MITAPIVAT for Pyruvate kinase deficiency

Inclusion criteria

• {"criterion_text":"- 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.\n- Aged 1 to <18 years. Subjects between 12 and 24 months of age must weigh a minimum of 7 kg.\n- 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\n- Six to 26 transfusion episodes in the 52-week period before providing informed consent/assent\n- Have complete records of transfusion history for the 52 weeks before providing informed consent/assent, defined as having all the following available: (1) all the transfusion dates, (2) the RBC transfusion volume (milliliters and/or number of units) for all the transfusions, and (3) Hb concentrations within 1 week before transfusion for at least 80% of the transfusions\n- 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\n- Female subjects 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

• {"criterion_text":"- Pregnant or breastfeeding\n- 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\n- History of malignancy\n- History of active and/or uncontrolled cardiac or pulmonary disease or clinically relevant QT prolongation within 6 months before providing informed consent/assent\n- 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× the 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)\n- Renal dysfunction as defined by an estimated glomerular filtration rate <60 mL/min/1.73 m2 (bedside Schwartz equation)\n- Nonfasting triglycerides >440 mg/dL (5 mmol/L)\n- Active uncontrolled infection requiring systemic antimicrobial therapy\n- Subjects with known active hepatitis B or hepatitis C virus infection\n- Subjects with known HIV infection\n- 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\n- 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\n- Prior exposure to gene therapy, or bone marrow or stem cell transplantation\n- 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\n- Receiving products that are strong inhibitors of cytochrome P450 (CYP)3A4/5 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\n- Receiving anabolic steroids, including testosterone preparations, that have not been stopped for at least 28 days before randomization\n- 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 FD&C Blue #2], Opadry® II White [hypromellose, titanium dioxide, lactose monohydrate, and triacetin], and magnesium stearate)\n- 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: • Subjects who are institutionalized by regulatory or court order • Subjects 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)\n- Receiving a pyruvate kinase activator that has not been stopped for ≥52 weeks before providing informed consent/assent"}

Primary endpoints

• {"endpoint_text":"- Transfusion reduction response (TRR), defined as achievement of a ≥33% reduction in the total red blood cell (RBC) transfusion volume from Week 9 through Week 32 of the Double-blind Period normalized by weight and actual study drug duration compared with the historical transfusion volume standardized by weight and to 24 weeks","definition_or_measurement_approach":"Achievement of a ≥33% reduction in the total RBC transfusion volume from Week 9 through Week 32 of the Double-blind Period, normalized by weight and actual study drug duration, compared with the historical transfusion volume standardized by weight and to 24 weeks."}

Netherlands

Earliest CTIS Part Ii Submission Date

29-07-2024

Latest Decision Or Authorization Date

17-11-2025

Processing Time Days

476

Number Of Sites

0

Number Of Participants

3

Spain

Earliest CTIS Part Ii Submission Date

29-07-2024

Latest Decision Or Authorization Date

17-11-2025

Processing Time Days

476

Number Of Sites

2

Number Of Participants

2

Czechia

Earliest CTIS Part Ii Submission Date

29-07-2024

Latest Decision Or Authorization Date

19-11-2025

Processing Time Days

478

Number Of Sites

1

Number Of Participants

2

Denmark

Earliest CTIS Part Ii Submission Date

29-07-2024

Latest Decision Or Authorization Date

19-11-2025

Processing Time Days

478

Number Of Sites

2

Number Of Participants

4

Primary sponsor

Full Name

Agios Pharmaceuticals Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Icon Clinical Research Limited

Responsibilities

duty code 4 (listed in sponsor duties; explicit textual description not provided)

Name

Firma Clinical Research

Responsibilities

Home health nursing

Name

Fortrea Inc.

Responsibilities

IDMC (and other duties indicated by codes)

Third parties

• {"country":"United States","full_name":"FCB Health New York","duties_or_roles":"Patient recruitment materials","organisation_type":"Industry"}
• {"country":"United States","full_name":"Fortrea Inc.","duties_or_roles":"IDMC (and other duties indicated by codes 1,12,2)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Firma Clinical Research","duties_or_roles":"Home health nursing","organisation_type":"Industry"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"Duty code 4 (role not specified in file)","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Lumanity Patient Centered Outcomes LLC","duties_or_roles":"Exit Interview","organisation_type":"Industry"}
• {"country":"Belgium","full_name":"AAC/Proximus","duties_or_roles":"24 Hour Medical support Coverage","organisation_type":"Industry"}
• {"country":"Germany","full_name":"Centogene GmbH","duties_or_roles":"Targeted Genotyping","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"QPS LLC","duties_or_roles":"Pharmacokinetics, pharmacodynamics","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Endpoint Clinical Inc.","duties_or_roles":"IVRS – treatment randomisation","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Intrinsic Lifesciences LLC","duties_or_roles":"Exploratory biomarkers","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Almac Clinical Technologies LLC","duties_or_roles":"Drug depot; Investigational Product Supply","organisation_type":"Industry"}
• {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"Medical image","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Medidata Solutions","duties_or_roles":"ePRO, eConsent (and additional duties coded as 7)","organisation_type":"Health care"}