The Effect of Voxelotor on Cerebral Hemodynamic Response in Children With Sickle Cell Anemia

NCT05018728 | Terminated Phase 2 DMC FDA Drug

• 1 other identifier: STUDY00002483
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 2

Brief Summary

Voxelotor is a new drug for adolescents and adults with sickle cell disease that improves hemoglobin levels and reduces the incidence of worsening anemia. However, it is unclear whether this increase in hemoglobin is associated with a reduction in cerebral metabolic stress. This study will measure the effects of voxelotor on cerebral hemodynamics.

Conditions

Sickle Cell Anemia in Children

Outcome Measures

Primary Outcomes (3)

• Change in cerebral blood flow (CBF)

  CBF will be measured by diffuse correlation spectroscopy and frequency domain near-infrared spectroscopy (DCS/FDNIRS).

  Baseline, Weeks 4 and 12

• Change in oxygen extraction fraction (OEF)

  OEF will be measured by DCS/FDNIRS. OEF is defined as the difference between arterial and venous oxygen content and it increases to keep up with metabolic demand.

  Baseline, Weeks 4 and 12

• Change in cerebral metabolic rate of oxygen (CMRO2)

  CMRO2 will be measured by DCS/FDNIRS. CMRO2 is the rate that the brain consumes oxygen and is a marker of brain health.

  Baseline, Weeks 4 and 12

Secondary Outcomes (2)

• Change in total hemoglobin

  Baseline, Weeks 4 and 12

• Change in RBC content of voxelotor-modified hemoglobin

  Baseline, Weeks 4 and 12

Study Arms (1)

Voxelotor

EXPERIMENTAL

Children with sickle cell anemia taking voxelotor for 12 weeks.

Drug: Voxelotor

Interventions

Voxelotor DRUG

Voxelotor is taken orally once a day. Participants 12 years or older will take 1500 mg/day. Participants younger than 12 years of age will receive a dose based on their body weight to provide exposure corresponding to the adult dose of 1500 mg/day.

Also known as: Oxbryta

Voxelotor

Eligibility Criteria

• Age: 4 Years - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Written informed parental/guardian consent and participant assent/consent has been obtained per institutional review board (IRB)/Ethics Committee (EC) policy and requirements, consistent with International Conference on Harmonization (ICH) guidelines
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Male or female participants, ages 4 to 30 years, inclusive
• Homozygous hemoglobin SS (HbSS) or hemoglobin S/beta\^0 thalassemia (HbS/β\^0 thal)
• Hemoglobin (Hb) ≤10.5 g/dL at baseline
• Concomitant hydroxyurea (HU) therapy is allowed if the dose has been stable for at least 3 months with no anticipated need for dose adjustments during the study and no sign of hematological toxicity
• Ability to take oral medication and willingness to adhere to daily voxelotor and scheduled DCS/NIRS assessments
• If sexually active and female, must agree to abstain from sexual intercourse or to use a highly effective method of contraception throughout the study period and for 30 days after discontinuation of study drug. If sexually active and male, must agree to abstain from sexual intercourse or willing to use barrier methods of contraception throughout the study period and for 30 days after discontinuation of study drug.
• Females of child-bearing potential, i.e., who have begun menstruation and are sexually active, are required to have a negative pregnancy test at screening before the initial administration of study drug.

You may not qualify if:

• Any one of the following requiring medical attention within 14 days prior to signing the informed consent form (ICF):
• Vaso-occlusive crisis (VOC)
• Acute chest syndrome (ACS)
• Splenic sequestration crisis
• Dactylitis
• Requires chronic transfusion therapy
• Red blood cell (RBC) transfusion within 60 days of signing the ICF
• Renal dysfunction requiring chronic dialysis or creatinine ≥1.5 mg/dL
• Hepatic dysfunction characterized by alanine aminotransferase (ALT) \>4× upper limit of normal (ULN) for age
• Clinically relevant cardiac abnormality, in the opinion of the Investigator, such as:
• Hemodynamically significant heart disease, e.g., congenital heart defect, uncompensated heart failure, or any unstable cardiac condition
• An arrhythmic heart condition requiring medical therapy
• Corrected QT interval by Fridericia (QTcF) \>450 msec, congenital long QT syndrome, second- or third-degree heart block at rest (with the exception of asymptomatic Mobitz type I second degree heart block)
• Received an investigational drug within 30 days or 5 half-lives, whichever is longer, of signing the ICF
• Heavy smoker (defined as smoking more than 10 cigarettes/day or its nicotine equivalent including e-cigarettes)

Sponsors & Collaborators

• Emory University: lead
• Pfizer: collaborator

Study Sites (2)

Children's Healthcare of Atlanta

Atlanta, Georgia, 30322, United States

Location

Aflac Sickle Cell Comprehensive Clinics at Children's Healthcare of Atlanta, Scottish Rite

Atlanta, Georgia, 30342, United States

Location

Related Publications (1)

• Brothers RO, Turrentine KB, Akbar M, Triplett S, Zhao H, Urner TM, Goldman-Yassen A, Jones RA, Knight-Scott J, Milla SS, Bai S, Tang A, Brown RC, Buckley EM. The influence of voxelotor on cerebral blood flow and oxygen extraction in pediatric sickle cell disease. Blood. 2024 May 23;143(21):2145-2151. doi: 10.1182/blood.2023022011.

  PMID: 38364110 DERIVED

MeSH Terms

Interventions

voxelotor

Study Officials

• Amy Tang, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 18, 2021
• First Posted: August 24, 2021
• Study Start: March 28, 2022
• Primary Completion: October 22, 2024
• Study Completion: October 22, 2024
• Last Updated: December 12, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: Data will be available for sharing immediately following publication, with no end date.
• Access Criteria: Data will be made available for sharing with researchers who provide a methodologically sound proposal, in order to achieve the aims in the approved proposal. Proposals should be directed to erin.buckley@emory.edu. To gain access, data requestors will need to sign a data access agreement.

Locations

US (2)