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
- Conditions
- Sickle Cell DiseaseHemolytic Anemia
- Interventions
- Registration Number
- NCT04610866
- Brief 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.
- Detailed Description
Study Description:
The objective of this extension study is to evaluate the safety and tolerability of mitapivat (AG-348) as long-term maintenance therapy for subjects with sickle cell disease (SCD) who have completed the Phase I dose escalation study of mitapivat (NCT04000165, protocol 19H0097). Subjects will be treated with a maintenance dose of mitapivat previously assessed for safety and tolerability in the Phase I study for an initial 48 weeks and undergo safety monitoring, evaluation of pharmacokinetics and pharmacodynamics, and assessment of secondary clinical endpoints at regular intervals over the study period. Exploratory endpoints will allow for investigation of the mechanisms by which mitapivat may modulate red cell metabolism and survival and lead to clinical benefits in SCD. Subjects benefiting from the study drug will have the option to continue therapy for an additional 5 years.
Objectives:
Primary Objective:
- To assess the long-term safety and tolerability of mitapivat in subjects with stable sickle cell disease.
Secondary Objectives:
* To evaluate the pharmacokinetic/pharmacodynamic profile of long-term dosing of mitapivat, as well as its mechanisms of action on the glycolytic pathway in SCD subjects.
* To evaluate hemoglobin (Hb) response, changes in hemolytic markers, functional status, cardiopulmonary function, and health-related quality of life in SCD subjects maintained on mitapivat long-term.
* To monitor SCD-related safety endpoints in SCD subjects maintained on mitapivat long-term.
Tertiary/Exploratory Objectives:
- To assess the feasibility and usability of digital health technology in a drug trial for patients with SCD.
Endpoints:
Primary Endpoints:
- Frequency and severity of AEs and changes in clinical and laboratory parameters over 6 years of therapy with mitapivat.
Secondary Endpoints:
* Change from baseline in pharmacokinetic and pharmacodynamic measures over time.
* Hemoglobin (Hb) response and changes in hemolytic markers at 24 and 48 weeks on mitapivat.
* Sustained Hb response from weeks 12-48.
* Change from baseline in functional and cardiopulmonary status at 24 and 48 weeks on mitapivat.
* Change from baseline in quality of life at 24 and 48 weeks on mitapivat.
* Frequency of acute vaso-occlusive clinical events at 24 and 48 weeks on mitapivat.
Tertiary/Exploratory Endpoints:
- Usability of SCD Warrior digital Microhealth application (app) by providers and participants through simple feedback tools at each protocol visit reviewing ease of use and patient satisfaction.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 15
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description 1 Mitapivat Subjects will be treated with a maintenance dose of mitapivat previously assessed for safety and tolerability in the Phase I study for an initial 48 weeks and undergo safety monitoring, evaluation of pharmacokinetics and pharmacodynamics, and assessment of secondary laboratory and clinical endpoints at pre-specified intervals during the study period.
- Primary Outcome Measures
Name Time Method Primary outcome measure: Long-term safety and tolerability of mitapivat in subjects with stable sickle cell disease 48 weeks Frequency and severity of AEs and changes in clinical and laboratory parameters over 48 weeks of maintenance therapy with mitapivat.
- Secondary Outcome Measures
Name Time Method To evaluate the pharmacokinetic 24 and 48 weeks Change from baseline in pharmacokinetic and pharmacodynamic measures over time.
To evaluate hemoglobin (Hb) response, changes in hemolytic markers, functional status, cardiopulmonary function, and health-related quality of life in SCD subjects maintained on mitapivat long-term. 24 and 48 weeks - Hemoglobin (Hb) response and changes in hemolytic markers at 24 and 48 weeks on mitapivat. Sustained Hb response from weeks 12-48. - Change from baseline in functional and cardiopulmonary status at 24 and 48 weeks on mitapivat. - Change from baseline in quality of life at 24 and 48 weeks on mitapivat
To monitor SCD-related safety endpoints in SCD subjects maintained on mitapivat long-term. 24 and 48 weeks - Frequency of acute vaso- occlusive events (acute vaso-occlusive pain crisis, acute chest syndrome, hepatic sequestration, splenic sequestration, and priapism) at 24 and 48 weeks on mitapivat.
Trial Locations
- Locations (1)
National Institutes of Health Clinical Center
🇺🇸Bethesda, Maryland, United States