Hydroxyurea and EPO in Sickle Cell Disease

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 60days prior to start of study drug) and plan to continue taking hydroxyurea at thesame dose and schedule during the study

• If receiving L-glutamine or crizanlizumab, must have been receiving the drug at astable dose for at least 60 days prior to screening and plan to continue taking thedrug at the same dose and schedule during the study

Exclusion Criteria:

• Participating in a chronic transfusion program (pre-planned series of transfusionsfor prophylactic purposes) and/or planning on undergoing an exchange transfusionduring the duration of the study; episodic transfusion in response to worsenedanemia or VOC is permitted, but participant should not have received a bloodtransfusion 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 ironwithin 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 diastolicblood pressure ≥100 mmHg; medical intervention indicated; more than one drug or moreintensive 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 5half-lives of that agent, whichever is greater) prior to start of study drug orplans to participate in another investigational drug trial