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Trial record 3 of 13 for:    AG-348

A Study Evaluating the Efficacy and Safety of AG-348 in Regularly Transfused Adult Participants With Pyruvate Kinase Deficiency (PKD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT03559699
Recruitment Status : Active, not recruiting
First Posted : June 18, 2018
Last Update Posted : February 18, 2020
Information provided by (Responsible Party):
Agios Pharmaceuticals, Inc.

Brief Summary:
Study AG348-C-007 is a multicenter study designed to evaluate the efficacy and safety of treatment with AG-348 in a minimum of 20, with up to 40, subjects with pyruvate kinase deficiency (PKD), who are regularly receiving blood transfusions. The study is comprised of two parts. During the Part 1 Dose Optimization Period of the study, all participants will start on a dose of 5 mg AG-348 administered twice daily. Over the course of Part 1 each participant's dose will be optimized individually, up to a maximum dose of 50 milligrams (mg), twice daily. During the Part 2 Fixed-Dose Period, participants will receive AG-348 at their optimized dose from Part 1.

Condition or disease Intervention/treatment Phase
Pyruvate Kinase Deficiency Anemia, Hemolytic Drug: AG-348 Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 27 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label Study To Evaluate the Efficacy and Safety of AG-348 in Regularly Transfused Adult Subjects With Pyruvate Kinase (PK) Deficiency
Actual Study Start Date : May 25, 2018
Estimated Primary Completion Date : January 2021
Estimated Study Completion Date : January 2021

Arm Intervention/treatment
Experimental: Part 1: Dose Optimization AG-348

Part 1 (Dose Optimization Period): Participants will receive AG-348 for up to 16 weeks.

Part 2 (Fixed Dose Period): Participants will receive their optimized dose of AG-348 as determined by the individual participant's transfusion cycle and response to AG-348 in Part 1.

Drug: AG-348

Part 1 (Dose Optimization Period): All participants will begin by receiving 5 milligrams (mg) orally, twice a day. Each participant's dose of AG-348 may be increased to 20 mg twice a day or 50 mg twice a day depending on their response to AG-348 and their tolerance.

Part 2 (Fixed Dose Period): Last dose received in Part 1, twice a day.

Primary Outcome Measures :
  1. Percentage of Participants Achieving a Reduction in Transfusion Burden in Part 2 [ Time Frame: From Part 2, Day 1 to the end of the study (Part 2, Week 24) ]

Secondary Outcome Measures :
  1. Number of RBC Units Transfused During the Study [ Time Frame: From Part 1, Day 1 to the end of the study (Part 2, Week 24) ]
  2. Number of Transfusion Episodes in Part 2 [ Time Frame: Part 2, Day 1 to the end of study (Part 2, Week 24) ]
  3. Percentage of Transfusion-Free Participants in Part 2 [ Time Frame: Part 2, Day 1 to the end of study (Part 2, Week 24) ]
  4. Percentage of Participants Achieving Normal Hemoglobin (Hb) Concentrations in Part 2 [ Time Frame: Part 2, Day 1 to the end of study (Part 2, Week 24) ]
  5. Bone Mineral Density T-Score [ Time Frame: Part 1, Day 1, Part 2, Day 1 and Part 2, Week 24 ]
  6. Bone Mineral Density Z-Score [ Time Frame: Part 1, Day 1, Part 2, Day 1 and Part 2, Week 24 ]
  7. Percentage of Participants Experiencing an Adverse Event [ Time Frame: Through 4 weeks after last dose (approximately Part 2, Week 31) ]
  8. Percentage of Participants Experiencing an Adverse Event of Special Interest (AESI) [ Time Frame: Through 4 weeks after last dose (approximately Part 2, Week 31) ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Informed consent;
  • Male or female, aged 18 or older;
  • Presence of at least 2 mutant alleles in the Pyruvate Kinase Liver and RBC (PKLR) gene, of which at least 1 is a missense mutation;
  • History of a minimum of 6 transfusion episodes in the 52-week period prior to date of informed consent;
  • Complete records of transfusion history for the 52 weeks prior to the date of informed consent, including all transfusion dates, number of blood units transfused for all the transfusions, and Hb concentrations within 1 week prior to transfusion for at least 80% of the transfusions;
  • Have received at least 0.8 mg of oral folic acid daily for at least 21 days prior to the first dose of study drug, to be continued daily during study participation;
  • Have adequate organ function;
  • Negative serum pregnancy test for women of reproductive potential;
  • For women of reproductive potential as well as fertile men and their partners who are women of reproductive potential: be abstinent 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 AG-348;
  • Willing to comply with all study procedures, in particular the individual transfusion trigger (TT) calculated based on 52 weeks of transfusion history, for the duration of the study.

Exclusion Criteria:

  • Homozygous for the R479H mutation or have 2 non-missense mutations, without the presence of another missense mutation, in the PKLR gene;
  • Significant medical condition that confers an unacceptable risk to participate in the study, and/or that could confound the interpretation of the study data;
  • History of transfusions occurring on average more frequently than once every 3 weeks during the 52 weeks prior to date of informed consent;
  • Splenectomy scheduled during the study treatment period or have undergone splenectomy within 12 months prior to signing informed consent;
  • Currently enrolled in another therapeutic clinical trial. Prior participation in the PK Deficiency Natural History Study (NHS) (NCT02053480) or PK Deficiency Registry is permitted;
  • Exposure to any investigational drug, device, or procedure within 3 months prior to the first dose of study drug;
  • Prior bone marrow or stem cell transplant;
  • Currently pregnant or breastfeeding;
  • History of major surgery within 6 months of signing informed consent;
  • Currently receiving medications that are strong inhibitors of CYP3A4, strong inducers of CYP3A4, strong inhibitors of P-glycoprotein (P-gp), or digoxin (a P-gp sensitive substrate medication) that have not been stopped for a duration of at least 5 days or 5 times their half-lives (whichever is longer) prior to start of study drug;
  • Currently receiving hematopoietic stimulating agents (eg, erythropoietins [EPOs], granulocyte colony stimulating factors, thrombopoietins) that have not been stopped for a duration of at least 28 days prior to the first dose of study drug;
  • History of allergy to sulfonamides if characterized by acute hemolytic anemia, drug induced liver injury, anaphylaxis, rash of erythema multiforme type or Stevens-Johnson syndrome, cholestatic hepatitis or other serious clinical manifestations;
  • Allergy to AG-348 or its excipients;
  • Currently receiving anabolic steroids, including testosterone preparations, within 28 days prior to the first dose of study drug.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03559699

Hide Hide 23 study locations
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United States, California
UCSF Benioff Children's Hospital
Oakland, California, United States, 94609
Stanford University
Palo Alto, California, United States, 94304
United States, Georgia
Emory University
Atlanta, Georgia, United States, 30322
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02115
United States, Washington
Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109
Toronto General Hospital, University Health Network
Toronto, Canada, M5G 2C4
University of Copenhagen, Herlev Hospital
Herlev, Denmark, 2730
Hopital Universitaire Henri Mondor
Créteil, France, 94010
Hôpital de la Timone
Marseille, Cedex 5, France, 13385
St James's Hospital Department of Haematology
Dublin, Ireland
Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico
Milano, Italy, 20122
AORN Cardarelli
Napoli, Italy, 80131
Ospedale Galliera
Napoli, Italy, 80131
AOU Policlinico, Università della Campania "Luigi Vanvitelli"
Napoli, Italy, 80138
Universitair Medisch Centrum Utrecht
Utrecht, Netherlands, 3584
Centre Hospitalier Universitaire Vaudois (CHUV)
Lausanne, Switzerland, 1011
Department of Paediatrics and Thalassaemia Center, Faculty of Medicine Siriraj Hospital, Mahidol University
Bangkok, Thailand, 10700
Hacettepe Üniversitesi Tıp Fakültesi
Ankara, Turkey
Ege University Children's Hospital
Izmir, Turkey
United Kingdom
Addenbrooke's Hospital
Cambridge, United Kingdom, CB2 0QQ
Imperial College Healthcare NHS Trust, Hammersmith Hospital
London, United Kingdom, W12 0NN
University College London
London, United Kingdom, WC1E 6BT
Manchester Royal Infirmary
Manchester, United Kingdom, M13 9WL
Sponsors and Collaborators
Agios Pharmaceuticals, Inc.
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Study Chair: Medical Affairs Agios Pharmaceuticals, Inc.

Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Agios Pharmaceuticals, Inc. Identifier: NCT03559699    
Other Study ID Numbers: AG348-C-007
First Posted: June 18, 2018    Key Record Dates
Last Update Posted: February 18, 2020
Last Verified: February 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Anemia, Hemolytic, Congenital Nonspherocytic
Anemia, Hemolytic
Pyruvate Metabolism, Inborn Errors
Anemia, Hemolytic, Congenital
Hematologic Diseases
Genetic Diseases, Inborn
Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Metabolic Diseases