Phase 3
N=90
Extension Study of AG-348 in Adult Participants With Pyruvate Kinase Deficiency Previously Enrolled in AG-348-006 or AG348-C-007
Pyruvate Kinase Deficiency
Bottom Line
View on ClinicalTrials.gov: NCT03853798 ↗Enrolled (actual)
90
Serious AEs
25.6%
Results posted
Nov 2025
Primary outcome: Primary: All Cohorts: Number of Participants With at Least One Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Related TEAEs and TEAEs With Severity Greater Than or Equal to Grade 3 — 37; 33; 15; 11 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Mitapivat (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Agios Pharmaceuticals, Inc.
- Primary completion
- Jul 2024
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY All Cohorts: Number of Participants With at Least One Treatment Emergent Adverse Events (TEAEs), Serious TEAEs, Related TEAEs and TEAEs With Severity Greater Than or Equal to Grade 3 |
37; 33; 15; 11; 8; 4 | — |
| PRIMARY All Cohorts: Number of Participants With TEAEs Leading to Dose Reduction, Treatment Interruption and Treatment Discontinuation |
2; 2; 1; 3; 4; 0 | — |
| PRIMARY All Cohorts: Number of Participants With Clinically Significant Abnormalities in Laboratory Parameters Reported as Grade Greater Than or Equal to (≥)3 TEAEs |
3; 1; 0; 1; 2; 0 | — |
| PRIMARY All Cohorts: Number of Participants With Clinically Significant Abnormalities in Vital Signs Measurements and Physical Examinations Reported as TEAEs |
0; 1; 1; 2; 0; 2 | — |
| PRIMARY All Cohorts: Number of Participants With Clinically Significant Abnormalities in Bone Mineral Density (BMD) |
0; 1; 0 | — |
| PRIMARY All Cohorts: Change From Baseline in Adjusted Spine T-score |
0.046; 0.234; 0.416 | — |
| PRIMARY All Cohorts: Change From Baseline in Adjusted Spine Z-score |
0.152; 0.332; 0.530 | — |
| PRIMARY All Cohorts: Change From Baseline in Femoral Total T-score |
-0.020; 0.047; 0.114 | — |
| PRIMARY All Cohorts: Change From Baseline in Femoral Total Z-score |
0.054; 0.126; 0.214 | — |
| PRIMARY All Cohorts: Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Parameters Reported as TEAEs |
0; 1; 0 | — |
| SECONDARY Cohort 1: Percentage of Participants Who Achieved a Hemoglobin (Hb) Response |
39.5 | — |
| SECONDARY Cohort 1: Average Change From Baseline in Hb Concentration at Weeks 16, 20, and 24 |
16.45 | — |
| SECONDARY Cohort 1: Area Under the Plasma Concentration-Time Curve From Time Zero to 8-hours Post-dose (AUC0-8) of Mitapivat |
3016 | — |
| SECONDARY Cohort 1: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUC0-last) of Mitapivat |
2990 | — |
| SECONDARY Cohort 1: Maximum Observed Plasma Concentration (Cmax) of Mitapivat |
1018 | — |
| SECONDARY Cohort 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Mitapivat |
1.00 | — |
| SECONDARY Cohort 1: Time of Last Quantifiable Concentration (Tlast) of Mitapivat |
7.61 | — |
| SECONDARY Cohort 1: Plasma Concentration (Ctrough) at the End of a Dosing Interval of Mitapivat |
62.8 | — |
| SECONDARY Cohort 1: Exposure-response (E-R) Relationship Between Safety Parameters and Mitapivat Concentration and Relevant Mitapivat Pharmacokinetic Parameters |
NA; NA; NA | — |
| SECONDARY Cohorts 1 and 2: Change From Baseline in Hb Concentration |
22.39; 21.32 | — |
| SECONDARY Cohorts 1 and 2: Change From Baseline in Indirect Bilirubin |
-57.50; -36.73 | — |
| SECONDARY Cohorts 1 and 2: Change From Baseline in Lactate Dehydrogenase (LDH) |
-46.10; -130.80 | — |
| SECONDARY Cohorts 1 and 2: Change From Baseline in Haptoglobin Levels |
0.254; 0.250 | — |
| SECONDARY Cohorts 1 and 2: Change From Baseline in Reticulocytes/Erythrocytes Ratio |
-0.1696; -0.1565 | — |
| SECONDARY Cohort 3: Change From Baseline in Number of Transfusion Episodes |
4.14 | — |
| SECONDARY Cohort 3: Change From Baseline in Number of Red Blood Cell (RBC) Units Transfused |
7.25 | — |
| SECONDARY All Cohorts: Change From Baseline in Health-Related Quality of Life (HRQoL) Patient-Reported Outcome (PRO) Scores: Pyruvate Kinase Deficiency Diary (PKDD) |
-3.75; -6.09; -5.04 | — |
| SECONDARY All Cohorts: Change From Baseline in HRQoL PRO Scores: Pyruvate Kinase Deficiency Impact Assessment (PKDIA) |
-3.9; -6.6; -5.4 | — |
Summary
This is an open-label, multicenter, extension study to evaluate the long-term safety, tolerability, and efficacy of treatment with mitapivat in participants who were previously enrolled in Study AG348-C-006 or Study AG348-C-007.
Eligibility Criteria
Inclusion Criteria
- Be willing and able to comply with study visits and procedures.
- Have signed written informed consent prior to participating in this extension study.
- Have completed either antecedent study AG348-C-006 or AG348-C-007 through the Part 2 Week 24 Visit.
- Cohorts 2 and 3: Have demonstrated clinical benefit from mitapivat treatment in the antecedent study, in the opinion of the Investigator.
- For women of reproductive potential, have a negative pregnancy test during screening of this extension study.
- For women of reproductive potential as well as men with partners who are women of reproductive potential, be abstinent as part of their usual lifestyle, or agree to use 2 forms of contraception, 1 of which must be considered highly effective, from the time of giving informed consent, during the study, and for 28 days following the last dose of study drug for women and 90 days following the last dose of study drug for men.
Exclusion Criteria
- Have a significant medical condition (including clinically significant laboratory abnormality) that developed during his/her antecedent AG- 348 study that confers an unacceptable risk to participating in this extension study, that could confound the interpretation of the study data, and/or that compromises the ability of the participant to complete study visits and procedures.
- Are currently pregnant or breastfeeding.
- Have a splenectomy scheduled during the study treatment period.
- Meet the withdrawal criteria of his/her antecedent mitapivat study during screening of this extension study.
- Are currently receiving medications that are strong inhibitors of cytochrome P450 (CYP)3A4 that have not been stopped for a duration of at least 5 days or a time frame equivalent to 5 half-lives (whichever is longer) before start of study drug; or strong inducers of CYP3A4 that have not been stopped for a duration of at least 28 days or a time frame equivalent to 5 half-lives (whichever is longer) before start of study drug on this extension study.
- Have received anabolic steroids, including testosterone preparations, within 28 days prior to start of study drug on this extension study.
- Have received hematopoietic stimulating agents (eg, erythropoietins, granulocyte colony stimulating factors, thrombopoietins) within 28 days prior to start of study drug on this extension study.
- Have exposure to any investigational drug other than mitapivat, device, or procedure within 3 months prior to start of study drug on this extension study.
Data sourced from ClinicalTrials.gov (NCT03853798). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.