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 range
18 Years – 70 Years
Sex
ALL
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
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.
Questions worth asking your doctor
Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.
1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?
Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.
Questions for the trial coordinator
The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.
1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?
A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.
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)
. 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
.1 Documented pyruvate kinase deficiency
.2 Screening hemoglobin level of \>= 11 g/dL
.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.