Realizing Effectiveness Across Continents With Hydroxyurea (REACH)

Realizing Effectiveness Across Continents With Hydroxyurea: A Phase I/II Prospective Trial of Hydroxyurea for Children With Sickle Cell Anemia

REACH is a prospective, phase I/II open-label dose escalation trial of hydroxyurea for children with confirmed SCA between 3 and 10 years of age. The short-term goal is to obtain critical pilot data regarding the feasibility, safety, and benefit of hydroxyurea for children with SCA in multiple distinct research settings in Africa. Based on that information, the longer-term goal is to make hydroxyurea more widely available for children with SCA in Africa, particularly those identified with SCA through expanded newborn screening programs.

Study Overview

• Status: Active, not recruiting
• Conditions: Children; Sickle Cell Disease
• Intervention / Treatment: Drug: Hydroxyurea; Drug: Hydroxyurea

Detailed Description

REACH is a prospective, phase I/II open-label dose escalation trial of hydroxyurea for children with confirmed SCA between 3 and 10 years of age. The short-term goal is to obtain critical pilot data regarding the feasibility, safety, and benefit of hydroxyurea for children with SCA in multiple distinct research settings in Africa. Based on that information, the longer-term goal is to make hydroxyurea more widely available for children with SCA in Africa, particularly those identified with SCA through expanded newborn screening programs. In the REACH prospective trial, the Original Cohort will receive long-term treatment while for the New Cohort, treatment will continue at least 4 years using PK-guided dosing after an initial 3-month screening period.

• Study Type: Interventional
• Enrollment (Actual): 811
• Phase: Phase 2

Contacts and Locations

Study Locations

• Angola
  • Luanda, Angola
    • Hospital Pediátrico David Bernardino
• Democratic Republic of the Congo
  • Kinshasa, Democratic Republic of the Congo
    • Centre Hospitalier Monkole
• Kenya
  • Kilifi, Kenya
    • KEMRI/Wellcome Trust Research
• Uganda
  • Mbale, Uganda
    • Mbale Regional Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

1. Pediatric patients with documented sickle cell anemia (typically HbSS supported by hemoglobin electrophoresis, complete blood count, and peripheral blood smear)
2. In the Original Cohort, age range of 1.00-9.99 years, inclusive, at the time of enrollment (now age 5.5 - 17.5 years); age range 3.0-10.0 years for the New Cohort
3. Weight at least 10.0 kg at the time of enrollment
4. Parent or guardian willing and able to provide written informed consent, with child's verbal assent as per local IRB/Ethics Board requirements
5. Willingness to comply with all study-related treatments, evaluations, and follow-up

Exclusion Criteria

1. Known medical condition making participation ill-advised (e.g., acute or chronic infectious disease, HIV, or malignancy)
2. Acute or chronic severe malnutrition determined by impaired growth parameters as defined by WHO (weight for length/height or height for age >3 z-scores below the median WHO growth standards.

3. Pre-existing severe hematological toxicity (temporary exclusions)

   1. Anemia: Hb <4.0 g/dL
   2. Anemia: Hb <6.0 g/dL with ARC <100 x 109/L
   3. Reticulocytopenia: ARC <80 x 109/L with Hb <7.0 g/dL
   4. Thrombocytopenia: Platelets <80 x 109/L
   5. Neutropenia: ANC <1.0 x 109/L
4. Blood transfusion within 60 days before enrollment (temporary exclusion)
5. In the Original Cohort, hydroxyurea use within 6 months before enrollment (temporary exclusion). In the New Cohort, the children should be hydroxyurea naïve, without any prior treatment exposure.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Original Cohort; The original REACH cohort continuing study treatment per the protocol schedule of evaluations.	Drug: Hydroxyurea; Hydroxyurea, approximately 20-30 mg/kg/day, with modifications for toxicity or for mild marrow suppression; Drug: Hydroxyurea; Hydroxyurea 15-35 mg/kg/day based on PK-guided dosing, with modifications for toxicity for mild marrow suppression
Experimental: New Cohort; Newly enrolled REACH participants consent, 3 months screening, and treatment per the protocol schedule of evaluations	Drug: Hydroxyurea; Hydroxyurea, approximately 20-30 mg/kg/day, with modifications for toxicity or for mild marrow suppression; Drug: Hydroxyurea; Hydroxyurea 15-35 mg/kg/day based on PK-guided dosing, with modifications for toxicity for mild marrow suppression

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of long-term Hydroxyurea treatment at MTD	The efficacy of hydroxyurea will be primarily assessed through fetal hemoglobin (HbF), comparing treatment with baseline values.	Assessed every 6 ± 1 months up to 204 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction of malaria incidents while on hydroxyurea at MTD.	Clinical malaria infections to identify associations of risk or protection comparing treated and untreated incidents.	Assessed every 4 ± 1 weeks, then every 3 ± 1months up to 204 months
Success of PK-guided dosing of hydroxyurea	Fetal Hemoglobin changes from hydroxyurea at MTD	Assessed every 6 ± 1 months up to 204 months

Collaborators and Investigators

• Sponsor: Children's Hospital Medical Center, Cincinnati
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Russell Ware, MD, PhD, Children's Hospital Medical Center, Cincinnati

Study record dates

Study Major Dates

• Study Start (Actual): October 27, 2023
• Primary Completion (Estimated): October 4, 2027
• Study Completion (Estimated): October 4, 2033

Study Registration Dates

• First Submitted: August 21, 2023
• First Submitted That Met QC Criteria: December 13, 2023
• First Posted (Actual): December 14, 2023

Study Record Updates

• Last Update Posted (Actual): April 21, 2026
• Last Update Submitted That Met QC Criteria: April 20, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hemoglobinopathies; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hemic and Lymphatic Diseases; Anemia, Sickle Cell; Organic Chemicals; Amides; Urea; Hydroxyurea
• Other Study ID Numbers: 2013-4221b; U01HL133883 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Investigators whose proposed use of the data has been approved by a review committee identified for this purpose, will be provided individual participant data that underlie the results reported from this study, after de-identification and publication. The data can be obtained via email to Dr. Ware as the corresponding author.
• IPD Sharing Time Frame: Nine months following publication ending 36 months following publication.
• IPD Sharing Access Criteria: For individual participant data meta-analysis after approval of a proposal and with a signed data access agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No