Clinical trial NCT06761560: Optimizing Hydroxyurea Dosage With Pharmakokinetic in Patients Suffering of Moderate to Severe Sickle Cell Anemia
Official title: Optimizing Hydroxyurea Dosage With Pharmakokinetic in Patients Suffering of Moderate to Severe Sickle Cell Anemia
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Sickle Cell Disease (SCD)
Keywords: hydroxyurea
pharmacokinetic
sickle cell disease
Lead sponsor: St. Justine's Hospital
Sponsor class: OTHER
Collaborators: name: St. Justine's Hospital
First posted: 2025-01-07
Enrollment: 29
Sex: ALL
Minimum age (years): 6
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Group A will receive dosing of hydroxyurea depending on the HU-AUC result at different timepoint until MTD Group B will receive dosing of hydroxyurea following the standard of care bloodwork follow-up until MTD Group C will undergo one pharmacokinetic testing after taking hydroxyurea for at least 12 months
Primary purpose: OTHER

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Evaluation of HU-PK at 6 months between group A and group B
timeFrame: At 6 months
Secondary outcomes:
measure: Time to reach maximal tolerated dose (MTD)
timeFrame: 3, 6, 9 and 12 months
measure: Fetal hemoglobin
timeFrame: at 3, 6 and 12 months
measure: Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) in group A and B
timeFrame: From enrollment to 12 months
measure: 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
timeFrame: At 12 months
Other outcomes:
Locations:
city: Montreal
country: Canada
facility: CHU Sainte-Justine
state: Quebec
Study officials:
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