A Study to Evaluate Efficacy and Safety of AG-348 in Not 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 participating in the study, and/or that could confound the interpretation of the study data;
• •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 involving ongoing therapy with any investigational or marketed product or placebo. Prior and subsequent participation in the PK Deficiency Natural History Study (NHS) (NCT02053480) or PK Deficiency Registry is permitted however, concurrent participation is not; participants enrolling in this current study will be expected to temporarily suspend participation in the NHS or Registry;
• •Exposure to any investigational drug, device, or procedure within 3 months prior to the first dose of study treatment;
• •Prior treatment with a pyruvate kinase activator;
• •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 cytochrome P450 (CYP)3A4, 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 a timeframe equivalent to 5 half-lives (whichever is longer) prior to the first dose of study treatment;
• •Currently receiving hematopoietic stimulating agents that have not been stopped for a duration of at least 28 days prior to the first dose of study treatment;
• •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;
• •History of allergy to AG-348 or its excipients;
• •Currently receiving anabolic steroids, including testosterone preparations, within 28 days prior to treatment.