Hydroxyurea and EPO in Sickle Cell Disease (ACHiEvE-SCD)

Assessing Combination Hydroxyurea and Exogenous Erythropoietin in Sickle Cell Disease

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).

Study Overview

• Status: Completed
• Conditions: Sickle Cell Disease; Anemia, Sickle Cell
• Intervention / Treatment: Drug: Hydroxyurea; Drug: Epoetin Alfa-BioSimilar

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.)

• Study Type: Interventional
• Enrollment (Actual): 17
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Nigeria
  • Lagos, Nigeria, 102215
    • Lagos University Teaching Hospital
• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • UPMC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: 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.

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Hemoglobin (Hb) Response	Hb response is defined as a Hb increase of ≥ 1.0 g/dL at 12 weeks compared to baseline	Baseline to 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Number of Blood Transfusions Per Year	Annualized number of units of simple red blood cell transfusions received in the 12 months before treatment initiation, compared to during the treatment period	Baseline to 12 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Tricuspid Valve Regurgitant Jet Velocity as Assessed by Echocardiography	Changes in tricuspid valve regurgitant jet velocity	Baseline to 12 weeks; Baseline to 24 weeks
Changes in Cardiac Index as Assessed by Echocardiography	Changes in cardiac index	Baseline to 12 weeks; Baseline to 24 weeks
Changes in Left Ventricular End-diastolic Volume as Assessed by Echocardiography	Changes in left ventricular end-diastolic volume	Baseline to 12 weeks; Baseline to 24 weeks
Changes in Exercise Capacity as Assessed by 6-minute Walk Test With Modified Borg Dyspnea Scale	Changes in 6-minute walk distance and Modified Borg Dyspnea scale (severity of dyspnea during the 6-minute walk test will be measured on a 10-point scale with 0=nothing at all and 10= maximum severity of breathlessness)	Baseline to 12 weeks; Baseline to 24 weeks
Changes in Hemoglobin (Hb)	Mean change in Hb at 12 weeks compared to baseline	Baseline to 12 weeks
Changes in Absolute Reticulocyte Count	Changes in absolute reticulocyte count	Baseline to 12 weeks; Baseline to 24 weeks
Changes in Lactate Dehydrogenase	Changes in lactate dehydrogenase	Baseline to 12 weeks; Baseline to 24 weeks
Changes in Renal Function	Changes in serum creatinine (and associated eGFR)	Baseline to 12 weeks; Baseline to 24 weeks
Changes in Urine Albumin-to-creatinine Ratio	Changes in urine albumin-to-creatinine ratio	Baseline to 12 weeks; Baseline to 24 weeks
Changes in Total and Indirect Bilirubin	Changes in total and indirect bilirubin	Baseline to 12 weeks; Baseline to 24 weeks
Changes in Ferritin	Changes in ferritin	Baseline to 12 weeks; Baseline to 24 weeks

Collaborators and Investigators

• Sponsor: Julia Xu
• Collaborators: Carnegie Mellon University; American Society of Hematology
• Investigators: Principal Investigator: Julia Z Xu, MD, MScGH, University of Pittsburgh

Study record dates

Study Major Dates

• Study Start (Actual): May 25, 2023
• Primary Completion (Actual): December 13, 2024
• Study Completion (Actual): February 27, 2025

Study Registration Dates

• First Submitted: June 24, 2022
• First Submitted That Met QC Criteria: July 6, 2022
• First Posted (Actual): July 11, 2022

Study Record Updates

• Last Update Posted (Estimated): January 7, 2026
• Last Update Submitted That Met QC Criteria: December 13, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Erythropoietin; Anemia; Hydroxyurea; Sickle cell disease; Sickle cell anemia
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; Anemia, Sickle Cell; Anemia; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Pharmacologic Actions; Chemical Actions and Uses; Therapeutic Uses; Biological Factors; Carbohydrates; Amides; Intercellular Signaling Peptides and Proteins; Glycoproteins; Glycoconjugates; Colony-Stimulating Factors; Hematopoietic Cell Growth Factors; Cytokines; Urea; Hematologic Agents; Hydroxyurea; Hematinics; Erythropoietin
• Other Study ID Numbers: STUDY21120027

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data collected may be shared with secondary researchers within or outside the participating centers upon request. The shared data will be deidentified.
• IPD Sharing Time Frame: Data will be available indefinitely.
• IPD Sharing Access Criteria: Data use agreement (DUA) may be needed for data to be shared.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No