. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
- •The investigator, or a person designated by the investigator, will obtain written informed assent from each study participant or the participant's legally acceptable representative, parent(s), or legal guardian and the participant's assent, when applicable, before any study-specific activity is performed. The investigator will retain the original copy of each participant's signed assent document.
排除标准
- •Have an estimated glomerular filtration rate (eGFR) as calculated by Schwartz Formula of less than 30 mL/minutes.
- •Have acute severe nephritis defined as a significant worsening of renal disease (for example [e.g.], the presence of urinary sediments and other lab abnormalities) that, in the opinion of the study investigator, may lead to the participant requiring induction therapy with intravenous (IV) cyclophosphamide, Mycophenolate mofetil (MMF) or high dose corticosteroids during the first 6 months of the study.
- •Have a history of a major organ transplant (e.g., heart, lung, kidney, liver) or hematopoietic stem cell/marrow transplant.
- •Have clinical evidence of significant, unstable or uncontrolled, acute or chronic diseases not due to SLE (cardiovascular, pulmonary, hematologic, gastrointestinal, hepatic, renal, neurological, malignancy or infectious diseases) which, in the opinion of the investigator, could confound the results of the study or put the participant at undue risk.
- •Have a planned surgical procedure or a history of any other medical disease (e.g., cardiopulmonary), laboratory abnormality, or condition (e.g., poor venous access) that, in the opinion of the investigator, makes the participant unsuitable for the study.
- •Have a history of malignant neoplasm within the last 5 years.
- •Have a history of a primary immunodeficiency.
- •Have an Immunoglobulin A (IgA) deficiency (IgA level less than [<]10 mg/deciliters [milligrams/dL]).
- •Have acute or chronic infections requiring management.
- •Have recent infections that, in the opinions of the investigator, makes the participant unsuitable for the study or could put the participant at undue risk.
- •Have current drug or alcohol abuse or dependence, or a history of drug or alcohol abuse or dependence within 364 days prior to Day
- •Have a Grade 3 or greater laboratory abnormality based on the protocol toxicity scale except for the following that are allowed:
- •Stable Grade 3 prothrombin time (PT) secondary to warfarin treatment.
- •Stable Grade 3 partial thromboplastin time (PTT) due to lupus anticoagulant and not related to liver disease or anti-coagulant therapy.
- •Stable Grade 3 hypoalbuminemia due to lupus nephritis and not related to liver disease or malnutrition.
- •Any grade proteinuria
- •Stable Grade 3 gamma glutamyl transferase (GGT) elevation due to lupus hepatitis and not related to alcoholic liver disease, uncontrolled diabetes or viral hepatitis. If present, any abnormalities in the Alanine aminotransferase (ALT) and/or Aspartate aminotransferase (AST) must be Grade
- •Stable Grade 3 neutropenia; or stable Grade 3 lymphopenia; or stable Grade 3 leukopenia, due to SLE
- •Have a history of an anaphylactic reaction to parenteral administration of contrast agents, human or murine proteins or monoclonal antibodies.
- •Have evidence of serious suicide risk including any history of suicidal behavior in the last 6 months or who in the investigator's judgment, poses a significant suicide risk.
- •Have received treatment with belimumab at any time.
- •Have received any of the following within 364 days of Day 0:
- •Treatment with any B-cell targeted
- •A biologic investigational agent
- •Have required 3 or more courses of systemic corticosteroids for concomitant conditions (e.g., asthma, atopic dermatitis) within 90 days of Day
- •Have received any of the following within 90 days of Day 0:
- •Anti-Tumour Necrosis Factor (TNF) or anti-interleukin (IL)-6 therapy (e.g., adalimumab, etanercept, infliximab, tocilizumab certolizumab, golimumab)
- •Interleukin-1 receptor antagonist (anakinra)
- •Intravenous immunoglobulin (IVIG)
- •Plasmapheresis
- •Have received any of the following within 30 days of Day 0:
- •IV cyclophosphamide
- •A non-biologic investigational agent (30 days window OR 5 half-lives, whichever is longer)
- •Any new immunosuppressive/immunomodulatory agent, anti-malarial, NSAID
- •High dose prednisone or equivalent (>1.5 mg/kilogram/day) or any intramuscular or intravenous steroid injection.
- •Have received a live or live-attenuated vaccine within 30 days of Day
- •Have active central nervous system (CNS) lupus (including seizures, psychosis, organic brain syndrome, cerebrovascular accident [CVA], cerebritis or CNS vasculitis) requiring therapeutic intervention within 60 days of Day
- •Have required renal replacement therapy (e.g., hemodialysis, peritoneal dialysis) within 90 days of Day 0 or be currently on renal replacement therapy.
- •Participation in an interventional clinical study either concurrently or within 6 months of screening. Participation in an observational study may be permitted.
- •Have a historically positive test or test positive at screening for Human immunodeficiency virus (HIV) antibody.
- •Evidence of active or latent tuberculosis (TB) as documented by medical history and examination, chest X-rays (posteroanterior) and a positive (not indeterminate) QuantiFERON-TB Gold Plus test.
- •Hepatitis B: Serologic evidence of Hepatitis B (HB) infection defined as Hepatitis B surface antigen positive (HBsAg+) or Hepatitis B core antibody positive (HBcAb+).
- •Hepatitis C: Positive test for Hepatitis C antibody at screening.
研究组 & 干预措施
Pediatric participants receiving belimumab
Experimental
干预措施: Belimumab (Drug)
Pediatric participants receiving belimumab
Experimental
干预措施: Standard therapy (Drug)
结局指标
主要结局
Number of Participants With Adverse Events of Special Interest (AESIs) Through Week 52
时间窗: Up to Week 52
An adverse event (AE) is defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. AESIs included malignancies, post-infusion systemic or hypersensitivity reactions, infections (including serious infections of special interest), and depression, suicide, or self-injury. Infections of special interest included opportunistic infections (OI), herpes zoster (HZ), tuberculosis (TB), and sepsis. Number of participants with AESIs as identified by custom Medical Dictionary for Regulatory Activities (MedDRA) query has been reported.
Number of Participants With Greater Than Equal to (>=) 4 Points Reduction From Baseline to Week 52 in Safety of Estrogen in Lupus National Assessment - Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) Score
时间窗: Baseline (Day 0) and Week 52
The SELENA-SLEDAI score is a cumulative and weighted index for assessing SLE disease activity in participants with SLE. It consists of 24 disease descriptors related to signs and symptoms, laboratory tests, and physician's assessment across 9 organ systems. Each descriptor is assigned a weighted score (8 descriptors with a weight of 8 each, 6 descriptors with a weight of 4 each, 7 descriptors with a weight of 2 each, and 3 descriptors with a weight of 1 each) which is added up if the descriptor is observed during a visit or within the preceding 10 days. The total score ranges from 0 (no disease activity) to 105 (all 24 descriptors present simultaneously). A higher score indicates a more significant degree of disease activity. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Number of participants with a decrease of 4 points or more in the score at Week 52 compared to their Baseline score is presented.
次要结局
- Number of Participants With AEs and Serious Adverse Events (SAEs) Through Week 52(Up to Week 52)
- Percentage of Participants With >=4 Points Reduction From Baseline in SELENA-SLEDAI Score by Each Visit(Baseline (Day 0) and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52)
- Change From Baseline to Week 52 in Parent Global Assessment (ParentGA)(Baseline (Day 0) and Week 52)
- Change From Baseline in Average Daily Prednisone Equivalent Dose at Week 52(Baseline (Day 0) and Week 52)
- Change From Baseline to Week 52 in Physician Global Assessment (PGA)(Baseline (Day 0) and Week 52)
- Apparent Total Clearance of Belimumab(Days 0, 7, and 14 days post first dose, and pre-infusion and post-infusion at Day 84)
- Time to First Flare Over 52 Weeks(Up to Week 52)
- Median Belimumab Concentration Levels at Day 0, 7, and 14 Days Post First Dose, and Pre-infusion and Post-infusion at Day 84(Days 0, 7, and 14 days post first dose, and pre-infusion and post-infusion at Day 84)
- Time to First Severe Flare Over 52 Weeks(Up to Week 52)
- Volume of Distribution of Belimumab(Days 0, 7, and 14 days post first dose, and pre-infusion and post-infusion at Day 84)
- Terminal Half-life (t1/2) of Belimumab(Days 0, 7, and 14 days post first dose, and pre-infusion and post-infusion at Day 84)
- Estimated Maximum Concentration (Cmax) of Belimumab at Steady State(Days 0, 7, and 14 days post first dose, and pre-infusion and post-infusion at Day 84)
- Estimated Minimum Concentration (Cmin) of Belimumab at Steady State(Days 0, 7, and 14 days post first dose, and pre-infusion and post-infusion at Day 84)
- Estimated Average Concentration (Cavg) of Belimumab at Steady State(Days 0, 7, and 14 days post first dose, and pre-infusion and post-infusion at Day 84)
- Area Under Plasma Concentration-time Curve (AUC) of Belimumab at Steady State(Days 0, 7, and 14 days post first dose, and pre-infusion and post-infusion at Day 84)
研究者
研究点 (9)
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