Clinical trial NCT05451940: Hydroxyurea and EPO in Sickle Cell Disease
Official title: Assessing Combination Hydroxyurea and Exogenous Erythropoietin in Sickle Cell Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Anemia, Sickle Cell
Sickle Cell Disease
Keywords: Sickle cell disease
Anemia
Erythropoietin
Hydroxyurea
Sickle cell anemia
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: Carnegie Mellon University
name: American Society of Hematology
First posted: 2022-07-11
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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).

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.)

Eligibility criteria: 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

Primary outcomes:
measure: Change in hemoglobin (Hb) level
timeFrame: Baseline to 12 weeks
Secondary outcomes:
measure: Change in frequency of blood transfusions
timeFrame: Baseline to 12 weeks
Other outcomes:
measure: Changes in tricuspid valve regurgitant jet velocity as assessed by echocardiography
timeFrame: Baseline to 12 weeks; Baseline to 24 weeks
measure: Changes in cardiac index as assessed by echocardiography
timeFrame: Baseline to 12 weeks; Baseline to 24 weeks
measure: Changes in left ventricular end-diastolic volume as assessed by echocardiography
timeFrame: Baseline to 12 weeks; Baseline to 24 weeks
measure: Changes in exercise capacity as assessed by 6-minute walk test with Modified Borg Dyspnea scale
timeFrame: Baseline to 12 weeks; Baseline to 24 weeks
measure: Changes in complete blood count parameters
timeFrame: Baseline to 12 weeks; Baseline to 24 weeks
measure: Changes in absolute reticulocyte count
timeFrame: Baseline to 12 weeks; Baseline to 24 weeks
measure: Changes in lactate dehydrogenase
timeFrame: Baseline to 12 weeks; Baseline to 24 weeks
measure: Changes in renal function
timeFrame: Baseline to 12 weeks; Baseline to 24 weeks
measure: Changes in urine albumin-to-creatinine ratio
timeFrame: Baseline to 12 weeks; Baseline to 24 weeks
measure: Changes in total and indirect bilirubin
timeFrame: Baseline to 12 weeks; Baseline to 24 weeks
measure: Changes in ferritin
timeFrame: Baseline to 12 weeks; Baseline to 24 weeks
Locations:
city: Pittsburgh
country: United States
facility: UPMC
state: Pennsylvania
city: Lagos
country: Nigeria
facility: Lagos University Teaching Hospital
Study officials:
affiliation: University of Pittsburgh
name: Julia Z Xu, MD, MScGH
role: PRINCIPAL_INVESTIGATOR
References: