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Hydroxyurea and EPO in Sickle Cell Disease (ACHiEvE-SCD)

Primary Purpose

Anemia, Sickle Cell, Sickle Cell Disease

Status

Recruiting

Phase

Phase 1

Locations

International

Study Type

Interventional

Intervention

Hydroxyurea

Epoetin Alfa

About this trial

This is an interventional treatment trial for Anemia, Sickle Cell focused on measuring Sickle cell disease, Anemia, Erythropoietin, Hydroxyurea, Sickle cell anemia

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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
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

Sites / Locations

UPMCRecruiting
Lagos University Teaching HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Erythropoietin

Arm Description

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.

Outcomes

Primary Outcome Measures

Change in hemoglobin (Hb) level

Hb response, defined as a Hb increase of ≥ 1.0 g/dL at 12 weeks compared to baseline

Secondary Outcome Measures

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.

Full Information

NCT ID

NCT05451940

First Posted

June 24, 2022

Last Updated

July 11, 2023

Sponsor

Julia Xu

Collaborators

Carnegie Mellon University, American Society of Hematology

1. Study Identification

Unique Protocol Identification Number

NCT05451940

Brief Title

Hydroxyurea and EPO in Sickle Cell Disease

Acronym

ACHiEvE-SCD

Official Title

Assessing Combination Hydroxyurea and Exogenous Erythropoietin in Sickle Cell Disease

Study Type

Interventional

2. Study Status

Record Verification Date

July 2023

Overall Recruitment Status

Recruiting

Study Start Date

May 25, 2023 (Actual)

Primary Completion Date

November 2024 (Anticipated)

Study Completion Date

August 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Julia Xu

Collaborators

Carnegie Mellon University, American Society of Hematology

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. 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).

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.)

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Anemia, Sickle Cell, Sickle Cell Disease

Keywords

Sickle cell disease, Anemia, Erythropoietin, Hydroxyurea, Sickle cell anemia

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

15 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Erythropoietin

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Hydroxyurea

Other Intervention Name(s)

Droxia, Hydrea, and hydroxycarbamide.

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Epoetin Alfa

Other Intervention Name(s)

EPO, epoetin, erythropoietin, erythropoiesis-stimulating agent, ESA, haematopoietin, haemopoietin

Intervention Description

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.

Primary Outcome Measure Information:

Title

Change in hemoglobin (Hb) level

Description

Hb response, defined as a Hb increase of ≥ 1.0 g/dL at 12 weeks compared to baseline

Time Frame

Baseline to 12 weeks

Secondary Outcome Measure Information:

Title

Change in frequency of blood transfusions

Description

Annualized number of units of simple red blood cell transfusions received in the 12 months before treatment initiation compared to during active treatment.

Time Frame

Baseline to 12 weeks

Other Pre-specified Outcome Measures:

Title

Changes in tricuspid valve regurgitant jet velocity as assessed by echocardiography

Description

Changes in tricuspid valve regurgitant jet velocity

Time Frame