Sickle Cell AnemiaNCT05675436
Investigating the Mechanistic Effects of Mitapivat in Subjects With Sickle Cell Disease
An observational study of Sickle Cell Anemia and Sickle Cell Thalassemia, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
Trial summary
Background: Sickle cell disease (SCD) is an inherited blood disorder. The disease affects the ability of red blood cells to carry oxygen; this in turn can injure organs including the heart, lungs, and kidneys. SCD can lead to serious illness and death. Read more about this study
- Who is it for?
- Ages 16 to 80 years
- Conditions the study is for
- Sickle Cell Anemia, Sickle Cell Thalassemia, Sickle Cell Pain
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- 9 May 2024to 27 Oct 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 16 to 80 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: primary clinical
Who may be able to join
- All subjects enrolled at NIH meeting eligibility for the parent study (AG348-C-020) are eligible for this study.
Who cannot join
- Subjects that did not meet eligibility criteria to the parent protocol (AG348-C-020) will not be eligible to enroll for this study.
- Subjects will be screened for implanted metal objects or devices that may be incompatible with MRI (i.e. cerebral aneurysm clip, cochlear implant, pacemaker, etc.) These subjects will be eligible to proceed with study enrollment, but will not undergo the optional MRI study.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892
About this study
Official title: Observational Study Investigating the Mechanistic Effects of Mitapivat in Subjects With Sickle Cell Disease
Background:
Sickle cell disease (SCD) is an inherited blood disorder. The disease affects the ability of red blood cells to carry oxygen; this in turn can injure organs including the heart, lungs, and kidneys. SCD can lead to serious illness and death. Treatments such as bone marrow transplants and gene therapies can cure SCD, but they are not widely available. Current drug treatments for SCD are not always effective. This natural history study will examine how a study drug (mitapivat) affects red blood cells in people with SCD.
Read more
Objective:
To learn how mitapivat affects red blood cells in people with SCD.
Eligibility:
People with SCD who are enrolled in the parent study, NIH protocol IRB001565-H.
Design:
Procedures for this study will be done during visits already scheduled for the parent study.
Participants will have additional blood drawn during study visits. The additional amount will be about 3.5 teaspoons.
Participants will undergo a test called near infrared spectroscopy (NIRS) up to 9 times. Probes will be placed on their skin. A blood pressure cuff will be placed on their arm. The cuff will be filled with air for up to 5 minutes and then released. Participants may be asked to breathe at a certain rate or to hold their breath during these measurements. NIRS measures oxygen levels, blood flow, and the makeup of skin and muscle.
Researchers will draw additional information for this study from participants medical records.
Read the detailed description
Study Description:
Subjects actively enrolled protocol AG348-C-020 (NIH protocol IRB001565-H), an industry-sponsored phase 2/3 study investigating the efficacy of mitapivat in treating sickle cell disease (SCD), will be invited to participate in this protocol simultaneously to further investigate the mechanistic effects of mitapivat. Subjects will be asked for a blood sample at study visits and undergo near infrared spectroscopy (NIRS) testing to investigate the mechanisms of action of mitapivat in subjects with SCD.
Objectives:
To evaluate the mechanisms of action of mitapivat in subjects with SCD.
Endpoints:
PRIMARY ENDPOINT DURING BLINDED PERIOD:
The percentage change in the oxygen affinity measure p50 (defined as the partial pressure of oxygen at which Hb is 50% saturated with oxygen) between baseline and the average value at 12, 24 and 52 weeks. This change will be compared between the placebo and mitapivat arms.
PRIMARY ENDPOINTS DURING OPEN LABEL EXTENSION (OLE):
- Evaluate the effect of mitapivat by comparing inter-patient and intra-patient changes between year one and year two.
- Evaluate the effects of long term use of mitapivat in patients who were randomized onto mitapivat during the first year of the study.
- Evaluate the intra-patient changes for patients who were randomized onto the placebo during the first year of the study and transition to mitapivat during year two.
SECONDARY ENDPOINTS DURING BLINDED PERIOD:
- The p50 changes will also be assessed at the individual time points of 12, 24, and 52 weeks.
- Percentage of sickled cells and time to 50% sickling (t50) under normal and hypoxic ex vivo conditions at regular time intervals on mitapivat and percentage change from baseline to the individual time points at 12, 24, and 52 weeks. This change will be compared between the placebo and mitapivat arms.
- Percentage change in intracellular reactive oxidative species (ROS) in red blood cells (RBCs) using a ROS sensitive fluorescent probe and mass spectrometry- based proteomics of RBC lysates between baseline and the individual time points at 12, 24, and 52 weeks. This change will be compared between the placebo and mitapivat arms.
- The percentage change in phosphatidylserine (PS) externalization using annexin V labeling (marker of red cell survival) by flow cytometry between baseline and the individual time points at 12, 24, and 52 weeks. This change will be compared between the placebo and mitapivat arms.
- Percentage change in muscle physiology, tissue oxygenation and blood flow using NIRS methodologies between baseline the individual time points at 12, 24, and 52 weeks. This change will be compared between the placebo and mitapivat arms.
- RBC deformability and sickling using osmotic and oxygen gradient ektacytometry
TERTIARY/EXPLORATORY ENDPOINTS DURING BLINDED PERIOD:
- Evaluate effect of mitapivat on RBC metabolomics and proteomics between baseline and various follow-up periods. This change will be compared between the placebo and mitapivat arms.
- Measurement of glycated Hb S level as a surrogate measure for red cell half-life between baseline and various follow-up periods. This change will be compared between the placebo and mitapivat arms.
- Evaluate effect of mitapivat on RBC band 3 tyrosine phosphorylation between baseline and various follow-up periods.
This change will be compared between the placebo and mitapivat arms.
- Correlation between potential exploratory biomarkers and clinical laboratory parameters.
- Evaluate change in cerebral hemodynamic measurements through magnetic resonance imaging (MRI) for cerebral blood flow, oxygen extraction fraction, and cerebral metabolic rate of oxygen consumption from baseline, at 12 and 52 weeks. This change will be compared between the placebo and mitapivat arms.
- Conditions
- Sickle Cell Anemia, Sickle Cell Thalassemia, Sickle Cell Pain, Hbss, Hbsc, Sickle Beta Thalassemia
- Keywords
- Sickle Cell Pain Crisis, Sickle Cell Anemia, Sickle Cell Treatment, Sickle Cell Therapy, Hemoglobin, Natural History
- Medical subject headings
- Anemia, Sickle Cell, Hemoglobin SC Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 1 | i. Phase 3: Mitapivat 50 mg BID | |
| 2 | ii. Phase 3: Mitapivat 100 mg BID | |
| 3 | iii. Phase 3: Mitapivat Open-Label Extension Period |
What is being measured
The primary outcome is the main question the study is designed to answer.
The percentage change in the oxygen affinity measure p50 (defined as the partial pressure of oxygen at which Hb is 50% saturated with oxygen) between baseline.
This change will be compared between the placebo and mitapivat arms.
Measured: 12, 24 and 52 weeks
Secondary outcomes (6)
The percentage change in phosphatidylserine (PS) externalization using annexin V labeling (marker of red cell survival) by flow cytometry between baseline and the individual time points
This change will be compared between the placebo and mitapivat arms.
Measured: 12, 24, and 52 weeks
The p50 changes will also be assessed at the individual time points
This change will be compared between the placebo and mitapivat arms.
Measured: 12, 24, and 52 weeks
Percentage change in muscle physiology, tissue oxygenation and blood flow using NIRS methodologies between baseline the individual time points
This change will be compared between the placebo and mitapivat arms.
Measured: 12, 24, 52, and 59 weeks
Percentage of sickled cells and time to 50% sickling (t50) under normal and hypoxic ex vivo conditions at regular time intervals on mitapivat and percentage change from baseline to the individual time points
This change will be compared between the placebo and mitapivat arms.
Measured: 12, 24, and 52 weeks
Percentage change in intracellular reactive oxidative species (ROS) in red blood cells (RBCs) using a ROS sensitive fluorescent probe and mass spectrometry- based proteomics of RBC lysates between baseline and the individual time points
This change will be compared between the placebo and mitapivat arms.
Measured: 12, 24, and 52 weeks
RBC deformability and sickling using osmotic and oxygen gradient ektacytometry
This change will be compared between the placebo and mitapivat arms.
Measured: 12, 24, and 52 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jan 2023
- Study start9 May 2024
- Primary completion27 Oct 2027 (estimated)
- Study completion27 Oct 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Sickle Cell AnemiaStudies of the same condition, open and under way.
- More trials run by National Heart, Lung, and Blood Institute (NHLBI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Swee Lay Thein, M.D., Principal investigator, National Heart, Lung, and Blood Institute (NHLBI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05675436
- Sponsor's protocol ID
- 10001061
- Other IDs
- 001061-H
- Status last verified
- 27 Oct 2026
- First submitted
- 6 Jan 2023
- Last updated
- 29 Oct 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Undecided: It is not yet known if there will be a plan to make IPD available
Study at a glance
From the registry record, last updated by the sponsor on 29 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Observational Study Investigating the Mechanistic Effects of Mitapivat in Subjects With Sickle Cell Disease
- ClinicalTrials.gov ID
- NCT05675436
- Acronym / sponsor ID
- 10001061
- Conditions
- Sickle Cell Anemia, Sickle Cell Thalassemia, Sickle Cell Pain, Hbss, Hbsc, Sickle Beta Thalassemia
- Keywords
- Sickle Cell Pain Crisis, Sickle Cell Anemia, Sickle Cell Treatment, Sickle Cell Therapy, Hemoglobin, Natural History
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 6 participants (actual)
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- 9 May 2024 (actual)
- Primary completion
- 27 Oct 2027 (estimated)
- Study completion
- 27 Oct 2027 (estimated)
- First posted
- 9 Jan 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
Sickle cell disease (SCD) is an inherited blood disorder. The disease affects the ability of red blood cells to carry oxygen; this in turn can injure organs including the heart, lungs, and kidneys. SCD can lead to serious illness and death. Treatments such as bone marrow transplants and gene therapies can cure SCD, but they are not widely available. Current drug treatments for SCD are not always effective. This natural history study will examine how a study drug (mitapivat) affects red blood cells in people with SCD.
Objective:
To learn how mitapivat affects red blood cells in people with SCD.
Eligibility:
People with SCD who are enrolled in the parent study, NIH protocol IRB001565-H.
Design:
Procedures for this study will be done during visits already scheduled for the parent study.
Participants will have additional blood drawn during study visits. The additional amount will be about 3.5 teaspoons.
Participants will undergo a test called near infrared spectroscopy (NIRS) up to 9 times. Probes will be placed on their skin. A blood pressure cuff will be placed on their arm. The cuff will be filled with air for up to 5 minutes and then released. Participants may be asked to breathe at a certain rate or to hold their breath during these measurements. NIRS measures oxygen levels, blood flow, and the makeup of skin and muscle.
Researchers will draw additional information for this study from participants medical records.
Detailed description
Study Description:
Subjects actively enrolled protocol AG348-C-020 (NIH protocol IRB001565-H), an industry-sponsored phase 2/3 study investigating the efficacy of mitapivat in treating sickle cell disease (SCD), will be invited to participate in this protocol simultaneously to further investigate the mechanistic effects of mitapivat. Subjects will be asked for a blood sample at study visits and undergo near infrared spectroscopy (NIRS) testing to investigate the mechanisms of action of mitapivat in subjects with SCD.
Objectives:
To evaluate the mechanisms of action of mitapivat in subjects with SCD.
Endpoints:
PRIMARY ENDPOINT DURING BLINDED PERIOD:
The percentage change in the oxygen affinity measure p50 (defined as the partial pressure of oxygen at which Hb is 50% saturated with oxygen) between baseline and the average value at 12, 24 and 52 weeks. This change will be compared between the placebo and mitapivat arms.
PRIMARY ENDPOINTS DURING OPEN LABEL EXTENSION (OLE):
- Evaluate the effect of mitapivat by comparing inter-patient and intra-patient changes between year one and year two.
- Evaluate the effects of long term use of mitapivat in patients who were randomized onto mitapivat during the first year of the study.
- Evaluate the intra-patient changes for patients who were randomized onto the placebo during the first year of the study and transition to mitapivat during year two.
SECONDARY ENDPOINTS DURING BLINDED PERIOD:
- The p50 changes will also be assessed at the individual time points of 12, 24, and 52 weeks.
- Percentage of sickled cells and time to 50% sickling (t50) under normal and hypoxic ex vivo conditions at regular time intervals on mitapivat and percentage change from baseline to the individual time points at 12, 24, and 52 weeks. This change will be compared between the placebo and mitapivat arms.
- Percentage change in intracellular reactive oxidative species (ROS) in red blood cells (RBCs) using a ROS sensitive fluorescent probe and mass spectrometry- based proteomics of RBC lysates between baseline and the individual time points at 12, 24, and 52 weeks. This change will be compared between the placebo and mitapivat arms.
- The percentage change in phosphatidylserine (PS) externalization using annexin V labeling (marker of red cell survival) by flow cytometry between baseline and the individual time points at 12, 24, and 52 weeks. This change will be compared between the placebo and mitapivat arms.
- Percentage change in muscle physiology, tissue oxygenation and blood flow using NIRS methodologies between baseline the individual time points at 12, 24, and 52 weeks. This change will be compared between the placebo and mitapivat arms.
- RBC deformability and sickling using osmotic and oxygen gradient ektacytometry
TERTIARY/EXPLORATORY ENDPOINTS DURING BLINDED PERIOD:
- Evaluate effect of mitapivat on RBC metabolomics and proteomics between baseline and various follow-up periods. This change will be compared between the placebo and mitapivat arms.
- Measurement of glycated Hb S level as a surrogate measure for red cell half-life between baseline and various follow-up periods. This change will be compared between the placebo and mitapivat arms.
- Evaluate effect of mitapivat on RBC band 3 tyrosine phosphorylation between baseline and various follow-up periods.
This change will be compared between the placebo and mitapivat arms.
- Correlation between potential exploratory biomarkers and clinical laboratory parameters.
- Evaluate change in cerebral hemodynamic measurements through magnetic resonance imaging (MRI) for cerebral blood flow, oxygen extraction fraction, and cerebral metabolic rate of oxygen consumption from baseline, at 12 and 52 weeks. This change will be compared between the placebo and mitapivat arms.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 1 | – | –i. Phase 3: Mitapivat 50 mg BID |
| 2 | – | –ii. Phase 3: Mitapivat 100 mg BID |
| 3 | – | –iii. Phase 3: Mitapivat Open-Label Extension Period |
Who may qualify
- Ages
- 16 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- primary clinical
Key inclusion criteria (1 listed)
- All subjects enrolled at NIH meeting eligibility for the parent study (AG348-C-020) are eligible for this study.
Key exclusion criteria (2 listed)
- Subjects that did not meet eligibility criteria to the parent protocol (AG348-C-020) will not be eligible to enroll for this study.
- Subjects will be screened for implanted metal objects or devices that may be incompatible with MRI (i.e. cerebral aneurysm clip, cochlear implant, pacemaker, etc.) These subjects will be eligible to proceed with study enrollment, but will not undergo the optional MRI study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
The percentage change in the oxygen affinity measure p50 (defined as the partial pressure of oxygen at which Hb is 50% saturated with oxygen) between baseline.
Time frame: 12, 24 and 52 weeks
This change will be compared between the placebo and mitapivat arms.
6 secondary outcomes
The percentage change in phosphatidylserine (PS) externalization using annexin V labeling (marker of red cell survival) by flow cytometry between baseline and the individual time points
Time frame: 12, 24, and 52 weeks
The p50 changes will also be assessed at the individual time points
Time frame: 12, 24, and 52 weeks
Percentage change in muscle physiology, tissue oxygenation and blood flow using NIRS methodologies between baseline the individual time points
Time frame: 12, 24, 52, and 59 weeks
Percentage of sickled cells and time to 50% sickling (t50) under normal and hypoxic ex vivo conditions at regular time intervals on mitapivat and percentage change from baseline to the individual time points
Time frame: 12, 24, and 52 weeks
Percentage change in intracellular reactive oxidative species (ROS) in red blood cells (RBCs) using a ROS sensitive fluorescent probe and mass spectrometry- based proteomics of RBC lysates between baseline and the individual time points
Time frame: 12, 24, and 52 weeks
RBC deformability and sickling using osmotic and oxygen gradient ektacytometry
Time frame: 12, 24, and 52 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Oct 2026.
- NIH Clinical Center Detailed Web PageLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided. Undecided: It is not yet known if there will be a plan to make IPD available
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Swee Lay Thein, M.D. principal investigator
National Heart, Lung, and Blood Institute (NHLBI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Sickle Cell Anemia and Sickle Cell Thalassemia, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 29 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The percentage change in the oxygen affinity measure p50 (defined as the partial pressure of oxygen at which Hb is 50% saturated with oxygen) between baseline. (time frame: 12, 24 and 52 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Oct 2026.