Sickle Cell DiseasePhase 3NCT07656415
A Study to Investigate the Effect of Mitapivat on Transfusion Burden in Subjects With Sickle Cell Disease (SCD)
A Phase 3 study testing Mitapivat in people with Sickle Cell Disease, run by Agios Pharmaceuticals, Inc. at 5 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 12 years and older
- Conditions the study is for
- Sickle Cell Disease
- What is being tested?
- Mitapivat
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 159 participants
- Where
- 5 sitesUnited States
- Study dates
- 21 Jul 2026to Aug 2030
- Phase
- Phase 3
- 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 12 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Show all 13Show fewer
- 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.
Who cannot join
- 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:
Show all 36Show fewer
- 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.
- Aspartate aminotransferase (AST) >2.5× ULN (unless due to hemolysis and/or hepatic iron deposition) and alanine aminotransferase (ALT) >2.5× ULN (unless due to hepatic iron deposition).
- Renal dysfunction as defined by an estimated glomerular filtration rate <30 milliliters per minute (mL/min)/1.73-meter square (m^2) by the Chronic Kidney Disease Epidemiology Collaboration creatinine equation.
- Active uncontrolled infection requiring systemic antimicrobial therapy.
- Positive test for hepatitis C virus (HCV) antibody (Ab) with evidence of active HCV infection, or positive test for hepatitis B surface antigen (HBsAg).
- Positive test for human immunodeficiency virus (HIV)-1 antibody or HIV-2 antibody.
- History of major surgery (including splenectomy) ≤16 weeks before providing informed assent/consent and/or planning on undergoing a major surgical procedure during the study.
- Current enrollment or past participation (within 90 days before randomization or a time frame equivalent to 5 half-lives of the investigational study drug, whichever is longer) in any other clinical study involving an investigational study drug or device.
- Past enrollment in a clinical study involving mitapivat.
- Prior exposure to gene therapy or prior bone marrow or stem cell transplantation.
- Currently receiving treatment with hematopoietic stimulating agents; the last dose must have been administered at least 90 days before randomization.
- Receiving products that are strong inhibitors of Cytochrome3A4/5 (CYP3A4/5) that have not been stopped for ≥5 days or a time frame equivalent to 5 half-lives (whichever is longer), or strong inducers of Cytochrome3A4 (CYP3A4) that have not been stopped for ≥28 days or a time frame equivalent to 5 half-lives (whichever is longer), prior to randomization.
- Receiving anabolic steroids that have not been stopped for at least 4 weeks before randomization. Testosterone replacement therapy to treat hypogonadism is allowed; the testosterone dose and preparation must be stable for ≥10 weeks before randomization.
- Known allergy to mitapivat or tablet excipients (microcrystalline cellulose, croscarmellose sodium, sodium stearyl fumarate, mannitol, magnesium stearate, and the Opadry Blue II film-coat [hypromellose, titanium dioxide, lactose monohydrate, triacetin, and FD\&C Blue #2]).
- Any medical, hematological, psychological, or behavioral condition(s), including alcohol use disorder, or prior or current therapy that, in the opinion of the Investigator, may confer an unacceptable risk to participating in the study and/or could confound the interpretation of the study data. Also excluded are:
- Subjects unable to receive RBC transfusions (eg, due to presence of allo-antibodies, lack of blood availability).
- Subjects deprived of liberty by court or administrative decision (eg, persons accommodated in an institution by order of an authority or court).
- Subjects undergoing psychiatric care without their consent.
- Subjects admitted to a health or social establishment for purposes other than research.
- Adult Subjects subject to a legal protection measure (guardian, curatorship, legal protection).
- Subjects unable to express their consent.
- Receiving herbal or dietary supplements that have not been stable in dose and preparation for ≥8 weeks prior to randomization.
Trial locations and contacts
5 sites in 1 country. Contact the study team or a site near you to ask about taking part.
5 sites in 1 country
United States5 sites, 5 recruiting
- Recruiting
Southern Specialty Clinic
Flowood, Mississippi, 39232
- Recruiting
The Cancer and Hematology Centers (CHC)
Grand Rapids, Michigan, 49503
- Recruiting
University of Texas Health Science Center at Houston
Houston, Texas, 77030
- Recruiting
Indiana Hemophilia & Thrombosis Center
Indianapolis, Indiana, 46260
- Recruiting
Icahn School of Medicine at Mount Sinai
New York, New York, 10029
About this study
Official title: A Phase 3, Double-Blind, Randomized, Placebo-Controlled, Multicenter Study to Evaluate the Effect of Mitapivat on Transfusion Burden in Subjects With Sickle Cell Disease
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
- Being tested
- Mitapivat Matched Placebo, Mitapivat
- Medical subject headings
- Anemia, Sickle Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mitapivat Matched PlaceboDrug
Tablets
MitapivatDrug
Also called AG-348, Mitapivat sulfate
Tablets
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Mitapivat Matched Placebo; Drug: Mitapivat |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Subjects who are Transfusion Free From Week 4 Through Week 52
Measured: Week 4 through Week 52
Secondary outcomes (12)
Number of Red Blood Cells (RBC) Units Transfused From Week 4 Through Week 52
Measured: Week 4 through Week 52
Percentage of Subjects Who Achieved a Hemoglobin (Hb) Response
Hb response is defined as a ≥1.0 grams per deciliter (g/dL) increase in average Hb concentration from Week 24 through Week 52 compared with baseline.
Measured: Baseline, Week 24 through Week 52
Average Change From Baseline in Hb Concentration From Week 24 Through Week 52
Measured: Baseline, Week 24 through Week 52
Average Change From Baseline in Indirect Bilirubin From Week 24 Through Week 52
Measured: Baseline, Week 24 through Week 52
Average Change From Baseline in Lactate Dehydrogenase (LDH) Concentration From Week 24 Through Week 52
Measured: Baseline, Week 24 through Week 52
Average Change From Baseline in Percent Reticulocyte From Week 24 Through Week 52
Measured: Baseline, Week 24 through Week 52
Average Change From Baseline in Absolute Reticulocyte From Week 24 Through Week 52
Measured: Baseline, Week 24 through Week 52
Number of Subjects With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Measured: From first dose of the study drug to the end of DB period (up to Week 52)
Percentage of Subjects With Sickle Cell Pain Crisis (SCPCs)
Measured: Up to Week 52
Plasma Concentration of Mitapivat
Measured: Pre-dose and at multiple timepoints post-dose at Week 4 and Week 8
Area Under the Plasma Concentration-Time Curve From Time 0 to Time t at Steady State (AUC0-t, ss) of Mitapivat
Measured: Pre-dose and at multiple timepoints post-dose at Week 4 and Week 8
Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of Mitapivat
Measured: Pre-dose and at multiple timepoints post-dose at Week 4 and Week 8
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2026
- Study start21 Jul 2026
- Primary completionAug 2029 (estimated)
- Study completionAug 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Sickle Cell DiseaseStudies of the same condition, open and under way.
- More trials run by Agios Pharmaceuticals, Inc.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
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 159 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Agios Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07656415
- Sponsor's protocol ID
- AG348-C-030
- Other IDs
- 2026-526778-18-00
- Status last verified
- Oct 2026
- First submitted
- 15 Jun 2026
- Last updated
- 28 Oct 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 3, Double-Blind, Randomized, Placebo-Controlled, Multicenter Study to Evaluate the Effect of Mitapivat on Transfusion Burden in Subjects With Sickle Cell Disease
- ClinicalTrials.gov ID
- NCT07656415
- Acronym / sponsor ID
- AG348-C-030
- Conditions
- Sickle Cell Disease
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 159 participants (estimated)
- Lead sponsor
- Agios Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 21 Jul 2026 (actual)
- Primary completion
- Aug 2029 (estimated)
- Study completion
- Aug 2030 (estimated)
- First posted
- 18 Jun 2026 (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.
The primary objective of this study is to determine the effect of mitapivat versus placebo on the need for transfusions in subjects with SCD.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Mitapivat | Experimental | Drug: MitapivatSubjects 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. |
| Placebo | Placebo comparator | Drug: Mitapivat Matched Placebo, Drug: MitapivatSubjects 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. |
Who may qualify
- Ages
- 12 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (13 listed)
- 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.
Key exclusion criteria (36 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Mitapivat Matched PlaceboTablets | Drug | Placebo |
| MitapivatAlso: AG-348, Mitapivat sulfateTablets | Drug | Mitapivat, Placebo |
Primary outcome
Percentage of Subjects who are Transfusion Free From Week 4 Through Week 52
Time frame: Week 4 through Week 52
12 secondary outcomes
Number of Red Blood Cells (RBC) Units Transfused From Week 4 Through Week 52
Time frame: Week 4 through Week 52
Percentage of Subjects Who Achieved a Hemoglobin (Hb) Response
Time frame: Baseline, Week 24 through Week 52
Average Change From Baseline in Hb Concentration From Week 24 Through Week 52
Time frame: Baseline, Week 24 through Week 52
Average Change From Baseline in Indirect Bilirubin From Week 24 Through Week 52
Time frame: Baseline, Week 24 through Week 52
Average Change From Baseline in Lactate Dehydrogenase (LDH) Concentration From Week 24 Through Week 52
Time frame: Baseline, Week 24 through Week 52
Average Change From Baseline in Percent Reticulocyte From Week 24 Through Week 52
Time frame: Baseline, Week 24 through Week 52
Average Change From Baseline in Absolute Reticulocyte From Week 24 Through Week 52
Time frame: Baseline, Week 24 through Week 52
Number of Subjects With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
Time frame: From first dose of the study drug to the end of DB period (up to Week 52)
Percentage of Subjects With Sickle Cell Pain Crisis (SCPCs)
Time frame: Up to Week 52
Plasma Concentration of Mitapivat
Time frame: Pre-dose and at multiple timepoints post-dose at Week 4 and Week 8
Area Under the Plasma Concentration-Time Curve From Time 0 to Time t at Steady State (AUC0-t, ss) of Mitapivat
Time frame: Pre-dose and at multiple timepoints post-dose at Week 4 and Week 8
Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of Mitapivat
Time frame: Pre-dose and at multiple timepoints post-dose at Week 4 and Week 8
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 28 Oct 2026.
- Individual participant dataSharing planned: No
Related trials for Sickle Cell Disease
Active, not recruitingPhase 1/2
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
Sickle Cell Disease, Hemolytic Anemia
RecruitingObservational study
HPC Offered for PRESERVE Expansion
Bone Marrow Transplant (BMT)
RecruitingPhase 1
Study to Evaluate the Safety and Tolerability of Escalating Doses of Fostamatinib in Subjects With Stable Sickle Cell Disease
Sickle Cell Disorders, Sickle Cell Disease
RecruitingPhase 4
Clinical and Biomarker Effects of Depot Medroxyprogesterone Acetate in Females With Sickle Cell Disease
Sickle Cell Disease (SCD), Vaso-Occlusive Pain Episode in Sickle Cell Disease
Not yet recruitingPhase 1
Buprenorphine for the Management of Pain in Children With Sickle Cell Disease
Sickle Cell Disease (SCD), Sickle Cell Disease Vaso-occlusive Crisis
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.
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Mitapivat in people with Sickle Cell Disease, run by Agios Pharmaceuticals, Inc. at 5 sites 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 13 inclusion and 36 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: looking for participants now, as of the sponsor's last update on 28 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 5 sites 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Contact Agios Medical Affairs (08332288474, medinfo@agios.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Subjects who are Transfusion Free From Week 4 Through Week 52 (time frame: Week 4 through Week 52). 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 28 Oct 2026.