Ignite Creation Date:
2025-12-25 @ 2:01 AM
Ignite Modification Date:
2025-12-26 @ 2:37 AM
Study NCT ID:
NCT06761560
Status:
NOT_YET_RECRUITING
Last Update Posted:
2025-01-07
First Post:
2024-12-12
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Optimizing Hydroxyurea Dosage With Pharmakokinetic in Patients Suffering of Moderate to Severe Sickle Cell Anemia
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D000755', 'term': 'Anemia, Sickle Cell'}], 'ancestors': [{'id': 'D000745', 'term': 'Anemia, Hemolytic, Congenital'}, {'id': 'D000743', 'term': 'Anemia, Hemolytic'}, {'id': 'D000740', 'term': 'Anemia'}, {'id': 'D006402', 'term': 'Hematologic Diseases'}, {'id': 'D006425', 'term': 'Hemic and Lymphatic Diseases'}, {'id': 'D006453', 'term': 'Hemoglobinopathies'}, {'id': 'D030342', 'term': 'Genetic Diseases, Inborn'}, {'id': 'D009358', 'term': 'Congenital, Hereditary, and Neonatal Diseases and Abnormalities'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2', 'PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'OTHER', 'interventionModel': 'PARALLEL', 'interventionModelDescription': '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'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 29}}, 'statusModule': {'overallStatus': 'NOT_YET_RECRUITING', 'startDateStruct': {'date': '2025-01-15', 'type': 'ESTIMATED'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-01', 'completionDateStruct': {'date': '2027-11-25', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-01-05', 'studyFirstSubmitDate': '2024-12-12', 'studyFirstSubmitQcDate': '2025-01-05', 'lastUpdatePostDateStruct': {'date': '2025-01-07', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2025-01-07', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2027-11-25', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Evaluation of HU-PK at 6 months between group A and group B', 'timeFrame': 'At 6 months', 'description': '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.'}], 'secondaryOutcomes': [{'measure': 'Time to reach maximal tolerated dose (MTD)', 'timeFrame': '3, 6, 9 and 12 months', 'description': '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.\n\nMTD 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)'}, {'measure': 'Fetal hemoglobin', 'timeFrame': 'at 3, 6 and 12 months', 'description': 'Comparing fetal hemoglobin between group A and B'}, {'measure': 'Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) in group A and B', 'timeFrame': 'From enrollment to 12 months', 'description': 'Evaluation of the incidence adverse events (AE) and serious adverse events (SAE) in both groups'}, {'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', 'description': '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.'}]}, 'oversightModule': {'oversightHasDmc': True, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'keywords': ['hydroxyurea', 'pharmacokinetic', 'sickle cell disease'], 'conditions': ['Sickle Cell Disease (SCD)']}, 'referencesModule': {'references': [{'pmid': '19797523', 'type': 'BACKGROUND', 'citation': 'Verduzco LA, Nathan DG. Sickle cell disease and stroke. Blood. 2009 Dec 10;114(25):5117-25. doi: 10.1182/blood-2009-05-220921.'}, {'pmid': '29803275', 'type': 'BACKGROUND', 'citation': 'Meier ER. Treatment Options for Sickle Cell Disease. Pediatr Clin North Am. 2018 Jun;65(3):427-443. doi: 10.1016/j.pcl.2018.01.005.'}, {'pmid': '31106898', 'type': 'BACKGROUND', 'citation': 'McGann PT, Niss O, Dong M, Marahatta A, Howard TA, Mizuno T, Lane A, Kalfa TA, Malik P, Quinn CT, Ware RE, Vinks AA. Robust clinical and laboratory response to hydroxyurea using pharmacokinetically guided dosing for young children with sickle cell anemia. Am J Hematol. 2019 Aug;94(8):871-879. doi: 10.1002/ajh.25510. Epub 2019 Jun 12.'}, {'pmid': '32869281', 'type': 'BACKGROUND', 'citation': 'Dong M, McGann PT. Changing the Clinical Paradigm of Hydroxyurea Treatment for Sickle Cell Anemia Through Precision Medicine. Clin Pharmacol Ther. 2021 Jan;109(1):73-81. doi: 10.1002/cpt.2028. Epub 2020 Oct 8.'}, {'pmid': '28847416', 'type': 'BACKGROUND', 'citation': 'Marahatta A, Ware RE. Hydroxyurea: Analytical techniques and quantitative analysis. Blood Cells Mol Dis. 2017 Sep;67:135-142. doi: 10.1016/j.bcmd.2017.08.009. Epub 2017 Aug 8.'}, {'pmid': '28131939', 'type': 'BACKGROUND', 'citation': 'Hai X, Guo M, Gao C, Zhou J. Quantification of hydroxyurea in human plasma by HPLC-MS/MS and its application to pharmacokinetics in patients with chronic myeloid leukaemia. J Pharm Biomed Anal. 2017 Apr 15;137:213-219. doi: 10.1016/j.jpba.2017.01.008. Epub 2017 Jan 10.'}, {'pmid': '21571150', 'type': 'BACKGROUND', 'citation': 'Wang WC, Ware RE, Miller ST, Iyer RV, Casella JF, Minniti CP, Rana S, Thornburg CD, Rogers ZR, Kalpatthi RV, Barredo JC, Brown RC, Sarnaik SA, Howard TH, Wynn LW, Kutlar A, Armstrong FD, Files BA, Goldsmith JC, Waclawiw MA, Huang X, Thompson BW; BABY HUG investigators. Hydroxycarbamide in very young children with sickle-cell anaemia: a multicentre, randomised, controlled trial (BABY HUG). Lancet. 2011 May 14;377(9778):1663-72. doi: 10.1016/S0140-6736(11)60355-3.'}, {'pmid': '22915643', 'type': 'BACKGROUND', 'citation': 'Thornburg CD, Files BA, Luo Z, Miller ST, Kalpatthi R, Iyer R, Seaman P, Lebensburger J, Alvarez O, Thompson B, Ware RE, Wang WC; BABY HUG Investigators. Impact of hydroxyurea on clinical events in the BABY HUG trial. Blood. 2012 Nov 22;120(22):4304-10; quiz 4448. doi: 10.1182/blood-2012-03-419879. Epub 2012 Aug 22.'}, {'pmid': '30206297', 'type': 'BACKGROUND', 'citation': 'Yahouedehou SCMA, Adorno EV, da Guarda CC, Ndidi US, Carvalho SP, Santiago RP, Aleluia MM, de Oliveira RM, Goncalves MS. Hydroxyurea in the management of sickle cell disease: pharmacogenomics and enzymatic metabolism. Pharmacogenomics J. 2018 Dec;18(6):730-739. doi: 10.1038/s41397-018-0045-1. Epub 2018 Sep 12.'}, {'pmid': '16713922', 'type': 'BACKGROUND', 'citation': 'Switzer JA, Hess DC, Nichols FT, Adams RJ. Pathophysiology and treatment of stroke in sickle-cell disease: present and future. Lancet Neurol. 2006 Jun;5(6):501-12. doi: 10.1016/S1474-4422(06)70469-0.'}, {'pmid': '24237976', 'type': 'BACKGROUND', 'citation': 'Quinn CT. Sickle cell disease in childhood: from newborn screening through transition to adult medical care. Pediatr Clin North Am. 2013 Dec;60(6):1363-81. doi: 10.1016/j.pcl.2013.09.006.'}, {'pmid': '24589261', 'type': 'BACKGROUND', 'citation': 'Hebbel RP. Ischemia-reperfusion injury in sickle cell anemia: relationship to acute chest syndrome, endothelial dysfunction, arterial vasculopathy, and inflammatory pain. Hematol Oncol Clin North Am. 2014 Apr;28(2):181-98. doi: 10.1016/j.hoc.2013.11.005.'}, {'pmid': '24589260', 'type': 'BACKGROUND', 'citation': 'Kuypers FA. Hemoglobin s polymerization and red cell membrane changes. Hematol Oncol Clin North Am. 2014 Apr;28(2):155-79. doi: 10.1016/j.hoc.2013.12.002. Epub 2014 Jan 22.'}, {'pmid': '25390139', 'type': 'BACKGROUND', 'citation': 'Pleasants S. Epidemiology: a moving target. Nature. 2014 Nov 13;515(7526):S2-3. doi: 10.1038/515S2a. No abstract available.'}], 'seeAlsoLinks': [{'url': 'https://www.chudequebec.ca/patient/maladies-soins-et-services/m-informer-sur-les-soins-et-services/programme-quebecois-de-depistage-neonatal-sanguin.aspx', 'label': 'Related Info'}]}, 'descriptionModule': {'briefSummary': '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.\n\nPatient 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.\n\nGroup 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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT'], 'maximumAge': '18 Years', 'minimumAge': '6 Months', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria (Group A and B) :\n\n* Have had confirmed diagnosis of SCD at CHU Sainte-Justine biochemistry lab with hemoglobin electrophoresis.\n* Be patients with SS, SBThal0.\n* Agree to take hydroxyurea for a period of 12 months\n* Be between age of 6months old and 18 years old.\n* Have consented for participation in the study.\n\nInclusion Criteria (Group C) :\n\n* Have had confirmed diagnosis of SCD at CHU Sainte-Justine biochemistry lab with hemoglobin electrophoresis.\n* Be patients with SS, SBThal0.\n* 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.\n* Be between age of 6months old and 18 years old.\n* Have consented for participation in the study.\n\nExclusion Criteria:\n\n* Patients with sickle cell genotype other than SS or SBThal0 (SC, SBThal+, SE or SD)\n* Patients on chronic transfusion program\n* Patients have received a blood transfusion in the last 4 weeks of study enrollment.\n* Have received a hematopoietic stem-cell transplantation\n* Creatinine \\>2x normal for age\n* ALT\\>2x normal for age\n* Sexually active females unwilling to comply with reliable method of birth control\n* Pregnancy\n* Conditions which in the opinion of the investigator, would compromise participation in the study will be excluded.'}, 'identificationModule': {'nctId': 'NCT06761560', 'acronym': 'OPTIMA', 'briefTitle': 'Optimizing Hydroxyurea Dosage With Pharmakokinetic in Patients Suffering of Moderate to Severe Sickle Cell Anemia', 'organization': {'class': 'OTHER', 'fullName': "St. Justine's Hospital"}, 'officialTitle': 'Optimizing Hydroxyurea Dosage With Pharmakokinetic in Patients Suffering of Moderate to Severe Sickle Cell Anemia', 'orgStudyIdInfo': {'id': '2023-4674'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Group A', 'description': 'Patient starting hydroxyurea that will have PK sample procurements at different timpoints over a period of 12 months until HU-AUC shows MTD', 'interventionNames': ['Diagnostic Test: Pharmacokinetic based dosage change']}, {'type': 'NO_INTERVENTION', 'label': 'Group B', 'description': 'Patient starting hydroxuyrea that will be followed as per standard of care over a period of 12 months until MTD has been reached'}, {'type': 'EXPERIMENTAL', 'label': 'Group C', 'description': 'Patient will undergo one PK sample procurement to evaluate level of HU-AUC after 12 months of taking hydroxyurea.', 'interventionNames': ['Diagnostic Test: Pharmacokinetic dosing']}], 'interventions': [{'name': 'Pharmacokinetic based dosage change', 'type': 'DIAGNOSTIC_TEST', 'description': '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', 'armGroupLabels': ['Group A']}, {'name': 'Pharmacokinetic dosing', 'type': 'DIAGNOSTIC_TEST', 'description': 'Patient with sickle cell disease will undergo one pharmacokinetic test after taking 12 months of hydroxyurea to evaluate HU-AUC at that timepoint', 'armGroupLabels': ['Group C']}]}, 'contactsLocationsModule': {'locations': [{'zip': 'H3T 1C5', 'city': 'Montreal', 'state': 'Quebec', 'country': 'Canada', 'contacts': [{'role': 'CONTACT', 'email': 'bianka.courcelle.hsj@ssss.gouv.qc.ca', 'phone': '5146090420'}], 'facility': 'CHU Sainte-Justine', 'geoPoint': {'lat': 45.50884, 'lon': -73.58781}}], 'centralContacts': [{'name': 'Yves Pastore, MD', 'role': 'CONTACT', 'email': 'yves.pastore.med@ssss.gouv.qc.ca', 'phone': '514-345-4931', 'phoneExt': '5027'}, {'name': 'Bianka Courcelle, Research nurse, RN', 'role': 'CONTACT', 'email': 'bianka.courcelle.hsj@ssss.gouv.qc.ca', 'phone': '514-345-4931', 'phoneExt': '3757'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO', 'description': 'This is a pilot study with a small group of participant.'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Yves Pastore', 'class': 'OTHER'}, 'collaborators': [{'name': "St. Justine's Hospital", 'class': 'OTHER'}], 'responsibleParty': {'type': 'SPONSOR_INVESTIGATOR', 'investigatorTitle': 'Co-director Sickle Cell Programm, Principal Investigator', 'investigatorFullName': 'Yves Pastore', 'investigatorAffiliation': "St. Justine's Hospital"}}}}