A Study of AG-348 in Adult Participants With Pyruvate Kin... | NCT02476916

ID	Type	Description	Link
2015-000484-13	EudraCT Number

Label	Type	Description	Intervention Names
AG-348 50 mg BID	Experimental	Participants with Pyruvate Kinase (PK) deficiency will receive AG-348, 50 milligrams (mg), as initial dose, twice daily (BID) for 24 weeks (Core Period). Participants will be assigned to initial doses, however, over the course of the Core Period they will be treated across a range of doses due to treatment emergent adverse events (AEs) and hemoglobin (Hb) levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who have safely tolerated AG-348 and demonstrating clinical activity in response to AG-348 will be rolled over to the Extension Period. During the extension period, participants will continue to receive AG-348 50 mg, BID, for up to 102 months.	Drug: AG-348
AG-348 300 mg BID	Experimental	Participants with PK deficiency will receive AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants will be assigned to initial doses, however, over the course of the Core Period they will be treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who have safely tolerated AG-348 and demonstrating clinical activity in response to AG-348 will be rolled over to the Extension Period. During the extension period, participants will continue to receive AG-348 300 mg, BID, up to 102 months.	Drug: AG-348

Name	Type	Description	Arm Group Labels	Other Names
AG-348	Drug	Tablets	AG-348 300 mg BID AG-348 50 mg BID

Measure	Description	Time Frame
Percentage of Participants Experiencing at Least One Adverse Event (AEs) in the Core Period	An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered study drug-related.	Up to Week 24

Measure	Description	Time Frame
Percentage of Participants Experiencing at Least One AE up to Month 102	An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered study drug-related. Safety data for cumulative period (Core period and Extension period) has been reported in this outcome measure.	Up to Month 102

Facility	Status	City	State	ZIP	Country	Contacts
Stanford University		Palo Alto	California	94304	United States
Boston Children's Hospital

PubMed Identifier	Type	Citation	Retractions
31483964	Result	Grace RF, Rose C, Layton DM, Galacteros F, Barcellini W, Morton DH, van Beers EJ, Yaish H, Ravindranath Y, Kuo KHM, Sheth S, Kwiatkowski JL, Barbier AJ, Bodie S, Silver B, Hua L, Kung C, Hawkins P, Jouvin MH, Bowden C, Glader B. Safety and Efficacy of Mitapivat in Pyruvate Kinase Deficiency. N Engl J Med. 2019 Sep 5;381(10):933-944. doi: 10.1056/NEJMoa1902678.
36594181

ID	Title	Description
FG000	AG-348 50 mg BID	Participants with Pyruvate Kinase (PK) deficiency received AG-348, 50 mg, as initial dose, twice daily (BID) for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent Adverse Events (AEs) and Hemoglobin (Hb) levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were rolled over to the Extension Period. During the extension period, participants continued to receive AG-348 50 mg, BID, up to 102 months.

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Jul 26, 2022	Mar 20, 2026

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percentage of Participants Experiencing at Least One Adverse Event (AEs) in the Core Period

An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered study drug-related.

The Safety Analysis Set included all participants who had received at least one dose of study drug.

Posted

Number

percentage of participants

Up to Week 24

ID	Title	Description
OG000	AG-348 50 mg BID	Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
OG001	AG-348 300 mg BID	Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.

Units	Counts
Participants	OG00027 OG00125

Title

Denominators

Categories

Title	Measurements
	OG00096.3 OG001100.0

Secondary

Percentage of Participants Experiencing at Least One AE up to Month 102

An AE was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered study drug-related. Safety data for cumulative period (Core period and Extension period) has been reported in this outcome measure.

The Safety Analysis Set included all participants who had received at least one dose of study drug.

Posted

Number

percentage of participants

Up to Month 102

ID	Title	Description
OG000	AG-348 50 mg BID	Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent adverse AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were rolled over to the Extension Period. During the extension period, participants continued to receive AG-348 50 mg, BID, up to 102 months.
OG001	AG-348 300 mg BID	Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were rolled over to the Extension Period. During the extension period, participants continued to receive AG-348 300 mg, BID, up to 102 months.

Secondary

Change From Baseline in Hemoglobin (Hb) Value at Week 24

Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Increased Hb values indicate improvement.

The Full Analysis Set included all randomized participants. Number analyzed is the number of participants with evaluable data at the given time-point.

Posted

Mean

Standard Deviation

grams per liter (g/L)

Baseline and Week 24

ID	Title	Description
OG000	AG-348 50 mg BID	Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
OG001	AG-348 300 mg BID	Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.

Secondary

Change From Baseline Hb Value up to Month 102

Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Increased Hb values indicate improvement.

The Full Analysis Set included all randomized participants. Overall number of participants analyzed is the number of participants with evaluable data for this outcome measure. Number analyzed is the number of participants with evaluable data at the given time-point.

Posted

Mean

Standard Deviation

g/L

Baseline, Months 12, 36, 60, 84, and 102

ID	Title	Description
OG000	AG-348 50 mg BID	Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were rolled over to the Extension Period. During the extension period, participants continued to receive AG-348 50 mg, BID, up to 102 months.
OG001	AG-348 300 mg BID	Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were rolled over to the Extension Period. During the extension period, participants continued to receive AG-348 300 mg, BID, up to 102 months.

Secondary

Change From Baseline in Hematocrit at Week 24

Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Increased hematocrit values indicate improvement.

The Full Analysis Set included all randomized participants. Number analyzed is the number of participants with evaluable data at the given time-point.

Posted

Mean

Standard Deviation

fraction of 1

Baseline and Week 24

ID	Title	Description
OG000	AG-348 50 mg BID	Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
OG001	AG-348 300 mg BID	Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.

Secondary

Change From Baseline in Hematocrit up to Month 102

Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Increased hematocrit values indicate improvement.

Posted

Mean

Standard Deviation

fraction of 1

Baseline, Months 12, 36, 60, 84, and 102

ID	Title	Description
OG000	AG-348 50 mg BID	Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were rolled over to the Extension Period. During the extension period, participants continued to receive AG-348 50 mg, BID, up to 102 months.
OG001	AG-348 300 mg BID	Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were rolled over to the Extension Period. During the extension period, participants continued to receive AG-348 300 mg, BID, up to 102 months.

Secondary

Change From Baseline in Reticulocyte Count at Week 24

Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased reticulocyte count values indicate improvement.

The Full Analysis Set included all randomized participants. Number analyzed is the number of participants with evaluable data at the given time-point.

Posted

Mean

Standard Deviation

cells * 10^9/liter

Baseline and Week 24

ID	Title	Description
OG000	AG-348 50 mg BID	Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
OG001	AG-348 300 mg BID	Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.

Secondary

Change From Baseline in Reticulocyte Count up to Month 102

Change (absolute change) from baseline will be calculated as post-baseline value - baseline value. Decreased reticulocyte count values indicate improvement.

Posted

Mean

Standard Deviation

cells * 10^9/liter

Baseline, Months 12, 36, 60, 84, and 102

ID	Title	Description
OG000	AG-348 50 mg BID	Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were rolled over to the Extension Period. During the extension period, participants continued to receive AG-348 50 mg, BID, up to 102 months.
OG001	AG-348 300 mg BID	Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were rolled over to the Extension Period. During the extension period, participants continued to receive AG-348 300 mg, BID, up to 102 months.

Secondary

Change From Baseline in Haptoglobin at Week 24

Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Increased haptoglobin values indicate improvement.

The Full Analysis Set included all randomized participants. Overall number of participants analyzed is the number of participants with evaluable data. Number analyzed is the number of participants with evaluable data at the given time-point.

Posted

Mean

Standard Deviation

g/L

Baseline and Week 24

ID	Title	Description
OG000	AG-348 50 mg BID	Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
OG001	AG-348 300 mg BID	Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.

Secondary

Change From Baseline in Haptoglobin up to Month 102

Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Increased haptoglobin values indicate improvement.

Posted

Mean

Standard Deviation

g/L

Baseline, Months 12, 36, 60, 84, and 102

ID	Title	Description
OG000	AG-348 50 mg BID	Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were rolled over to the Extension Period. During the extension period, participants continued to receive AG-348 50 mg, BID, up to 102 months.
OG001	AG-348 300 mg BID	Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were rolled over to the Extension Period. During the extension period, participants continued to receive AG-348 300 mg, BID, up to 102 months.

Secondary

Change From Baseline in Carboxyhemoglobin (COHb) at Week 24

Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased COHb values indicate improvement.

The Full Analysis Set included all participants who were randomized. Overall number of participants analyzed is the number of participants with evaluable data. Number analyzed is the number of participants with evaluable data at the given time-point.

Posted

Mean

Standard Deviation

percentage Hb bound to CO

Baseline and Week 24

ID	Title	Description
OG000	AG-348 50 mg BID	Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
OG001	AG-348 300 mg BID	Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.

Secondary

Change From Baseline in COHb up to Month 30

Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased COHb values indicate improvement.

Posted

Mean

Standard Deviation

percentage Hb bound to CO

Baseline, Months 12, 18, 24, and 30

ID	Title	Description
OG000	AG-348 50 mg BID	Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were rolled over to the Extension Period. During the extension period, participants continued to receive AG-348 50 mg, BID, up to 102 months.
OG001	AG-348 300 mg BID	Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were rolled over to the Extension Period. During the extension period, participants continued to receive AG-348 300 mg, BID, up to 102 months.

Secondary

Change From Baseline in Lactate Dehydrogenase (LDH) at Week 24

Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased LDH values indicate improvement.

The Full Analysis Set included all randomized participants. Number analyzed is the number of participants with evaluable data at the given time-point.

Posted

Mean

Standard Deviation

units per liter (U/L)

Baseline and Week 24

ID	Title	Description
OG000	AG-348 50 mg BID	Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
OG001	AG-348 300 mg BID	Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.

Secondary

Change From Baseline in LDH up to Month 30

Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased LDH values indicate improvement.

Posted

Mean

Standard Deviation

U/L

Baseline, Months 12, 18, 24, and 30

ID	Title	Description
OG000	AG-348 50 mg BID	Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were rolled over to the Extension Period. During the extension period, participants continued to receive AG-348 50 mg, BID, up to 102 months.
OG001	AG-348 300 mg BID	Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were rolled over to the Extension Period. During the extension period, participants continued to receive AG-348 300 mg, BID, up to 102 months.

Secondary

Change From Baseline in Total Bilirubin at Week 24

Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased total bilirubin values indicate improvement.

The Full Analysis Set included all randomized participants. Number analyzed is the number of participants with evaluable data at the given time-point.

Posted

Mean

Standard Deviation

micromole per liter (umol/L)

Baseline and Week 24

ID	Title	Description
OG000	AG-348 50 mg BID	Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
OG001	AG-348 300 mg BID	Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.

Secondary

Change From Baseline in Total Bilirubin up to Month 102

Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased total bilirubin values indicate improvement.

Posted

Mean

Standard Deviation

umol/L

Baseline, Months 12, 36, 60, 84, and 102

ID	Title	Description
OG000	AG-348 50 mg BID	Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were rolled over to the Extension Period. During the extension period, participants continued to receive AG-348 50 mg, BID, up to 102 months.
OG001	AG-348 300 mg BID	Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were rolled over to the Extension Period. During the extension period, participants continued to receive AG-348 300 mg, BID, up to 102 months.

Secondary

Change From Baseline in Indirect Bilirubin at Week 24

Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased indirect bilirubin values indicate improvement.

The Full Analysis Set included all randomized participants. Number analyzed is the number of participants with evaluable data at the given time-point.

Posted

Mean

Standard Deviation

umol/L

Baseline and Week 24

ID	Title	Description
OG000	AG-348 50 mg BID	Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
OG001	AG-348 300 mg BID	Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.

Secondary

Change From Baseline in Indirect Bilirubin up to Month 102

Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased indirect bilirubin values indicate improvement.

Posted

Mean

Standard Deviation

umol/L

Baseline, Months 12, 36, 60, 84, and 102

ID	Title	Description
OG000	AG-348 50 mg BID	Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were rolled over to the Extension Period. During the extension period, participants continued to receive AG-348 50 mg, BID, up to 102 months.
OG001	AG-348 300 mg BID	Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were rolled over to the Extension Period. During the extension period, participants continued to receive AG-348 300 mg, BID, up to 102 months.

Secondary

Change From Baseline in Erythropoietin (EPO) at Week 24

Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased EPO values indicate improvement.

The Full Analysis Set included all randomized participants. Number analyzed is the number of participants with evaluable data at the given time-point.

Posted

Mean

Standard Deviation

international units per liter (IU/L)

Baseline and Week 24

ID	Title	Description
OG000	AG-348 50 mg BID	Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
OG001	AG-348 300 mg BID	Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.

Secondary

Change From Baseline in (EPO) up to Month 30

Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased EPO values indicate improvement.

Posted

Mean

Standard Deviation

IU/L

Baseline, Months 12, 18, 24, and 30

ID	Title	Description
OG000	AG-348 50 mg BID	Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were rolled over to the Extension Period. During the extension period, participants continued to receive AG-348 50 mg, BID, up to 102 months.
OG001	AG-348 300 mg BID	Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were rolled over to the Extension Period. During the extension period, participants continued to receive AG-348 300 mg, BID, up to 102 months.

Secondary

Change From Baseline in Hepcidin at Week 24

Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased hepcidin values indicate improvement.

Posted

Mean

Standard Deviation

nanograms per liter (ng/L)

Baseline and Week 24

ID	Title	Description
OG000	AG-348 50 mg BID	Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
OG001	AG-348 300 mg BID	Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.

Secondary

Change From Baseline in Hepcidin up to Month 30

Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased hepcidin values indicate improvement.

Posted

Mean

Standard Deviation

ng/L

Baseline, Months 12, 18, 24, and 30

ID	Title	Description
OG000	AG-348 50 mg BID	Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were rolled over to the Extension Period. During the extension period, participants continued to receive AG-348 50 mg, BID, up to 102 months.
OG001	AG-348 300 mg BID	Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were rolled over to the Extension Period. During the extension period, participants continued to receive AG-348 300 mg, BID, up to 102 months.

Secondary

Change From Baseline in Ferritin at Week 24

Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased ferritin values indicate improvement.

The Full Analysis Set included all randomized participants. Number analyzed is the number of participants with evaluable data at the given time-point.

Posted

Mean

Standard Deviation

micrograms per liter (ug/L)

Baseline and Week 24

ID	Title	Description
OG000	AG-348 50 mg BID	Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
OG001	AG-348 300 mg BID	Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.

Secondary

Change From Baseline in Ferritin up to Month 102

Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased ferritin values indicate improvement.

Posted

Mean

Standard Deviation

ug/L

Baseline, Months 12, 36, 60, 84, and 102

ID	Title	Description
OG000	AG-348 50 mg BID	Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were rolled over to the Extension Period. During the extension period, participants continued to receive AG-348 50 mg, BID, up to 102 months.
OG001	AG-348 300 mg BID	Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were rolled over to the Extension Period. During the extension period, participants continued to receive AG-348 300 mg, BID, up to 102 months.

Secondary

Change From Baseline in Transferrin Saturation at Week 24

Transferrin saturation is the ratio of serum iron to iron-binding capacity. Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased transferrin saturation values indicate improvement.

Posted

Mean

Standard Deviation

fraction of 1

Baseline and Week 24

ID	Title	Description
OG000	AG-348 50 mg BID	Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
OG001	AG-348 300 mg BID	Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.

Secondary

Change From Baseline in Transferrin Saturation up to Month 102

Posted

Mean

Standard Deviation

fraction of 1

Baseline, Months 12, 36, 60, 84, and 102

ID	Title	Description
OG000	AG-348 50 mg BID	Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were rolled over to the Extension Period. During the extension period, participants continued to receive AG-348 50 mg, BID, up to 102 months.
OG001	AG-348 300 mg BID	Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were rolled over to the Extension Period. During the extension period, participants continued to receive AG-348 300 mg, BID, up to 102 months.

Secondary

Area Under the Concentration-time Curve From Time Zero to the Last Non-zero Concentration (AUC0-t) for AG-348 and Its Metabolite AGI-8702

Participants with pre-dose concentrations on Day 1 were excluded from the pharmacokinetics analysis, if any.

The Pharmacokinetic Analysis Set included all participants from Core Period, without major protocol violation, who were enrolled and received any dose of study treatment, with sufficient plasma sample or whole blood data to assess pharmacokinetic parameters. Number analyzed is the number of participants with evaluable data at the given time-point.

Posted

Geometric Mean

Geometric Coefficient of Variation

nanograms*hours per milliliter(hr*ng/mL)

pre-dose, 0.5, 1, 2, 4, 8, 12 hours post-dose Day 1 and pre-dose, 0.5, 1, 2, 4, 8 hours post-dose Day 15

ID	Title	Description
OG000	AG-348 50 mg BID	Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
OG001	AG-348 300 mg BID

Secondary

Maximum Plasma Concentration (Cmax) for AG-348 and Its Metabolite AGI-8702

Participants with pre-dose concentrations on Day 1 were excluded from the pharmacokinetics analysis, if any.

Posted

Geometric Mean

Geometric Coefficient of Variation

nanograms per milliliter (ng/mL)

pre-dose, 0.5, 1, 2, 4, 8, 12 hours post-dose Day 1 and pre-dose, 0.5, 1, 2, 4, 8 hours post-dose Day 15

ID	Title	Description
OG000	AG-348 50 mg BID	Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
OG001	AG-348 300 mg

Secondary

Time to Reach Peak Plasma Concentration (Tmax) for AG-348 and Its Metabolite AGI-8702

Participants with pre-dose concentrations on Day 1 were excluded from the pharmacokinetics analysis, if any.

Posted

Median

Full Range

hour (hr)

pre-dose, 0.5, 1, 2, 4, 8, 12 hours post-dose Day 1 and pre-dose, 0.5, 1, 2, 4, 8 hours post-dose Day 15

ID	Title	Description
OG000	AG-348 50 mg BID	Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
OG001	AG-348 300 mg BID	Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.

Secondary

Apparent Clearance at Steady-State (Clss/F) for AG-348 and Its Metabolite AGI-8702

Participants with pre-dose concentrations on Day 1 were excluded from the pharmacokinetics analysis, if any.

Posted

Geometric Mean

Geometric Coefficient of Variation

liter per hour (L/hr)

pre-dose, 0.5, 1, 2, 4, 8 hours post-dose Day 15

ID	Title	Description
OG000	AG-348 50 mg BID	Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
OG001	AG-348 300 mg BID	Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.

Secondary

Maximum Change From Baseline Response Value Over 12 Hours Post-dose (BRmax) for Adenosine Triphosphate (ATP)

Pre-dose concentration observed on Day 1 was used as Baseline for calculation of change from baseline.

The Pharmacodynamic (PD) Analysis Set included all participants from Core Period, without major protocol violation, who were enrolled and received any dose of study treatment, with sufficient plasma sample or whole blood data to assess PD parameters. Overall number of participants analyzed is the number of participants with evaluable data at the given time-point.

Posted

Mean

Standard Deviation

microgram per milliliter (µg/mL)

pre-dose, 0.5, 1, 2, 4, 8, 12 hours post-dose Day 1

ID	Title	Description
OG000	AG-348 50 mg BID	Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
OG001	AG-348 300 mg BID	Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.

Secondary

Maximum Change From Baseline Response Value Over 8 Hours Post-dose at Steady State (BRmax ss) for ATP

Pre-dose concentration observed on Day 1 was used as Baseline for calculation of change from baseline.

The PD Analysis Set included all participants from Core Period, without major protocol violation, who were enrolled and received any dose of study treatment, with sufficient plasma sample or whole blood data to assess PD parameters. Overall number of participants analyzed is the number of participants with evaluable data at the given time-point.

Posted

Mean

Standard Deviation

µg/mL

pre-dose, 0.5, 1, 2, 4, 8 hours post-dose Day 15

ID	Title	Description
OG000	AG-348 50 mg BID	Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
OG001	AG-348 300 mg	Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.

Secondary

BRmax for 2,3 - Diphosphoglycerate (2,3-DPG)

Pre-dose concentration observed on Day 1 was used as Baseline for calculation of change from baseline.

Posted

Mean

Standard Deviation

µg/mL

pre-dose, 0.5, 1, 2, 4, 8, 12 hours post-dose Day 1

ID	Title	Description
OG000	AG-348 50 mg BID	Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
OG001	AG-348 300 mg BID	Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.

Secondary

BRmax ss for 2,3-DPG

Pre-dose concentration observed on Day 1 was used as Baseline for calculation of change from baseline.

Posted

Mean

Standard Deviation

µg/mL

pre-dose, 0.5, 1, 2, 4, 8 hours post-dose Day 15

ID	Title	Description
OG000	AG-348 50 mg BID	Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.
OG001	AG-348 300 mg	Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were potentially eligible to immediately roll over to the Extension Period for continued treatment. If participants chose not to enroll, they were followed up to four weeks after the last dose of AG-348.

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Pharyngitis	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0001 affected27 at risk EG0010 affected25 at risk
Influenza	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0001 affected27 at risk EG0010 affected25 at risk
Haemolysis	Blood and lymphatic system disorders	MedDRA 27.1	Systematic Assessment	EG0000 affected27 at risk EG0011 affected25 at risk
Cholelithiasis	Hepatobiliary disorders	MedDRA 27.1	Systematic Assessment	EG0001 affected27 at risk EG0010 affected25 at risk
Hypertriglyceridaemia	Metabolism and nutrition disorders	MedDRA 27.1	Systematic Assessment	EG0000 affected27 at risk EG0011 affected25 at risk
Osteoporosis	Musculoskeletal and connective tissue disorders	MedDRA 27.1	Systematic Assessment	EG0001 affected27 at risk EG0010 affected25 at risk
Cellulitis	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0000 affected27 at risk EG0011 affected25 at risk
Gastroenteritis	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0000 affected27 at risk EG0011 affected25 at risk
Gastroenteritis clostridial	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0001 affected27 at risk EG0010 affected25 at risk
Gastroenteritis viral	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0001 affected27 at risk EG0010 affected25 at risk
Infected bite	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0000 affected27 at risk EG0011 affected25 at risk
Suspected COVID-19	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0001 affected27 at risk EG0010 affected25 at risk
Colitis	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG0001 affected27 at risk EG0010 affected25 at risk
Inguinal hernia	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG0000 affected27 at risk EG0011 affected25 at risk
Mesenteric vein thrombosis	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG0001 affected27 at risk EG0010 affected25 at risk
Fibula fracture	Injury, poisoning and procedural complications	MedDRA 27.1	Systematic Assessment	EG0001 affected27 at risk EG0010 affected25 at risk
Post procedural haemorrhage	Injury, poisoning and procedural complications	MedDRA 27.1	Systematic Assessment	EG0001 affected27 at risk EG0010 affected25 at risk
Tibia fracture	Injury, poisoning and procedural complications	MedDRA 27.1	Systematic Assessment	EG0001 affected27 at risk EG0010 affected25 at risk
Anxiety	Psychiatric disorders	MedDRA 27.1	Systematic Assessment	EG0001 affected27 at risk EG0010 affected25 at risk
Depression	Psychiatric disorders	MedDRA 27.1	Systematic Assessment	EG0001 affected27 at risk EG0010 affected25 at risk
Initial insomnia	Psychiatric disorders	MedDRA 27.1	Systematic Assessment	EG0000 affected27 at risk EG0011 affected25 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA 27.1	Systematic Assessment	EG0001 affected27 at risk EG0010 affected25 at risk
Nephrolithiasis	Renal and urinary disorders	MedDRA 27.1	Systematic Assessment	EG0001 affected27 at risk EG0010 affected25 at risk
Haemolytic anaemia	Blood and lymphatic system disorders	MedDRA 27.1	Systematic Assessment	EG0002 affected27 at risk EG0011 affected25 at risk
Fracture delayed union	Musculoskeletal and connective tissue disorders	MedDRA 27.1	Systematic Assessment	EG0001 affected27 at risk EG0010 affected25 at risk
Renal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 27.1	Systematic Assessment	EG0001 affected27 at risk EG0010 affected25 at risk
Headache	Nervous system disorders	MedDRA 27.1	Systematic Assessment	EG0001 affected27 at risk EG0010 affected25 at risk
Endometriosis	Reproductive system and breast disorders	MedDRA 27.1	Systematic Assessment	EG0000 affected27 at risk EG0011 affected25 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA 27.1	Systematic Assessment	EG0000 affected27 at risk EG0011 affected25 at risk

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Nausea	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG00012 affected27 at risk EG00112 affected25 at risk
Vomiting	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG0003 affected27 at risk EG0018 affected25 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG0006 affected27 at risk EG0016 affected25 at risk
Dyspepsia	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG0003 affected27 at risk EG0014 affected25 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG0002 affected27 at risk EG0015 affected25 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG0000 affected27 at risk EG0015 affected25 at risk
Headache	Nervous system disorders	MedDRA 27.1	Systematic Assessment	EG00013 affected27 at risk EG00115 affected25 at risk
Dizziness	Nervous system disorders	MedDRA 27.1	Systematic Assessment	EG0005 affected27 at risk EG0015 affected25 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 27.1	Systematic Assessment	EG0006 affected27 at risk EG0017 affected25 at risk
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 27.1	Systematic Assessment	EG0004 affected27 at risk EG0015 affected25 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	MedDRA 27.1	Systematic Assessment	EG0004 affected27 at risk EG0011 affected25 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA 27.1	Systematic Assessment	EG0001 affected27 at risk EG0016 affected25 at risk
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 27.1	Systematic Assessment	EG0002 affected27 at risk EG0013 affected25 at risk
Influenza	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0007 affected27 at risk EG0012 affected25 at risk
Gastroenteritis	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0003 affected27 at risk EG0014 affected25 at risk
Sinusitis	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0003 affected27 at risk EG0013 affected25 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0003 affected27 at risk EG0013 affected25 at risk
Insomnia	Psychiatric disorders	MedDRA 27.1	Systematic Assessment	EG0007 affected27 at risk EG00116 affected25 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA 27.1	Systematic Assessment	EG0004 affected27 at risk EG0015 affected25 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 27.1	Systematic Assessment	EG0006 affected27 at risk EG0015 affected25 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 27.1	Systematic Assessment	EG0004 affected27 at risk EG0012 affected25 at risk
Musculoskeletal chest pain	Musculoskeletal and connective tissue disorders	MedDRA 27.1	Systematic Assessment	EG0001 affected27 at risk EG0015 affected25 at risk
Fatigue	General disorders	MedDRA 27.1	Systematic Assessment	EG0007 affected27 at risk EG0018 affected25 at risk
Pyrexia	General disorders	MedDRA 27.1	Systematic Assessment	EG0001 affected27 at risk EG0019 affected25 at risk
Chest discomfort	General disorders	MedDRA 27.1	Systematic Assessment	EG0001 affected27 at risk EG0016 affected25 at risk
Asthenia	General disorders	MedDRA 27.1	Systematic Assessment	EG0004 affected27 at risk EG0014 affected25 at risk
Non-cardiac chest pain	General disorders	MedDRA 27.1	Systematic Assessment	EG0000 affected27 at risk EG0013 affected25 at risk
Night sweats	Skin and subcutaneous tissue disorders	MedDRA 27.1	Systematic Assessment	EG0000 affected27 at risk EG0014 affected25 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA 27.1	Systematic Assessment	EG0001 affected27 at risk EG0014 affected25 at risk
Skin ulcer	Skin and subcutaneous tissue disorders	MedDRA 27.1	Systematic Assessment	EG0000 affected27 at risk EG0013 affected25 at risk
Hot flush	Vascular disorders	MedDRA 27.1	Systematic Assessment	EG0002 affected27 at risk EG0017 affected25 at risk
Flushing	Vascular disorders	MedDRA 27.1	Systematic Assessment	EG0002 affected27 at risk EG0012 affected25 at risk
Dysmenorrhoea	Reproductive system and breast disorders	MedDRA 27.1	Systematic Assessment	EG0003 affected27 at risk EG0014 affected25 at risk
Hypertriglyceridaemia	Metabolism and nutrition disorders	MedDRA 27.1	Systematic Assessment	EG0005 affected27 at risk EG0014 affected25 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA 27.1	Systematic Assessment	EG0001 affected27 at risk EG0012 affected25 at risk
Palpitations	Cardiac disorders	MedDRA 27.1	Systematic Assessment	EG0001 affected27 at risk EG0013 affected25 at risk
Gastrooesophageal reflux disease	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG0000 affected27 at risk EG0012 affected25 at risk
Nasopharyngitis	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG00011 affected27 at risk EG0019 affected25 at risk
COVID-19	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0003 affected27 at risk EG0015 affected25 at risk
Urinary tract infection	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0002 affected27 at risk EG0013 affected25 at risk
Gastroenteritis viral	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0000 affected27 at risk EG0012 affected25 at risk
Herpes simplex	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0000 affected27 at risk EG0012 affected25 at risk
Influenza like illness	General disorders	MedDRA 27.1	Systematic Assessment	EG0003 affected27 at risk EG0012 affected25 at risk
Pain	General disorders	MedDRA 27.1	Systematic Assessment	EG0000 affected27 at risk EG0012 affected25 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 27.1	Systematic Assessment	EG0003 affected27 at risk EG0012 affected25 at risk
Osteopenia	Musculoskeletal and connective tissue disorders	MedDRA 27.1	Systematic Assessment	EG0001 affected27 at risk EG0012 affected25 at risk
Tendonitis	Musculoskeletal and connective tissue disorders	MedDRA 27.1	Systematic Assessment	EG0000 affected27 at risk EG0013 affected25 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA 27.1	Systematic Assessment	EG0000 affected27 at risk EG0012 affected25 at risk
Paraesthesia	Nervous system disorders	MedDRA 27.1	Systematic Assessment	EG0002 affected27 at risk EG0014 affected25 at risk
Anosmia	Nervous system disorders	MedDRA 27.1	Systematic Assessment	EG0002 affected27 at risk EG0010 affected25 at risk
Alanine aminotransferase increased	Investigations	MedDRA 27.1	Systematic Assessment	EG0003 affected27 at risk EG0014 affected25 at risk
Haemoglobin decreased	Investigations	MedDRA 27.1	Systematic Assessment	EG0003 affected27 at risk EG0012 affected25 at risk
Blood bilirubin increased	Investigations	MedDRA 27.1	Systematic Assessment	EG0002 affected27 at risk EG0011 affected25 at risk
Blood triglycerides increased	Investigations	MedDRA 27.1	Systematic Assessment	EG0002 affected27 at risk EG0010 affected25 at risk
Haemoglobin increased	Investigations	MedDRA 27.1	Systematic Assessment	EG0000 affected27 at risk EG0012 affected25 at risk
Initial insomnia	Psychiatric disorders	MedDRA 27.1	Systematic Assessment	EG0001 affected27 at risk EG0012 affected25 at risk
Middle insomnia	Psychiatric disorders	MedDRA 27.1	Systematic Assessment	EG0000 affected27 at risk EG0012 affected25 at risk
Dyspnoea exertional	Respiratory, thoracic and mediastinal disorders	MedDRA 27.1	Systematic Assessment	EG0000 affected27 at risk EG0013 affected25 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA 27.1	Systematic Assessment	EG0002 affected27 at risk EG0011 affected25 at risk
Lymphadenopathy	Blood and lymphatic system disorders	MedDRA 27.1	Systematic Assessment	EG0002 affected27 at risk EG0010 affected25 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 27.1	Systematic Assessment	EG0000 affected27 at risk EG0012 affected25 at risk
Pruritus	Skin and subcutaneous tissue disorders	MedDRA 27.1	Systematic Assessment	EG0001 affected27 at risk EG0014 affected25 at risk
Hypertension	Vascular disorders	MedDRA 27.1	Systematic Assessment	EG0000 affected27 at risk EG0012 affected25 at risk
Superficial vein thrombosis	Vascular disorders	MedDRA 27.1	Systematic Assessment	EG0002 affected27 at risk EG0010 affected25 at risk
Ocular icterus	Hepatobiliary disorders	MedDRA 27.1	Systematic Assessment	EG0002 affected27 at risk EG0011 affected25 at risk
Haemolysis	Blood and lymphatic system disorders	MedDRA 27.1	Systematic Assessment	EG0000 affected27 at risk EG0012 affected25 at risk
Dry Mouth	Gastrointestinal disorders	MedDRA 27.1	Systematic Assessment	EG0002 affected27 at risk EG0010 affected25 at risk
Chills	General disorders	MedDRA 27.1	Systematic Assessment	EG0002 affected27 at risk EG0011 affected25 at risk
Peripheral Swelling	General disorders	MedDRA 27.1	Systematic Assessment	EG0000 affected27 at risk EG0012 affected25 at risk
Rhinitis	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0001 affected27 at risk EG0012 affected25 at risk
Pharyngitis	Infections and infestations	MedDRA 27.1	Systematic Assessment	EG0000 affected27 at risk EG0012 affected25 at risk
Muscle Spasms	Musculoskeletal and connective tissue disorders	MedDRA 27.1	Systematic Assessment	EG0001 affected27 at risk EG0012 affected25 at risk
Limb Discomfort	Musculoskeletal and connective tissue disorders	MedDRA 27.1	Systematic Assessment	EG0000 affected27 at risk EG0012 affected25 at risk
Neck Pain	Musculoskeletal and connective tissue disorders	MedDRA 27.1	Systematic Assessment	EG0000 affected27 at risk EG0012 affected25 at risk
Taste Disorder	Nervous system disorders	MedDRA 27.1	Systematic Assessment	EG0000 affected27 at risk EG0012 affected25 at risk
Anxiety	Psychiatric disorders	MedDRA 27.1	Systematic Assessment	EG0001 affected27 at risk EG0012 affected25 at risk
Breast Enlargement	Reproductive system and breast disorders	MedDRA 27.1	Systematic Assessment	EG0000 affected27 at risk EG0012 affected25 at risk
Heavy menstrual bleeding	Reproductive system and breast disorders	MedDRA 27.1	Systematic Assessment	EG0000 affected27 at risk EG0012 affected25 at risk
Sneezing	Respiratory, thoracic and mediastinal disorders	MedDRA 27.1	Systematic Assessment	EG0002 affected27 at risk EG0010 affected25 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA 27.1	Systematic Assessment	EG0001 affected27 at risk EG0012 affected25 at risk
Dermatitis contact	Skin and subcutaneous tissue disorders	MedDRA 27.1	Systematic Assessment	EG0002 affected27 at risk EG0010 affected25 at risk
Tinnitus	Ear and labyrinth disorders	MedDRA 27.1	Systematic Assessment	EG0001 affected27 at risk EG0012 affected25 at risk
Ear congestion	Ear and labyrinth disorders	MedDRA 27.1	Systematic Assessment	EG0000 affected27 at risk EG0012 affected25 at risk
Ear pain	Ear and labyrinth disorders	MedDRA 27.1	Systematic Assessment	EG0000 affected27 at risk EG0012 affected25 at risk
Chromaturia	Renal and urinary disorders	MedDRA 27.1	Systematic Assessment	EG0000 affected27 at risk EG0013 affected25 at risk
Vision blurred	Eye disorders	MedDRA 27.1	Systematic Assessment	EG0000 affected27 at risk EG0012 affected25 at risk
Seasonal allergy	Immune system disorders	MedDRA 27.1	Systematic Assessment	EG0000 affected27 at risk EG0012 affected25 at risk
Scratch	Injury, poisoning and procedural complications	MedDRA 27.1	Systematic Assessment	EG0000 affected27 at risk EG0012 affected25 at risk
Aspartate aminotransferase increased	Investigations	MedDRA 27.1	Systematic Assessment	EG0002 affected27 at risk EG0012 affected25 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA 27.1	Systematic Assessment	EG0002 affected27 at risk EG0010 affected25 at risk
Skin lesion	Skin and subcutaneous tissue disorders	MedDRA 27.1	Systematic Assessment	EG0000 affected27 at risk EG0012 affected25 at risk

ID	Term
C564858	Pyruvate Kinase Deficiency of Red Cells
D000743	Anemia, Hemolytic

ID	Term
D000740	Anemia
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases

ID	Title	Description
BG000	AG-348 50 mg BID	Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were rolled over to the Extension Period. During the extension period, participants continued to receive AG-348 50 mg, BID, up to 102 months.
BG001	AG-348 300 mg BID	Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were rolled over to the Extension Period. During the extension period, participants continued to receive AG-348 300 mg, BID, up to 102 months.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	AG-348 50 mg BID (Core Period+ Extension Period)	Participants with PK deficiency received AG-348, 50 mg, as initial dose, BID, for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were rolled over to the Extension Period. During the extension period, participants continued to receive AG-348 50 mg, BID, up to 102 months.	0	27	12	27	27	27
EG001	AG-348 300 mg BID (Core Period + Extension Period)	Participants with PK deficiency received AG-348, 300 mg, as initial dose, BID, for 24 weeks (Core Period). Participants were assigned to initial doses, however, over the course of the Core Period were treated across a range of doses due to treatment emergent AEs and Hb levels exceeding mid-point of sex-adjusted ranges. At the Week 24 visit, Core Period participants who had safely tolerated AG-348 and demonstrated clinical activity in response to AG-348 were rolled over to the Extension Period. During the extension period, participants continued to receive AG-348 300 mg, BID, up to 102 months.	0	25	7	25	25	25