What side effects are associated with this type of intervention?

Hydroxyurea, a common treatment for Sickle Cell Anemia, can cause side effects such as myelosuppression (reduced bone marrow activity), which leads to lower blood cell counts, and gastrointestinal issues. It may also increase the risk of infections due to lower white blood cell counts. Voxelotor, another treatment that improves hemoglobin levels, is generally well-tolerated but can cause headaches, diarrhea, abdominal pain, and fatigue. Both treatments require careful monitoring to manage these potential side effects effectively.

What prior FDA approvals exist?

Hydroxyurea is one of the most established FDA-approved treatments for Sickle Cell Anemia, known for reducing vaso-occlusive episodes and improving hemoglobin levels. Voxelotor, another FDA-approved drug, specifically targets hemoglobin polymerization, thereby improving hemoglobin levels and reducing anemia. Additionally, L-glutamine has been approved to reduce acute complications of Sickle Cell Disease. These treatments aim to manage symptoms and improve the quality of life for patients with Sickle Cell Anemia.

What other types of research exist?

Promising novel alternatives to Voxelotor for Sickle Cell Anemia patients include Crizanlizumab and Hydroxyurea. Crizanlizumab reduces vaso-occlusive pain crises by inhibiting P-selectin, a cell adhesion molecule. Hydroxyurea, which has a long history of use, increases fetal hemoglobin levels and reduces vaso-occlusive complications. Both therapies offer different mechanisms of action compared to Voxelotor.

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Hemoglobin Modifiers

Voxelotor for Sickle Cell Anemia (VoxSCAN Trial)

Phase 2

Waitlist Available

Led By Clark Brown, MD

Research Sponsored by Robert Clark Brown

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Homozygous hemoglobin SS (HbSS) or hemoglobin S/beta^0 thalassemia (HbS/β^0 thal)

Ability to take oral medication and willingness to adhere to daily voxelotor and scheduled DCS/NIRS assessments

Must not have

Acute bacterial infection requiring antibiotic use, known active hepatitis A, B, or C infection or human immunodeficiency virus (HIV)-positive, known active malaria, pregnant patients, evidence of abnormal high blood flow velocities on transcranial doppler (TCD) of 200 cm/sec or more

Hepatic dysfunction characterized by alanine aminotransferase (ALT) >4× upper limit of normal (ULN) for age

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline, weeks 4 and 12

Awards & highlights

No Placebo-Only Group

Summary

This trial tests voxelotor, a drug that boosts hemoglobin levels, in adolescents and adults with sickle cell disease. The study will see if it improves brain blood flow and oxygen use over a few months. Voxelotor is a hemoglobin S polymerization inhibitor approved in 2019 for treating sickle cell disease.

Who is the study for?

Children aged 4-17 with sickle cell anemia can join this trial if they have stable doses of hydroxyurea, no severe heart issues, and are not on chronic transfusion therapy. They must be able to take oral meds and follow the study plan. Girls who can get pregnant need a negative pregnancy test and agree to use birth control.

What is being tested?

The trial is testing Voxelotor's effect on brain blood flow in kids with sickle cell disease. It checks if higher hemoglobin from the drug lowers stress in the brain. Participants will regularly take Voxelotor orally and undergo special assessments.

What are the potential side effects?

Possible side effects of Voxelotor include headache, diarrhea, abdominal pain, nausea, fatigue, rash, fever; however specific side effects related to cerebral hemodynamics are being studied.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I have sickle cell disease (either HbSS or HbS/β^0 thalassemia).

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I can take pills and will follow the treatment and testing schedule.

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I am between 4 and 30 years old.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My liver enzyme (ALT) levels are more than four times the normal limit.

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I am on chronic dialysis or my creatinine level is 1.5 mg/dL or higher.

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I do not have significant heart disease or conditions affecting my heart's rhythm.

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I have had a blood transfusion or experienced specific sickle cell complications recently.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline, weeks 4 and 12

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline, weeks 4 and 12

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline, weeks 4 and 12 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Change in cerebral blood flow (CBF)

Change in cerebral metabolic rate of oxygen (CMRO2)

Change in oxygen extraction fraction (OEF)

Secondary study objectives

Change in RBC content of voxelotor-modified hemoglobin

Change in total hemoglobin

Side effects data

From 2022 Phase 4 trial • 25 Patients • NCT04400487

32%

Sickle cell anaemia with crisis

Acute chest syndrome

100%

80%

60%

40%

20%

Study treatment Arm

Voxelotor: SCD Related

Voxelotor: Non-SCD Related

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: VoxelotorExperimental Treatment1 Intervention

Children with sickle cell anemia taking voxelotor for 12 weeks.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Voxelotor

2023

Completed Phase 4

~90

0 / 8Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Hydroxyurea works by increasing fetal hemoglobin (Hb F) levels, which reduces the formation of sickle-shaped cells and decreases the frequency of pain crises and other complications. L-glutamine helps to reduce oxidative stress in red blood cells, thereby decreasing the frequency of vaso-occlusive crises (VOC). Voxelotor improves hemoglobin levels by inhibiting hemoglobin S polymerization, which prevents red blood cells from sickling and thus reduces anemia and VOC. Crizanlizumab is a monoclonal antibody that targets P-selectin, reducing the adhesion of sickled red blood cells to the blood vessel walls and thereby decreasing the frequency of VOC. These treatments are crucial for Sickle Cell Anemia patients as they help manage symptoms, reduce complications, and improve overall quality of life.

A reanalysis of pain crises data from the pivotal l-glutamine in sickle cell disease trial.Comparing the Safety and Efficacy of L-Glutamine, Voxelotor, and Crizanlizumab for Reducing the Frequency of Vaso-Occlusive Crisis in Sickle Cell Disease: A Systematic Review.