Promoting Utilization and Safety of Hydroxyurea Using Precision in Africa

NCT05285917 | Recruiting Phase 3 DMC FDA Drug

• 2 other identifiers: BrUOG 419U01HL157872
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 1

Brief Summary

Sickle cell anemia (SCA) is among the world's most common and devastating blood disorders, affecting more than 300,000 newborns per year. Most infants with SCA are born in the low-resource settings of sub- Saharan Africa, where an estimated 50-90% will die before 5 years of age due to lack of early diagnosis and appropriate care. Hydroxyurea is a safe and effective once-daily oral medication that has become the standard of care for the treatment of children with SCA in high-resource settings. There is now a growing body of evidence to support the safety and clinical benefits of hydroxyurea for the treatment of SCA in sub-Saharan Africa. The requirement for frequent laboratory monitoring, uncertainties about appropriate, most effective dosing, and the concern for hematologic laboratory toxicities, however, will continue to limit widespread hydroxyurea utilization and real-world effectiveness. The investigators have recently developed and prospectively evaluated an individualized, pharmacokinetics-guided hydroxyurea dosing strategy for children with SCA that has demonstrated optimal clinical and laboratory benefits with minimal toxicity. In this research study, the investigators aim to extend this precision medicine approach to Africa.

Conditions

Sickle Cell Anemia in Children; Sickle Cell Disease

Outcome Measures

Primary Outcomes (2)

• Rate of clinical, sickle cell adverse events (grade ≥ 3) as assessed by CTCAE v5.0

  These events will primarily include vaso-occlusive painful events, acute chest syndrome, stroke, acute splenic sequestration, and death. Data regarding adverse events, including severity grade and relatedness to SCA will be determined on site by the local investigator. All events will be centrally adjudicated by a blinded hematologist who is not a primary study investigator (Medical Safety Monitor) for inclusion in this endpoint.

  From start of study treatment through first 12 months of treatment.

• Number of non-SCA related adverse events (grade ≥3), including death as assessed by CTCAE v5.0

  The clinical event rate with limited laboratory monitoring will be compared to the 3-months prior to hydroxyurea therapy.

  From start of study treatment through treatment completion, approximately 24 months.

Secondary Outcomes (1)

• Hematologic response at 12 months

  From start of study treatment through first 12 months of treatment.

Other Outcomes (1)

• Health-Related Quality of Life Questionnaires

  From start of study treatment through treatment completion, approximately 24 months.

Study Arms (2)

Weight Based Starting Dose

ACTIVE COMPARATOR

25 mg/kg starting dose Hydroxyurea

Drug: Hydroxyurea

PK-guided starting dose

EXPERIMENTAL

Individualized, PK-guided starting dose Hydroxyurea

Drug: Hydroxyurea

Interventions

Hydroxyurea DRUG

Hydroxyurea has a narrow therapeutic window such that selection of the correct dose is essential to optimize benefits and avoid toxicity.

Also known as: Hydrea, Droxia

PK-guided starting dose; Weight Based Starting Dose

Eligibility Criteria

• Age: 6 Months - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Diagnosis of sickle cell anemia (HbSS or HbS/B0-thalassemia)
• Age 6 months- 12 years of age at enrollment
• Parent or guardian willing and able to provide written or informed consent

You may not qualify if:

• Splenomegaly with evidence of hypersplenism as defined by platelet count \<150,000, hemoglobin \<5 g/dL or absolute neutrophil count \<1.0 x10\^9/L
• Hydroxyurea use within the past 6 months
• Pregnancy

Sponsors & Collaborators

• Brown University: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• Novartis: collaborator

Study Sites (1)

Hospital Geral dos Cajueiros

Luanda, Angola

RECRUITING

MeSH Terms

Conditions

Anemia, Sickle Cell

Interventions

Hydroxyurea

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Urea; Amides; Organic Chemicals

Study Officials

• Patrick T McGann, MD, MS

  Rhode Island Hospital and Hasbro Children's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

BrUOG

CONTACT

401-863-3000; BrUOG@brown.edu

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 1, 2022
• First Posted: March 18, 2022
• Study Start: November 15, 2023
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2027
• Last Updated: April 9, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

AN (1)