Optimizing Hydroxyurea Dosage With Pharmakokinetic in Patients Suffering of Moderate to Severe Sickle Cell Anemia (OPTIMA)

January 5, 2025 updated by: Yves Pastore

The goal of this study is to evaluate if patients with sickle cell disease can achieve a maximum tolerate dose of hydroxuyrea (HU) over a period of 12 months faster with pharmacokinetic testing than the standard of care bloodwork follow-up. Pharmacokinetic test is used to evaluate the process by which drugs are absorbed, distributed in the body, localized in the tissues, and is excreted.

Patient will be a randomized (coin toss method) into 2 groups. Group A will have an increase of their HU dosage with pharmacokinetic results and Group B will have an increase of their HU dosage following the standard of care bloodwork follow-up.

Group C will include patient with sickle cell disease that has been taking HU for at least 12 months and will undergo a pharmacokinetic dosage to check the level of HU only one time.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

29

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria (Group A and B) :

  • Have had confirmed diagnosis of SCD at CHU Sainte-Justine biochemistry lab with hemoglobin electrophoresis.
  • Be patients with SS, SBThal0.
  • Agree to take hydroxyurea for a period of 12 months
  • Be between age of 6months old and 18 years old.
  • Have consented for participation in the study.

Inclusion Criteria (Group C) :

  • Have had confirmed diagnosis of SCD at CHU Sainte-Justine biochemistry lab with hemoglobin electrophoresis.
  • Be patients with SS, SBThal0.
  • Have taken hydroxyurea for a period of at least 12 months, and have received HU at a stable dose and at MTD for at least 6 months.
  • Be between age of 6months old and 18 years old.
  • Have consented for participation in the study.

Exclusion Criteria:

  • Patients with sickle cell genotype other than SS or SBThal0 (SC, SBThal+, SE or SD)
  • Patients on chronic transfusion program
  • Patients have received a blood transfusion in the last 4 weeks of study enrollment.
  • Have received a hematopoietic stem-cell transplantation
  • Creatinine >2x normal for age
  • ALT>2x normal for age
  • Sexually active females unwilling to comply with reliable method of birth control
  • Pregnancy
  • Conditions which in the opinion of the investigator, would compromise participation in the study will be excluded.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Group A
Patient starting hydroxyurea that will have PK sample procurements at different timpoints over a period of 12 months until HU-AUC shows MTD
Diagnostic test: Pharmacokinetic based dosage change
This study will compare 2 groups of sickle cell patients that are receiving hydroxyurea. Group A will have an increase in their dosage based on the pharmacokinetic result over a period of 12 months and Group B will have an increase in their dosage based on the standard of care follow-up over a period of 12 months. The aim is to evaluate if the group A can reach MTD faster than than the Group B
No Intervention: Group B
Patient starting hydroxuyrea that will be followed as per standard of care over a period of 12 months until MTD has been reached
Experimental: Group C
Patient will undergo one PK sample procurement to evaluate level of HU-AUC after 12 months of taking hydroxyurea.
Diagnostic test: Pharmacokinetic dosing
Patient with sickle cell disease will undergo one pharmacokinetic test after taking 12 months of hydroxyurea to evaluate HU-AUC at that timepoint

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Evaluation of HU-PK at 6 months between group A and group B
Time Frame: At 6 months
Pharmakocinetic dosage of hydroxyurea will be determined at 6 months in group A and group B. We hypothesize that HU-PK in group B may be lower (suboptimal) compared to group A.
At 6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to reach maximal tolerated dose (MTD)
Time Frame: 3, 6, 9 and 12 months

Time (weeks) to achieve MTD in groups A and B will be determined by evaluating the % of patients reaching MTD (at 3 , 6, 9 and 12 months) in each group.

MTD is defined by hematological parameters: Absolute neutrophile count 0.8-1.5x10*9/L or platelet 80-120x10*9/L or absolute reticulocyte count 50-80x10*9/L)
3, 6, 9 and 12 months
Fetal hemoglobin
Time Frame: at 3, 6 and 12 months
Comparing fetal hemoglobin between group A and B
at 3, 6 and 12 months
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) in group A and B
Time Frame: From enrollment to 12 months
Evaluation of the incidence adverse events (AE) and serious adverse events (SAE) in both groups
From enrollment to 12 months
Evaluation of % of patients reaching AUC of 115 +/- 15mg*h/L at 12 months compared to the percentage of patients in group C reaching the same AUC
Time Frame: At 12 months
Percentage of patients in the HU-AUC (group A) with an AUC of 115 mg*h/L at 12 months will be compared to the percentage of patients in group C with an AUC of 115 +/-15 mg*h/L.
At 12 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Yves Pastore

Collaborators

St. Justine's Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

January 15, 2025

Primary Completion (Estimated)

November 25, 2027

Study Completion (Estimated)

November 25, 2027

Study Registration Dates

First Submitted

December 12, 2024

First Submitted That Met QC Criteria

January 5, 2025

First Posted (Actual)

March 25, 2025

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

January 5, 2025

Last Verified

January 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2023-4674

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

This is a pilot study with a small group of participant.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Sickle Cell Disease (SCD)

Clinical Trials on Pharmacokinetic based dosage change

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Switzerland

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe