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WithdrawnNCT05228821Updated Aug 9, 2024

Voxelotor Brain Oxygenation and Neurocognitive Study

A Phase 4 interventional study of Voxelotor Oral Tablet in Sickle Cell Disease, sponsored by Pfizer. Withdrawn at 2 sites in United States. Open to participants aged 12 Years to 30 Years. Per ClinicalTrials.gov, last updated 2024-08-09.

Sponsored by Pfizer · Phase 4, Interventional, and Treatment

Why this study was withdrawn
The study has been stopped due to Sponsor's business reasons. The termination is not a result of any safety concerns or change in the benefit-risk ratio.
Phase
Phase 4
Study type
Interventional
Enrollment
0
Allocation
Not applicable
Ages
12 Years to 30 Years
Sex
All
01

Study 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).

Read the detailed description

Eligible participants will receive daily treatment with 1500 mg voxelotor for 24 weeks. During screening, at 12 and 24 weeks, participants will undergo an MRI for evaluation of cerebral blood flow and oxygen extraction fraction as well as NIH toolbox testing for evaluation of executive function, processing speed, and nonexecutive function.

02

Conditions studied

  • Sickle Cell Disease

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03

In context

Anemia, Sickle Cell

1,103 studies on the registry are indexed under Anemia, Sickle Cell; 235 are open to participants now.

Browse Anemia, Sickle Cell studies →

Lead sponsor

Pfizer is the lead sponsor of 3,244 studies on the registry; 139 are open to participants now.

Of its 582 completed or terminated interventional studies of FDA-regulated products, 381 (65%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
12 Years to 30 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. 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.
  2. Aged 12 to 30 years.
  3. Screening Hb level ≥ 5.5 and ≤ 10.5 g/dL.
  4. Must meet site-specific compliance requirements for a diagnostic MRI scan.
  5. Able to answer NIH Toolbox Module questions in English
  6. 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.
  7. 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.
  8. 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.
  9. Females of child-bearing potential must have a negative pregnancy test before the administration of study drug.
  10. 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.
  11. Capable of complying with the requirements and restrictions in the protocol, and willing to participate in the study.

Exclusion criteria

Exclusion Criteria:

  1. History of overt stroke including hemorrhagic stroke, transient ischemic attacks, or spinal cord injury.
  2. 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.
  3. Non-MRI compatible metal hardware and/or metal braces.
  4. 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.
  5. Participant is taking or has received voxelotor (Oxbryta®) within 90 days prior to the Screening Visit.
  6. Participant is taking or has received crizanlizumab (Adakveo®) within 90 days prior to the Screening Visit.
  7. Vaso-occlusive event requiring intravenous opioids within 28 days prior to Day 1.
  8. 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).
  9. Surgery within 8 weeks before Day 1 or planned elective surgery during the study.
  10. Anemia due to bone marrow failure (eg, myelodysplasia).
  11. Absolute reticulocyte count (ARC) \< 100 × 10\^9/L.
  12. Screening alanine aminotransferase or aspartate aminotransferase > 4× upper limit of normal (ULN).
  13. Severe renal dysfunction (estimated glomerular filtration rate [eGFR] \<45 mL/min/1.73 m\^2) or on chronic dialysis.

  14. Clinically significant bacterial, fungal, parasitic, or viral infection which requires therapy

    1. Acute bacterial infection requiring antibiotic use should delay Screening/enrollment until the course of antibiotic therapy has been completed.
    2. Known active hepatitis A, B, or C or are known to be human immunodeficiency virus (HIV) positive.
  15. Symptomatic coronavirus disease of 2019 (COVID-19) infection.
  16. Females who are breast-feeding or pregnant.
  17. History of hematopoietic stem cell transplant or gene therapy.
  18. Participants taking concomitant medications such as sensitive CYP3A4 substrates with a narrow therapeutic range, or strong CYP3A4 inducers.
  19. 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).
  20. 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 (particularly the MRI scan).
05

Study design

Phase
Phase 4
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
0 participants (actual)

Study arms

  • Experimental
    Active Drug

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

    Drug: Voxelotor Oral Tablet

Interventions

  • DrugVoxelotor Oral Tablet

    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

06

What researchers measure

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).

    Time frame: Baseline to Week 24

Secondary outcomes

  1. Change in executive functioning.

    Change from Baseline through Week 24 in the executive cognitive abilities composite score (using Dimensional Change Card Sort Test, Flanker Inhibitory Control and Attention Test, and List Sorting Test) as assessed by the National Institutes of Health Toolbox Cognition Module.

    Time frame: Baseline to Week 24

  2. Change in processing speed

    Change from Baseline through Week 24 in processing speed (using Pattern Comparison Test) as assessed by the NIH Toolbox Cognition Module

    Time frame: Baseline to Week 24

  3. Change in nonexecutive functioning

    Change from Baseline through Week 24 in nonexecutive cognitive abilities composite score (using Picture Vocabulary Test, Oral Reading Recognition Test, and Picture Sequence Memory Test) as assessed by the NIH Toolbox Cognition Module.

    Time frame: Baseline to Week 24

Other outcomes

  1. Change in Hb and hemolysis over time

    Change and percent change from Baseline through Week 24 in hemolysis measures, including unconjugated bilirubin, absolute reticulocyte, % reticulocytes, and lactate dehydrogenase (LDH).

    Time frame: Baseline to week 24

  2. Change in cerebral dynamics

    Change from baseline through Week 24 in cerebral blood flow, oxygen extraction, and oxygen metabolism as measured by diffusion correlation spectroscopy (DCS)/frequency domain near infrared spectroscopy (FDNIRS) (if available) Correlation of cerebral hemodynamics measured by DCS/FDNIRS (if available) and cerebral hemodynamics measured by MRI.

    Time frame: Baseline to week 24

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

    Change from Baseline to Week 24 in global OEF as measured using TRUST (if available)).

    Time frame: Baseline to week 24

  4. Change in regional CBF within the grey matter

    Change from Baseline through Week 24 in regional CBF within the grey matter.

    Time frame: Baseline to Week 24

  5. Change in regional CBF within the white matter

    Change in HRQOL scores using: Change from Baseline through Week 24 in regional CBF within the white matter

    Time frame: Baseline to Week 24

  6. Change in regional OEF as measured using ASE (If available)

    Change from Baseline to Week 24 in regional OEF as measured using ASE (if available)

    Time frame: Baseline to week 24

  7. Correlation between changes from Baseline in CBF (MRI and DCS/FDNIRS)

    Correlation between changes from Baseline in CBF (MRI and DCS/FDNIRS) and changes from Baseline in Hb levels

    Time frame: Baseline to Week 24

  8. Correlation of changes from Baseline in OEF (MRI and DCS/FDNIRS)

    Correlation of changes from Baseline in OEF (MRI and DCS/FDNIRS) and changes from Baseline in Hb levels

    Time frame: Baseline to Week 24

  9. Correlation of change from Baseline in Hb

    Correlation of change from Baseline in Hb and change from Baseline in executive abilities composite score

    Time frame: Baseline to Week 24

  10. Change in HRQOL scores

    Change in HRQOL scores using Patient Global Impression of Severity (PGI-S)

    Time frame: Baseline to Week 24

  11. Change in HRQOL scores using Clinician Global Impression of Severity.

    Change in HRQOL scores using Clinician Global Impression of Severity (CGI-S)

    Time frame: Baseline to Week 24

  12. Incidence and severity of treatment-emergent AEs (TEAEs)

    Incidence and severity of treatment-emergent AEs (TEAEs) baseline through week 24.

    Time frame: Baseline to Week 24

07

Study locations

2 sites
  • Washington University School of Medicine
    Saint Louis, Missouri 63110, United States
  • The Children's Hospital at Montefiore
    Bronx, New York 10467, United States
08

References and documents

Individual participant data

Plan to share: Yes — Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Aug 9, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT05228821
Lead sponsor
Pfizer
Responsible party
Sponsor
First posted
Feb 8, 2022
Start date
Aug 9, 2023
Primary completion
Aug 23, 2023
Completion
Aug 23, 2023
Last update
Aug 9, 2024

Study contacts

Pfizer CT.gov Call Center
study director · Pfizer

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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This study is withdrawn, as verified in Aug 2024. You cannot join it, but the record below documents what was studied.

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