An Open-Label, Multicenter, Extension Study of AG-348 in Adult Subjects With Pyruvate Kinase Deficiency Previously Enrolled in AG-348 Studies

JRCT ID: jRCT2031210513

Registered date:25/12/2021

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Pyruvate Kinase Deficiency
• Date of first enrollment: 30/10/2019
• Target sample size: 8
• Countries of recruitment: United States,Japan,Canada,Japan,France,Japan,Germany,Japan,the Netherlands,Japan,Italy,Japan,Spain,Japan,United Kingdom,Japan,Denmark,Japan,Ireland,Japan,South Krea,Japan,Brazil,Japan,Switzeralnd,Japan,Turkey,Japan,Thailand,Japan
• Study type: Interventional
• Intervention(s): Investigational drug AG348 tablets for oral administration

Outcome(s)

Primary Outcome

- Type, incidence, severity, and relationship to study drug of treatment-emergent adverse events (TEAEs); serious adverse events (SAEs); adverse events of special interest (AESIs); and TEAEs leading to dose reduction, treatment interruption, and treatment discontinuation
- Changes from baseline in clinical laboratory tests (ie, serum chemistry, liver function tests [LFTs], hematology, lipids, sex steroids, coagulation, urinalysis), physical examination (PE) findings, bone mineral density T- and Z-scores (total hip, femoral neck, and lumbar spine), vital signs, and 12-lead electrocardiogram (ECG) data

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

1. Have provided signed written informed consent prior to participating in this extension study.
2. Have completed the antecedent AG-348 study (ie, through the Part 2 Week 24 Visit of Study AG348-C-006 or AG348-C-007).
3. Cohorts 2 and 3: Have demonstrated clinical benefit from AG-348 treatment in the antecedent study, in the opinion of the Investigator.
4. For women of reproductive potential, have a negative local serum or urine pregnancy test on Screening/Day 1 of this extension study. Women of reproductive potential are defined as sexually mature women who have not undergone a hysterectomy, bilateral oophorectomy, or tubal occlusion; or who have not been naturally postmenopausal (ie, who have not menstruated at all for at least the preceding 12 months prior to Screening/Day 1 of this extension study and have an elevated follicle-stimulating hormone [FSH] level indicative of menopause on Screening/Day 1 of this extension study or at Screening of the antecedent study). If the result from FSH testing conducted on Screening/Day 1 of this extension study is not available on the same day, the woman must have a negative local serum or urine pregnancy test on Screening/Day 1 and follow contraception requirements (Inclusion Criterion #5) until an elevated FSH result indicative of menopause is confirmed.
5. 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 (both men and women) following the last dose of study drug. A highly effective form of contraception is defined as combined (estrogen and progestin containing) hormonal contraceptives (oral or transdermal) known to be associated with inhibition of ovulation; progestin-only hormonal contraceptives (oral or implantable) known to be associated with inhibition of ovulation; intrauterine device; intrauterine hormone releasing system; bilateral tube occlusion; or vasectomized partner. The second form of contraception can include an acceptable barrier method, which includes male or female condoms with or without spermicide, and diaphragm or sponge with spermicide. Women of reproductive potential using hormonal contraception as a highly effective form of contraception must also utilize an acceptable barrier method while enrolled in the study and for at least 28 days after their last dose of study drug.
6. Be willing and able to comply with study visits and procedures.

Exclude criteria

1. 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 subject to complete study visits and procedures.
2. Are currently pregnant or breastfeeding.
3. Have a splenectomy scheduled during the study treatment period.
4. Meet the withdrawal criteria of his/her antecedent AG-348 study at the Screening/Day 1 Visit of this study.
5. Are currently receiving medications that are strong inhibitors of cytochrome P450 (CYP)3A4, strong inducers of CYP3A4, strong inhibitors of P-glycoprotein (P-gp), or digoxin (a P-gp sensitive substrate medication) that have not been stopped for a duration of at least 5 days or a timeframe equivalent to 5 half-lives (whichever is longer) prior to Screening/Day 1 of this extension study.
6. Have received anabolic steroids, including testosterone preparations, within 28 days prior to Screening/Day 1 of this extension study.
7. Have received hematopoietic stimulating agents (eg, erythropoietins, granulocyte colony stimulating factors, thrombopoietins) within 28 days prior to Screening/Day 1 of this extension study.
8. Have exposure to any investigational drug other than AG-348, device, or procedure within 3 months prior to Screening/Day 1 of this extension study.

Related Information

• Primary Sponsor: Ide Shunta
• Secondary ID(s): NCT03853798