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

Phase 3

Recruiting

• Conditions: ack of Pyruvate Kinase enzyme/ Pyruvate Kinase Deficiency; Pyruvate kinase (PK) deficiency; 10038158

• Registration Number: NL-OMON52866
• Lead Sponsor: Agios Pharmaceuticals, Inc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 15 April 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: Not specified
• Target Recruitment: 6

Inclusion Criteria

Subjects must meet all of the following criteria to be eligible for inclusion
in this extension study:
1. Have provided signed written informed consent prior to participating in this
extension study.
2. Have completed the antecedent AG-348 study 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*:
a. In Cohort 1, have a negative local serum (human chorionic gonadotropin
[hCG]) pregnancy test during screening of this extension study.
b. In Cohort 2 or 3, have a negative local urine pregnancy test during
screening 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 of this extension study
and have an elevated follicle-stimulating hormone [FSH] level indicative of
menopause during screening of this extension study or at screening of the
antecedent study). If the result from FSH testing conducted during screening of
this extension study is not available on the same day, the woman must have a
negative local serum (hCG) or urine pregnancy test during screening 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 following the last dose of study drug for women and 90 days following
the last dose of study drug for men. A highly effective form of contraception
is defined as combined (estrogen and progestin containing) hormonal
contraceptives (oral, intravaginal, or transdermal) known to be associated with
inhibition of ovulation; progestin-only hormonal contraceptives (oral,
injectable, 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 cervical cap, 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.

Exclusion Criteria

Subjects who meet any of the following criteria will not be enrolled in this
extension study:
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 during
screening of this extension study.
Withdrawal criteria of the antecedent AG-348 studies are as follows:
• Withdrawal of consent
• Development of an intercurrent medical condition that precludes further
participation in the study
• Subject requires use of a prohibited concomitant medication
• Investigator decision
• Persistent nonadherence to protocol requirements
• Pregnancy
• Lost to follow-up
5. Are currently receiving medications that are strong inhibitors of CYP3A4
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.
6. Have received anabolic steroids, including testosterone preparations, within
28 days prior to start of study drug on this extension study.
7. 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.
8. Have exposure to any investigational drug other than AG-348, device, or
procedure within 3 months prior to start of study drug on this extension study.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Primary:<br /><br>• To evaluate the long-term safety and tolerability of AG-348</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>Secondary:<br /><br>• To evaluate the long-term efficacy of AG-348<br /><br>• To evaluate the efficacy of AG-348 in increasing hemoglobin (Hb)<br /><br>concentrations in subjects who previously received placebo in Study AG348-C-006<br /><br>(Cohort 1 only)<br /><br>• To determine the effect of AG-348 on health-related quality of life (HRQoL)<br /><br>using patient reported outcomes (PROs)<br /><br>• To evaluate the pharmacokinetics of AG-348 after oral administration (Cohort<br /><br>1 only)<br /><br>• To evaluate the relationship between AG-348 pharmacokinetics and safety<br /><br>parameters (Cohort 1 only)</p><br>