Study AG348-C-006 will evaluate the efficacy and safety of orally administered AG-348 as compared with placebo in participants with pyruvate kinase deficiency (PKD), who are not regularly receiving blood transfusions. Participants will be randomized 1:1 to receive either AG-348 or matching placebo. The study is comprised of two parts. During the Part 1 Dose Optimization Period of the study, 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.
Name: AG-348Description: Part 1 (Dose Optimization Period): 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 daily.Type: Drug
Name: PlaceboDescription: Part 1 (Dose Optimization Period): Participants will begin by receiving placebo matching AG-348 orally, twice a day. Each participant's dose of placebo matching AG-348 may be increased to 20 mg twice a day or 50 mg twice a day depending on their response to the placebo matching AG-348 and their tolerance. Part 2 (Fixed Dose Period): Last dose received in Part 1, twice daily.Type: Drug
There is one SNP
- Adequate organ function; - Women of reproductive potential, have a negative serum pregnancy test; - 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 (both men and women) following the last dose of study treatment; - Willing to comply with all study procedures 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 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. --- R479H ---