A Phase 2 interventional study of AG-348 in Pyruvate Kinase Deficiency, sponsored by Agios Pharmaceuticals, Inc.. Completed at 13 sites in 6 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-05-01.
Sponsored by Agios Pharmaceuticals, Inc. · Phase 2, Interventional, and Treatment
Among 35 studies in Anemia, Hemolytic with a site in United States — 8 open to participants now, 11 under way, 1 of them phase 3. Anemia, Hemolytic · United States.
Among the 35 studies in Anemia, Hemolytic with a site in United States, this one is the 10th largest by enrollment of the 26 interventional ones, is the only one that started in 2015, is one of 7 in phase 2, and was the 13th registered.
56 studies on the registry are indexed under Anemia, Hemolytic; 16 are open to participants now.
This study's enrollment of 52 is close to the median of 48 across 39 interventional studies indexed under Anemia, Hemolytic.
Browse Anemia, Hemolytic studies →8 of the 35 studies in Anemia, Hemolytic with a site in United States are open now, in 12 countries. Each count lists the studies.
Of the 8 Anemia, Hemolytic studies recruiting now, 3 (38%) set no upper age limit and 4 (50%) stop at 75 or younger; 6 take children under 18; 0 take healthy volunteers.
This study: 18 Years and older · all sexes · no healthy volunteers.
The full table on the hub →35 studies; the count open now beside each. This study's row is marked.
First in 1997; this study’s year is marked. 1 started in 2015.
Median enrollment 47 across the 26 interventional studies, 254 across the 9 observational. Of the 22 that completed or were terminated, 10 (45%) have results posted.
15 of 35 have an industry lead sponsor. The 10 most frequent:
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.
Agios Pharmaceuticals, Inc. has 5 studies filed under Anemia, Hemolytic — fewer than ten, so there is no comparison to draw.
2 of the studies in Anemia, Hemolytic with a site in United States that are under way reach primary completion within a year, 0 of them phase 3. Phase 3 first, then by date:
| Study | Primary completion |
|---|---|
| NCT07566494National Heart, Lung, and Blood Institute (NHLBI)Escalating Doses of VAS-101 in Subjects With Stable Sickle Cell Disease | 2027-04-27 |
| NCT07612345University of UtahHigh-Dose Vitamin C in G6PDA and Pyruvate Kinase Deficiency: A Safety Study | 2027-07-15 |
Among the 35 studies in Anemia, Hemolytic with a site in United States, from their registry updates:
Nothing recorded among them since 2026-09-25.
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.
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.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Women must not be breastfeeding
For entry into the Extension Period, patients must meet criteria # 15-16:
Exclusion criteria
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CYP3A (CYP3A4) inhibitors and inducers
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
QT and QTc
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Drug: AG-348
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.
Drug: AG-348
Tablets
Also known as: Mitapivat
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.
Time frame: Up to Week 24
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
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
Participants with pre-dose concentrations on Day 1 were excluded from the pharmacokinetics analysis, if any.
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
Participants with pre-dose concentrations on Day 1 were excluded from the pharmacokinetics analysis, if any.
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
Participants with pre-dose concentrations on Day 1 were excluded from the pharmacokinetics analysis, if any.
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
Participants with pre-dose concentrations on Day 1 were excluded from the pharmacokinetics analysis, if any.
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)
Pre-dose concentration observed on Day 1 was used as Baseline for calculation of change from baseline.
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
Pre-dose concentration observed on Day 1 was used as Baseline for calculation of change from baseline.
Time frame: 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.
Time frame: 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.
Time frame: pre-dose, 0.5, 1, 2, 4, 8 hours post-dose Day 15
Participants took part in the study across multiple study sites in 6 countries from 26 June 2015 to 02 April 2025.
| Milestone | AG-348 50 mg BID | AG-348 300 mg BID |
|---|---|---|
| Started | 27 | 25 |
| Completed | 21 | 22 |
| Not completed | 6 | 3 |
| Withdrew: Adverse event | 2 | 2 |
| Withdrew: Physician decision | 1 | 1 |
| Withdrew: Withdrawal by participant | 3 | 0 |
| Milestone | AG-348 50 mg BID | AG-348 300 mg BID |
|---|---|---|
| Started | 18 | 18 |
| Completed | 1 | 2 |
| Not completed | 17 | 16 |
| Withdrew: Adverse event | 1 | 0 |
| Withdrew: Withdrawal by participant | 1 | 0 |
| Withdrew: Physician decision | 5 | 5 |
| Withdrew: Approved drug available for indication | 5 | 6 |
| Withdrew: Non-compliance with study drug | 1 | 1 |
| Withdrew: Lost to follow-up | 1 | 1 |
| Withdrew: Reason not specified | 3 | 3 |
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.
| percentage of participants | AG-348 50 mg BID | AG-348 300 mg BID |
|---|---|---|
| Percentage of Participants Experiencing at Least One Adverse Event (AEs) in the Core Period | 96.3 | 100.0 |
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.
| percentage of participants | AG-348 50 mg BID | AG-348 300 mg BID |
|---|---|---|
| Percentage of Participants Experiencing at Least One AE up to Month 102 | 100.0 | 100.0 |
Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Increased Hb values indicate improvement.
| grams per liter (g/L) | AG-348 50 mg BID | AG-348 300 mg BID |
|---|---|---|
| Baseline | 92.43 ± 14.760 | 86.36 ± 11.668 |
| Change at Week 24 | 13.10 ± 13.644 | 16.65 ± 16.874 |
Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Increased Hb values indicate improvement.
| g/L | AG-348 50 mg BID | AG-348 300 mg BID |
|---|---|---|
| Change at Month 12 | 15.25 ± 16.046 | 23.93 ± 18.005 |
| Change at Month 36 | 23.14 ± 8.212 | 25.23 ± 13.009 |
| Change at Month 60 | 22.43 ± 7.606 | 28.95 ± 12.712 |
| Change at Month 84 | 20.14 ± 8.037 | 26.92 ± 17.440 |
| Change at Month 102 | 20.92 ± 9.075 | 25.50 ± 9.918 |
Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Increased hematocrit values indicate improvement.
| fraction of 1 | AG-348 50 mg BID | AG-348 300 mg BID |
|---|---|---|
| Baseline | 0.2881 ± 0.04494 | 0.2693 ± 0.03325 |
| Change at Week 24 | 0.0360 ± 0.03916 | 0.0444 ± 0.04745 |
Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Increased hematocrit values indicate improvement.
| fraction of 1 | AG-348 50 mg BID | AG-348 300 mg BID |
|---|---|---|
| Change at Month 12 | 0.0428 ± 0.04823 | 0.0673 ± 0.04854 |
| Change at Month 36 | 0.0550 ± 0.02836 | 0.0598 ± 0.04136 |
| Change at Month 60 | 0.0565 ± 0.02264 | 0.0726 ± 0.03137 |
| Change at Month 84 | 0.0475 ± 0.02330 | 0.0690 ± 0.04855 |
| Change at Month 102 | 0.0482 ± 0.01296 | 0.0550 ± 0.04525 |
Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased reticulocyte count values indicate improvement.
| cells * 10^9/liter | AG-348 50 mg BID | AG-348 300 mg BID |
|---|---|---|
| Baseline | 459.39 ± 230.621 | 474.19 ± 233.868 |
| Change at Week 24 | -73.77 ± 300.971 | -3.96 ± 327.426 |
Change (absolute change) from baseline will be calculated as post-baseline value - baseline value. Decreased reticulocyte count values indicate improvement.
| cells * 10^9/liter | AG-348 50 mg BID | AG-348 300 mg BID |
|---|---|---|
| Change at Month 12 | -272.65 ± 267.001 | -32.51 ± 348.744 |
| Change at Month 36 | -225.83 ± 265.429 | -83.61 ± 291.972 |
| Change at Month 60 | -188.36 ± 226.949 | -106.67 ± 291.400 |
| Change at Month 84 | -157.58 ± 268.248 | -161.47 ± 263.235 |
| Change at Month 102 | -64.06 ± 58.277 | -293.01 ± 300.258 |
Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Increased haptoglobin values indicate improvement.
| g/L | AG-348 50 mg BID | AG-348 300 mg BID |
|---|---|---|
| Baseline | 0.360 ± 0.2568 | 0.460 ± 0.5362 |
| Change at Week 24 | 0.230 ± 0.2475 | 0.260 ± 0.4503 |
Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Increased haptoglobin values indicate improvement.
| g/L | AG-348 50 mg BID | AG-348 300 mg BID |
|---|---|---|
| Change at Month 12 | 0.343 ± 0.3865 | 0.523 ± 0.6261 |
| Change at Month 36 | 0.135 ± 0.2051 | 0.940 ± NA |
| Change at Month 60 | 0.110 ± NA | 0.710 ± NA |
| Change at Month 84 | 0.760 ± NA | 1.700 ± NA |
| Change at Month 102 | 0.390 ± NA | 0.610 ± NA |
Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased COHb values indicate improvement.
| percentage Hb bound to CO | AG-348 50 mg BID | AG-348 300 mg BID |
|---|---|---|
| Baseline | 5.5 ± 1.42 | 6.2 ± 2.31 |
| Change at Week 24 | -1.3 ± 2.26 | -0.6 ± 1.89 |
Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased COHb values indicate improvement.
| percentage Hb bound to CO | AG-348 50 mg BID | AG-348 300 mg BID |
|---|---|---|
| Change at Month 12 | 0.0 ± 1.73 | -0.1 ± 1.79 |
| Change at Month 18 | -0.7 ± 1.63 | -1.1 ± 1.54 |
| Change at Month 24 | -1.0 ± 2.00 | -0.6 ± 3.26 |
| Change at Month 30 | -0.2 ± 0.84 | -1.2 ± 1.47 |
Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased LDH values indicate improvement.
| units per liter (U/L) | AG-348 50 mg BID | AG-348 300 mg BID |
|---|---|---|
| Baseline | 287.17 ± 172.172 | 257.42 ± 129.110 |
| Change at Week 24 | -36.74 ± 140.291 | -4.89 ± 148.024 |
Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased LDH values indicate improvement.
| U/L | AG-348 50 mg BID | AG-348 300 mg BID |
|---|---|---|
| Change at Month 12 | -38.13 ± 137.244 | -33.78 ± 155.946 |
| Change at Month 18 | -8.50 ± 185.778 | -29.92 ± 166.593 |
| Change at Month 24 | -130.28 ± 209.075 | -76.30 ± 169.040 |
| Change at Month 30 | -148.25 ± 174.606 | -73.84 ± 169.661 |
Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased total bilirubin values indicate improvement.
| micromole per liter (umol/L) | AG-348 50 mg BID | AG-348 300 mg BID |
|---|---|---|
| Baseline | 92.91 ± 53.178 | 93.44 ± 54.169 |
| Change at Week 24 | -36.05 ± 34.231 | -49.85 ± 40.027 |
Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased total bilirubin values indicate improvement.
| umol/L | AG-348 50 mg BID | AG-348 300 mg BID |
|---|---|---|
| Change at Month 12 | -45.61 ± 34.686 | -55.86 ± 46.161 |
| Change at Month 36 | -41.66 ± 41.309 | -42.14 ± 42.841 |
| Change at Month 60 | -39.71 ± 37.754 | -41.78 ± 38.803 |
| Change at Month 84 | -47.04 ± 38.220 | -46.81 ± 46.865 |
| Change at Month 102 | -65.85 ± 57.731 | -96.16 ± 63.521 |
Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased indirect bilirubin values indicate improvement.
| umol/L | AG-348 50 mg BID | AG-348 300 mg BID |
|---|---|---|
| Baseline | 85.74 ± 52.881 | 86.64 ± 53.717 |
| Change at Week 24 | -36.69 ± 31.979 | -53.99 ± 40.081 |
Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased indirect bilirubin values indicate improvement.
| umol/L | AG-348 50 mg BID | AG-348 300 mg BID |
|---|---|---|
| Change at Month 12 | -46.32 ± 35.996 | -54.92 ± 45.237 |
| Change at Month 36 | -41.17 ± 42.994 | -45.81 ± 42.396 |
| Change at Month 60 | -39.46 ± 39.129 | -45.04 ± 39.308 |
| Change at Month 84 | -47.52 ± 39.990 | -49.57 ± 46.674 |
| Change at Month 102 | -68.42 ± 58.135 | -95.69 ± 60.128 |
Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased EPO values indicate improvement.
| international units per liter (IU/L) | AG-348 50 mg BID | AG-348 300 mg BID |
|---|---|---|
| Baseline | 85.45 ± 159.409 | 60.90 ± 19.519 |
| Change at Week 24 | -7.11 ± 34.754 | -12.61 ± 26.596 |
Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased EPO values indicate improvement.
| IU/L | AG-348 50 mg BID | AG-348 300 mg BID |
|---|---|---|
| Change at Month 12 | 10.17 ± 38.685 | -11.09 ± 38.484 |
| Change at Month 18 | 1.17 ± 33.991 | -18.89 ± 24.148 |
| Change at Month 24 | -15.50 ± 28.899 | -26.46 ± 20.701 |
| Change at Month 30 | -12.01 ± 15.495 | -21.80 ± 24.400 |
Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased hepcidin values indicate improvement.
| nanograms per liter (ng/L) | AG-348 50 mg BID | AG-348 300 mg BID |
|---|---|---|
| Baseline | 9471.7 ± 9501.70 | 10708.3 ± 10109.53 |
| Change at Week 24 | -1011.7 ± 6156.16 | -4684.0 ± 5631.56 |
Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased hepcidin values indicate improvement.
| ng/L | AG-348 50 mg BID | AG-348 300 mg BID |
|---|---|---|
| Change at Month 12 | -2755.0 ± 12485.25 | -6606.0 ± 8980.10 |
| Change at Month 18 | 3900.0 ± 3334.29 | -1633.3 ± 864.08 |
| Change at Month 24 | 7076.7 ± 2918.17 | -7930.0 ± NA |
| Change at Month 30 | 4400.0 ± 3450.93 | -3650.0 ± NA |
Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased ferritin values indicate improvement.
| micrograms per liter (ug/L) | AG-348 50 mg BID | AG-348 300 mg BID |
|---|---|---|
| Baseline | 857.667 ± 681.0690 | 868.600 ± 492.1219 |
| Change at Week 24 | 60.333 ± 406.5114 | -7.286 ± 232.9322 |
Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased ferritin values indicate improvement.
| ug/L | AG-348 50 mg BID | AG-348 300 mg BID |
|---|---|---|
| Change at Month 12 | -20.692 ± 207.6064 | 2.265 ± 196.0776 |
| Change at Month 36 | -25.286 ± 396.5967 | -136.150 ± 136.3716 |
| Change at Month 60 | -162.667 ± 615.9044 | -279.944 ± 220.8130 |
| Change at Month 84 | 136.000 ± 163.1086 | -385.722 ± 285.6371 |
| Change at Month 102 | 193.333 ± 80.7548 | -361.000 ± 163.9909 |
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.
| fraction of 1 | AG-348 50 mg BID | AG-348 300 mg BID |
|---|---|---|
| Baseline | 0.501 ± 0.2374 | 0.643 ± 0.2188 |
| Change at Week 24 | -0.055 ± 0.1490 | -0.036 ± 0.1819 |
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.
| fraction of 1 | AG-348 50 mg BID | AG-348 300 mg BID |
|---|---|---|
| Change at Month 12 | -0.039 ± 0.1999 | -0.034 ± 0.2431 |
| Change at Month 36 | -0.074 ± 0.3472 | -0.067 ± 0.2666 |
| Change at Month 60 | 0.060 ± 0.2128 | -0.031 ± 0.1483 |
| Change at Month 84 | -0.190 ± 0.2176 | 0.056 ± 0.1319 |
| Change at Month 102 | -0.207 ± 0.4200 | 0.117 ± 0.3150 |
Participants with pre-dose concentrations on Day 1 were excluded from the pharmacokinetics analysis, if any.
| nanograms*hours per milliliter(hr*ng/mL) | AG-348 50 mg BID | AG-348 300 mg BID |
|---|---|---|
| Day 1: AG-348 | 3287 ± 20.9 | 27930 ± 38.1 |
| Day 15: AG-348 | 3609 ± 38.2 | 11610 ± 11.3 |
| Day 1: AGI-8702 | 235.6 ± 32.6 | 2637 ± 34.9 |
| Day 15: AGI-8702 | 425.8 ± 21.8 | 2235 ± 19.4 |
Participants with pre-dose concentrations on Day 1 were excluded from the pharmacokinetics analysis, if any.
| nanograms per milliliter (ng/mL) | AG-348 50 mg BID | AG-348 300 mg |
|---|---|---|
| Day 1: AG-348 | 870.0 ± 9.2 | 7606 ± 41.8 |
| Day 15: AG-348 | 943.4 ± 30.7 | 5259 ± 35.6 |
| Day 1: AGI-8702 | 41.03 ± 43.6 | 414.7 ± 35.6 |
| Day 15: AGI-8702 | 71.94 ± 22.0 | 533.7 ± 25.6 |
Participants with pre-dose concentrations on Day 1 were excluded from the pharmacokinetics analysis, if any.
| hour (hr) | AG-348 50 mg BID | AG-348 300 mg BID |
|---|---|---|
| Day 1: AG-348 | 1.92 (0.97 to 2.03) | 1.97 (1.00 to 2.08) |
| Day 15: AG-348 | 1.00 (0.97 to 1.90) | 1.00 (0.42 to 2.00) |
| Day 1: AGI-8702 | 2.00 (1.92 to 2.03) | 1.97 (1.00 to 2.13) |
| Day 15: AGI-8702 | 2.00 (1.95 to 4.00) | 1.00 (0.93 to 4.00) |
Participants with pre-dose concentrations on Day 1 were excluded from the pharmacokinetics analysis, if any.
| liter per hour (L/hr) | AG-348 50 mg BID | AG-348 300 mg BID |
|---|---|---|
| Day 15: AG-348 | 12.27 ± 40.3 | 25.31 ± 11.7 |
| Day 15: AGI-8702 | 91.50 ± 31.0 | 128.2 ± 18.8 |
Pre-dose concentration observed on Day 1 was used as Baseline for calculation of change from baseline.
| microgram per milliliter (µg/mL) | AG-348 50 mg BID | AG-348 300 mg BID |
|---|---|---|
| Maximum Change From Baseline Response Value Over 12 Hours Post-dose (BRmax) for Adenosine Triphosphate (ATP) | 16.50 ± 11.790 | 20.67 ± 6.8896 |
Pre-dose concentration observed on Day 1 was used as Baseline for calculation of change from baseline.
| µg/mL | AG-348 50 mg BID | AG-348 300 mg |
|---|---|---|
| Maximum Change From Baseline Response Value Over 8 Hours Post-dose at Steady State (BRmax ss) for ATP | 1.500 ± 31.032 | 45.50 ± 60.995 |
Pre-dose concentration observed on Day 1 was used as Baseline for calculation of change from baseline.
| µg/mL | AG-348 50 mg BID | AG-348 300 mg BID |
|---|---|---|
| BRmax for 2,3 - Diphosphoglycerate (2,3-DPG) | 42.25 ± 38.836 | 59.57 ± 58.569 |
Pre-dose concentration observed on Day 1 was used as Baseline for calculation of change from baseline.
| µg/mL | AG-348 50 mg BID | AG-348 300 mg |
|---|---|---|
| BRmax ss for 2,3-DPG | -65.50 ± 69.745 | 8.200 ± 195.13 |
Collected over Up to Month 102. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| AG-348 50 mg BID (Core Period+ Extension Period) | 0/27 (0%) | 12/27 (44.4%) | 27/27 (100%) |
| AG-348 300 mg BID (Core Period + Extension Period) | 0/25 (0%) | 7/25 (28%) | 25/25 (100%) |
| Event | AG-348 50 mg BID (Core Period+ Extension Period) | AG-348 300 mg BID (Core Period + Extension Period) |
|---|---|---|
| Haemolytic anaemiaBlood and lymphatic system disorders | 2/27 | 1/25 |
| HaemolysisBlood and lymphatic system disorders | 0/27 | 1/25 |
| HypertriglyceridaemiaMetabolism and nutrition disorders | 0/27 | 1/25 |
| CellulitisInfections and infestations | 0/27 | 1/25 |
| GastroenteritisInfections and infestations | 0/27 | 1/25 |
| Infected biteInfections and infestations | 0/27 | 1/25 |
| Inguinal herniaGastrointestinal disorders | 0/27 | 1/25 |
| Initial insomniaPsychiatric disorders | 0/27 | 1/25 |
| EndometriosisReproductive system and breast disorders | 0/27 | 1/25 |
| AnaemiaBlood and lymphatic system disorders | 0/27 | 1/25 |
| Event | AG-348 50 mg BID (Core Period+ Extension Period) | AG-348 300 mg BID (Core Period + Extension Period) |
|---|---|---|
| InsomniaPsychiatric disorders | 7/27 | 16/25 |
| HeadacheNervous system disorders | 13/27 | 15/25 |
| NauseaGastrointestinal disorders | 12/27 | 12/25 |
| NasopharyngitisInfections and infestations | 11/27 | 9/25 |
| PyrexiaGeneral disorders | 1/27 | 9/25 |
| VomitingGastrointestinal disorders | 3/27 | 8/25 |
| FatigueGeneral disorders | 7/27 | 8/25 |
| CoughRespiratory, thoracic and mediastinal disorders | 6/27 | 7/25 |
| Hot flushVascular disorders | 2/27 | 7/25 |
| InfluenzaInfections and infestations | 7/27 | 2/25 |
The Full Analysis Set included all randomized participants.
| Age, Continuous(years) | AG-348 50 mg BID | AG-348 300 mg BID | Total |
|---|---|---|---|
| Mean | 30.6 ± 11.20 | 37.6 ± 12.02 | 34.0 ± 12.01 |
| Sex: Female, Male(Participants) | AG-348 50 mg BID | AG-348 300 mg BID | Total |
|---|---|---|---|
| Female | 9 | 11 | 20 |
| Male | 18 | 14 | 32 |
| Ethnicity (NIH/OMB)(Participants) | AG-348 50 mg BID | AG-348 300 mg BID | Total |
|---|---|---|---|
| Hispanic or Latino | 0 | 0 | 0 |
| Not Hispanic or Latino | 24 | 23 | 47 |
| Unknown or Not Reported | 3 | 2 | 5 |
| Race/Ethnicity, Customized(Participants) | AG-348 50 mg BID | AG-348 300 mg BID | Total |
|---|---|---|---|
| Race — American Indian or Alaska Native | 0 | 0 | 0 |
| Race — Asian | 2 | 1 | 3 |
| Race — Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Race — Black or African American | 0 | 0 | 0 |
| Race — White | 22 | 21 | 43 |
| Race — Other | 1 | 2 | 3 |
| Race — Unknown or Not Reported | 2 | 1 | 3 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: No
Ran from Jun 2015 to primary completion in May 2017, 22 months.
Results were first posted in Jun 2020, 3 years 1 month after primary completion. A results delay was requested in May 2018.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Apr 2026. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Studies of the drug tested here: Mitapivat