Hydroxyurea Optimization Through Precision Study

NCT03789591 | Completed Phase 3 DMC FDA Drug

• 1 other identifier: CCHMC_HOPS
• Study Type: interventional
• Target: 104
• Locations: 1 country
• Sites: 13

Brief Summary

Hydroxyurea Optimization through Precision Study (HOPS) is a prospective, multi-center, randomized trial that will directly compare a novel, individualized dosing strategy of hydroxyurea to standard weight-based dosing for children with SCA. The primary objective of the study is to evaluate whether a pharmacokinetics-based starting hydroxyurea dose thieves superior fetal hemoglobin response to to standard weight-based initial dosing. Patients will be recruited from the pediatric sickle cell clinic at Cincinnati Children's Hospital Medical Center and from additional pediatric sickle cell centers within the United States.

Conditions

Sickle Cell Disease; Sickle Cell Anemia

Keywords

Hydroxyurea; HbSS; HbSD; TREAT

Outcome Measures

Primary Outcomes (1)

• Fetal Hemoglobin (HbF) Response Following Six Months of Hydroxyurea Therapy

  The primary outcome will be HbF response six months after starting hydroxyurea therapy with the hypothesis that participants in the Alternative Arm (PK-guided starting dose) will have at least 5% higher HbF than the Standard Arm (20 mg/kg starting dose)

  6 months after starting daily hydroxyurea therapy

Secondary Outcomes (2)

• F Cells

  Baseline, 6 and 12 months after initiating daily hydroxyurea therapy

• Gene Expression Patterns of Study Participants

  6 Months after initial Hydroxyurea therapy

Study Arms (2)

Standard Arm

ACTIVE COMPARATOR

Participants randomized to the standard arm will receive a starting dose of hydroxyurea of 20 mg/kg/day.

Drug: Hydroxyurea

Alternative Arm

EXPERIMENTAL

Participants randomized to the alternative arm will receive a pharmacokinetic guided starting dose of hydroxyurea based on PK labs drawn at a baseline visit to target an area under the curve (AUC) of 115 mg\*h/L in an attempt to approximate maximum tolerated dose (MTD). This dose will not exceed the maximum tolerated dose of 35 mg/kg/day.

Drug: Hydroxyurea

Interventions

Hydroxyurea DRUG

The alternative arm will use PK data to choose a starting hydroxyurea dose to achieve an AUC of 115 mg\*h/L to approximate maximum tolerated dose. On the standard arm, participants will start at the traditional, weight-based dose of 20 mg/kg/day. Following selection of the starting dose, all participants will follow the same dose escalation and laboratory monitoring procedures.

Alternative Arm; Standard Arm

Eligibility Criteria

• Age: 6 Months - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Diagnosis of sickle cell anemia (HbSS, HbSD, HbS/β0-thalassemia, or similarly severe SCA genotype)
• Age 6 months to 21 years at the time of enrollment
• Clinical decision by patient, family, and healthcare providers to initiate hydroxyurea therapy

You may not qualify if:

• Current treatment with chronic, monthly blood transfusions or erythrocytapheresis
• Treatment with hydroxyurea within the past 3 months
• Hemoglobin SC disease, HbS/β+-thalassemia
• Current treatment with other investigational sickle cell medications
• Current known pregnancy or lactation

Sponsors & Collaborators

• Lifespan: lead
• Doris Duke Charitable Foundation: collaborator

Study Sites (13)

Phoenix Children's Hospital

Phoenix, Arizona, 85016, United States

Location

Children's Healthcare of Atlanta

Atlanta, Georgia, 30342, United States

Location

Children's Hospital of Illinois

Peoria, Illinois, 61637, United States

Location

Carle Foundation Hospital

Urbana, Illinois, 61801, United States

Location

Riley Hospital for Children at Indiana University Health

Indianapolis, Indiana, 46202, United States

Location

Indiana Hemophilia & Thrombosis Center, Inc. (IHTC)

Indianapolis, Indiana, 46260, United States

Location

Boston Children's Hospital

Boston, Massachusetts, 02215, United States

Location

Children's Hospitals and Clinics of Minnesota

Minneapolis, Minnesota, 55404, United States

Location

Cohen Children's Medical Center/Northwell Health

New Hyde Park, New York, 11040, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Rainbow Babies / University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Nationwide Children's Hospital.

Columbus, Ohio, 43205, United States

Location

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (1)

• Meier ER, Creary SE, Heeney MM, Dong M, Appiah-Kubi AO, Nelson SC, Niss O, Piccone C, Quarmyne MO, Quinn CT, Saving KL, Scott JP, Talati R, Latham TS, Pfeiffer A, Shook LM, Vinks AA, Lane A, McGann PT. Hydroxyurea Optimization through Precision Study (HOPS): study protocol for a randomized, multicenter trial in children with sickle cell anemia. Trials. 2020 Nov 27;21(1):983. doi: 10.1186/s13063-020-04912-z.

  PMID: 33246482 DERIVED

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 Niss, MD

  Lifespan

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: The study is designed with a double-blind design. The clinical provider and participant/family will be aware of the absolute (mg) starting dose and could theoretically calculate the mg/kg starting dose, but the treatment assignment will not explicitly be provided to the provider or the family, and the same procedures will be used for dose escalation or reduction. Although most doses in the Alternative Arm will be different than 20 mg/kg, there are some patients on the standard arm who may have a PK-guided dose that is close to or at 20 mg/kg. Thus, although it may be possible to deduce the study arm, the study is designed technically in a double-blind fashion.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Brown University Health Comprehensive Sickle Cell Center

Study Record Dates

• First Submitted: November 27, 2018
• First Posted: December 28, 2018
• Study Start: January 17, 2019
• Primary Completion: March 19, 2025
• Study Completion: March 19, 2025
• Last Updated: June 18, 2025

Record last verified: 2025-04

Locations

US (13)