Voxelotor for Sickle Cell Anemia with Chronic Kidney Disease

Overseen By Charity Ball, RN

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Illinois at Chicago

Must be taking: Hydroxyurea, Endari, ACE-inhibitors

Must not be taking: Erythropoietin

Disqualifiers: Pregnancy, Blood transfusions, Infections, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 48 weeks

12 Participants Needed

Trial Summary

Do I need to stop my current medications for the trial?

The trial requires that if you are taking hydroxyurea, Endari, or an ACE-inhibitor/angiotensin receptor blocker, your dose must be stable for at least 90 days before starting the trial, with no expected changes during the study. Other medications are not specifically mentioned, so it's best to discuss with the study team.

Is voxelotor safe for humans?

Voxelotor has been studied in both healthy adults and patients with sickle cell disease, showing it is generally safe and well-tolerated. It has been approved for use in adults and children with sickle cell disease, and a case report showed it was used successfully in a patient with sickle cell disease and chronic kidney disease without affecting kidney function. ^{1 2 3 4 5}

What makes the drug Voxelotor unique for treating sickle cell anemia with chronic kidney disease?

Voxelotor is unique because it works by increasing the amount of normal hemoglobin (the protein in red blood cells that carries oxygen) in the blood, which can help reduce the sickling of red blood cells in sickle cell anemia. This mechanism is different from other treatments that primarily focus on managing symptoms or complications of the disease. ^{6 7 8 9 10}

What is the purpose of this trial?

This study is a single center, prospective exploratory pilot study of Sickle Cell Anemia (SCA) participants. The study will enroll patients with early stages of sickle cell nephropathy (Chronic Kidney Disease (CKD) stage 1 or 2) who are at the highest risk of CKD progression (presence of both hemoglobinuria and urine albumin concentration ≥ 30 mg/g creatinin

Eligibility Criteria

Adults over 18 with Sickle Cell Anemia (SCA) who are at high risk of worsening kidney disease, specifically those with early-stage sickle cell nephropathy and stable medication doses. Participants must not be pregnant or breastfeeding, have no severe infections or recent blood transfusions, and agree to use effective contraception.

Inclusion Criteria

I am using or willing to use effective birth control during and for 30 days after the study.

My sickle cell disease is confirmed by lab tests.

You have had blood in your urine on two recent visits to the doctor's office.

Exclusion Criteria

I haven't had major surgery on my stomach or small intestine.

I do not have active hepatitis A, B, C, or HIV.

Medical, psychological, or behavioral conditions, which, in the opinion of the Investigator, may preclude safe participation, confound study interpretation, interfere with compliance, or preclude informed consent

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Voxelotor 1500mg once a day for the treatment of sickle cell anemia

48 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Voxelotor

Trial Overview The trial is testing Voxelotor in patients with SCA at an early stage of chronic kidney disease but high risk for progression. It's a forward-looking study where all participants receive the same treatment without a comparison group.

Participant Groups

Group I: Voxelot Experimental Treatment 1 Intervention

Voxelotor 1500mg once a day

Group II: Standard of Care (SOC) Experimental Treatment 1 Intervention

Observational while receiving SOC

Voxelotor is already approved in United States, European Union for the following indications:

Approved in United States as Oxbryta for:

• Sickle Cell Disease in patients aged 4 years and older

Approved in European Union as Oxbryta for:

• Hemolytic anemia due to sickle cell disease in adults and pediatric patients 12 years of age and older as monotherapy or in combination with hydroxyurea

Who Is Running the Clinical Trial?

University of Illinois at Chicago

Lead Sponsor

Trials

653

Recruited

1,574,000+

Global Blood Therapeutics

Industry Sponsor

Trials

36

Recruited

3,200+

Findings from Research

Voxelotor (Oxbryta) has been granted accelerated approval for treating sickle cell disease in children aged 4 to 11 years, marking a new treatment option for this age group.

The drug works by preventing red blood cells from sickling, which helps reduce tissue and red blood cell damage associated with sickle cell disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sickle Cell Drug Approved for Children Ages Four to 11. Aschenbrenner, DS.[2023]

Voxelotor, a new oral medication for sickle cell disease, was found to be well tolerated in both healthy volunteers and SCD patients, indicating a good safety profile during the study involving 48 participants.

The drug effectively increased hemoglobin's affinity for oxygen, which could help reduce the sickling of red blood cells, demonstrating its potential mechanism of action in treating sickle cell disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and pharmacodynamics of voxelotor (GBT440) in healthy adults and patients with sickle cell disease. Hutchaleelaha, A., Patel, M., Washington, C., et al.[2021]

Voxelotor is a novel treatment for sickle cell disease (SCD) that has been shown to significantly increase hemoglobin levels compared to placebo, with a mean increase of 1.1 g/dL in a phase 3 trial.

The medication is generally well tolerated, with common side effects including headache, diarrhea, nausea, and joint pain, making it a viable option for patients who cannot tolerate hydroxyurea or have ongoing anemia despite its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Voxelotor: A Novel Treatment for Sickle Cell Disease. Herity, LB., Vaughan, DM., Rodriguez, LR., et al.[2021]

Oxbryta (voxelotor) is an effective treatment for sickle cell disease, with a recommended dose of 1500 mg once daily, supported by a population pharmacokinetic model that describes its behavior in the body over 72 weeks.

The pharmacokinetics of voxelotor are linear and consistent across adults and adolescents, with no significant covariates identified that would require dose adjustments, ensuring its safety and efficacy in the target population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Model-informed drug development of voxelotor in sickle cell disease: Population pharmacokinetics in whole blood and plasma. Savic, RM., Green, ML., Jorga, K., et al.[2022]

Voxelotor, a hemoglobin S polymerization inhibitor, has been successfully used in a 49-year-old man with sickle cell disease and stage IV chronic kidney disease, leading to reduced transfusion needs and fewer painful crises.

The treatment did not negatively impact kidney function, suggesting that voxelotor may be a safe and effective option for managing sickle cell disease in patients with chronic kidney disease, although more data is needed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Case report: Safety and efficacy of voxelotor in a patient with sickle cell disease and stage IV chronic kidney disease. Alshurafa, A., Yassin, MA.[2022]

In a study of 154 African-American patients with end-stage renal disease, those with abnormal hemoglobin variants (like sickle trait) were found to require significantly higher doses of erythropoiesis-stimulating agents (ESA), with an odds ratio of 3.31 for needing higher doses compared to those with normal hemoglobin.

The presence of hemoglobin variants may help explain the disparities in ESA dosing between African-American and Caucasian patients, suggesting that genetic factors could play a role in treatment requirements for anemia in kidney disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Variant hemoglobin phenotypes may account for differential erythropoiesis-stimulating agent dosing in African-American hemodialysis patients. Derebail, VK., Nachman, PH., Key, NS., et al.[2022]

Epoetin delta effectively maintained average hemoglobin levels at 11.3 g/dL over 52 weeks in predialysis patients with chronic kidney disease, with over 80% of hemoglobin measurements above the target level of 10 g/dL.

The treatment was well tolerated, with no significant changes in dosing and no development of neutralizing anti-erythropoietin antibodies, indicating a favorable safety profile for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epoetin delta, erythropoietin produced in a human cell line, in the management of anaemia in predialysis chronic kidney disease patients. Kwan, JT., Pratt, RD.[2017]

In a study of 45 hemodialysis patients, higher doses of sevelamer were independently associated with improved responsiveness to erythropoiesis-stimulating agents (ESA), suggesting a potential role in managing anemia in these patients.

The study also found that transferrin saturation rate (TSAT) was a significant factor influencing ESA resistance, highlighting the importance of monitoring these parameters in chronic kidney disease management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential influence of sevelamer hydrochloride on responsiveness to erythropoiesis-stimulating agents in haemodialysis patients. Ikee, R., Tsunoda, M., Sasaki, N., et al.[2018]

Epoetin-delta, a new human cell line-derived erythropoietin, was found to be as effective as the standard epoetin-alpha in managing anemia in patients with chronic kidney disease, with similar average hemoglobin levels maintained throughout the study.

The treatment was well tolerated, showing a comparable incidence of adverse events to epoetin-alpha, indicating that epoetin-delta is a safe alternative for patients requiring anemia management during hemodialysis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The first human cell line-derived erythropoietin, epoetin-delta (Dynepo), in the management of anemia in patients with chronic kidney disease. Martin, KJ.[2019]

In a 12-week study involving dialysis patients with chronic kidney disease, epoetin delta significantly increased hemoglobin levels, achieving total success in 55.6% of patients at higher doses (150 and 300 IU/kg) compared to only 4.5% at the lowest dose (15 IU/kg).

Epoetin delta demonstrated similar efficacy to epoetin alfa at a dose of 50 IU/kg, with adverse events occurring at expected rates for this patient population, indicating it is a safe and effective treatment option for anemia in CKD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Epoetin delta is effective for the management of anaemia associated with chronic kidney disease. Spinowitz, BS., Pratt, RD.[2017]

References

1. United States pubmed.ncbi.nlm.nih.gov

Sickle Cell Drug Approved for Children Ages Four to 11. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and pharmacodynamics of voxelotor (GBT440) in healthy adults and patients with sickle cell disease. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Voxelotor: A Novel Treatment for Sickle Cell Disease. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Model-informed drug development of voxelotor in sickle cell disease: Population pharmacokinetics in whole blood and plasma. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Case report: Safety and efficacy of voxelotor in a patient with sickle cell disease and stage IV chronic kidney disease. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Variant hemoglobin phenotypes may account for differential erythropoiesis-stimulating agent dosing in African-American hemodialysis patients. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Epoetin delta, erythropoietin produced in a human cell line, in the management of anaemia in predialysis chronic kidney disease patients. [2017]

8. Australia pubmed.ncbi.nlm.nih.gov

Potential influence of sevelamer hydrochloride on responsiveness to erythropoiesis-stimulating agents in haemodialysis patients. [2018]

9. Germany pubmed.ncbi.nlm.nih.gov

The first human cell line-derived erythropoietin, epoetin-delta (Dynepo), in the management of anemia in patients with chronic kidney disease. [2019]

10. England pubmed.ncbi.nlm.nih.gov

Epoetin delta is effective for the management of anaemia associated with chronic kidney disease. [2017]