Investigating the Mechanistic Effects of Mitapivat in Subjects With Sickle Cell Disease

NCT05675436 | Active Not Recruiting

• 2 other identifiers: 10001061001061-H
• Study Type: observational
• Target: 6
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Hbsc; Hbss; Sickle Beta Thalassemia; Sickle Cell Anemia; Sickle Cell Thalassemia; Sickle Cell Pain; Sickle Beta Zero Thalassemia; Sickle Cell Syndrome Variant

Keywords

Sickle Cell Pain Crisis; Sickle Cell Anemia; Sickle Cell Treatment; Sickle Cell Therapy; Hemoglobin; Natural History

Outcome Measures

Primary Outcomes (1)

• 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.

  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

  12, 24, and 52 weeks

• The p50 changes will also be assessed at the individual time points

  12, 24, and 52 weeks

• Percentage change in muscle physiology, tissue oxygenation and blood flow using NIRS methodologies between baseline the individual time points

  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

  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

  12, 24, and 52 weeks

Study Arms (3)

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

Eligibility Criteria

• Age: 16 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

primary clinical

You may qualify if:

• All subjects enrolled at NIH meeting eligibility for the parent study (AG348-C-020) are eligible for this study.

You may not qualify if:

• 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.

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Anemia, Sickle Cell; Hemoglobin SC Disease

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Swee Lay Thein, M.D.

  National Heart, Lung, and Blood Institute (NHLBI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 6, 2023
• First Posted: January 9, 2023
• Study Start: May 9, 2024
• Primary Completion (Estimated): October 27, 2027
• Study Completion (Estimated): October 27, 2027
• Last Updated: April 29, 2026

Record last verified: 2026-01-27

Locations

US (1)