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

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.