Study to determine the effect of Voxelotor in patients with Sickle Cell Disease assessed by MRI to define cerebral perfusion and oxygenatio
- Conditions
- Sickle Cell DiseaseTherapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2019-003766-41-NL
- Lead Sponsor
- Amsterdam UMC-AMC
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 20
1. Documented SCD genotype (HbSS, HbSC, HbS-ß thalassemia or other sickle cell syndrome variants) which may be based on history of laboratory testing or must be confirmed by laboratory testing during screening.
2. Age 18 and above
3. Hemoglobin (Hb) =10.5 g/dL
4. For participants taking hydroxyurea (HU), the dose of HU (mg/kg) must be stable for at least 90 days prior to participation and with no anticipated need for dose adjustments.
5. Participants, who if female and of child bearing potential, are using highly effective methods of contraception from study start to 30 days after the last dose of study drug, and who if male are willing to use barrier methods of contraception, from study start to 30 days after the last dose of study drug.
6. Participant has provided documented informed consent or assent (the informed consent form [ICF] must be reviewed and signed by each participant; the participant’s legal representative or legal guardian, and the participant’s assent must be obtained).
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
1. No informed consent has been given
2. Contra-indication for MRI or acetazolamide
3. Female who is breast feeding or pregnant.
4. Patients who are receiving regularly scheduled blood (RBC) transfusion therapy (also termed chronic, prophylactic, or preventive transfusion) or have received a RBC transfusion for any reason within 90 days before participation.
5. Hospitalized for sickle cell crisis or other vaso-occlusive event within 14 days prior participation.
6. Hepatic dysfunction characterized by alanine aminotransferase (ALT) >4 × ULN.
7. Participants with clinically significant bacterial, fungal, parasitic or viral infection which require therapy:
• Participants with acute bacterial infection requiring antibiotic use should delay screening/enrollment until the course of antibiotic therapy has been completed.
• Participants with known active hepatitis A, B, or C or who are known to be human immunodeficiency virus (HIV) positive.
8. Severe renal dysfunction (estimated glomerular filtration rate <30mL/min).
9. History of malignancy within the past 2 years prior to participation requiring chemotherapy and/or radiation (with the exception of local therapy for non-melanoma skin malignancy).
10. History of unstable or deteriorating cardiac or pulmonary disease within 6 months prior to consent including but not limited to the following:
• Unstable angina pectoris or myocardial infarction or elective coronary intervention.
• Congestive heart failure requiring hospitalization.
• Uncontrolled clinically significant arrhythmias.
11. Any condition affecting drug absorption, such as major surgery involving the stomach or small intestine (prior cholecystectomy is acceptable).
12. Participated in another clinical trial of an investigational agent (or medical device) within 30 days or 5 half-lives of date of informed consent, whichever is longer, or is currently participating in another trial of an investigational agent (or medical device).
13. Medical, psychological, or behavioral conditions, which, in the opinion of the investigator, may preclude safe participation, confound study interpretation, interfere with compliance, or preclude informed consent.
14. Receipt of erythropoietin or other hematopoietic growth factors within 28 days of signing ICF or anticipated need for such agents during the study.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: In this study, the effect of voxelotor on the hemodynamics of the cerebral vasculature (CBF and CVR) will be studied.;Secondary Objective: In addition, the oxygen utilization (CMRO2) and oxygen extraction fraction (OEF) will be studied as an exploratory endpoint in parallel by special MRI techniques. As well as the effect of the improved hemoglobin on the quality of life and the processing speed as a measure of neurocognitive function of patients before and after treatment with voxelotor.;Primary end point(s): The effect of voxelotor on the cerebral vascular reserve capacity (CVR);Timepoint(s) of evaluation of this end point: After inclusion but before the start of the study medication (baseline) and 3, 6 and 12 months after initiation of study medication.
- Secondary Outcome Measures
Name Time Method Secondary end point(s): The effect of voxelotor on cerebral blood flow (CBF) The effect of voxelotor on neurocognitive function (processing speed) The effect of voxelotor on the Quality of Life;Timepoint(s) of evaluation of this end point: After inclusion but before the start of the study medication (baseline) and 3, 6 and 12 months after initiation of study medication. Quality of life and neurocognitive processing speed testing: at baseline and 12 months upon voxelotor administration.