Ignite Creation Date:
2025-12-24 @ 4:28 PM
Ignite Modification Date:
2025-12-25 @ 2:20 PM
Study NCT ID:
NCT04610866
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2025-12-17
First Post:
2020-10-30
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
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
Sponsor:
National Heart, Lung, and Blood Institute (NHLBI)
Organization:
Study Overview
Official Title:
Evaluation of the 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
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2025-12-15
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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.
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.
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.
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| 000049-H | None | None | View |