PEACE (Pegzilarginase Effect on Arginase 1 Deficiency Clinical Endpoints): A Randomized, Double-blind, Placebo-controlled Phase 3 Study of the Efficacy and Safety of Pegzilarginase in Children and Adults With Arginase 1 Deficiency
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 32
- 试验地点
- 48
- 主要终点
- Change From Baseline in Plasma Arginine Concentration After 24 Weeks of Treatment
研究概览
简要总结
CAEB1102-300A is a multi-center randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of pegzilarginase in patients with ARG1-D. This study will consist of a screening period; a randomized, double-blind treatment period; a long-term extension; and a follow up visit for final safety assessments.
详细描述
CAEB1102-300A is a multi-center randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of pegzilarginase in patients with ARG1-D. This study will consist of a screening period; a randomized, double-blind treatment period; a long-term extension; and a follow up visit for final safety assessments.
Subjects will be randomized to treatment following completion of all screening assessments and confirmation of study eligibility in a 2:1 ratio to receive weekly IV infusions of pegzilarginase plus individualized disease management (IDM) or placebo plus IDM during the 24-week double blind treatment period. After completion of the 24-week double-blind treatment period, each subject will enter the long term, open-label extension, the first 8 weeks of which are blinded. During the long-term extension, all subjects receive pegzilarginase plus IDM. After 8 weeks of the LTE study, patients have the option to receive treatment by subcutaneous administration (SC).
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
- 2 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subjects are eligible to be included in the study only if all the following criteria apply:
- •The subject and/or parent/guardian provides written informed consent/assent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol
- •A current diagnosis of ARG1 D as documented in medical records, which must include 1 of the following: elevated plasma arginine levels, a mutation analysis that results in a pathogenic variant, or reduced RBC arginase activity. For entry into this study, subjects must also fulfill the following plasma arginine criteria:
- •The average of all measured values of plasma arginine during the screening period prior to the randomization visit (Visit 1, Study Day 1) is ≥ 250 µmol/L
- •If a subject is re-screened, the only values that are considered for eligibility assessment are those in the current screening period
- •Subjects must be ≥ 2 years of age on the date of informed consent/assent
- •The subject must be assessable for clinically meaningful within-subject change (clinical response) on at least one component of one assessment included in the key secondary/other secondary endpoints. To be considered assessable, the subject must be able to complete the assessment, and must have a baseline deficit in at least one component as defined in the protocol
- •Have received documented confirmation from the investigator and/or dietician that the subject can maintain their diet in accordance with dietary information presented in the protocol, ie, can maintain the current level of protein consumption, including natural protein and EAA supplementation
- •Subjects receiving ammonia scavenger therapy, anti-epileptic drugs, and/or medications for spasticity (eg, baclofen) must be on a stable dose of the medication for at least 4 weeks prior to randomization and be willing to remain on a stable dose during the double-blind portion and blinded follow-up portions of the study
- •Female and male subjects may participate. Female subjects of childbearing potential must have a negative serum pregnancy test during the screening period before receiving the first dose of study treatment, and a negative urine pregnancy test on the day of the first dose, prior to the first dose. If the subject (male or female) is engaging in sexual activity that could lead to pregnancy, must be surgically sterile, postmenopausal (no menses for 12 months without an alternative medical cause or a high FSH level in the postmenopausal range in women not using hormonal contraception or hormonal replacement therapy), or must agree to use a highly effective method of birth control during the study and for a minimum of 30 days after the last study drug administration. Highly effective methods of contraception include: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation; progesterone-only hormonal contraception associated with inhibition of ovulation; intrauterine device (IUD); intrauterine hormone-releasing system (IUS); or abstinence (refraining from heterosexual intercourse during the entire period of risk associated with study treatment).
排除标准
- •Hyperammonemic episode (defined as an event in which a subject has an ammonia level ≥100 µM with one or more symptoms related to hyperammonemia requiring hospitalization or emergency room management) within the 6 weeks before the first dose of study drug is administered
- •Active infection requiring anti-infective therapy within 3 weeks prior to first dose
- •Known active infection with human immunodeficiency virus (HIV), hepatitis B, or hepatitis C
- •Extreme mobility deficit, defined as either the inability to be assessed on the GFAQ or a score of 1 on the GFAQ
- •Other medical conditions or comorbidities that, in the opinion of the investigator would interfere with study compliance or data interpretation (eg, severe intellectual disability precluding required study assessments)
- •Has participated in a previous interventional study with pegzilarginase
- •Has a history of hypersensitivity to polyethylene glycol (PEG) that, in the judgment of the investigator, puts the subject at unacceptable risk for adverse events
- •Subject is being treated with botulinum toxin-containing regimens or plans to initiate such regimens during the double-blind or blinded follow-up portions of the study or received surgical or botulinum-toxin treatment for spasticity-related complications within the 16 weeks prior to the first dose of study treatment in this study
- •Is currently participating in another therapeutic clinical trial or has received any investigational agent within 30 days (or 5 half-lives whichever is longer) prior to the first dose of study treatment in this study
- •Previous liver or hematopoietic transplant procedure.
研究组 & 干预措施
Pegzilarginase
Weekly IV infusions of pegzilarginase plus individualized disease management for 24 weeks
干预措施: Pegzilarginase (Drug)
Placebo
Weekly IV infusions of placebo plus individualized disease management for 24 weeks
干预措施: Placebo (Drug)
Pegzilarginase Long Term Extension
After completion of 24 weeks DB treatment, weekly IV infusions of pegzilarginase plus individualized disease management for an additional 150 weeks, with the option to receive treatment by SC after 8 weeks of the LTE study.
干预措施: Pegzilarginase (Drug)
结局指标
主要结局
Change From Baseline in Plasma Arginine Concentration After 24 Weeks of Treatment
时间窗: Baseline through Week 24
The primary analysis will test the change in the level of plasma arginine between baseline and completion of week 24 assessments. It will compare the change from baseline in plasma arginine between participants treated with pegzilarginase and those treated with placebo.
次要结局
- Proportion of Participants With Plasma Arginine Levels Below Target Guidance(Baseline and week 24)
- Proportion of Participants With Plasma Arginine Levels in Normal Range(Baseline to Week 24)
- Change in Ornithine(Baseline and week 24)
- Change in Guanidino Compound-ARGA(Baseline to week 24)
- Mean Change From Baseline in the Mobility Assessments of the Key Secondary Outcome Measure of the 2 Minute Walk Test(Baseline through Week 24)
- Mean Change From Baseline in the Mobility Assessments of the Key Secondary Outcome Measure of GMFM-E(Baseline through Week 24)
- Change in Guanidino Compound - GAA(Baseline to week 24)
- Change in Guanidino Compound - GVA(Baseline to week 24)
- Change in Guanidino Compound - NAArg(Baseline to week 24)
- Mean Change From Baseline at Week 24 in Other Aspects of Mobility Assessed by GMFM-D(Baseline to week 24)
- Mean Change From Baseline at Week 24 in Other Aspects of Mobility Assessed by the Gillette Functional Assessment Questionnaire (GFAQ)(Baseline to week 24)
- Mean Change From Baseline at Week 24 in Adaptive Behavior Assessed Using the Vineland Adaptive Behavior Scales (VABS)-II(Baseline to week 24)
- Evaluate Safety of Pegzilarginase(Reporting will be from signing consent through follow-up (Baseline to Week 24))
- Evaluate Immunogenicity of Pegzilarginase(Baseline to week 24)
- Mean Change From Baseline at Week 24 in Other Aspects of Mobility Assessed by the Functional Mobility Scale (FMS)(Baseline to week 24)