ACHiEvE-SCD: Hydroxyurea and EPO in Sickle Cell Disease
Study Details
Study Description
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1/Phase 2 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Erythropoietin 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
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.
Other Names:
Drug: 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.
Other Names:
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Outcome Measures
Primary Outcome Measures
- Change in hemoglobin (Hb) level [Baseline to 12 weeks]
Hb response, defined as a Hb increase of ≥ 1.0 g/dL at 12 weeks compared to baseline
Secondary Outcome Measures
- Frequency of adverse events (AEs) [Baseline to 12 weeks]
Frequency of treatment-emergent adverse events (AEs), including vaso-occlusive events and thrombotic events, as assessed by CTCAE v5.0
- Changes in hematological and hemolytic parameters [Baseline to 12 weeks; Baseline to 24 weeks]
Changes in complete blood count, reticulocyte count, and lactate dehydrogenase
- Changes in markers of organ function and erythropoiesis [Baseline to 12 weeks; Baseline to 24 weeks]
Changes in comprehensive metabolic panel, urine albumin-to-creatinine ratio, erythropoietin levels, and iron studies
- Changes in cardiopulmonary function as assessed by echocardiographic measurements [Baseline to 12 weeks; Baseline to 24 weeks]
Changes in 2D and Doppler echocardiographic assessments of left and right ventricular systolic/diastolic function and right ventricular systolic pressure (tricuspid regurgitant jet velocity)
- Changes in exercise capacity as assessed by 6-minute walk test with Modified Borg Dyspnea scale [Baseline to 12 weeks; Baseline to 24 weeks]
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)
- Changes in pain measured by Visual Analog Scale [Baseline to 4 weeks; Baseline to 8 weeks; Baseline to 12 weeks; Baseline to 24 weeks;]
Changes in pain score as measured by the Visual Analog Scale,10 cm long, with verbal anchors at either end. "No pain" on the far left and "the most intense pain imaginable" on the far right.
- Changes in pain measured using novel pain assessment tool [Baseline to 4 weeks; Baseline to 8 weeks; Baseline to 12 weeks; Baseline to 24 weeks;]
Changes in pain experience as measured by use of animations and graphical images
- Changes in health-related quality of life [Baseline to 12 weeks; Baseline to 24 weeks]
Changes in health-related quality of life using select survey items from Adult Sickle Cell Quality of Life Measurement System (ASCQ-Me), Patient-Reported Outcome Measurement Information System (PROMIS), and 36-Item Short Form Health Survey (SF-36) questionnaires
Eligibility Criteria
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 ≥ 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:
-
Hemoglobin SC (HbSC), S/β+-thalassemia, or other compound heterozygous SCD genotypes
-
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
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Arterial or venous thrombosis within 180 days of screening
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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
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Unstable angina, uncontrolled seizure disorder, or active malignancy
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End-stage renal disease requiring hemodialysis
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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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | UPMC | Pittsburgh | Pennsylvania | United States | 15213 |
| 2 | Lagos University Teaching Hospital | Lagos | Nigeria | 102215 |
Sponsors and Collaborators
- Julia Xu
- Carnegie Mellon University
- American Society of Hematology
Investigators
- Principal Investigator: Julia Z Xu, MD, MScGH, University of Pittsburgh
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- STUDY21120027