Gender
All
Age Group
1 Year to 17 Years
Accepting Healthy Volunteers
No
Inclusion Criteria:
- Written informed consent from the participant, or the participant's legally
authorized representative, parent(s), or legal guardian, and the participant's
assent, where applicable (informed consent/assent) must be obtained before any
study-related procedures are conducted, and participants must be willing to comply
with all study procedures for the duration of the study;
- Aged 1 to <18 years. Participants between 12 and 24 months of age must weigh a
minimum of 7 kilograms (kg);
- Clinical laboratory confirmation of pyruvate kinase deficiency (PKD), defined as
documented presence of at least 2 mutant alleles in the pyruvate kinase L/R (PKLR)
gene, of which at least 1 is a missense mutation, as determined per the genotyping
performed by the study central genotyping laboratory;
- No more than 5 red blood cell (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;
- Hemoglobin concentration ≤10 grams per deciliter (g/dL) for participants 12 to <18
years of age or ≤9 g/dL for participants 1 to <12 years of age during the screening
period. Hb concentration must be based on an average of at least 2 Hb concentration
measurements (separated by ≥7 days) collected during the screening period;
- 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;
- Female participants who have attained menarche and/or breast development in Tanner
Stage 2 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). The second form of contraception can include an acceptable
barrier method.
Exclusion Criteria:
- Pregnant or breastfeeding;
- 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;
- History of malignancy;
- History of active and/or uncontrolled cardiac or pulmonary disease or clinically
relevant QT prolongation within 6 months before providing informed consent/assent;
- Hepatobiliary disorders including, but not limited to:
- Liver disease with histopathological evidence of cirrhosis or severe fibrosis;
- Clinically symptomatic cholelithiasis or cholecystitis (participants with prior
cholecystectomy are eligible);
- History of drug-induced cholestatic hepatitis;
- Aspartate aminotransferase >2.5×upper limit of normal (ULN) (unless due to
hemolysis and/or hepatic iron deposition) and alanine aminotransferase >2.5×ULN
(unless due to hepatic iron deposition);
- Renal dysfunction as defined by an estimated glomerular filtration rate <60
milliliters per minute (mL/min)/1.73 m^2;
- Nonfasting triglycerides >440 milligrams per deciliter (mg/dL) (5 millimoles per
liter [mmol/L]);
- Active uncontrolled infection requiring systemic antimicrobial therapy;
- Participants with known active hepatitis B or hepatitis C virus infection;
- Participants with known human immunodeficiency virus (HIV) infection;
- 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;
- 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;
- Prior exposure to gene therapy, or bone marrow or stem cell transplantation;
- 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;
- 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;
- Receiving anabolic steroids, including testosterone preparations, that have not been
stopped for at least 28 days before randomization;
- Known allergy, or other contraindication, to mitapivat or its excipients
(microcrystalline cellulose, croscarmellose sodium, sodium stearyl fumarate,
mannitol, Opadry® II Blue [hypromellose, titanium dioxide, lactose monohydrate,
triacetin, and Food, Drug, and Cosmetics blue dye number 2 (FD&C Blue #2)], Opadry®
II White [hypromellose, titanium dioxide, lactose monohydrate, and triacetin], and
magnesium stearate);
- 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; also included are:
- Participants who are institutionalized by regulatory or court order.
- Participants with any condition(s) that could create undue influence (including
but not limited to incarceration, involuntary psychiatric confinement, and
financial or familial affiliation with the Investigator or Sponsor).
- Receiving a pyruvate kinase activator that has not been stopped for ≥52 weeks before
providing informed consent/assent.