Hydroxyurea and EPO in Sickle Cell Disease

Study Overview
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Brief Summary
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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
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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.)

Official Title
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Assessing Combination Hydroxyurea and Exogenous Erythropoietin in Sickle Cell Disease

Conditions
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Anemia, Sickle Cell, Sickle Cell Disease

Intervention / Treatment
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* Drug: Hydroxyurea
* Drug: Epoetin Alfa


Participation Criteria
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Eligibility Criteria
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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 ≥ 100 ng/mL Must be on stable-dose hydroxyurea treatment (i.e., no changes in dose within 60 days prior to screening) 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 screening Received voxelotor or EPO within 60 days of screening Untreated iron deficiency, or had initiation or change in dose of supplemental iron within 30 days of screening Ongoing acute illness, infection, or VOC within 2 weeks of screening Arterial or venous thrombosis within 180 days of screening 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 the screening visit or plans to participate in another investigational drug trial

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Erythropoietin<br>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<br>* 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.<br>* Other names: Droxia, Hydrea, and hydroxycarbamide.;Drug: Epoetin Alfa<br>* Epoetin alfa is a first-generation erythropoiesis-stimulating agent (ESA), 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.<br>* Other names: EPO, epoetin, erythropoietin, erythropoiesis-stimulating agent, ESA, haematopoietin, haemopoietin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in hemoglobin (Hb) level | Hb response, 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 frequency of blood transfusions | Annualized number of units of simple red blood cell transfusions received in the 12 months before treatment initiation compared to during active treatment. | Baseline to 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sickle cell disease, Anemia, Erythropoietin, Hydroxyurea, Sickle cell anemia