Voxelotor Brain Oxygenation and Neurocognitive Study

NCT05228821 | Withdrawn Phase 4 FDA Drug

• 2 other identifiers: GBT440-043C5341027
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

This is an open label, single arm multicenter trial to evaluate the effect of voxelotor treatment on cerebral blood flow (CBF) and neurocognitive function in adolescent and young adult participants (12-30 years of age) with sickle cell disease (SCD).

Conditions

Sickle Cell Disease

Outcome Measures

Primary Outcomes (1)

• Change in CBF

  Change from Baseline in CBF through Week 24 measured by magnetic resonance imaging (MRI) using pseudo-continuous arterial spin labeling (pCASL).

  Baseline to Week 24

Secondary Outcomes (3)

• Change in executive functioning.

  Baseline to Week 24

• Change in processing speed

  Baseline to Week 24

• Change in nonexecutive functioning

  Baseline to Week 24

Other Outcomes (12)

• Change in Hb and hemolysis over time

  Baseline to week 24

• Change in cerebral dynamics

  Baseline to week 24

• Change in global OEF as measured using T2-Relaxation-Under-Spin-Tagging (TRUST)

  Baseline to week 24

Study Arms (1)

Active Drug

EXPERIMENTAL

Generic Name: Voxelotor Dosage Form: tablet Dosage: 1500mg Frequency: QD Duration: 24 weeks

Drug: Voxelotor Oral Tablet

Interventions

Voxelotor Oral Tablet DRUG

During the Treatment Period, participants will receive 1500 mg of voxelotor once daily (administered as tablets) for 24 weeks in addition to ongoing current standard of care (SOC) treatment

Also known as: Oxbryta

Active Drug

Eligibility Criteria

• Age: 12 Years - 30 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 with HbSS or Hbβ0 thalassemia genotype. Documentation of SCD genotype is required and may be based on documented history of laboratory testing or confirmed by laboratory testing during Screening.
• Aged 12 to 30 years.
• Screening Hb level ≥ 5.5 and ≤ 10.5 g/dL.
• Must meet site-specific compliance requirements for a diagnostic MRI scan.
• Able to answer NIH Toolbox Module questions in English
• If participant is receiving hydroxyurea (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.
• Written informed consent (≥ 18 years) or parental/guardian consent and participant assent (≥ 12-17 years) per Institutional Review Board (IRB) policy and requirements, consistent with 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:

• History of overt stroke including hemorrhagic stroke, transient ischemic attacks, or spinal cord injury.
• Grade 4 vasculopathy defined as moderate stenosis (50% to 69%) in more than 2 major cerebral arteries or severe stenosis (\> 70%) in any major cerebral artery.
• Non-MRI compatible metal hardware and/or metal braces.
• 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.
• Participant is taking or has received crizanlizumab (Adakveo®) within 90 days prior to the Screening Visit.
• Vaso-occlusive event requiring intravenous opioids within 28 days prior to Day 1.
• 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).
• 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 or aspartate aminotransferase \> 4× upper limit of normal (ULN).
• Severe renal dysfunction (estimated glomerular filtration rate \[eGFR\] \<45 mL/min/1.73 m\^2) or on chronic dialysis.
• Clinically significant bacterial, fungal, parasitic, or viral infection which requires therapy
• Acute bacterial infection requiring antibiotic use should delay Screening/enrollment until the course of antibiotic therapy has been completed.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (2)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

The Children's Hospital at Montefiore

The Bronx, New York, 10467, United States

Location

Related Links

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

MeSH Terms

Conditions

Anemia, Sickle Cell

Interventions

voxelotor

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

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 10, 2022
• First Posted: February 8, 2022
• Study Start: August 9, 2023
• Primary Completion: August 23, 2023
• Study Completion: August 23, 2023
• Last Updated: August 9, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will share

Locations

US (2)