Voxelotor Neurocognitive Function Study

NCT05228834 | Terminated Phase 3 Results FDA Drug

• 2 other identifiers: GBT440-044C5341028
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

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.

Conditions

Sickle Cell Disease

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Executive Abilities Composite Score Assessed Using NIH Toolbox Cognition Module At 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.

  Baseline (last assessment prior to first dose of study treatment), Week 12

Secondary Outcomes (8)

• 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 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 Hemoglobin Level Up to Week 12

  Baseline (last assessment prior to first dose of study treatment) up to 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 Percentage Reticulocyte Up to Week 12

  Baseline (last assessment prior to first dose of study treatment) up to Week 12

Other Outcomes (1)

• Number of Participants With Treatment Emergent Adverse Events (TEAEs)

  From start of study treatment (Day 1) up to Week 12

Study Arms (2)

Active Drug

EXPERIMENTAL

Voxelotor 1500mg or equivalent daily as a tablet or powder for oral suspension

Drug: Voxelotor Only Product in Oral Dose Form

Placebo

PLACEBO COMPARATOR

Matching Placebo

Drug: Placebo

Interventions

Voxelotor Only Product in Oral Dose Form DRUG

During the Randomized Treatment Period, participants will be randomized in a 1:1 ratio to receive 1500 mg of voxelotor (or the weight-adjusted equivalent dose for participants \< 12 years old), once daily (administered orally as tablets/PFOS) or matching placebo for 12 weeks in addition to ongoing standard of care (SOC) treatment.

Active Drug

Placebo DRUG

During the Randomized Treatment Period, participants will be randomized in a 1:1 ratio to receive 1500 mg of voxelotor (or the weight-adjusted equivalent dose for participants \< 12 years old), once daily (administered orally as tablets/PFOS) or matching placebo for 12 weeks in addition to ongoing standard of care (SOC) treatment.

Placebo

Eligibility Criteria

• Age: 8 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (1)

University of Maryland Medical Center

Baltimore, Maryland, 21201, United States

Location

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Anemia, Sickle Cell

Interventions

Dosage Forms

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Pharmaceutical Preparations; Technology, Pharmaceutical; Investigative Techniques

Limitations and Caveats

The study was terminated due to slow enrollment and resource reprioritization at L-GBT. Based on the low enrolment data was not reported due to risk of re-identification of participant.

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 10, 2022
• First Posted: February 8, 2022
• Study Start: June 24, 2022
• Primary Completion: September 30, 2022
• Study Completion: September 30, 2022
• Last Updated: May 2, 2024
• Results First Posted: May 2, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will share

Locations

US (1)