Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Long-term Mitapivat Dosing in Sub… (NCT04610866) | Clinical Trial Compass
Active — Not RecruitingPhase 1/2
Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Long-term Mitapivat Dosing in Subjects With Stable Sickle Cell Disease: An Extension of a Phase I Pilot Study of Mitapivat
United States15 participantsStarted 2020-12-09
Plain-language summary
Background:
Sickle cell disease (SCD) is a disorder that causes episodes of acute pain and progressive organ damage. Ways to manage SCD have evolved slowly. Treatments do not always work. Researchers want to see if a drug called mitapivat can help people with SCD.
Objective:
To test the long-term tolerability and safety of mitapivat (or AG-348) in people with SCD.
Eligibility:
Adults age 18-70 with SCD who took part in and benefited from NIH study #19H0097.
Design:
Participants will be screened with a medical history and physical exam. They will give a blood sample. They will have an electrocardiogram to test heart function.
Participants will repeat some of the screening tests during the study.
Participants will complete 6-minute walk tests to measure mobility and function. They will have transthoracic echocardiograms to measure heart and lung function. They will have dual-energy X-ray absorptiometry scans to measure bone health. They will complete online questionnaires that measure their overall health and well-being.
Participants will take the study drug in the form of a tablet twice a day.
Participants will keep a study diary. They will record any symptoms they may have.
Participation will last for about 54 weeks. After 48 weeks, participants can either keep taking the study drug for 48 more weeks or be tapered off of the study drug to complete the study. Those who are on the study for 1 year will have 10 study visits. Those who are on the study for 2 years will have 14 study visits.
Who can participate
Age range18 Years – 70 Years
SexALL
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Inclusion criteria
✓.1 Have provided signed written informed consent prior to performing any study procedure, including screening procedures.
✓.2 Age between 18-70 years
✓.3 Unequivocal diagnosis of HbSS confirmed by hemoglobin electrophoresis performed on patients at least 90 days after a blood transfusion if previously transfused, or DNA genotyping
✓.4 No transfusion in the 12 weeks prior to signing consent, or absence of Hb A on hemoglobin analysis (by high-performance liquid chromatography; HPLC)
✓.5 Have adequate organ function, as defined by:
✓. Serum aspartate aminotransferase (AST) \<=2.5 x Upper Limit of Normal (ULN) (unless the increased AST is assessed by the Investigator as due to hemolysis) and alanine aminotransferase (ALT) \<=2.5 x ULN.
✓. Serum creatinine \<=1.25 x ULN. If serum creatinine is \>1.25 x ULN, then glomerular filtration rate (based on creatinine) must be \>=60 mL/min.
✓. Absolute neutrophil count \>=1.0 x 10\^9/L.
Exclusion criteria
What they're measuring
1
Primary outcome measure: Long-term safety and tolerability of mitapivat in subjects with stable sickle cell disease
Timeframe: 48 weeks
Trial details
NCT IDNCT04610866
SponsorNational Heart, Lung, and Blood Institute (NHLBI)
✕.3 Have a significant medical condition that confers an unacceptable risk to participating in the study, and/or that could confound the interpretation of the study data. Such significant medical conditions include, but are not limited to the following:
✕. Poorly controlled hypertension (defined as systolic blood pressure \[BP\] \>150 mmHg or diastolic BP \>90 mmHg) refractory to medical management.
✕. History of recent (within 24 weeks prior to signing consent) decompensated congestive heart failure; myocardial infarction or unstable angina pectoris; hemorrhagic, embolic, or thrombotic stroke; deep venous thrombosis; or pulmonary or arterial embolism.
✕. Cardiac dysrhythmias judged as clinically significant by the Investigator.
✕. Heart-rate corrected QT interval-Fredericia's method (QTcF) \>480 msec with the exception of subjects with right or left bundle branch block.
✕. Clinically symptomatic cholelithiasis or cholecystitis. Prior cholecystectomy is not exclusionary. Subjects with symptomatic cholelithiasis or cholecystitis may be rescreened once the disorder has been treated and clinical symptoms have resolved.