Summary

for people ages 18 years and up (full criteria)
at Oakland, California and other locations
study started
estimated completion:

Description

Summary

Study AG348-C-007 is a multicenter study designed to evaluate the efficacy and safety of treatment with AG-348 in approximately 15-20 adult participants 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.

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

Keywords

Pyruvate Kinase Deficiency Anemia, Hemolytic Anemia, Hemolytic, Congenital Nonspherocytic Pyruvate Metabolism, Inborn Errors AG-348

Eligibility

You can join if…

Open to people ages 18 years and up

  • 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 levels within 1 week prior to transfusion for at least 80% of the transfusions;
  • 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 effective forms of contraception from the time of giving informed consent, during the study, and for 30 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.

You CAN'T join if...

  • Homozygous for the R479H mutation or have 2 non-missense mutations 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 60 days prior to the Screening Visit;
  • 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 providing 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 times their half-life prior to start of study drug dosing (Day 1 of Part 1);
  • History of allergy to sulfonamides if characterized by acute hemolytic anemia,anaphylaxis, or rash of erythema multiforme type or Stevens-Johnson syndrome, or other serious clinical manifestations;
  • History of hypersensitivity to AG-348 or its excipients.

Locations

  • UCSF Benioff Children's Hospital, Oakland not yet accepting patients
    Oakland California 94609 United States
  • Stanford University not yet accepting patients
    Palo Alto California 94304 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Agios Pharmaceuticals, Inc.
ID
NCT03559699
Phase
Phase 3
Study Type
Interventional
Last Updated
June 6, 2018