Hydroxyurea and EPO in Sickle Cell Disease

NCT ID: NCT05451940

Last Updated: 2026-01-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 17 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-05-25
• Study Completion Date: 2025-02-27

Brief Summary

The proposed study is a Phase 1/2 multi-center study evaluating the safety and efficacy of erythropoietin (EPO) in combination with hydroxyurea in the treatment of chronic anemia in patients with sickle cell disease (SCD).

Detailed Description

Sickle cell disease (SCD) is a devastating inherited hemoglobin disorder characterized by recurrent episodes of pain and chronic hemolytic anemia. Chronic anemia contributes to multi-organ damage and decreased life expectancy in SCD. However, there are limited treatment options for anemia in SCD. Erythropoietin (EPO) is the standard of care for treatment of anemia related to chronic kidney disease (CKD) and is also used ad hoc in patients with SCD. However, there is limited data on the safety and efficacy of EPO in patients with SCD, especially in combination with hydroxyurea. Therefore, this study aims to treat patients on stable hydroxyurea therapy with subcutaneous EPO, with the goal of assessing the safety of EPO therapy and its effect on chronic anemia in SCD.

(Note: Outcome measure changes were in place prior to study initiation.)

Conditions

Anemia, Sickle Cell; Sickle Cell Disease

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Erythropoietin

Subjects on a stable dose of hydroxyurea will be treated with increasing doses of subcutaneous erythropoietin (EPO) as tolerated for an initial 12 weeks, during which the main safety and efficacy endpoints (including the primary endpoint of hemoglobin response) will be assessed. Subjects may continue on treatment for an additional 12 weeks as clinically indicated, with assessment of additional endpoints at the end of the 24-week study period.

Group Type: EXPERIMENTAL

Hydroxyurea

Intervention Type: DRUG

Hydroxyurea is an orally available antimetabolite medication that has been shown to reduce the frequency of painful crises and acute chest syndrome in adults and children with sickle cell disease. Hydroxyurea treats sickle cell disease by a number of different mechanisms, including increasing the expression of fetal hemoglobin (HbF), which reduces sickling of red blood cells.

Epoetin Alfa-BioSimilar

Intervention Type: DRUG

Epoetin alfa and its biosimilars are first-generation erythropoiesis-stimulating agents (ESAs), which are recombinant versions of erythropoietin (EPO) produced using recombinant DNA technology. Erythropoietin (EPO) is a glycoprotein hormone, naturally produced mainly in the kidneys in response to hypoxia and stimulates red blood cell production (erythropoiesis) in the bone marrow.

Interventions

Hydroxyurea

Hydroxyurea is an orally available antimetabolite medication that has been shown to reduce the frequency of painful crises and acute chest syndrome in adults and children with sickle cell disease. Hydroxyurea treats sickle cell disease by a number of different mechanisms, including increasing the expression of fetal hemoglobin (HbF), which reduces sickling of red blood cells.

Intervention Type: DRUG

Epoetin Alfa-BioSimilar

Epoetin alfa and its biosimilars are first-generation erythropoiesis-stimulating agents (ESAs), which are recombinant versions of erythropoietin (EPO) produced using recombinant DNA technology. Erythropoietin (EPO) is a glycoprotein hormone, naturally produced mainly in the kidneys in response to hypoxia and stimulates red blood cell production (erythropoiesis) in the bone marrow.

Intervention Type: DRUG

Other Intervention Names

Droxia, Hydrea, and hydroxycarbamide.; EPO, epoetin, erythropoietin, erythropoiesis-stimulating agent, ESA, haematopoietin, haemopoietin

Eligibility Criteria

Inclusion Criteria

• Aged ≥ 18 years
• Confirmed diagnosis of SCD (HbSS or HbS/β0-thalassemia genotypes)
• Screening Hb ≤ 9.0 g/dL
• Screening transferrin saturation ≥ 20% and ferritin ≥ 50 ng/mL
• Must be on stable-dose hydroxyurea treatment (i.e., no changes in dose within 60 days prior to start of study drug) and plan to continue taking hydroxyurea at the same dose and schedule during the study
• If receiving L-glutamine or crizanlizumab, must have been receiving the drug at a stable dose for at least 60 days prior to screening and plan to continue taking the drug at the same dose and schedule during the study

Exclusion Criteria

• Participating in a chronic transfusion program (pre-planned series of transfusions for prophylactic purposes) and/or planning on undergoing an exchange transfusion during the duration of the study; episodic transfusion in response to worsened anemia or VOC is permitted, but participant should not have received a blood transfusion within 60 days of start of study drug
• Received voxelotor or EPO within 30 days of start of study drug
• Untreated iron deficiency, or had initiation or change in dose of supplemental iron within 30 days of start of study drug
• Ongoing acute illness, infection, or VOC within 2 weeks of start of study drug
• Arterial or venous thrombosis within 180 days of start of study drug
• Grade 3 hypertension (defined as systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg; medical intervention indicated; more than one drug or more intensive therapy than previously used indicated) on two consecutive measurements
• Unstable angina, uncontrolled seizure disorder, or active malignancy
• End-stage renal disease requiring hemodialysis
• Current pregnancy or breastfeeding
• Received active treatment on another investigational trial within 30 days (or 5 half-lives of that agent, whichever is greater) prior to start of study drug or plans to participate in another investigational drug trial

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Carnegie Mellon University

OTHER

Sponsor Role: collaborator

American Society of Hematology

OTHER

Sponsor Role: collaborator

Julia Xu

OTHER

Sponsor Role: lead

Responsible Party

Julia Xu

Assistant Professor

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Julia Z Xu, MD, MScGH

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Locations

UPMC

Pittsburgh, Pennsylvania, United States

Lagos University Teaching Hospital

Lagos, , Nigeria

Countries

United States; Nigeria

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

STUDY21120027

Identifier Type: -

Identifier Source: org_study_id