Extension Study of AG-348 in Adult Participants With Pyruvate Kinase Deficiency Previously Enrolled in AG-348-006 or AG348-C-007

Agios Pharmaceuticals

Status and phase: Completed; Phase 3

Conditions: Pyruvate Kinase Deficiency

Treatments: Drug: Mitapivat

Study type: Interventional

Funder types: Industry

Identifiers

NCT03853798

2018-003459-39 (EudraCT Number)

AG348-C-011

Details and patient eligibility

About

This is an open-label, multicenter, extension study to evaluate the long-term safety, tolerability, and efficacy of treatment with mitapivat in participants who were previously enrolled in Study AG348-C-006 or Study AG348-C-007.

Enrollment: 90 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Be willing and able to comply with study visits and procedures.
• Have signed written informed consent prior to participating in this extension study.
• Have completed either antecedent study AG348-C-006 or AG348-C-007 through the Part 2 Week 24 Visit.
• Cohorts 2 and 3: Have demonstrated clinical benefit from mitapivat treatment in the antecedent study, in the opinion of the Investigator.
• For women of reproductive potential, have a negative pregnancy test during screening of this extension study.
• For women of reproductive potential as well as men with partners who are women of reproductive potential, be abstinent 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 giving informed consent, during the study, and for 28 days following the last dose of study drug for women and 90 days following the last dose of study drug for men.

Exclusion criteria

• Have a significant medical condition (including clinically significant laboratory abnormality) that developed during his/her antecedent AG- 348 study that confers an unacceptable risk to participating in this extension study, that could confound the interpretation of the study data, and/or that compromises the ability of the participant to complete study visits and procedures.
• Are currently pregnant or breastfeeding.
• Have a splenectomy scheduled during the study treatment period.
• Meet the withdrawal criteria of his/her antecedent mitapivat study during screening of this extension study.
• Are currently receiving medications that are strong inhibitors of cytochrome P450 (CYP)3A4 that have not been stopped for a duration of at least 5 days or a time frame equivalent to 5 half-lives (whichever is longer) before start of study drug; or strong inducers of CYP3A4 that have not been stopped for a duration of at least 28 days or a time frame equivalent to 5 half-lives (whichever is longer) before start of study drug on this extension study.
• Have received anabolic steroids, including testosterone preparations, within 28 days prior to start of study drug on this extension study.
• Have received hematopoietic stimulating agents (eg, erythropoietins, granulocyte colony stimulating factors, thrombopoietins) within 28 days prior to start of study drug on this extension study.
• Have exposure to any investigational drug other than mitapivat, device, or procedure within 3 months prior to start of study drug on this extension study.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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90 participants in 3 patient groups

Cohort 1

Experimental group

Description:

Participants who received placebo in Study AG348-C-006 and met the eligibility criteria of this extension study were enrolled to receive mitapivat tablets, 5 milligrams (mg), twice daily (BID), administered orally, for 4 weeks as a starting dose, followed by two potential sequential dose level increases to 20 mg and 50 mg BID at Weeks 4 and 8 respectively as determined by the investigator based on safety and efficacy. The optimized dose for each participant was determined at Week 12, and participants then received that optimized dose for a period of 12 weeks (Weeks 13-24) as a fixed dose and from Week 25 to Week 193, until study withdrawal, or the study was closed.

Treatment:

Drug: Mitapivat

Cohort 2

Experimental group

Description:

Participants who received mitapivat at a dose of 5 mg, 20 mg, or 50 mg, BID, in the fixed dose period of Study AG348-C-006 and met the eligibility criteria of this extension study continued to receive the same mitapivat dose up to Week 193 or until study withdrawal, or the study was closed.

Treatment:

Drug: Mitapivat

Cohort 3

Experimental group

Description:

Participants who received mitapivat at a dose of 5 mg, 20 mg, or 50 mg, BID, in the fixed dose period of Study AG348-C-007 and met the eligibility criteria of this extension study continued to receive the same mitapivat dose up to Week 193 or until study withdrawal, or the study was closed.

Treatment:

Drug: Mitapivat