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- 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\n- 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.\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- 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\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"}

Primary endpoints

• {"endpoint_text":"- Hb response, defined as a ≥1.5 g/dL (0.93 mmol/L) increase in Hb concentration from baseline that is sustained at 2 or more scheduled assessments at Weeks 12, 16, and 20 during the Double-blind Period. The individual subject’s baseline Hb concentration is defined as the average of all available Hb concentrations collected for that subject during the Screening Period up to the first dose of study drug","definition_or_measurement_approach":"Hb response defined as ≥1.5 g/dL increase from baseline sustained at ≥2 scheduled assessments at Weeks 12, 16, and 20 during the Double-blind Period. Baseline Hb is the average of all available Hb concentrations collected during the Screening Period up to first dose."}

Methods

• Patient recruitment materials (FCB Health New York) — provider of recruitment materials (no further detail provided in CTIS record).
• Home health nursing services (Firma Clinical Research) — listed as a sponsor duty.
• ePRO and eConsent (Medidata Solutions) — electronic patient-reported outcomes and electronic consent provision.
• IVRS – treatment randomisation (Endpoint Clinical Inc.) — interactive voice/web response system for randomisation.
• Targeted genotyping (Centogene GmbH) and central genotyping laboratory services for eligibility confirmation.

France

Latest Decision Or Authorization Date

16-07-2024

Number Of Sites

1

Number Of Participants

2

Germany

Latest Decision Or Authorization Date

29-07-2024

Number Of Sites

2

Number Of Participants

2

Italy

Latest Decision Or Authorization Date

28-08-2024

Number Of Sites

1

Number Of Participants

1

Spain

Latest Decision Or Authorization Date

16-07-2024

Number Of Sites

2

Number Of Participants

8

Netherlands

Latest Decision Or Authorization Date

09-07-2024

Number Of Sites

1

Number Of Participants

1

Primary sponsor

Full Name

Agios Pharmaceuticals Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Firma Clinical Research

Responsibilities

Home health nursing

Name

Icon Clinical Research Limited

Name

Almac Clinical Technologies LLC

Responsibilities

Drug depot; Investigational Product Supply

Third parties

• {"country":"United States","full_name":"Firma Clinical Research","duties_or_roles":"Home health nursing","organisation_type":"Industry"}
• {"country":"United States","full_name":"QPS LLC","duties_or_roles":"Pharmacokinetics, pharmacodynamics","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"FCB Health New York","duties_or_roles":"Patient recruitment materials","organisation_type":"Industry"}
• {"country":"United States","full_name":"Medidata Solutions","duties_or_roles":"ePRO, eConsent","organisation_type":"Health care"}
• {"country":"United States","full_name":"Endpoint Clinical Inc.","duties_or_roles":"IVRS – treatment randomisation","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":"Germany","full_name":"Centogene GmbH","duties_or_roles":"Targeted Genotyping","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Lumanity Patient Centered Outcomes LLC","duties_or_roles":"Exit Interview","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Intrinsic Lifesciences LLC","duties_or_roles":"Exploratory biomarkers","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Fortrea Inc.","duties_or_roles":"IDMC","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"AAC/Proximus","duties_or_roles":"24 Hour Medical support Coverage","organisation_type":"Industry"}
• {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"Medical image","organisation_type":"Laboratory/Research/Testing facility"}