A Phase 2/3 interventional study of Mitapivat and Mitapivat-matching placebo in Sickle Cell Disease, sponsored by Agios Pharmaceuticals, Inc.. Active, not recruiting at 91 sites in 16 countries. Open to participants aged 16 Years and older. Per ClinicalTrials.gov, last updated 2026-06-23.
Sponsored by Agios Pharmaceuticals, Inc. · Phase 2/3, Interventional, and Treatment
This clinical trial is a Phase 2/3 study that will determine the recommended dose of mitapivat and evaluate the efficacy and safety of mitapivat in sickle cell disease by testing how well mitapivat works compared to placebo to increase the amount of hemoglobin in the blood and to reduce or prevent the occurrence of sickle cell pain crises. In addition, the long-term effect of mitapivat on efficacy and safety will be explored in an open-label extension portion.
Mitapivat is a small molecule, oral activator of pyruvate kinase R (PKR). PKR is involved with maintaining health, energy, and longevity of red blood cells (RBCs). The study aims to evaluate the efficacy and safety of treatment with mitapivat in participants with sickle cell disease. The study is a Phase 2/3 study in which the recommended dose of mitapivat will be selected and further evaluated. The Phase 2 portion includes a 12-week randomized, placebo-controlled period in which participants will be randomized in a 1:1:1 ratio to receive 2 dose levels of mitapivat or placebo. The Phase 3 portion includes a 52-week randomized, placebo-controlled period in which participants will be randomized in a 2:1 ratio to receive the recommended mitapivat dose level or placebo. Participants who complete either the Phase 2 or Phase 3 portion will have the option to move into a 216-week open label extension period to receive mitapivat.
1,103 studies on the registry are indexed under Anemia, Sickle Cell; 235 are open to participants now.
This study's enrollment of 286 is above the median of 40 across 750 interventional studies indexed under Anemia, Sickle Cell.
Browse Anemia, Sickle Cell studies →Agios Pharmaceuticals, Inc. is the lead sponsor of 52 studies on the registry; 6 are open to participants now.
Of its 23 completed or terminated interventional studies of FDA-regulated products, 4 (17%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Double-blind Period: Mitapivat 50 milligrams (mg) twice daily (BID) for 12 weeks.
Drug: Mitapivat
Double-blind Period: Mitapivat 100 mg BID for 12 weeks.
Drug: Mitapivat
Double-blind Period: Mitapivat-matching placebo for 12 weeks.
Other: Mitapivat-matching placebo
Participants who received mitapivat 50mg BID in the double-blind period may choose to receive mitapivat 50mg BID for 216 weeks after. Participants who received mitapivat 100mg BID in the double-blind period may choose to receive mitapivat 100 mg BID for 216 weeks after. Participants who received mitapivat-matching placebo in the double-blind period, may be randomized to receive either mitapivat 50 mg or 100 mg BID for 216 weeks after.
Drug: Mitapivat
Double-blind Period: Mitapivat 100 mg BID for 52 weeks.
Drug: Mitapivat
Double-blind Period: Mitapivat-matching placebo for 52 weeks.
Other: Mitapivat-matching placebo
Participants may choose to receive mitapivat 100 mg BID for 216 weeks after the Double-blind Period. Participants who received mitapivat-matching placebo in the double-blind period, may choose to receive mitapivat 100 mg BID for 216 weeks after the Double-blind Period.
Drug: Mitapivat
Mitapivat tablets
Also known as: AG-348, Mitapivat Sulfate
Placebo to match 50 mg or 100 mg tablets
Placebo to match 100 mg tablets
Phase 2: Percentage of Participants With Hemoglobin (Hb) Response
Time frame: Week 12
Phase 2: Percentage of Participants With Treatment-Emergent Adverse Events (AEs) and Treatment-Emergent Serious AEs (SAEs)
Time frame: Up to Week 12
Phase 3: Percentage of Participants With Hb Response
Time frame: Week 52
Phase 3: Annualized Rate of Sickle Cell Pain Crises (SCPCs)
Time frame: Up to Week 52
Phase 2: Change From Baseline in Hb Concentration
Time frame: Baseline, Week 10 up to Week 12
Phase 2: Change From Baseline in Indirect Bilirubin
Time frame: Baseline, Week 10 up to Week 12
Phase 2: Change From Baseline in Lactate Dehydrogenase (LDH)
Time frame: Baseline, Week 10 up to Week 12
Phase 2: Change From Baseline in Absolute Reticulocytes Count
Time frame: Baseline, Week 10 up to Week 12
Phase 2: Change From Baseline in Percent Reticulocytes
Time frame: Baseline, Week 10 up to Week 12
Phase 2: Change From Baseline in Erythropoietin
Time frame: Baseline, Week 10 up to Week 12
Phase 2: Change From Baseline in Patient-Reported Outcomes Measurement Information System® (PROMIS®) Fatigue 13a Short Form (SF) Score
Time frame: Baseline, Week 10 up to Week 12
Phase 2: Annualized Rate of SCPCs
Time frame: Up to Week 12
Phase 2: Pharmacokinetic/Pharmacodynamic Relationship: Evaluate the Exposure of Mitapivat to the Change in Adenosine Triphosphate (ATP) and 2,3-Diphosphoglycerate (2,3-DPG)
Time frame: Day 1 up to Week 8
Phase 2: Mitapivat Concentration Over Time
Time frame: Day 1 up to Week 8
Phase 2: Mitapivat Area Under the Concentration
Time frame: Day 1 up to Week 8
Phase 2: Mitapivat Maximum (Peak) Concentration
Time frame: Day 1 up to Week 8
Phase 3: Change From Baseline in Hb Concentration
Time frame: Baseline, Week 24 up to Week 52
Phase 3: Change From Baseline in Indirect Bilirubin
Time frame: Baseline, Week 24 up to Week 52
Phase 3: Change From Baseline in Percent Reticulocytes
Time frame: Baseline, Week 24 up to Week 52
Phase 3: Change From Baseline in PROMIS® Fatigue 13a SF Scores
Time frame: Baseline, Week 24 up to Week 52
Phase 3: Annualized Frequency of Hospitalizations for SCPC
Time frame: Up to Week 52
Phase 3: Change From Baseline in LDH Concentration
Time frame: Baseline, Week 24 up to Week 52
Phase 3: Change From Baseline in Absolute Reticulocytes
Time frame: Baseline, Week 24 up to Week 52
Phase 3: Change From Baseline in Erythropoietin
Time frame: Baseline, Week 24 up to Week 52
Phase 3: Percentage of Participants With Improvement in the Patient Global Impression of Severity (PGIS) -Fatigue
Time frame: Baseline, Weeks 24, 28, 40, and 52
Phase 3: Percentage of Participants With Improvement in the Patient Global Impression of Change (PGIC) -Fatigue
Time frame: Baseline, Weeks 24, 28, 40, and 52
Phase 3: Time to First SCPC
Time frame: Up to Week 52
Phase 3: Time to Second SCPC
Time frame: Up to Week 52
Phase 3: Annualized Rate of Hospitalization Days for SCPC
Time frame: Up to Week 52
Phase 3: Annualized Rate of Emergency Room Visits for SCPC
Time frame: Up to Week 52
Phase 3: Change From Baseline in 6-Minute Walk Test (6MWT)
Time frame: Baseline, Week 52
Phase 3: Change From Baseline in PROMIS Pain Intensity
Time frame: Baseline, Week 24 and 52
Phase 3: Change From Baseline in Adult Sickle Cell Quality of Life Measurement Information System (ASCQ-Me) Pain Impact
Time frame: Baseline, Week 24 and 52
Phase 3: PGIC of Pain
Time frame: Baseline, Week 52
Phase 3: Change From Baseline in PGIS of Pain
Time frame: Baseline, Week 52
Phase 3: Percentage of Participants With Treatment-Emergent Adverse Events (AEs) and Treatment-Emergent Serious AEs (SAEs)
Time frame: Up to 56 weeks
Phase 3: Pharmacokinetic/Pharmacodynamic Relationship: Evaluate the Exposure of Mitapivat to the Change in ATP and 2,3-DPG Levels
Time frame: Day 1 up to Week 40
Phase 3: Mitapivat Concentration Over Time
Time frame: Day 1 up to Week 40
Phase 3: Mitapivat Area Under the Concentration Curve
Time frame: Day 1 up to Week 40
Phase 3: Mitapivat Maximum (Peak) Concentration
Time frame: Day 1 up to Week 40
Plan to share: No
This study is active, not recruiting, as verified in Jun 2026. You cannot join it, but the record below documents what was studied.
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Agios Pharmaceuticals, Inc.