Study to Evaluate how effective and safe the investigationall product, Mitapivat, is when administred to Pediatric Subjects With Pyruvate Kinase Deficiency, who are not receiving regular blood transfusions, followed by a 5-Year Open-label Extension Period, where subjects will be given the option to receive mitapivat for an additional 5 years.

Phase 1

• Conditions: Pyruvate Kinase Deficiency; MedDRA version: 21.1Level: PTClassification code 10037682Term: Pyruvate kinase deficiency anaemiaSystem Organ Class: 10010331 - Congenital, familial and genetic disorders; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2021-003333-11-FR
• Lead Sponsor: Agios Pharmaceuticals, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2022-03-25
• Last Update Posted: 22 July 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

1.Written informed consent from the subject, or the subject’s legally authorized representative, parent(s), or legal guardian, and the subject’s assent, where applicable (informed consent/assent) must be obtained before any study-related procedures are conducted and subjects must be willing to comply with all study procedures for the duration of the study.
2.Aged 1 to <18 years. Subjects between 12 and 24 months of age must weigh a minimum of 7 kg.
3.Clinical laboratory confirmation of PK deficiency, defined as documented presence of at least 2 mutant alleles in the PKLR gene, of which at least 1 is a missense mutation, as determined per the genotyping performed by the study central genotyping laboratory
4.No more than 5 RBC transfusions in the 52-week period before providing informed consent/assent and no RBC transfusions =12 weeks before administration of the first dose of study drug
5.Hemoglobin concentration =10 g/dL for subjects 12 to <18 years of age or =9 g/dL for subjects 1 to <12 years of age during the Screening Period. Hemoglobin concentration must be based on an average of at least 2 Hb concentration measurements (separated by =7 days) collected during the Screening Period.
6.Receiving folic acid supplementation as part of routine clinical care for at least 21 days before administration of the first dose of study drug, to be continued during study participation
7.Female subjects who have attained menarche and/or breast development in Tanner Stage 2, as well as male subjects with partners who have attained menarche, must be abstinent of sexual activities that may induce pregnancy 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 informed consent/assent, throughout the study, and for 28 days after the last dose of study drug (including the time required to dose taper) for female subjects who have attained menarche and 90 days after the last dose of study drug (including the time required to dose taper) for male subjects. The second form of contraception can include an acceptable barrier method (see Appendix 2 for the definition of women of childbearing potential and acceptable contraception methods).

Are the trial subjects under 18? yes
Number of subjects for this age range: 30
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Subjects are excluded from the study if any of the following criteria apply:
1.Pregnant or breastfeeding
2.Homozygous for the R479H mutation or have 2 nonmissense mutations, without the presence of another missense mutation, in the PKLR gene as determined per the genotyping performed by the study central genotyping laboratory
3.History of malignancy
4.History of active and/or uncontrolled cardiac or pulmonary disease or clinically relevant QT prolongation within 6 months before providing informed consent/assent
5.Hepatobiliary disorders including, but not limited to:
a.Liver disease with histopathological evidence of cirrhosis or severe fibrosis
b.Clinically symptomatic cholelithiasis or cholecystitis (subjects with prior cholecystectomy are eligible)
c.History of drug-induced cholestatic hepatitis
d.Aspartate aminotransferase >2.5×ULN (unless due to hemolysis and/or hepatic iron deposition) and alanine aminotransferase >2.5×ULN (unless due to hepatic iron deposition)
6.Renal dysfunction as defined by an estimated glomerular filtration rate <60 mL/min/1.73 m2 (bedside Schwartz equation; Schwartz et al, 2009)
7.Nonfasting triglycerides >440 mg/dL (5 mmol/L)
8.Active uncontrolled infection requiring systemic antimicrobial therapy
9.Subjects with a high likelihood of exposure to, or parental history of, hepatitis B or hepatitis C who subsequently test positive for hepatitis B antigen or hepatitis C virus antibody with signs of active hepatitis B or hepatitis C virus infection
10.Subjects with a high likelihood of exposure to, or parental history of, HIV who subsequently test positive for HIV 1 or 2 antibodies
11.History of major surgery (including splenectomy) =6 months before providing informed consent/assent and/or planning on undergoing a major surgical procedure during the Screening or Double-blind Period
12.Current enrollment or past participation (within 90 days before the first dose of study drug or a time frame equivalent to 5 half-lives of the investigational study drug, whichever is longer) in any other clinical study involving an investigational study drug or device
13.Prior bone marrow or stem cell transplantation
14.Currently receiving hematopoietic stimulating agents; the last dose must have been administered at least 28 days or a time frame equivalent to 5 half-lives (whichever is longer) before randomization
15.Receiving products that are strong inhibitors of CYP3A4/5 that have not been stopped for =5 days or a time frame equivalent to 5 half-lives (whichever is longer), or strong inducers of CYP3A4 that have not been stopped for =28 days or a time frame equivalent to 5 half-lives (whichever is longer), before randomization
16.Receiving anabolic steroids, including testosterone preparations, that have not been stopped for at least 28 days before randomization
17.Known allergy to mitapivat or its excipients (microcrystalline cellulose, croscarmellose sodium, sodium stearyl fumarate, mannitol, and magnesium stearate)
18.Any medical, hematologic, psychological, or behavioral condition(s) or prior or current therapy that, in the opinion of the Investigator, may confer an unacceptable risk to participating in the study and/or could confound the interpretation of the study data

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified