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).

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.)

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

Data collected may be shared with secondary researchers within or outside the participating centers upon request. The shared data will be deidentified.

Data will be available indefinitely.

Data use agreement (DUA) may be needed for data to be shared.

All participants completing the 12-week treatment period were included in the analysis.

From study drug initiation to the end of the treatment period (up to 12 weeks)

The sponsor provided the study drug (EPO) for the duration of the treatment period (12 weeks). However, the sponsor was not able to provide study drug for a longer study, and participants who wanted to continue on EPO treatment during the observation period had to pay out of pocket or get insurance coverage. Thus, most participants had to discontinue EPO after the treatment period. The long-term safety of EPO treatment in patients with sickle cell disease cannot be evaluated from this study.