SNPMiner Trials (Home Page)
Report for Mutation R479H
Developed by Shray Alag, 2020.
SNP Clinical Trial Gene
There are 2 clinical trials
Clinical Trials
1 A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of AG-348 in Not Regularly Transfused Adult Subjects With Pyruvate Kinase Deficiency
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 of AG-348 may be sequentially increased to 20 mg twice a day, followed by 50 mg twice a day depending on their tolerance. During the Part 2 Fixed-Dose Period, participants will receive AG-348 at their optimized dose from Part 1.
NCT03548220 Pyruvate Kinase Deficiency Anemia, Hemolytic Drug: AG-348 Drug: Placebo MeSH:Anemia, Hemolytic, Congenital Nonspherocytic Anemia, Hemolytic Pyruvate Metabolism, Inborn Errors
HPO:Hemolytic anemia Microangiopathic hemolytic anemia
- 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 following the last dose of study treatment for women and 90 days for men 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 ---
Primary Outcomes
Measure: Percentage of Participants Achieving a Hemoglobin Response (HR) in Part 2 Time: Baseline, Part 2: Weeks 16, 20, 24Secondary Outcomes
Measure: Change from Baseline in Hb Concentration at Weeks 16, 20 and 24 in Part 2 Time: Baseline, Part 2: Weeks 16, 20, 24Measure: Maximum Change from Baseline in Hb Concentration Time: Baseline, Part 2, up to Week 24
Measure: Time to Achieve an Increase in Hb Concentration of 1.5 g/dL or More Time: Baseline, Part 2, up to Week 24
Measure: Change from Baseline in Bilirubin at Weeks 16, 20 and 24 in Part 2 Time: Baseline, Part 2: Weeks 16, 20, 24
Measure: Change from Baseline in Lactic Acid Dehydrogenase (LDH) at Weeks 16, 20 and 24 in Part 2 Time: Baseline, Part 2: Weeks 16, 20, 24
Measure: Change from Baseline in Haptoglobin at Weeks 16, 20 and 24 in Part 2 Time: Baseline, Part 2: Weeks 16, 20, 24
Measure: Change from Baseline in Reticulocyte Percentages at Weeks 16, 20 and 24 in Part 2 Time: Baseline, Part 2: Weeks 16, 20, 24
Measure: Change from Baseline in Pyruvate Kinase Deficiency Diary (PKDD) Score Time: Baseline, up to Week 24
Measure: Change from Baseline in Pyruvate Kinase Deficiency Impact Assessment (PKDIA) Score Time: Baseline, up to Week 24
Measure: Percentage of Participants Experiencing an Adverse Event Time: Through 4 weeks after last dose (approximately Part 2, Week 31)
Measure: Percentage of Participants Experiencing an Adverse Event of Special Interest (AESI) Time: Through 4 weeks after last dose (approximately Part 2, Week 31)
Measure: Change from Baseline in Bone Mineral Density Z-Score at Week 24 in Part 2 Time: Baseline, Part 2: Week 24
Measure: Change from Baseline in Bone Mineral Density T-Score at Week 24 in Part 2 Time: Baseline, Part 2: Week 24
Measure: Area Under the Curve From Time 0 to the Last Quantifiable Concentration [AUC(0-last)] for AG-348 at Week 12 Time: Week 12, pre-dose, 30 minutes and 1, 2, 4 and 8 hours post-dose
Measure: Maximum Plasma Concentration (Cmax) for AG-348 Time: Week 12, pre-dose, 30 minutes and 1, 2, 4 and 8 hours post-dose
Measure: Time to Cmax (Tmax) for AG-348 Time: Week 12, pre-dose, 30 minutes and 1, 2, 4 and 8 hours post-dose
Measure: Time to Last Measurable Concentration (Tlast) for AG-348 Time: Week 12, pre-dose, 30 minutes and 1, 2, 4 and 8 hours post-dose
2 An Open-Label Study To Evaluate the Efficacy and Safety of AG-348 in Regularly Transfused Adult Subjects With Pyruvate Kinase (PK) Deficiency
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.
NCT03559699 Pyruvate Kinase Deficiency Anemia, Hemolytic Drug: AG-348 MeSH:Anemia, Hemolytic, Congenital Nonspherocytic Anemia, Hemolytic Pyruvate Metabolism, Inborn Errors
HPO:Hemolytic anemia Microangiopathic hemolytic anemia
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. --- R479H ---
Primary Outcomes
Measure: Percentage of Participants Achieving a Reduction in Transfusion Burden in Part 2 Time: From Part 2, Day 1 to the end of the study (Part 2, Week 24)Secondary Outcomes
Measure: Number of RBC Units Transfused During the Study Time: From Part 1, Day 1 to the end of the study (Part 2, Week 24)Measure: Number of Transfusion Episodes in Part 2 Time: Part 2, Day 1 to the end of study (Part 2, Week 24)
Measure: Percentage of Transfusion-Free Participants in Part 2 Time: Part 2, Day 1 to the end of study (Part 2, Week 24)
Measure: Percentage of Participants Achieving Normal Hemoglobin (Hb) Concentrations in Part 2 Time: Part 2, Day 1 to the end of study (Part 2, Week 24)
Measure: Bone Mineral Density T-Score Time: Part 1, Day 1, Part 2, Day 1 and Part 2, Week 24
Measure: Bone Mineral Density Z-Score Time: Part 1, Day 1, Part 2, Day 1 and Part 2, Week 24
Measure: Percentage of Participants Experiencing an Adverse Event Time: Through 4 weeks after last dose (approximately Part 2, Week 31)
Measure: Percentage of Participants Experiencing an Adverse Event of Special Interest (AESI) Time: Through 4 weeks after last dose (approximately Part 2, Week 31)