A Study to Investigate the Effect of Mitapivat on Transfusion Burden in Subjects With Sickle Cell Disease (SCD)

NCT07656415 | Not Yet Recruiting Phase 3 FDA Drug

• 2 other identifiers: AG348-C-0302026-526778-18-00
• Study Type: interventional
• Target: 159
• Locations: 0 countries
• Sites: N/A

Brief Summary

The primary objective of this study is to determine the effect of mitapivat versus placebo on the need for transfusions in subjects with SCD.

Conditions

Sickle Cell Disease

Outcome Measures

Primary Outcomes (1)

• Percentage of Subjects who are Transfusion Free From Week 4 Through Week 52

  Week 4 through Week 52

Secondary Outcomes (12)

• Number of Red Blood Cells (RBC) Units Transfused From Week 4 Through Week 52

  Week 4 through Week 52

• Percentage of Subjects Who Achieved a Hemoglobin (Hb) Response

  Baseline, Week 24 through Week 52

• Average Change From Baseline in Hb Concentration From Week 24 Through Week 52

  Baseline, Week 24 through Week 52

• Average Change From Baseline in Indirect Bilirubin From Week 24 Through Week 52

  Baseline, Week 24 through Week 52

• Average Change From Baseline in Lactate Dehydrogenase (LDH) Concentration From Week 24 Through Week 52

  Baseline, Week 24 through Week 52

Study Arms (2)

Mitapivat

EXPERIMENTAL

Subjects will receive oral mitapivat 100 milligrams (mg), twice daily (BID), for up to 52 Weeks during the double blind (DB) period. Subjects who will complete the DB period may continue receiving mitapivat for up to 52 weeks in the open-label extension (OLE) period.

Drug: Mitapivat

Placebo

PLACEBO COMPARATOR

Subjects will receive oral mitapivat matching placebo, BID, for up to 52 weeks during the DB period. Subjects who will complete the DB period may continue to receive mitapivat for up to 52 weeks in the OLE period.

Drug: Mitapivat Matched Placebo; Drug: Mitapivat

Interventions

Mitapivat Matched Placebo DRUG

Tablets

Placebo

Mitapivat DRUG

Tablets

Also known as: AG-348, Mitapivat sulfate

Mitapivat; Placebo

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥12 years.
• Documented diagnosis of SCD (hemoglobin SS (HbSS), combined heterozygosity for hemoglobins S and C (HbSC), sickle cell hemoglobin (HbS)/β0-thalassemia, HbS/β+-thalassemia, or other sickle cell syndrome variants).
• No more than 10 SCPCs in the 12 months before providing informed assent/consent.
• At least 1 transfusion of packed RBCs in the 12 months before informed assent/consent.
• Hb ≥5.5 and ≤10.5 g/dL. Hb concentration must be based on an average of at least 2 Hb concentration measurements (separated by ≥7 days) collected during the Screening Period.
• Additional signs or symptoms of hemolysis, as evidenced by any laboratory assessment during the Screening Period with
• Hb \<8 g/dL, or
• Absolute reticulocyte count \> upper limit of normal (ULN), or
• Indirect bilirubin \>ULN, or
• LDH \>ULN
• If taking hydroxyurea, the hydroxyurea dose must be stable for at least 90 days prior to randomization. Discontinuation of hydroxyurea requires a 90-day washout prior to informed assent/consent.
• Women of childbearing potential (WOCBP) and pediatric female subjects who have attained menarche must be abstinent of sexual activities that may induce pregnancy as part of their usual lifestyle or agree to use a highly effective method of contraception from the time of providing informed assent/consent, throughout the study, and for 28 days after the last dose of study drug; if the highly effective method of contraception is hormonal contraception, then an acceptable barrier method must also be used.
• Written informed assent/consent (for subjects under 18 years of age, or prior to the age at which a subject is considered legally an adult per local regulations, parental permission and child assent will be obtained) must be obtained before any study-related procedures are conducted and subjects must be willing to comply with all study procedures for the duration of the study.

You may not qualify if:

• Pregnant, breastfeeding, or parturient.
• Receiving regularly scheduled RBC transfusion therapy (also termed chronic, prophylactic, or preventative transfusion); episodic transfusion in response to worsened anemia or vaso-occlusive crisis (VOC) is permitted. Additionally, a subject who requires episodic transfusion(s) may not have received a transfusion(s) within 60 days before providing informed assent/consent or during the Screening Period.
• Hospitalized for an SCPC and/or other vaso-occlusive event within 14 days prior to providing informed assent/consent or during the Screening Period. A hospitalization is defined as an in-patient admission to a hospital that may or may not be preceded by an emergency room or outpatient clinic visit. A visit to an emergency room that does not result in an in-patient admission does not meet the definition of hospitalization.
• Currently receiving treatment with a disease-modifying therapy for SCD (eg, voxelotor, crizanlizumab, L-glutamine), with the exception of hydroxyurea. The last dose of voxelotor, crizanlizumab, and L-glutamine must have been administered at least 90 days before randomization.
• History of any malignancy except for nonmelanomatous skin cancer in situ, cervical carcinoma in situ, or breast carcinoma in situ. Subjects must not have active disease or received anticancer treatment ≤5 years before providing informed assent/consent.
• History of active and uncontrolled cardiac or pulmonary disease within 6 months before randomization, including but not limited to:
• New York Heart Association Class III or IV heart failure or clinically significant dysrhythmia.
• Myocardial infarction or unstable angina pectoris; hemorrhagic, embolic, or thrombotic stroke; deep venous thrombosis; or pulmonary or arterial embolism.
• Heart rate-corrected QT interval using Fridericia's method of ≥470 milliseconds for female subjects and ≥450 milliseconds for male subjects, except for right or left bundle branch block.
• Severe pulmonary fibrosis as defined by severe hypoxia, evidence of right-sided heart failure, and radiographic pulmonary fibrosis \>50%.
• Severe pulmonary hypertension as defined by severe symptoms associated with hypoxia, right heart failure, and oxygen indicated.
• Hepatobiliary disorders including but not limited to:
• Liver disease with histopathological evidence or clinical diagnosis of cirrhosis or severe fibrosis.
• Clinically symptomatic cholelithiasis or cholecystitis (subjects with prior cholecystectomy are eligible).
• History of drug-induced cholestatic hepatitis.

Sponsors & Collaborators

• Agios Pharmaceuticals, Inc.: lead

MeSH Terms

Conditions

Anemia, Sickle Cell

Interventions

mitapivat

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

Central Study Contacts

Agios Medical Affairs

CONTACT

08332288474; medinfo@agios.com

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 15, 2026
• First Posted: June 18, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): August 1, 2029
• Study Completion (Estimated): August 1, 2030
• Last Updated: July 30, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share