NCT02476916 is a Phase 2 clinical trial of AG-348 in Pyruvate Kinase Deficiency, sponsored by Agios Pharmaceuticals, Inc..

Who is sponsoring NCT02476916?

NCT02476916 is sponsored by Agios Pharmaceuticals, Inc..

What drugs are being tested in NCT02476916?

Interventions in NCT02476916: AG-348.

What condition does NCT02476916 study?

NCT02476916 studies Pyruvate Kinase Deficiency.

Is NCT02476916 still recruiting?

NCT02476916 is currently completed. Last updated 2 May 2025.

Are results published for NCT02476916?

Yes — primary outcome results have been posted to ClinicalTrials.gov. See the outcomes section above for details.

Last reviewed 2025-05-02 · How we verify

NCT02476916

Name: Drug Landscape Pharmaceutical Database
Creator: Drug Landscape
Published: 2026-01-01
License: https://creativecommons.org/licenses/by/4.0/

A Study of AG-348 in Adult Participants With Pyruvate Kinase (PK) Deficiency

Completed Phase 2 Results posted Last updated 2 May 2025

What this trial tests

Phase 2 trial testing AG-348 in Pyruvate Kinase Deficiency in 52 participants. Completed in 2 April 2025.

Timeline

26 June 2015

Primary endpoint
8 May 2017

2 April 2025

Quick facts

Lead sponsor	Agios Pharmaceuticals, Inc.
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	52
Start date	26 June 2015
Primary completion	8 May 2017
Estimated completion	2 April 2025
Sites	13 locations across France, Italy, Netherlands, United Kingdom, Canada, United States

Drugs / interventions tested

AG-348 — full drug profile →

Conditions studied

Pyruvate Kinase Deficiency — all drugs for Pyruvate Kinase Deficiency →

Sponsor

Agios Pharmaceuticals, Inc. — full company profile →

Who can join

18 and older, any sex, with Pyruvate Kinase Deficiency. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants Experiencing at Least One Adverse Event (AEs) in the Core Period Primary · 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.

Group	Value	95% CI
AG-348 50 mg BID	96.3
AG-348 300 mg BID	100.0

Change From Baseline in Hemoglobin (Hb) Value at Week 24 Secondary · Baseline and Week 24

Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Increased Hb values indicate improvement.

Baseline

Group	Value	95% CI
AG-348 50 mg BID	9.243	± 1.4757
AG-348 300 mg BID	8.636	± 1.1664

Change at Week 24

Group	Value	95% CI
AG-348 50 mg BID	1.205	± 1.4181
AG-348 300 mg BID	1.611	± 1.7058

Change From Baseline in Hematocrit at Week 24 Secondary · Baseline and Week 24

Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Increased hematocrit values indicate improvement.

Baseline

Group	Value	95% CI
AG-348 50 mg BID	0.289	± 0.0470
AG-348 300 mg BID	0.268	± 0.0367

Change at Week 24

Group	Value	95% CI
AG-348 50 mg BID	0.033	± 0.0414
AG-348 300 mg BID	0.045	± 0.0499

Change From Baseline in Reticulocyte Count at Week 24 Secondary · Baseline and Week 24

Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased reticulocyte count values indicate improvement.

Baseline

Group	Value	95% CI
AG-348 50 mg BID	493.248	± 234.2242
AG-348 300 mg BID	549.436	± 291.5301

Change at Week 24

Group	Value	95% CI
AG-348 50 mg BID	-99.248	± 309.9473
AG-348 300 mg BID	-46.222	± 351.9823

Change From Baseline in Haptoglobin at Week 24 Secondary · Baseline and Week 24

Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Increased haptoglobin values indicate improvement.

Baseline

Group	Value	95% CI
AG-348 50 mg BID	0.246	± 0.1474
AG-348 300 mg BID	0.240	± 0.2082

Change at Week 24

Group	Value	95% CI
AG-348 50 mg BID	0.128	± 0.2845
AG-348 300 mg BID	0.139	± 0.2726

Change From Baseline in Carbon Monoxide at Week 24 Secondary · Baseline and Week 24

Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased carbon monoxide values indicate improvement.

Baseline

Group	Value	95% CI
AG-348 50 mg BID	5.263	± 1.7270
AG-348 300 mg BID	6.200	± 2.3079

Change at Week 24

Group	Value	95% CI
AG-348 50 mg BID	-1.063	± 2.2940
AG-348 300 mg BID	-1.706	± 3.2742

Change From Baseline in Lactate Dehydrogenase (LDH) at Week 24 Secondary · Baseline and Week 24

Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased LDH values indicate improvement.

Baseline

Group	Value	95% CI
AG-348 50 mg BID	282.074	± 188.3558
AG-348 300 mg BID	254.840	± 122.3587

Change at Week 24

Group	Value	95% CI
AG-348 50 mg BID	-26.292	± 145.3151
AG-348 300 mg BID	-8.913	± 139.8509

Change From Baseline in Total Bilirubin at Week 24 Secondary · Baseline and Week 24

Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased total bilirubin values indicate improvement.

Baseline

Group	Value	95% CI
AG-348 50 mg BID	5.152	± 2.3407
AG-348 300 mg BID	5.608	± 3.4625

Change at Week 24

Group	Value	95% CI
AG-348 50 mg BID	-1.921	± 1.9465
AG-348 300 mg BID	-3.017	± 2.5848

Change From Baseline in Indirect Bilirubin at Week 24 Secondary · Baseline and Week 24

Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased indirect bilirubin values indicate improvement.

Baseline

Group	Value	95% CI
AG-348 50 mg BID	4.752	± 2.3629
AG-348 300 mg BID	5.208	± 3.4272

Change at Week 24

Group	Value	95% CI
AG-348 50 mg BID	-1.967	± 1.8318
AG-348 300 mg BID	-3.195	± 2.5537

Change From Baseline in Erythropoietin (EPO) at Week 24 Secondary · Baseline and Week 24

Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased EPO values indicate improvement.

Baseline

Group	Value	95% CI
AG-348 50 mg BID	85.448	± 159.4090
AG-348 300 mg BID	60.900	± 19.5188

Change at Week 24

Group	Value	95% CI
AG-348 50 mg BID	-7.738	± 33.1934
AG-348 300 mg BID	-13.675	± 26.5065

Change From Baseline in Hepcidin at Week 24 Secondary · Baseline and Week 24

Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased hepcidin values indicate improvement.

Baseline

Group	Value	95% CI
AG-348 50 mg BID	3.392	± 3.4013
AG-348 300 mg BID	4.988	± 4.0416

Change at Week 24

Group	Value	95% CI
AG-348 50 mg BID	0.095	± 1.4795
AG-348 300 mg BID	-2.310	± 2.5061

Change From Baseline in Ferritin at Week 24 Secondary · Baseline and Week 24

Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased ferritin values indicate improvement.

Baseline

Group	Value	95% CI
AG-348 50 mg BID	860.852	± 682.6346
AG-348 300 mg BID	859.680	± 490.2734

Change at Week 24

Group	Value	95% CI
AG-348 50 mg BID	68.875	± 388.1866
AG-348 300 mg BID	-37.870	± 308.0896

Adverse events — posted to ClinicalTrials.gov

Time frame: Up to Week 24. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

AG-348 50 mg BID

Serious: 5/27 (19%)

Deaths: 0/27

AG-348 300 mg BID

Serious: 3/25 (12%)

Deaths: 0/25

Serious adverse events (7 terms)

Reaction	System	AG-348 50 mg BID	AG-348 300 mg BID
Pharyngitis	Infections and infestations	—	—
Influenza	Infections and infestations	—	—
Haemolytic anaemia	Blood and lymphatic system disorders	—	—
Haemolysis	Blood and lymphatic system disorders	—	—
Cholelithiasis	Hepatobiliary disorders	—	—
Hypertriglyceridaemia	Metabolism and nutrition disorders	—	—
Osteoporosis	Musculoskeletal and connective tissue disorders	—	—

Other adverse events (40 terms — click to expand)

Reaction	System	AG-348 50 mg BID	AG-348 300 mg BID
Insomnia	Psychiatric disorders	—	—
Headache	Nervous system disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Viral upper respiratory tract infection	Infections and infestations	—	—
Hot flush	Vascular disorders	—	—
Influenza	Infections and infestations	—	—
Vomiting	Gastrointestinal disorders	—	—
Dizziness	Nervous system disorders	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—
Pyrexia	General disorders	—	—
Cough	Respiratory, thoracic and mediastinal disorders	—	—
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—
Fatigue	General disorders	—	—
Chest discomfort	General disorders	—	—
Night sweats	Skin and subcutaneous tissue disorders	—	—
Dysmenorrhoea	Reproductive system and breast disorders	—	—
Hypertriglyceridaemia	Metabolism and nutrition disorders	—	—
Diarrhoea	Gastrointestinal disorders	—	—
Abdominal pain	Gastrointestinal disorders	—	—
Abdominal pain upper	Gastrointestinal disorders	—	—
Dysgeusia	Nervous system disorders	—	—
Nasal congestion	Respiratory, thoracic and mediastinal disorders	—	—
Dyspnoea	Respiratory, thoracic and mediastinal disorders	—	—
Gastroenteritis	Infections and infestations	—	—
Asthenia	General disorders	—	—
Non-cardiac chest pain	General disorders	—	—
Rash	Skin and subcutaneous tissue disorders	—	—
Skin ulcer	Skin and subcutaneous tissue disorders	—	—
Dyspepsia	Gastrointestinal disorders	—	—
Epistaxis	Respiratory, thoracic and mediastinal disorders	—	—
Sinusitis	Infections and infestations	—	—
Upper respiratory tract infection	Infections and infestations	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	—	—
Musculoskeletal pain	Musculoskeletal and connective tissue disorders	—	—
Pruritus generalised	Skin and subcutaneous tissue disorders	—	—
Flushing	Vascular disorders	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—
Palpitations	Cardiac disorders	—	—

Most-reported serious reactions: Pharyngitis, Influenza, Haemolytic anaemia, Haemolysis, Cholelithiasis, Hypertriglyceridaemia, Osteoporosis.

Data from ClinicalTrials.gov NCT02476916 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

Safety and Efficacy of Mitapivat in Pyruvate Kinase Deficiency.
Grace RF, Rose C, Layton DM, Galactéros F, et al · · 2019 · cited 112× · PMID 31483964 · DOI 10.1056/nejmoa1902678
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.
Rab MAE, Van Oirschot BA, Kosinski PA, Hixon J, et al · · 2021 · cited 52× · PMID 31974203 · DOI 10.3324/haematol.2019.238865
Mitapivat, a novel pyruvate kinase activator, for the treatment of hereditary hemolytic anemias.
Al-Samkari H, van Beers EJ. · · 2021 · cited 41× · PMID 34987744 · DOI 10.1177/20406207211066070
Glutathione-S-transferase P promotes glycolysis in asthma in association with oxidation of pyruvate kinase M2.
van de Wetering C, Manuel AM, Sharafi M, Aboushousha R, et al · · 2021 · cited 39× · PMID 34624602 · DOI 10.1016/j.redox.2021.102160
Genetics and Genomics Approaches for Diagnosis and Research Into Hereditary Anemias.
Russo R, Marra R, Rosato BE, Iolascon A, et al · · 2020 · cited 37× · PMID 33414725 · DOI 10.3389/fphys.2020.613559
Decreased activity and stability of pyruvate kinase in sickle cell disease: a novel target for mitapivat therapy.
Rab MAE, Bos J, van Oirschot BA, van Straaten S, et al · · 2021 · cited 31× · PMID 33690814 · DOI 10.1182/blood.2020008635
Pyruvate Kinase Deficiency: Current Challenges and Future Prospects.
Fattizzo B, Cavallaro F, Marcello APML, Vercellati C, et al · · 2022 · cited 20× · PMID 36072510 · DOI 10.2147/jbm.s353907
Research in Sickle Cell Disease: From Bedside to Bench to Bedside.
Salinas Cisneros G, Thein SL. · · 2021 · cited 19× · PMID 34095767 · DOI 10.1097/hs9.0000000000000584

Verify or expand the search:

Other trials of AG-348

Trials testing the same drug.

NCT04000165 — A Dose-Finding Study of AG-348 in Sickle Cell Disease · EARLY_PHASE1 · completed
NCT03692052 — A Study to Determine the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of AG-348 in Adult Participants With N · Phase 2 · active not recruiting
NCT03548220 — A Study to Evaluate Efficacy and Safety of AG-348 in Not Regularly Transfused Adult Participants With Pyruvate Kinase De · Phase 3 · completed
NCT03559699 — A Study Evaluating the Efficacy and Safety of AG-348 in Regularly Transfused Adult Participants With Pyruvate Kinase Def · Phase 3 · completed
NCT03703505 — A Study to Evaluate the Absorption, Distribution, Metabolism, Excretion and Absolute Bioavailability of AG-348 in Health · Phase 1 · completed

Other recruiting trials for Pyruvate Kinase Deficiency

Currently open trials in the same condition.

NCT04902833 — Acquired Pyruvate Kinase Deficiency In Clonal Myeloid Neoplasms · active not recruiting
NCT03481738 — Pyruvate Kinase Deficiency Global Longitudinal Registry · active not recruiting

Other Agios Pharmaceuticals, Inc. trials

Trials by the same sponsor.

NCT07075640 — A Study to Determine the Safety and Tolerability of AG-236 and How it is Absorbed, Broken Down, and Eliminated From the · Phase 1 · recruiting
NCT06745271 — A Study to Determine How Tebapivat is Absorbed, Broken Down, and Removed From the Body and the Extent to Which Tebapivat · Phase 1 · completed
NCT06648824 — Study of How Mitapivat Affects Midazolam Blood Levels in Healthy Participants · Phase 1 · completed
NCT06286033 — Single and Multiple Ascending Dose Study and Food Effect Study for AG181 · Phase 1 · completed
NCT05610657 — A Pharmacokinetic Study of Mitapivat in Participants With Moderate Hepatic Impairment Compared to Matched Healthy Contro · Phase 1 · completed

Verify against primary sources

ClinicalTrials.gov — authoritative US registry record
WHO ICTRP — international registry index
EU Clinical Trials Register
Sponsor press releases (Google)

Data sources for this page

Trial protocol + status: ClinicalTrials.gov NCT02476916 (US National Library of Medicine, public domain)
Publications: Europe PMC API search by NCT ID, retrieved 10 June 2026
Drug + disease cross-links: matched in real time against Drug Landscape's normalised drug + company + condition tables
Sponsor: as reported to ClinicalTrials.gov by Agios Pharmaceuticals, Inc.
Last refreshed: 2 May 2025

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT02476916.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing

NCT02476916

Quick facts

Drugs / interventions tested

Conditions studied

Sponsor

Who can join

Results — posted to ClinicalTrials.gov

Adverse events — posted to ClinicalTrials.gov

Serious adverse events (7 terms)

Sponsor's own description

Publications & conference data

Related trials

Other trials of AG-348

Other recruiting trials for Pyruvate Kinase Deficiency

Other Agios Pharmaceuticals, Inc. trials

Verify against primary sources