NCT05228834终止3 期
A Phase 3b, Randomized, Double-blind, Placebo-controlled, Multicenter Study to Evaluate the Treatment Effect of Voxelotor on Neurocognitive Function in Pediatric Participants 8 to < 18 Years of Age With Sickle Cell Disease
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- Pfizer
- 入组人数
- 1
- 试验地点
- 1
- 主要终点
- Change From Baseline in Executive Abilities Composite Score Assessed Using NIH Toolbox Cognition Module At Week 12
研究概览
简要总结
This is a Phase 3b, randomized, double-blind, placebo-controlled, multicenter study to assess the treatment effect of voxelotor on neurocognitive function as assessed by the National Institute of Health (NIH) Toolbox Cognition Module of executive abilities in pediatric participants (8 to < 18 years) with SCD.
详细描述
Eligible participants will receive daily treatment with 1500 mg voxelotor or matching placebo for 12 weeks. During screening and at the end of 12 weeks participants will undergo a series of tests to measure the change in neurocognitive functions.
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
- 8 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female participants with confirmed diagnosis of SCD (all genotypes). Documentation of SCD genotype is required and may be based on documented history of laboratory testing or confirmed by laboratory testing during Screening.
- •Aged 8 to < 18 years.
- •Screening Hb level 5.5 to 10.5 g/dL.
- •Able to answer NIH Toolbox Module questions validated and normed based on age and maternal education on tablet.
- •If participant is receiving HU they must have been on a stable dose for at least 90 days prior to signing the ICF/AF, with no dose modifications or initiation of HU planned or anticipated by the Investigator.
- •If participant is receiving erythropoiesis-stimulating agents (ESAs) they must have been on a stable dose for at least 12 weeks before enrollment with no dose modifications planned or anticipated by the Investigator.
- •Participants, who if female and of child-bearing potential, agree to use highly effective methods of contraception from study start to 30 days after the last dose of study drug and who if male, agree to use barrier methods of contraception and refrain from donating sperm from study start to 30 days after the last dose of study drug.
- •Females of child-bearing potential must have a negative pregnancy test before the administration of study drug.
- •Parental/guardian consent and participant assent (between ≥ 12 and < 18 years) per Institutional Review Board (IRB)/Independent ethics committee (IEC) policy and requirements, consistent with International Council for Harmonisation (ICH) guidelines.
- •Capable of complying with the requirements and restrictions in the protocol, and willing to participate in the study.
排除标准
- •Receiving chronic transfusion therapy.
- •Red blood cell (RBC) transfusion within 3 months before initiation of study drug or receives scheduled RBC transfusion therapy (also termed chronic, prophylactic, or preventive transfusion).
- •History of overt stroke including hemorrhagic stroke or transient ischemic attack (TIA) or spinal cord injury, magnetic resonance angiography (MRA)-defined vasculopathy, or magnetic resonance imaging (MRI)/transcranial doppler (TCD)-documented silent cerebral infarcts.
- •Congenital brain malformation, previously diagnosed severe developmental disability (eg, autism and/or intelligence quotient [IQ] < 60, and/or severe attention deficit hyperactivity disorder [ADHD]), or impairment that would prevent the use of a computer tablet.
- •Participant is taking or has received voxelotor (Oxbryta®) within 90 days prior to the Screening Visit.
- •Surgery within 8 weeks before Day 1 or planned elective surgery during the study.
- •Anemia due to bone marrow failure (eg, myelodysplasia).
- •Absolute reticulocyte count (ARC) < 100 × 10^9/L.
- •Screening alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 4× upper limit of normal (ULN).
- •Severe renal dysfunction (estimated glomerular filtration rate [eGFR] < 30 mL/min/1.73 m^2) or is on chronic dialysis.
- •Clinically significant bacterial, fungal, parasitic, or viral infection which requires therapy.
- •Patients with acute bacterial infection requiring antibiotic use should delay screening /enrollment until the course of antibiotic therapy has been completed.
- •Patients with known active hepatitis A, B, or C or who are known to be human immunodeficiency virus (HIV) positive.
- •Symptomatic coronavirus disease of 2019 (COVID-19) infection.
- •Females who are breast-feeding or pregnant.
- •History of hematopoietic stem cell transplant or gene therapy.
- •Participants taking concomitant medications such as sensitive cytochrome P450 (CYP)3A4 substrates with a narrow therapeutic range, or strong CYP3A4 inducers
- •Participated in another clinical trial of an investigational product (or medical device) within 30 days or 5 half-lives of date of informed consent, whichever is longer, or is currently participating in another trial of an investigational product (or medical device).
- •Medical, psychological, or behavioral condition that, in the opinion of the Investigator, would confound or interfere with evaluation of safety and/or efficacy of the study drug, prevent compliance with the study protocol; preclude informed consent; or, render the participant unable/unlikely to comply with the study procedures.
研究组 & 干预措施
Active Drug
Experimental
Voxelotor 1500mg or equivalent daily as a tablet or powder for oral suspension
干预措施: Voxelotor Only Product in Oral Dose Form (Drug)
Placebo
Placebo Comparator
Matching Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Change From Baseline in Executive Abilities Composite Score Assessed Using NIH Toolbox Cognition Module At Week 12
时间窗: Baseline (last assessment prior to first dose of study treatment), Week 12
The NIH toolbox cognition module is a standardized cognitive battery comprising of executive function, episodic memory, language, processing speed, working memory, and attention as subdomains. The toolbox is comprised of 7 test instruments that measure 8 abilities within 6 major cognitive domains and have been categorized as executive abilities (Dimensional Change Card Sort Test, Flanker Inhibitory Control and Attention Test, and List Sorting Test) and nonexecutive abilities (Picture Vocabulary Test, Oral Reading Recognition Test, and Picture Sequence Memory Test). The NIH toolbox standard score has a mean of 100 and standard deviation (SD) of 15. The higher the score, the better the performance.
次要结局
- Change From Baseline in Unconjugated Bilirubin Up to Week 12(Baseline (last assessment prior to first dose of study treatment) up to Week 12)
- Change From Baseline in Nonexecutive Cognitive Abilities Composite Score Assessed Using NIH Toolbox Cognition Module Up to Week 12(Baseline (last assessment prior to first dose of study treatment) up to Week 12)
- Change From Baseline in Pattern Comparison Processing Speed Test Scores Assessed Using NIH Toolbox Cognition Module at Week 12(Baseline (last assessment prior to first dose of study treatment), Week 12)
- Change From Baseline in Absolute Reticulocyte Count Up to Week 12(Baseline (last assessment prior to first dose of study treatment) up to Week 12)
- Change From Baseline in Hemoglobin Level Up to Week 12(Baseline (last assessment prior to first dose of study treatment) up to Week 12)
- Change From Baseline in Percentage Reticulocyte Up to Week 12(Baseline (last assessment prior to first dose of study treatment) up to Week 12)
- Change From Baseline in Lactate Dehydrogenase (LDH) Up to Week 12(Baseline (last assessment prior to first dose of study treatment) up to Week 12)
- Percent Change From Baseline in Unconjugated Bilirubin, Absolute Reticulocyte, Percentage Reticulocytes, Lactate Dehydrogenase (LDH) Up to Week 12(Baseline (last assessment prior to first dose of study treatment) up to Week 12)
研究者
研究点 (1)
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