A Phase III, Randomized, Double-blind, Parallel-group, Placebo-controlled Study to Evaluate the Pharmacokinetics, Pharmacodynamics, Efficacy, and Safety of IV Anifrolumab in Pediatric Participants 5 to < 18 Years of Age With Moderate to Severe Active Systemic Lupus Erythematosus While on Background Standard of Care Therapy
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- AstraZeneca
- 入组人数
- 100
- 试验地点
- 106
- 主要终点
- Part A - Maximum observed serum (peak) drug concentration (Cmax)
研究概览
简要总结
A Study to Evaluate the Pharmacokinetics (PK), Pharmacodynamics (PD), Efficacy, and Safety of Anifrolumab in Children with Moderate to Severe Active Systemic Lupus Erythematosus (SLE)
详细描述
This study aims to characterize the pharmacokinetics, pharmacodynamics, efficacy, and safety of anifrolumab solution for infusion compared with placebo solution for infusion in pediatric participants with severe active systemic lupus erythematosus who are on background standard of care therapy.
The study duration for a participant will be approximately 116 weeks, which includes:
- Screening period of up to 30 days.
- Part A consists of a four-week, double-blind, placebo-controlled, randomised, pharmacokinetic period.
- Part B is a double-blind, placebo-controlled, randomised, safety/efficacy period lasting 48 weeks (for rollover participants from Part A) or 52 weeks (for de novo participants).
- Part C is a 52-week open-label extension period.
- Part D is a safety follow-up period. One safety visit at 12 weeks post last dose.
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
- 5 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participant's parent/caregiver/legally authorized representative and participant (if required per local country regulation) capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol. Informed assent is to be provided by the participant per local country regulation.
- •Diagnosis of SLE according to the 2019 European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) criteria for at least 3 months prior to signing the ICF.
- •At Screening, participant must have moderate to severe active SLE disease, as adjudicated by the Central Adjudication Committee, defined as:
- •(a) SLEDAI-2K activity of: (i) ≥ 6 points with at least 4 points (≥ 4 points) coming from the following clinical components ('Clinical' SLEDAI-2K score): arthritis, myositis, rash, alopecia, mucosal ulcers, pleurisy, pericarditis, or vasculitis and excluding points attributed to a fever, SLE headache, and organic brain syndrome (ii) Clinical SLEDAI score of ≥ 4 points verified at Day 1 (b) BILAG-2004 activity of: (i) ≥ 1 BILAG A score; or (ii) ≥ 2 BILAG B scores (c) PGA score ≥ 1.0 on a 0 to 3 VAS
- •Participant should meet all of following tuberculosis (TB) criteria:
- •A. No signs or symptoms of active TB B. No medical history or past physical examinations suggestive of active TB C. No recent contact with a person with active TB or if there has been such contact, referral to a TB specialist for evaluation and initiation of treatment for latent TB, if warranted, prior to the first administration of study intervention in accordance with local SoC D. No history of latent TB without documented completion of treatment prior to initial screening visit
- •Female participants of childbearing potential must have a negative serum pregnancy test at screening and negative urine pregnancy test at randomization.
- •Female participants of childbearing and male participants must adhere to the contraception methods.
排除标准
- •Known diagnosis of an IFN-mediated autoinflammatory interferonopathy.
- •History of, or current diagnosis of, clinically significant non-SLE-related vasculitides.
- •In participants aged 11 years and above: history or evidence of suicidal ideation.
- •History of any non-SLE disease that has required treatment with oral or parenteral corticosteroids for more than a total of 2 weeks within the last 24 weeks prior to signing the ICF.
- •Any positive result on screening for human immunodeficiency virus.
- •Active hepatitis B surface antigen OR hepatitis B core antibody (HBcAb), hepatitis C virus (HCV) antibody and detectable HCV ribonucleic acid (RNA) or any active or recent case of Herpes Zoster infection.
- •Any clinical cytomegalovirus or Epstein-Barr virus infection that has not completely resolved within 12 weeks prior to signing the ICF.
- •History of severe COVID-19 infection requiring hospitalization, intensive care unit care, or assisted ventilation or any prior COVID-19 infection with unresolved sequelae. Any mild/asymptomatic COVID-19 infection (laboratory confirmed or suspected based on clinical symptoms).
- •Prior use of anifrolumab.
- •Prior treatment with directly acting cytotoxic B-cell depleting therapeutics (eg, rituximab) < 26 weeks prior to ICF signature.
- •Blood transfusion or receipt of blood products except albumin within 4 weeks prior to signing the ICF.
研究组 & 干预措施
Placebo
Randomized participants will receive matching placebo via IV infusion
干预措施: Placebo (Drug)
Anifrolumab
Randomized participants will receive anifrolumab via intravenous (IV) infusion every 4 weeks
干预措施: Anifrolumab (Biological)
结局指标
主要结局
Part A - Maximum observed serum (peak) drug concentration (Cmax)
时间窗: Up to Day 29
The serum PK will be characterised and the dose of anifrolumab will be defined in pediatric participants with moderate to severely active SLE.
Part A - Area under the serum concentration curve (AUC)
时间窗: Up to Day 29
The serum PK will be characterised and the dose of anifrolumab will be defined in pediatric participants with moderate to severe active SLE.
Part A - Minimum observed serum concentration (Cmin)
时间窗: Up to Day 29
The serum PK will be characterised and the dose of anifrolumab will be defined in pediatric participants with moderate to severe active SLE.
Part B - Number of participants who are British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) responders (yes/no)
时间窗: At Week 52
BICLA response is defined as: * Reduction of all baseline British Isles Lupus Assessment Group BILAG-2004 A to B/C/D and B to C/D, and no BILAG-2004 worsening in other organ systems, as defined by ≥ 1 new BILAG-2004 A or ≥ 2 new BILAG- 2004 B. * No worsening from baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), defined as an increase from baseline of \> 0 points. * No worsening from baseline in participant's lupus disease activity, defined by an increase ≥ 0.30 points on a Physician's Global Assessment (PGA) 3-point visual analogue scale (VAS).
Part A - Maximum observed serum (peak) drug concentration (Cmax)
时间窗: Up to Day 29
The serum PK will be characterised and the dose of anifrolumab will be defined in pediatric participants with moderate to severely active SLE.
Part A - Area under the serum concentration curve (AUC)
时间窗: Up to Day 29
The serum PK will be characterised and the dose of anifrolumab will be defined in pediatric participants with moderate to severe active SLE.
Part A - Minimum observed serum concentration (Cmin)
时间窗: Up to Day 29
The serum PK will be characterised and the dose of anifrolumab will be defined in pediatric participants with moderate to severe active SLE.
Part B - Number of participants who are British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) responders (yes/no)
时间窗: At Week 52
BICLA response is defined as: * Reduction of all baseline British Isles Lupus Assessment Group BILAG-2004 A to B/C/D and B to C/D, and no BILAG-2004 worsening in other organ systems, as defined by ≥ 1 new BILAG-2004 A or ≥ 2 new BILAG- 2004 B. * No worsening from baseline in SLEDAI-2K, defined as an increase from baseline of \> 0 points. * No worsening from baseline in participant's lupus disease activity, defined by an increase ≥ 0.30 points on a PGA 3-point visual analogue scale (VAS).
Part A- Anifrolumab serum concentration
时间窗: Pre-dose Day 29
The serum concentration will be characterised and the dose of anifrolumab will be defined in pediatric participants with moderate to severely active SLE.
次要结局
- Number of participants who are Pediatric Rheumatology International Trials Organization/American College of Rheumatology (PRINTO/ACR) childhood-onset systemic lupus erythematosus (cSLE) responders (yes/no)(At Week 52)
- Part B - Number of participants who are Systemic Lupus Erythematosus Responder Index of ≥ 4 SRI(4) responders (yes/no)(At Week 52)
- Part B - Number of participants who are Systemic Lupus Erythematosus Responder Index of ≥ 4 SRI(4) responders (yes/no)(At Week 52)
- Part B - Time to first flare(Through Week 52)
- Number of participants who are Pediatric Rheumatology International Trials Organization/American College of Rheumatology (PRINTO/ACR) childhood-onset systemic lupus erythematosus (cSLE) responders (yes/no)(At Week 52)
- Part B - The mean percentage reduction from Baseline through Week 52 in oral corticosteroid(s) (OCS) background dose(Baseline, Week 52)
- Part B - Change from baseline through Week 52 in type I interferon (IFN) 21-gene signature(Baseline, Week 52)
- Part B - Anifrolumab serum concentration(Pre-dose Week 12, Pre-dose Week 24, Pre-dose Week 52)
- Part - B Change from baseline through Week 52 in antidrug antibody (ADA)(Up to Week 52)
- Part - B Change from baseline in anti-double stranded deoxyribonucleic acid antibodies(At Week 12 and Week 52)
- Part - B Change from baseline in total hemolytic complement (CH50)(At Week 12 and Week 52)
- Part - B Change from baseline in complement component (C3)(At Week 12 and Week 52)
- Part - B Change from baseline in complement component (C4)(At Week 12 and Week 52)
- Part B - The mean percentage reduction from Baseline through Week 52 in oral corticosteroid(s) (OCS) background dose(At Week 52)
- Part B - Change from baseline through Week 52 in type I interferon (IFN) 21-gene signature(At Week 52)