Sickle Cell Disease Clinical Trial
Official title:
Pilot Pharmacokinetic Study In Patients With Inadequate Response To Deferasirox (Exjade)
This purpose of this study is to understand the differences between people who have a good response to deferasirox (exjade) compared to people who have a poor response to this medication when used for transfusion-dependent iron overload. The hypothesis is that patients with poor responses have physiologic barriers to deferasirox that may include absorption, pharmacokinetics of drug metabolism, hepatic clearance and/or genetic factors.
The purpose of this trial is to examine three potential mechanisms of inadequate response to Exjade® in patients with transfusion dependent iron overload including patients with thalassemia syndromes, sickle cell disease and bone marrow failure. Hypothesis: Patients have physiologic barriers to adequately respond to deferasirox that may include absorption, pharmacokinetics of drug metabolism, hepatic clearance and/or genetic factors. Study objectives Primary objective - To evaluate three potential mechanisms for inadequate response to deferasirox in a small cohort of patients with hemoglobinopathies. - Oral pharmacokinetics measured with Cmax and AUC following standard dose deferasirox. - Hepatobiliary excretory function - Accessibility of chelatable iron pool by deferoxamine challenge Secondary objective(s) - To identify risk factors that can predict adequate response including demographics, disease status, presence and severity of liver disease, trough levels of deferasirox at outpatient visits and pharmacogenomics. - To investigate usefulness of potential surrogate measures of response including serum deferasirox levels, Hepatobiliary Iminodiacetic Acid (HIDA)nuclear medicine scan to evaluate hepatic excretory function and urinary iron excretion by deferoxamine challenge. This is an investigator-initiated, pilot-scale, open-label physiological assessment of patients who respond poorly to deferasirox compared with patients who respond well. We plan to study 2 groups of patients: a)10 patients who have demonstrated poor responses and b) 5 control patients with good responses as defined further in the protocol. The study has two parts. Part I: Both groups of patients will have inpatient physiological assessments with a dose of 35mg/kg of deferasirox. Part II: Inadequate responders eligible to continue on deferasirox will continue on a dose of 35 mg/kg for three months during which time serial pharmacokinetic levels will be studied. The control patients will resume their previous clinically appropriate dosing (likely less than 35 mg/kg) and for three months have serial pharmacokinetic levels drawn as well. The study will begin with an outpatient screening visit when demographics and historical information as well as a physical examination will be obtained and reviewed for eligibility. At that visit patients will be able to sign informed consent. Shortly thereafter patients will be admitted to the GCRC at Children's Hospital Boston for part I of the study, a 2-3 day stay during which PK and nuclear medicine studies will be performed as well as the deferoxamine urinary iron excretion challenge. Patients who are eligible will continue on to part II of the study, and for 3 months and will be monitored for compliance, PK and ferritin changes on appropriate deferasirox doses. ;
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT02227472 -
Working Memory and School Readiness in Preschool-Aged Children With Sickle Cell Disease
|
||
Recruiting |
NCT06301893 -
Uganda Sickle Surveillance Study (US-3)
|
||
Recruiting |
NCT04398628 -
ATHN Transcends: A Natural History Study of Non-Neoplastic Hematologic Disorders
|
||
Completed |
NCT02522104 -
Evaluation of the Impact of Renal Function on the Pharmacokinetics of SIKLOS ® (DARH)
|
Phase 4 | |
Recruiting |
NCT04688411 -
An mHealth Strategy to Improve Medication Adherence in Adolescents With Sickle Cell Disease
|
N/A | |
Terminated |
NCT03615924 -
Effect of Ticagrelor vs. Placebo in the Reduction of Vaso-occlusive Crises in Pediatric Patients With Sickle Cell Disease
|
Phase 3 | |
Not yet recruiting |
NCT06300723 -
Clinical Study of BRL-101 in Severe SCD
|
N/A | |
Recruiting |
NCT03937817 -
Collection of Human Biospecimens for Basic and Clinical Research Into Globin Variants
|
||
Completed |
NCT04134299 -
To Assess Safety, Tolerability and Physiological Effects on Structure and Function of AXA4010 in Subjects With Sickle Cell Disease
|
N/A | |
Completed |
NCT04917783 -
Health Literacy - Neurocognitive Screening in Pediatric SCD
|
N/A | |
Completed |
NCT02580565 -
Prevalence of Problematic Use of Equimolar Mixture of Oxygen and Nitrous Oxide and Analgesics in the Sickle-cell Disease
|
||
Recruiting |
NCT04754711 -
Interest of Nutritional Care of Children With Sickle Cell Disease on Bone Mineral Density and Body Composition
|
N/A | |
Completed |
NCT04388241 -
Preliminary Feasibility and Efficacy of Behavioral Intervention to Reduce Pain-Related Disability in Pediatric SCD
|
N/A | |
Recruiting |
NCT05431088 -
A Phase 2/3 Study in Adult and Pediatric Participants With SCD
|
Phase 2/Phase 3 | |
Completed |
NCT01158794 -
Genes Influencing Iron Overload State
|
||
Recruiting |
NCT03027258 -
Point-of-Delivery Prenatal Test Results Through mHealth to Improve Birth Outcome
|
N/A | |
Withdrawn |
NCT02960503 -
Macrolide Therapy to Improve Forced Expiratory Volume in 1 Second in Adults With Sickle Cell Disease
|
Phase 1/Phase 2 | |
Withdrawn |
NCT02630394 -
A Pilot Study of Azithromycin Prophylaxis for Acute Chest Syndrome in Sickle Cell Disease
|
Phase 1 | |
Not yet recruiting |
NCT02525107 -
Prevention of Vaso-occlusive Painful Crisis by Using Omega-3 Fatty Acid Supplements
|
Phase 3 | |
Completed |
NCT02567695 -
A Single-Dose Relative Bioavailability Study Of GBT440 300 mg Capsules in Healthy Subjects
|
Phase 1 |