Extension Study of AG-348 in Adult Participants With Pyruvate Kinase Deficiency Previously Enrolled in AG-348-006 or AG348-C-007

NCT ID: NCT03853798

Last Updated: 2025-11-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 90 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-03-21
• Study Completion Date: 2024-07-03

Brief 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.

Conditions

Pyruvate Kinase Deficiency

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1

Participants who received placebo in Study AG348-C-006 and met the eligibility criteria of this extension study were enrolled to receive mitapivat tablets, 5 milligrams (mg), twice daily (BID), administered orally, for 4 weeks as a starting dose, followed by two potential sequential dose level increases to 20 mg and 50 mg BID at Weeks 4 and 8 respectively as determined by the investigator based on safety and efficacy. The optimized dose for each participant was determined at Week 12, and participants then received that optimized dose for a period of 12 weeks (Weeks 13-24) as a fixed dose and from Week 25 to Week 193, until study withdrawal, or the study was closed.

Group Type: EXPERIMENTAL

Mitapivat

Intervention Type: DRUG

Tablets

Cohort 2

Participants who received mitapivat at a dose of 5 mg, 20 mg, or 50 mg, BID, in the fixed dose period of Study AG348-C-006 and met the eligibility criteria of this extension study continued to receive the same mitapivat dose up to Week 193 or until study withdrawal, or the study was closed.

Group Type: EXPERIMENTAL

Mitapivat

Intervention Type: DRUG

Tablets

Cohort 3

Participants who received mitapivat at a dose of 5 mg, 20 mg, or 50 mg, BID, in the fixed dose period of Study AG348-C-007 and met the eligibility criteria of this extension study continued to receive the same mitapivat dose up to Week 193 or until study withdrawal, or the study was closed.

Group Type: EXPERIMENTAL

Mitapivat

Intervention Type: DRUG

Tablets

Interventions

Mitapivat

Tablets

Intervention Type: DRUG

Other Intervention Names

AG-348; AG-348 sulfate hydrate; Mitapivat sulfate

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Agios Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Affairs

Role: STUDY_CHAIR

Agios Pharmaceuticals, Inc.

Locations

Phoenix Children's Hospital

Phoenix, Arizona, United States

UCSF Benioff Children's Hospital, Oakland

Oakland, California, United States

Emory-Children's Center

Atlanta, Georgia, United States

Indiana Hemophilia & Thrombosis Center Inc.

Indianapolis, Indiana, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Boston Children's Hospital

Boston, Massachusetts, United States

Wayne State University School of Medicine

Detroit, Michigan, United States

Duke University Medical Center

Durham, North Carolina, United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Houston Methodist Research Institute

Houston, Texas, United States

University of Utah

Salt Lake City, Utah, United States

Seattle Cancer Care Alliance

Seattle, Washington, United States

UNICAMP - Hemocentro

São Paulo, , Brazil

McMaster University

Hamilton, Ontario, Canada

Herlev University Hospital

Herlev, , Denmark

CHU Hopitaux de Bordeaux - Hôpital Saint-André

Bordeaux, , France

CHU Hôpital Henri Mondor

Créteil, , France

Hospital La Timone

Marseille, , France

Institut Universitaire du Cancer de Toulouse - Oncopole

Toulouse, , France

Charite - UB - CVK - Medizinische Klinik

Berlin, , Germany

Universitätsklinik Würzburg

Würzburg, , Germany

St James's Hospital

Dublin, , Ireland

Ospedale Galliera

Genova, , Italy

Osp Maggiore Policlinico Milano

Milan, , Italy

AORN Cardarelli

Napoli, , Italy

Università della Campania "Luigi Vanvitelli"

Napoli, , Italy

Mie University Hospital

Tsu, Mie-ken, Japan

Tohoku University Hospital

Sendai, Miyagi, Japan

Kyoto Katsura Hospital

Kyoto, , Japan

Kansai Medical University, Dep. of Pediatrics, Hirakata Hospital

Osaka, , Japan

Toho University Omori Medical Center

Tokyo, , Japan

Van Creveldkliniek

Utrecht, , Netherlands

Yeungnam University Hospital

Daegu, , South Korea

Hospital. U. Vall d'Hebron

Barcelona, , Spain

Hospital Universitario La Paz

Madrid, , Spain

Htal Clínico Universitario Virgen de la Arrixaca.

Murcia, , Spain

Centre Hospitalier Universitaire Vaudois (CHUV)

Vaud (Lausanne), , Switzerland

Faculty of Medicine Siriraj Hospital

Bangkok, , Thailand

Hacettepe University Faculty of Medicine

Ankara, , Turkey (Türkiye)

Addenbrooke's Hospital

Cambridge, , United Kingdom

Imperial College Healthcare NHS Trust

London, , United Kingdom

University College London

London, , United Kingdom

Countries

United States; Brazil; Canada; Denmark; France; Germany; Ireland; Italy; Japan; Netherlands; South Korea; Spain; Switzerland; Thailand; Turkey (Türkiye); United Kingdom

References

van Beers EJ, Al-Samkari H, Grace RF, Barcellini W, Glenthoj A, DiBacco M, Wind-Rotolo M, Xu R, Beynon V, Patel P, Porter JB, Kuo KHM. Mitapivat improves ineffective erythropoiesis and iron overload in adult patients with pyruvate kinase deficiency. Blood Adv. 2024 May 28;8(10):2433-2441. doi: 10.1182/bloodadvances.2023011743.

Reference Type: DERIVED

PMID: 38330179 (View on PubMed)

Rab 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.

Reference Type: DERIVED

PMID: 31974203 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2018-003459-39

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

AG348-C-011

Identifier Type: -

Identifier Source: org_study_id