Hydroxyurea and EPO in Sickle Cell Disease

Sickle Cell Disease Clinical Trial

— ACHiEvE-SCD  

Official title:

Assessing Combination Hydroxyurea and Exogenous Erythropoietin in Sickle Cell Disease

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05451940
• Other study ID #: STUDY21120027
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: May 25, 2023
• Est. completion date: August 2025

Study information

• Verified date: July 2023
• Source: University of Pittsburgh
• Contact: Nelly K Kiriza, MD, MPH
• Phone: (412) 246-6009
• Email: nkk18[@]pitt.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.)

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 15
• Est. completion date: August 2025
• Est. primary completion date: November 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Aged = 18 years

• Confirmed diagnosis of SCD (HbSS or HbS/ß0-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

Related Conditions & MeSH terms

• Anemia
• Anemia, Sickle Cell
• Sickle Cell Disease

Intervention

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.
• Epoetin Alfa
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.

Locations

Country	Name	City	State
Nigeria	Lagos University Teaching Hospital	Lagos
United States	UPMC	Pittsburgh	Pennsylvania

Sponsors (3)

Lead Sponsor	Collaborator
Julia Xu	American Society of Hematology, Carnegie Mellon University

Countries where clinical trial is conducted

United States,  Nigeria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	Changes in cardiac index as assessed by echocardiography	Changes in cardiac index	Baseline to 12 weeks; Baseline to 24 weeks
Other	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
Other	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
Other	Changes in complete blood count parameters	Changes in complete blood count parameters	Baseline to 12 weeks; Baseline to 24 weeks
Other	Changes in absolute reticulocyte count	Changes in absolute reticulocyte count	Baseline to 12 weeks; Baseline to 24 weeks
Other	Changes in lactate dehydrogenase	Changes in lactate dehydrogenase	Baseline to 12 weeks; Baseline to 24 weeks
Other	Changes in renal function	Changes in serum creatinine (and associated eGFR)	Baseline to 12 weeks; Baseline to 24 weeks
Other	Changes in urine albumin-to-creatinine ratio	Changes in urine albumin-to-creatinine ratio	Baseline to 12 weeks; Baseline to 24 weeks
Other	Changes in total and indirect bilirubin	Changes in total and indirect bilirubin	Baseline to 12 weeks; Baseline to 24 weeks
Other	Changes in ferritin	Changes in ferritin	Baseline to 12 weeks; Baseline to 24 weeks
Primary	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	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