Hydroxyurea Optimization Through Precision Study

Sickle Cell Disease Clinical Trial

— HOPS  

Official title:

Hydroxyurea Optimization Through Precision Study (HOPS): A Prospective, Multi-center, Randomized Trial of Personalized, Pharmacokinetics-guided Dosing of Hydroxyurea Versus Standard Weight-based Dosing for Children With Sickle Cell Anemia.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03789591
• Other study ID #: CCHMC_HOPS
• Status: Recruiting
• Phase: Phase 3
• Start date: January 17, 2019
• Est. completion date: December 31, 2023

Study information

• Verified date: March 2023
• Source: Children's Hospital Medical Center, Cincinnati
• Contact: Patrick McGann, MD
• Phone: 513-736-2246
• Email: PMcGann[@]Lifespan.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

The trial will recruit patients who have decided to initiate hydroxyurea therapy. All participants will have pharmacokinetics studies performed at baseline, following a 20 mg/kg oral dose of hydroxyurea. Pharmacokinetic sampling will use a sparse sampling approach, requiring collection of blood at 3 time points (15 minutes, 60 minutes, 180 minutes) following the hydroxyurea dose. Enrolled participants will be randomized to receive either hydroxyurea using a starting dose of 20 mg/kg/day (Standard Arm) or a personalized PK-guided dose (Alternative Arm) to target an area under the curve (AUC) of 115 mg*h/L based to approximate hydroxyurea exposure seen when patients are escalated to maximum tolerated dose (MTD).

Following randomization and selection of the initial dose, participants in both arms will follow the same procedures of laboratory medication holds for hematological toxicity. The primary endpoint is fetal hemoglobin (HbF) six months following the initiation of hydroxyurea therapy with the hypothesis that participants starting with a PK-guided dose will achieve HbF at least 5% greater than those starting with a 20 mg/kg dose. Based upon the estimated number of new hydroxyurea starts at each site, it is anticipated that it will take 24 months to enroll the 116 participants required to achieve sufficient power to assess the primary endpoint. The study will conclude for each participant 12 months following hydroxyurea initiation.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 116
• Est. completion date: December 31, 2023
• Est. primary completion date: December 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 21 Years

Eligibility

Inclusion Criteria:

• Diagnosis of sickle cell anemia (HbSS, HbSD, HbS/ß0-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

Exclusion Criteria:

• Current treatment with chronic, monthly blood transfusions or erythrocytapheresis

• Treatment with hydroxyurea within the past 3 months

• Hemoglobin SC disease, HbS/ß+-thalassemia

• Current treatment with other investigational sickle cell medications

• Current known pregnancy or lactation

Related Conditions & MeSH terms

• Anemia
• Anemia, Sickle Cell
• Sickle Cell Anemia
• Sickle Cell Disease

Intervention

Drug:
• Hydroxyurea
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.

Locations

Country	Name	City	State
United States	Children's Healthcare of Atlanta	Atlanta	Georgia
United States	Boston Children's Hospital	Boston	Massachusetts
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Cleveland Clinic Children's	Cleveland	Ohio
United States	Rainbow Babies / University Hospitals Cleveland Medical Center	Cleveland	Ohio
United States	Nationwide Children's Hospital.	Columbus	Ohio
United States	Indiana Hemophilia & Thrombosis Center, Inc. (IHTC)	Indianapolis	Indiana
United States	Riley Hospital for Children at Indiana University Health	Indianapolis	Indiana
United States	Children's Hospital of Wisconsin	Milwaukee	Wisconsin
United States	Children's Hospitals and Clinics of Minnesota	Minneapolis	Minnesota
United States	Cohen Children's Medical Center/Northwell Health	New Hyde Park	New York
United States	Children's Hospital of Illinois	Peoria	Illinois
United States	Phoenix Children's Hospital	Phoenix	Arizona
United States	Carle Foundation Hospital	Urbana	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
Children's Hospital Medical Center, Cincinnati	Doris Duke Charitable Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	F Cells	In addition to traditional %HbF measurement, F cells will be measured at baseline, 6 months, and 12 months	Baseline, 6 and 12 months after initiating daily hydroxyurea therapy
Secondary	Gene Expression Patterns of Study Participants	The epigenomic signature and gene expression patterns of study participants receiving hydroxyurea therapy at MTD. MTD is defined as a stable dose without any dose increases (except to account for weight gain), holds, or decreases within 8 weeks with laboratory criteria within the target range. This outcome will explain the mechanisms that yield high HbF responses.	6 Months after initial Hydroxyurea therapy