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
Overview
- Phase
- Phase 3
- Intervention
- Voxelotor Only Product in Oral Dose Form
- Conditions
- Sickle Cell Disease
- Sponsor
- Pfizer
- Enrollment
- 1
- Locations
- 1
- Primary Endpoint
- Change From Baseline in Executive Abilities Composite Score Assessed Using NIH Toolbox Cognition Module At Week 12
- Status
- Terminated
- Last Updated
- 2 years ago
Overview
Brief Summary
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.
Detailed Description
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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.
Exclusion Criteria
- •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.
Arms & Interventions
Active Drug
Voxelotor 1500mg or equivalent daily as a tablet or powder for oral suspension
Intervention: Voxelotor Only Product in Oral Dose Form
Placebo
Matching Placebo
Intervention: Placebo
Outcomes
Primary Outcomes
Change From Baseline in Executive Abilities Composite Score Assessed Using NIH Toolbox Cognition Module At Week 12
Time Frame: 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.
Secondary Outcomes
- 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)