Pyruvate Kinase DeficiencyPhase 2NCT02476916
A Study of AG-348 in Adult Participants With Pyruvate Kinase (PK) Deficiency
A Phase 2 study testing AG-348 in people with Pyruvate Kinase Deficiency, run by Agios Pharmaceuticals, Inc. at 13 sites in 6 countries.
Trial summary
Study AG348-C-003 is a multicenter study designed to evaluate the safety and efficacy of different dose levels of AG-348 (mitapivat) in participants with PK deficiency. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pyruvate Kinase Deficiency
- What is being tested?
- AG-348
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 52 participants
- Where
- 13 sitesin 6 countries
- Study dates
- 26 Jun 2015to 2 Apr 2025
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Informed consent
- Male or female, aged 18 years and older
- Known medical history of PK deficiency
- PK deficiency confirmed by enzymatic assay at Screening
- Genotypic characterization of PKR gene at Screening
- Genotypic characterization of uridine-5'-diphosphate-glucuronyltransferase-A1 (UGTA1) gene to document underlying Gilbert's disease (Gilbert's disease patients are eligible)
Show all 17Show fewer
- Males Hb ≤ 12.0 g/dL, females Hb ≤ 11 g/dL
- Transfusion independent, defined as no more than 3 units of red blood cells (RBC) transfused in 12 months prior to the first day of study dosing and no transfusions within 4 months of first day of study dosing
- Splenectomized patients must have had the procedure at least 6 months prior to Screening and must be up-to-date in recommended vaccinations
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
- Must be taking at least 1 mg folic acid daily in the 21 days prior to screening
- Adequate organ function defined by liver function, kidney function, platelet count and coagulation assessments
- Agreement to use approved contraceptive measures
- Women must not be breastfeeding
- For entry into the Extension Period, patients must meet criteria # 15-16:
- Must have completed 24 weeks of treatment during the Core Period and tolerated AG-348
- The treating Investigator agrees that there is a potential for clinical benefit to continued treatment and recommends participation in the Extension Period and the Medical Monitor approves
Who cannot join
- Hb ˃ 12.0 g/dL if male, Hb ˃11.0 g/dL if female
- Additional diagnosis of other congenital or acquired blood disorder
- Iron overload sufficiently severe to result in cardiac, hepatic or pancreatic insufficiency
- Bone marrow or stem cell transplant
- Clinically symptomatic cholelithiasis or cholecystitis
- Currently enrolled in any other investigational trial. Participation in the PK Deficiency Natural History Study (NCT02053480) is permitted
Show all 17Show fewer
- Exposure to any investigational drug, device or procedure within 28 days prior to screening or during trial participation
- Concurrent medical condition such as poorly controlled hypertension, heart failure, active infection, frequent post-splenectomy sepsis, Hepatitis B or C, Human Immunodeficiency Virus type 1 (HIV1) or Human Immunodeficiency Virus type 2 (HIV2) infection, poorly controlled diabetes mellitus, history of primary malignancy with the exception of curatively treated nonmelanomatous skin cancer, cervical cancer of breast cancer in situ
- Major surgery in the last 6 months
- Psychiatric disorder that could compromise the ability of the patient to cooperate with the study
- Serum bilirubin higher to the upper limit of normal attributable to factors other than hemolysis or Gilbert's Syndrome
- Use of restricted products known to strongly inhibit cytochrome P450 (CYP) 3A4 metabolism within 5 days prior to Prior Day 1 dosing, or to strongly induce cytochrome P450 3A4 (CYP3A4) metabolism within 28 days prior to Day 1 dosing, or to strongly inhibit P-glycoprotein transporter within 5 days prior to Day 1 dosing, or digoxin within 5 days prior to Day 1 dosing.
- Heart-rate corrected QT interval - Fridericia's method (QTcF) interval ˃ 450 ms in male, QTcF > 470 ms in female, with the exception of patients with a left Bundle Branch Block
- Cardiac arrhythmias that are clinically significant or treated with drugs that are substrates of CYP3A4
- Allergy to sulfonamides if characterized by acute hemolytic anemia, anaphylaxis, rash of erythema multiforme type or Stevens-Johnson Syndrome
- Any other medical or psychological condition deemed by the Investigator to be likely to interfere with a patient's ability to participate in the study
- Patients will not be permitted to enter the Extension Period if: The patient experienced AEs during the Core Period that are considered by the treating Investigator or the Sponsor's designated Medical Monitor to pose a significant safety risk to the patient if treatment were to be extended
Trial locations and contacts
13 sites in 6 countries.
13 sites in 6 countries
United States7 sites
Central Pennsylvania Clinic
Belleville, Pennsylvania, 17004
Boston Children's Hospital
Boston, Massachusetts, 02215
Wayne State University School of Medicine - Children's Hospital of Michigan
Detroit, Michigan, 48201
New York Presbyterian Hospital- Weil Cornell Medical College
New York, New York, 10065
Stanford University
Palo Alto, California, 94304
Children Hospital of Philadelphia (CHOP)
Philadelphia, Pennsylvania, 19104
University of Utah
Salt Lake City, Utah, 84113
France2 sites
Hôpital Henri Mondor
Créteil, Île-de-France Region, 94010
Hôpital Saint-Vincent de Paul
Lille, Nord, 59000
Italy1 site
UOC Oncoematologia Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico
Milan, 20122
About this study
Official title: A Phase 2, Open Label, Randomized, Dose Ranging, Safety, Efficacy, Pharmacokinetic and Pharmacodynamic Study of AG-348 in Adult Patients With Pyruvate Kinase Deficiency
Study AG348-C-003 is a multicenter study designed to evaluate the safety and efficacy of different dose levels of AG-348 (mitapivat) in participants with PK deficiency.
Read the detailed description
This is a Phase 2, open label, two arm, multicenter, randomized, dose-ranging study during which adult participants with PK deficiency will receive multiple doses of AG-348 for up to 24 weeks (Core Period); eligible participants may enter an Extension Period to receive AG-348 for up to 8 additional years. Data will be reviewed on a regular basis and study design, dose and schedule will be adapted based on these reviews. The study will evaluate the safety and tolerability of multiple doses of AG-348, pharmacokinetic and pharmacodynamic (PD) profile of AG-348 and early indicators of clinical efficacy.
- Conditions
- Pyruvate Kinase Deficiency
- Being tested
- AG-348
- Keywords
- Pyruvate Kinase Deficiency, Hemolytic anemia, Pyruvate Kinase Isoform R (PKR), Drive PK
- Medical subject headings
- Pyruvate Kinase Deficiency of Red Cells, Anemia, Hemolytic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AG-348Drug
Also called Mitapivat
Tablets
| Study group | Role | What they receive |
|---|---|---|
| AG-348 50 mg BID | Experimental | Participants with Pyruvate Kinase (PK) deficiency will receive AG-348, 50 milligrams (mg), as initial dose, twice daily (BID) for 24 weeks (Core Period). Participants will be assigned to initial doses, however, over the course of the Core Period they will be treated across a range of doses due to treatment emergent adverse events (AEs) and hemoglobin (Hb) levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who have safely tolerated AG-348 and demonstrating clinical activity in response to AG-348 will be rolled over to the Extension Period. During the extension period, participants will continue to receive AG-348 50 mg, BID, for up to 102 months. Receives: Drug: AG-348 |
| AG-348 300 mg BID | Experimental | Participants with PK deficiency will receive AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants will be assigned to initial doses, however, over the course of the Core Period they will be treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who have safely tolerated AG-348 and demonstrating clinical activity in response to AG-348 will be rolled over to the Extension Period. During the extension period, participants will continue to receive AG-348 300 mg, BID, up to 102 months. Receives: Drug: AG-348 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants Experiencing at Least One Adverse Event (AEs) in the Core Period
An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered study drug-related.
Measured: Up to Week 24
Secondary outcomes (33)
Percentage of Participants Experiencing at Least One AE up to Month 102
An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered study drug-related. Safety data for cumulative period (Core period and Extension period) has been reported in this outcome measure.
Measured: Up to Month 102
Change From Baseline in Hemoglobin (Hb) Value at Week 24
Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Increased Hb values indicate improvement.
Measured: Baseline and Week 24
Change From Baseline Hb Value up to Month 102
Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Increased Hb values indicate improvement.
Measured: Baseline, Months 12, 36, 60, 84, and 102
Change From Baseline in Hematocrit at Week 24
Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Increased hematocrit values indicate improvement.
Measured: Baseline and Week 24
Change From Baseline in Hematocrit up to Month 102
Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Increased hematocrit values indicate improvement.
Measured: Baseline, Months 12, 36, 60, 84, and 102
Change From Baseline in Reticulocyte Count at Week 24
Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased reticulocyte count values indicate improvement.
Measured: Baseline and Week 24
Change From Baseline in Reticulocyte Count up to Month 102
Change (absolute change) from baseline will be calculated as post-baseline value - baseline value. Decreased reticulocyte count values indicate improvement.
Measured: Baseline, Months 12, 36, 60, 84, and 102
Change From Baseline in Haptoglobin at Week 24
Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Increased haptoglobin values indicate improvement.
Measured: Baseline and Week 24
Change From Baseline in Haptoglobin up to Month 102
Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Increased haptoglobin values indicate improvement.
Measured: Baseline, Months 12, 36, 60, 84, and 102
Change From Baseline in Carboxyhemoglobin (COHb) at Week 24
Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased COHb values indicate improvement.
Measured: Baseline and Week 24
Change From Baseline in COHb up to Month 30
Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased COHb values indicate improvement.
Measured: Baseline, Months 12, 18, 24, and 30
Change From Baseline in Lactate Dehydrogenase (LDH) at Week 24
Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased LDH values indicate improvement.
Measured: Baseline and Week 24
Change From Baseline in LDH up to Month 30
Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased LDH values indicate improvement.
Measured: Baseline, Months 12, 18, 24, and 30
Change From Baseline in Total Bilirubin at Week 24
Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased total bilirubin values indicate improvement.
Measured: Baseline and Week 24
Change From Baseline in Total Bilirubin up to Month 102
Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased total bilirubin values indicate improvement.
Measured: Baseline, Months 12, 36, 60, 84, and 102
Change From Baseline in Indirect Bilirubin at Week 24
Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased indirect bilirubin values indicate improvement.
Measured: Baseline and Week 24
Change From Baseline in Indirect Bilirubin up to Month 102
Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased indirect bilirubin values indicate improvement.
Measured: Baseline, Months 12, 36, 60, 84, and 102
Change From Baseline in Erythropoietin (EPO) at Week 24
Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased EPO values indicate improvement.
Measured: Baseline and Week 24
Change From Baseline in (EPO) up to Month 30
Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased EPO values indicate improvement.
Measured: Baseline, Months 12, 18, 24, and 30
Change From Baseline in Hepcidin at Week 24
Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased hepcidin values indicate improvement.
Measured: Baseline and Week 24
Change From Baseline in Hepcidin up to Month 30
Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased hepcidin values indicate improvement.
Measured: Baseline, Months 12, 18, 24, and 30
Change From Baseline in Ferritin at Week 24
Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased ferritin values indicate improvement.
Measured: Baseline and Week 24
Change From Baseline in Ferritin up to Month 102
Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased ferritin values indicate improvement.
Measured: Baseline, Months 12, 36, 60, 84, and 102
Change From Baseline in Transferrin Saturation at Week 24
Transferrin saturation is the ratio of serum iron to iron-binding capacity. Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased transferrin saturation values indicate improvement.
Measured: Baseline and Week 24
Change From Baseline in Transferrin Saturation up to Month 102
Transferrin saturation is the ratio of serum iron to iron-binding capacity. Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased transferrin saturation values indicate improvement.
Measured: Baseline, Months 12, 36, 60, 84, and 102
Area Under the Concentration-time Curve From Time Zero to the Last Non-zero Concentration (AUC0-t) for AG-348 and Its Metabolite AGI-8702
Participants with pre-dose concentrations on Day 1 were excluded from the pharmacokinetics analysis, if any.
Measured: pre-dose, 0.5, 1, 2, 4, 8, 12 hours post-dose Day 1 and pre-dose, 0.5, 1, 2, 4, 8 hours post-dose Day 15
Maximum Plasma Concentration (Cmax) for AG-348 and Its Metabolite AGI-8702
Participants with pre-dose concentrations on Day 1 were excluded from the pharmacokinetics analysis, if any.
Measured: pre-dose, 0.5, 1, 2, 4, 8, 12 hours post-dose Day 1 and pre-dose, 0.5, 1, 2, 4, 8 hours post-dose Day 15
Time to Reach Peak Plasma Concentration (Tmax) for AG-348 and Its Metabolite AGI-8702
Participants with pre-dose concentrations on Day 1 were excluded from the pharmacokinetics analysis, if any.
Measured: pre-dose, 0.5, 1, 2, 4, 8, 12 hours post-dose Day 1 and pre-dose, 0.5, 1, 2, 4, 8 hours post-dose Day 15
Apparent Clearance at Steady-State (Clss/F) for AG-348 and Its Metabolite AGI-8702
Participants with pre-dose concentrations on Day 1 were excluded from the pharmacokinetics analysis, if any.
Measured: pre-dose, 0.5, 1, 2, 4, 8 hours post-dose Day 15
Maximum Change From Baseline Response Value Over 12 Hours Post-dose (BRmax) for Adenosine Triphosphate (ATP)
Pre-dose concentration observed on Day 1 was used as Baseline for calculation of change from baseline.
Measured: pre-dose, 0.5, 1, 2, 4, 8, 12 hours post-dose Day 1
Maximum Change From Baseline Response Value Over 8 Hours Post-dose at Steady State (BRmax ss) for ATP
Pre-dose concentration observed on Day 1 was used as Baseline for calculation of change from baseline.
Measured: pre-dose, 0.5, 1, 2, 4, 8 hours post-dose Day 15
BRmax for 2,3 - Diphosphoglycerate (2,3-DPG)
Pre-dose concentration observed on Day 1 was used as Baseline for calculation of change from baseline.
Measured: pre-dose, 0.5, 1, 2, 4, 8, 12 hours post-dose Day 1
BRmax ss for 2,3-DPG
Pre-dose concentration observed on Day 1 was used as Baseline for calculation of change from baseline.
Measured: pre-dose, 0.5, 1, 2, 4, 8 hours post-dose Day 15
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jun 2015 (estimated)
- Study start26 Jun 2015
- Primary completion8 May 2017
- Study completion2 Apr 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Pyruvate Kinase DeficiencyStudies 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 52 participants (actual)
Sponsor and investigators
- Lead sponsor
- Agios Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02476916
- Sponsor's protocol ID
- AG348-C-003
- Other IDs
- 2015-000484-13, 2015
- Status last verified
- Apr 2026
- First submitted
- 10 Jun 2015
- Last updated
- 1 May 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Grace RF, Rose C, Layton DM, Galacteros F, Barcellini W, Morton DH, van Beers EJ, Yaish H, Ravindranath Y, Kuo KHM, Sheth S, Kwiatkowski JL, Barbier AJ, Bodie S, Silver B, Hua L, Kung C, Hawkins P, Jouvin MH, Bowden C, Glader B. Safety and Efficacy of Mitapivat in Pyruvate Kinase Deficiency. N Engl J Med. 2019 Sep 5;381(10):933-944. doi: 10.1056/NEJMoa1902678.
PubMed 31483964Al-Samkari H, Grace RF, Glenthoj A, Andres O, Barcellini W, Galacteros F, Kuo KHM, Layton DM, Morado Arias M, Viprakasit V, Dong Y, Tai F, Hawkins P, Gheuens S, Morales-Arias J, Gilroy KS, Porter JB, van Beers EJ. Early-onset reduced bone mineral density in patients with pyruvate kinase deficiency. Am J Hematol. 2023 Mar;98(3):E57-E60. doi: 10.1002/ajh.26830. Epub 2023 Jan 9. No abstract available.
PubMed 36594181Rab MAE, Van Oirschot BA, Kosinski PA, Hixon J, Johnson K, Chubukov V, Dang L, Pasterkamp G, Van Straaten S, Van Solinge WW, Van Beers EJ, Kung C, Van Wijk R. AG-348 (Mitapivat), an allosteric activator of red blood cell pyruvate kinase, increases enzymatic activity, protein stability, and ATP levels over a broad range of PKLR genotypes. Haematologica. 2021 Jan 1;106(1):238-249. doi: 10.3324/haematol.2019.238865.
PubMed 31974203
Study at a glance
From the registry record, last updated by the sponsor on 1 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2, Open Label, Randomized, Dose Ranging, Safety, Efficacy, Pharmacokinetic and Pharmacodynamic Study of AG-348 in Adult Patients With Pyruvate Kinase Deficiency
- ClinicalTrials.gov ID
- NCT02476916
- Acronym / sponsor ID
- AG348-C-003
- Conditions
- Pyruvate Kinase Deficiency
- Keywords
- Pyruvate Kinase Deficiency, Hemolytic anemia, Pyruvate Kinase Isoform R (PKR), Drive PK
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 52 participants (actual)
- Lead sponsor
- Agios Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 26 Jun 2015 (actual)
- Primary completion
- 8 May 2017 (actual)
- Study completion
- 2 Apr 2025 (actual)
- First posted
- 22 Jun 2015 (estimated)
- Results
- Posted 11 Jun 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Study AG348-C-003 is a multicenter study designed to evaluate the safety and efficacy of different dose levels of AG-348 (mitapivat) in participants with PK deficiency.
Detailed description
This is a Phase 2, open label, two arm, multicenter, randomized, dose-ranging study during which adult participants with PK deficiency will receive multiple doses of AG-348 for up to 24 weeks (Core Period); eligible participants may enter an Extension Period to receive AG-348 for up to 8 additional years. Data will be reviewed on a regular basis and study design, dose and schedule will be adapted based on these reviews. The study will evaluate the safety and tolerability of multiple doses of AG-348, pharmacokinetic and pharmacodynamic (PD) profile of AG-348 and early indicators of clinical efficacy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| AG-348 50 mg BID | Experimental | Drug: AG-348Participants with Pyruvate Kinase (PK) deficiency will receive AG-348, 50 milligrams (mg), as initial dose, twice daily (BID) for 24 weeks (Core Period). Participants will be assigned to initial doses, however, over the course of the Core Period they will be treated across a range of doses due to treatment emergent adverse events (AEs) and hemoglobin (Hb) levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who have safely tolerated AG-348 and demonstrating clinical activity in response to AG-348 will be rolled over to the Extension Period. During the extension period, participants will continue to receive AG-348 50 mg, BID, for up to 102 months. |
| AG-348 300 mg BID | Experimental | Drug: AG-348Participants with PK deficiency will receive AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants will be assigned to initial doses, however, over the course of the Core Period they will be treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who have safely tolerated AG-348 and demonstrating clinical activity in response to AG-348 will be rolled over to the Extension Period. During the extension period, participants will continue to receive AG-348 300 mg, BID, up to 102 months. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Informed consent
- Male or female, aged 18 years and older
- Known medical history of PK deficiency
- PK deficiency confirmed by enzymatic assay at Screening
- Genotypic characterization of PKR gene at Screening
Key exclusion criteria (17 listed)
- Hb ˃ 12.0 g/dL if male, Hb ˃11.0 g/dL if female
- Additional diagnosis of other congenital or acquired blood disorder
- Iron overload sufficiently severe to result in cardiac, hepatic or pancreatic insufficiency
- Bone marrow or stem cell transplant
- Clinically symptomatic cholelithiasis or cholecystitis
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 |
|---|---|---|
| AG-348Also: MitapivatTablets | Drug | AG-348 300 mg BID, AG-348 50 mg BID |
Primary outcome
Percentage of Participants Experiencing at Least One Adverse Event (AEs) in the Core Period
Time frame: Up to Week 24
An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered study drug-related.
33 secondary outcomes
Percentage of Participants Experiencing at Least One AE up to Month 102
Time frame: Up to Month 102
Change From Baseline in Hemoglobin (Hb) Value at Week 24
Time frame: Baseline and Week 24
Change From Baseline Hb Value up to Month 102
Time frame: Baseline, Months 12, 36, 60, 84, and 102
Change From Baseline in Hematocrit at Week 24
Time frame: Baseline and Week 24
Change From Baseline in Hematocrit up to Month 102
Time frame: Baseline, Months 12, 36, 60, 84, and 102
Change From Baseline in Reticulocyte Count at Week 24
Time frame: Baseline and Week 24
Change From Baseline in Reticulocyte Count up to Month 102
Time frame: Baseline, Months 12, 36, 60, 84, and 102
Change From Baseline in Haptoglobin at Week 24
Time frame: Baseline and Week 24
Change From Baseline in Haptoglobin up to Month 102
Time frame: Baseline, Months 12, 36, 60, 84, and 102
Change From Baseline in Carboxyhemoglobin (COHb) at Week 24
Time frame: Baseline and Week 24
Change From Baseline in COHb up to Month 30
Time frame: Baseline, Months 12, 18, 24, and 30
Change From Baseline in Lactate Dehydrogenase (LDH) at Week 24
Time frame: Baseline and Week 24
Change From Baseline in LDH up to Month 30
Time frame: Baseline, Months 12, 18, 24, and 30
Change From Baseline in Total Bilirubin at Week 24
Time frame: Baseline and Week 24
Change From Baseline in Total Bilirubin up to Month 102
Time frame: Baseline, Months 12, 36, 60, 84, and 102
Change From Baseline in Indirect Bilirubin at Week 24
Time frame: Baseline and Week 24
Change From Baseline in Indirect Bilirubin up to Month 102
Time frame: Baseline, Months 12, 36, 60, 84, and 102
Change From Baseline in Erythropoietin (EPO) at Week 24
Time frame: Baseline and Week 24
Change From Baseline in (EPO) up to Month 30
Time frame: Baseline, Months 12, 18, 24, and 30
Change From Baseline in Hepcidin at Week 24
Time frame: Baseline and Week 24
Change From Baseline in Hepcidin up to Month 30
Time frame: Baseline, Months 12, 18, 24, and 30
Change From Baseline in Ferritin at Week 24
Time frame: Baseline and Week 24
Change From Baseline in Ferritin up to Month 102
Time frame: Baseline, Months 12, 36, 60, 84, and 102
Change From Baseline in Transferrin Saturation at Week 24
Time frame: Baseline and Week 24
Change From Baseline in Transferrin Saturation up to Month 102
Time frame: Baseline, Months 12, 36, 60, 84, and 102
Area Under the Concentration-time Curve From Time Zero to the Last Non-zero Concentration (AUC0-t) for AG-348 and Its Metabolite AGI-8702
Time frame: pre-dose, 0.5, 1, 2, 4, 8, 12 hours post-dose Day 1 and pre-dose, 0.5, 1, 2, 4, 8 hours post-dose Day 15
Maximum Plasma Concentration (Cmax) for AG-348 and Its Metabolite AGI-8702
Time frame: pre-dose, 0.5, 1, 2, 4, 8, 12 hours post-dose Day 1 and pre-dose, 0.5, 1, 2, 4, 8 hours post-dose Day 15
Time to Reach Peak Plasma Concentration (Tmax) for AG-348 and Its Metabolite AGI-8702
Time frame: pre-dose, 0.5, 1, 2, 4, 8, 12 hours post-dose Day 1 and pre-dose, 0.5, 1, 2, 4, 8 hours post-dose Day 15
Apparent Clearance at Steady-State (Clss/F) for AG-348 and Its Metabolite AGI-8702
Time frame: pre-dose, 0.5, 1, 2, 4, 8 hours post-dose Day 15
Maximum Change From Baseline Response Value Over 12 Hours Post-dose (BRmax) for Adenosine Triphosphate (ATP)
Time frame: pre-dose, 0.5, 1, 2, 4, 8, 12 hours post-dose Day 1
Maximum Change From Baseline Response Value Over 8 Hours Post-dose at Steady State (BRmax ss) for ATP
Time frame: pre-dose, 0.5, 1, 2, 4, 8 hours post-dose Day 15
BRmax for 2,3 - Diphosphoglycerate (2,3-DPG)
Time frame: pre-dose, 0.5, 1, 2, 4, 8, 12 hours post-dose Day 1
BRmax ss for 2,3-DPG
Time frame: pre-dose, 0.5, 1, 2, 4, 8 hours post-dose Day 15
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 May 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 31483964Grace RF, Rose C, Layton DM, Galacteros F, Barcellini W, Morton DH, van Beers EJ, Yaish H, Ravindranath Y, Kuo KHM, Sheth S, Kwiatkowski JL, Barbier AJ, Bodie S, Silver B, Hua L, Kung C, Hawkins P, Jouvin MH, Bowden C, Glader B. Safety and Efficacy of Mitapivat in Pyruvate Kinase Deficiency. N Engl J Med. 2019 Sep 5;381(10):933-944. doi: 10.1056/NEJMoa1902678.
- Derived from this study: PubMed 36594181Al-Samkari H, Grace RF, Glenthoj A, Andres O, Barcellini W, Galacteros F, Kuo KHM, Layton DM, Morado Arias M, Viprakasit V, Dong Y, Tai F, Hawkins P, Gheuens S, Morales-Arias J, Gilroy KS, Porter JB, van Beers EJ. Early-onset reduced bone mineral density in patients with pyruvate kinase deficiency. Am J Hematol. 2023 Mar;98(3):E57-E60. doi: 10.1002/ajh.26830. Epub 2023 Jan 9. No abstract available.
- Derived from this study: PubMed 31974203Rab MAE, Van Oirschot BA, Kosinski PA, Hixon J, Johnson K, Chubukov V, Dang L, Pasterkamp G, Van Straaten S, Van Solinge WW, Van Beers EJ, Kung C, Van Wijk R. AG-348 (Mitapivat), an allosteric activator of red blood cell pyruvate kinase, increases enzymatic activity, protein stability, and ATP levels over a broad range of PKLR genotypes. Haematologica. 2021 Jan 1;106(1):238-249. doi: 10.3324/haematol.2019.238865.
- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
13 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing AG-348 in people with Pyruvate Kinase Deficiency, run by Agios Pharmaceuticals, Inc. at 13 sites in 6 countries.
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 17 inclusion and 17 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: finished, as of the sponsor's last update on 1 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in United States, France, Canada, Italy, Netherlands and 1 more country. 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. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Jun 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants Experiencing at Least One Adverse Event (AEs) in the Core Period (time frame: Up to Week 24). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02476916, which also lists 3 linked publications.
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 1 May 2026.