SNPMiner Trials by Shray Alag


SNPMiner Trials: Clinical Trial Report


Report for Clinical Trial NCT03559699

Developed by Shray Alag, 2019.
SNP Clinical Trial Gene

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
MeSH: Anemia, Hemolytic, Congenital Nonspherocytic Pyruvate Metabolism, Inborn Errors Anemia, Hemolytic
HPO: Hemolytic anemia Microangiopathic hemolytic anemia

1 Interventions

Name: AG-348

Description: Part 1 (Dose Optimization Period): All 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 a day.

Type: Drug

Part 1: Dose Optimization AG-348


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)

Purpose: Treatment

Single Group Assignment


There is one SNP

SNPs


1 R479H

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 ---



HPO Nodes


HPO:
Hemolytic anemia
Genes 104
COL4A1 CFH GPI KRAS TPP2 RAG1 HK1 ATP7B NRAS ANK1 WAS GALT WIPF1 TNFSF12 NT5C3A HLA-DRB1 PIEZO1 SPTA1 SPTB GPX1 GATA1 ABCB6 CASP10 NBN NLRP1 DGKE CD46 ADAMTS13 NHLRC2 HMOX1 CPOX LCAT PFKM CFI FAS ADA FASLG CR2 ADAR RFX5 RFXAP PGK1 ZAP70 SLC2A1 STAT1 RHAG PGM3 STAT3 GSS SLC4A1 HELLPAR CASK TNFRSF4 TTC7A STIM1 RASGRP1 PIGT CD3G KMT2D ICOS BPGM PIGA LAT CD19 MS4A1 CIITA GCLC RFXANK GYPC BTNL2 NFKB1 NFKB2 FECH CD40LG PKLR TNFRSF13C CD59 KCNN4 TNFRSF13B AK1 PRKCD ATP11C CD81 ALAD CTLA4 TNFAIP3 LRBA UROD UROS HBA1 HBA2 ALDOA HBB IL2RA G6PD KDM6A ABCG5 ABCG8 EPB41 EPB42 GP1BA PNP FOXP3 TPI1
Microangiopathic hemolytic anemia
Genes 5
CFI CFH CD46 ADAMTS13 HELLPAR