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A Study of AG-348 in Adult Participants With Pyruvate Kinase (PK) Deficiency

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ClinicalTrials.gov Identifier: NCT02476916
Recruitment Status : Active, not recruiting
First Posted : June 22, 2015
Results First Posted : June 11, 2020
Last Update Posted : June 8, 2021
Sponsor:
Information provided by (Responsible Party):
Agios Pharmaceuticals, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Pyruvate Kinase Deficiency
Intervention Drug: AG-348
Enrollment 52
Recruitment Details Participants were recruited in the core period of the study at 14 investigative sites in the 6 countries from 13 July 2015 to 14 July 2017 (data cut-off date). The core period is completed, and results of this period are reported. The extension period is ongoing.
Pre-assignment Details A total of 52 participants were enrolled in the Core Period of the study. Out of 52 participants, 9 discontinued during the core period, and 43 completed the core period. Out of these 43, 36 entered the extension period, and 7 did not enter the extension period and were followed up to 4 weeks after their last dose of AG-348 in the core study.
Arm/Group Title AG-348 50 mg BID AG-348 300 mg BID
Hide Arm/Group Description Participants with Pyruvate Kinase (PK) deficiency received AG-348, 50 milligrams (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 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. 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.
Period Title: Core Period
Started 27 25
Completed 21 22
Not Completed 6 3
Reason Not Completed
Adverse Event             2             2
Investigator decision             1             1
Withdrawal by Subject             3             0
Period Title: Extension Period
Started [1] 18 18
Completed 0 0
Not Completed 18 18
Reason Not Completed
Prematurely Discontinued Treatment             6             1
On Treatment             12             17
[1]
A total of 36 participants who had clinical activity and tolerated dose entered Extension Period.
Arm/Group Title AG-348 50 mg BID AG-348 300 mg BID Total
Hide Arm/Group Description 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. 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. Total of all reporting groups
Overall Number of Baseline Participants 27 25 52
Hide Baseline Analysis Population Description
The Safety Analysis Set included all participants who had received at least one dose of study drug.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 27 participants 25 participants 52 participants
30.7  (11.26) 37.7  (12.03) 34.1  (12.05)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 27 participants 25 participants 52 participants
Female
9
  33.3%
11
  44.0%
20
  38.5%
Male
18
  66.7%
14
  56.0%
32
  61.5%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 27 participants 25 participants 52 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
0
   0.0%
Not Hispanic or Latino
24
  88.9%
23
  92.0%
47
  90.4%
Unknown or Not Reported
3
  11.1%
2
   8.0%
5
   9.6%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 27 participants 25 participants 52 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
2
   7.4%
1
   4.0%
3
   5.8%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
White
22
  81.5%
21
  84.0%
43
  82.7%
More than one race
1
   3.7%
2
   8.0%
3
   5.8%
Unknown or Not Reported
2
   7.4%
1
   4.0%
3
   5.8%
1.Primary Outcome
Title Percentage of Participants Experiencing at Least One Adverse Event (AEs) in the Core Period
Hide Description 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.
Time Frame Up to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Analysis Set included all participants who had received at least one dose of study drug.
Arm/Group Title AG-348 50 mg BID AG-348 300 mg BID
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 27 25
Measure Type: Number
Unit of Measure: percentage of participants
96.3 100.0
2.Secondary Outcome
Title Change From Baseline in Hemoglobin (Hb) Value at Week 24
Hide Description Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Increased Hb values indicate improvement.
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The Efficacy Analysis Set included all participants who enrolled and received any study treatment for at least 3 weeks. Number analyzed is the number of participants with evaluable data at the given time-point.
Arm/Group Title AG-348 50 mg BID AG-348 300 mg BID
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 27 25
Mean (Standard Deviation)
Unit of Measure: grams per deciliter (g/dL)
Baseline Number Analyzed 27 participants 25 participants
9.243  (1.4757) 8.636  (1.1664)
Change at Week 24 Number Analyzed 23 participants 24 participants
1.205  (1.4181) 1.611  (1.7058)
3.Secondary Outcome
Title Change From Baseline in Hematocrit at Week 24
Hide Description Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Increased hematocrit values indicate improvement.
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Analysis Set included all participants who had received at least one dose of study drug. Number analyzed is the number of participants with evaluable data at the given time-point.
Arm/Group Title AG-348 50 mg BID AG-348 300 mg BID
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 27 25
Mean (Standard Deviation)
Unit of Measure: volume per volume (V/V)
Baseline Number Analyzed 27 participants 25 participants
0.289  (0.0470) 0.268  (0.0367)
Change at Week 24 Number Analyzed 23 participants 23 participants
0.033  (0.0414) 0.045  (0.0499)
4.Secondary Outcome
Title Change From Baseline in Reticulocyte Count at Week 24
Hide Description Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased reticulocyte count values indicate improvement.
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Analysis Set included all participants who had received at least one dose of study drug. Number analyzed is the number of participants with evaluable data at the given time-point.
Arm/Group Title AG-348 50 mg BID AG-348 300 mg BID
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 27 25
Mean (Standard Deviation)
Unit of Measure: cells * 10^9/liter
Baseline Number Analyzed 27 participants 25 participants
493.248  (234.2242) 549.436  (291.5301)
Change at Week 24 Number Analyzed 23 participants 23 participants
-99.248  (309.9473) -46.222  (351.9823)
5.Secondary Outcome
Title Change From Baseline in Haptoglobin at Week 24
Hide Description Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Increased haptoglobin values indicate improvement.
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Analysis Set included all participants who had received at least one dose of study drug. Number analyzed is the number of participants with evaluable data at the given time-point.
Arm/Group Title AG-348 50 mg BID AG-348 300 mg BID
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 27 25
Mean (Standard Deviation)
Unit of Measure: gram per liter (g/L)
Baseline Number Analyzed 24 participants 25 participants
0.246  (0.1474) 0.240  (0.2082)
Change at Week 24 Number Analyzed 18 participants 23 participants
0.128  (0.2845) 0.139  (0.2726)
6.Secondary Outcome
Title Change From Baseline in Carbon Monoxide at Week 24
Hide Description Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased carbon monoxide values indicate improvement.
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Analysis Set included all participants who had received at least one dose of study drug. Number analyzed is the number of participants with evaluable data at the given time-point.
Arm/Group Title AG-348 50 mg BID AG-348 300 mg BID
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 27 25
Mean (Standard Deviation)
Unit of Measure: percentage Hb bound to carbon monoxide
Baseline Number Analyzed 19 participants 20 participants
5.263  (1.7270) 6.200  (2.3079)
Change at Week 24 Number Analyzed 16 participants 17 participants
-1.063  (2.2940) -1.706  (3.2742)
7.Secondary Outcome
Title Change From Baseline in Lactate Dehydrogenase (LDH) at Week 24
Hide Description Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased LDH values indicate improvement.
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Analysis Set included all participants who had received at least one dose of study drug. Number analyzed is the number of participants with evaluable data at the given time-point.
Arm/Group Title AG-348 50 mg BID AG-348 300 mg BID
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 27 25
Mean (Standard Deviation)
Unit of Measure: units per liter (U/L)
Baseline Number Analyzed 27 participants 25 participants
282.074  (188.3558) 254.840  (122.3587)
Change at Week 24 Number Analyzed 24 participants 23 participants
-26.292  (145.3151) -8.913  (139.8509)
8.Secondary Outcome
Title Change From Baseline in Total Bilirubin at Week 24
Hide Description Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased total bilirubin values indicate improvement.
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Analysis Set included all participants who had received at least one dose of study drug. Number analyzed is the number of participants with evaluable data at the given time-point.
Arm/Group Title AG-348 50 mg BID AG-348 300 mg BID
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 27 25
Mean (Standard Deviation)
Unit of Measure: milligrams per deciliter (mg/dL)
Baseline Number Analyzed 27 participants 25 participants
5.152  (2.3407) 5.608  (3.4625)
Change at Week 24 Number Analyzed 24 participants 24 participants
-1.921  (1.9465) -3.017  (2.5848)
9.Secondary Outcome
Title Change From Baseline in Indirect Bilirubin at Week 24
Hide Description Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased indirect bilirubin values indicate improvement.
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Analysis Set included all participants who had received at least one dose of study drug. Number analyzed is the number of participants with evaluable data at the given time-point.
Arm/Group Title AG-348 50 mg BID AG-348 300 mg BID
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 27 25
Mean (Standard Deviation)
Unit of Measure: mg/dL
Baseline Number Analyzed 27 participants 25 participants
4.752  (2.3629) 5.208  (3.4272)
Change at Week 24 Number Analyzed 24 participants 22 participants
-1.967  (1.8318) -3.195  (2.5537)
10.Secondary Outcome
Title Change From Baseline in Erythropoietin (EPO) at Week 24
Hide Description Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased EPO values indicate improvement.
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Analysis Set included all participants who had received at least one dose of study drug. Number analyzed is the number of participants with evaluable data at the given time-point.
Arm/Group Title AG-348 50 mg BID AG-348 300 mg BID
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 27 25
Mean (Standard Deviation)
Unit of Measure: international units per liter (IU/L)
Baseline Number Analyzed 27 participants 25 participants
85.448  (159.4090) 60.900  (19.5188)
Change at Week 24 Number Analyzed 24 participants 24 participants
-7.738  (33.1934) -13.675  (26.5065)
11.Secondary Outcome
Title Change From Baseline in Hepcidin at Week 24
Hide Description Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased hepcidin values indicate improvement.
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Analysis Set included all participants who had received at least one dose of study drug. Number analyzed is the number of participants with evaluable data at the given time-point.
Arm/Group Title AG-348 50 mg BID AG-348 300 mg BID
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 27 25
Mean (Standard Deviation)
Unit of Measure: nanomoles per liter (nmol/L)
Baseline Number Analyzed 6 participants 4 participants
3.392  (3.4013) 4.988  (4.0416)
Change at Week 24 Number Analyzed 4 participants 3 participants
0.095  (1.4795) -2.310  (2.5061)
12.Secondary Outcome
Title Change From Baseline in Ferritin at Week 24
Hide Description Change (absolute change) from baseline was calculated as post-baseline value - baseline value. Decreased ferritin values indicate improvement.
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Analysis Set included all participants who had received at least one dose of study drug. Number analyzed is the number of participants with evaluable data at the given time-point.
Arm/Group Title AG-348 50 mg BID AG-348 300 mg BID
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 27 25
Mean (Standard Deviation)
Unit of Measure: ng/mL
Baseline Number Analyzed 27 participants 25 participants
860.852  (682.6346) 859.680  (490.2734)
Change at Week 24 Number Analyzed 24 participants 23 participants
68.875  (388.1866) -37.870  (308.0896)
13.Secondary Outcome
Title Change From Baseline in Transferrin Saturation at Week 24
Hide Description 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.
Time Frame Baseline and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
The Safety Analysis Set included all participants who had received at least one dose of study drug. Number analyzed is the number of participants with evaluable data at the given time-point.
Arm/Group Title AG-348 50 mg BID AG-348 300 mg BID
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 27 25
Mean (Standard Deviation)
Unit of Measure: percentage of saturation
Baseline Number Analyzed 21 participants 24 participants
50.143  (23.7388) 64.292  (22.0779)
Change at Week 24 Number Analyzed 16 participants 20 participants
-3.625  (16.1777) -5.750  (19.8968)
14.Secondary Outcome
Title 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
Hide Description Pre-dose pharmacokinetic concentrations, if any, were excluded from the pharmacokinetic analyses.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title AG-348 50 mg BID AG-348 300 mg BID
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 5 7
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanograms*hours per milliliter(hr*ng/mL)
Day 1: AG-348 Number Analyzed 5 participants 7 participants
3287
(20.9%)
27930
(38.1%)
Day 15: AG-348 Number Analyzed 5 participants 5 participants
3609
(38.2%)
11610
(11.3%)
Day 1: AGI-8702 Number Analyzed 5 participants 7 participants
235.6
(32.6%)
2637
(34.9%)
Day 15: AGI-8702 Number Analyzed 5 participants 5 participants
425.8
(21.8%)
2235
(19.4%)
15.Secondary Outcome
Title Maximum Plasma Concentration (Cmax) for AG-348 and Its Metabolite AGI-8702
Hide Description Pre-dose pharmacokinetic concentrations, if any, were excluded from the pharmacokinetic analyses.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title AG-348 50 mg BID AG-348 300 mg
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 5 7
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: nanograms per milliliter (ng/mL)
Day 1: AG-348 Number Analyzed 5 participants 7 participants
870.0
(9.2%)
7606
(41.8%)
Day 15: AG-348 Number Analyzed 5 participants 5 participants
943.4
(30.7%)
5259
(35.6%)
Day 1: AGI-8702 Number Analyzed 5 participants 7 participants
41.03
(43.6%)
414.7
(35.6%)
Day 15: AGI-8702 Number Analyzed 5 participants 5 participants
71.94
(22.0%)
533.7
(25.6%)
16.Secondary Outcome
Title Time to Reach Peak Plasma Concentration (Tmax) for AG-348 and Its Metabolite AGI-8702
Hide Description Pre-dose pharmacokinetic concentrations, if any, were excluded from the pharmacokinetic analyses.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title AG-348 50 mg BID AG-348 300 mg BID
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 5 7
Median (Full Range)
Unit of Measure: hour (hr)
Day 1: AG-348 Number Analyzed 5 participants 7 participants
1.92
(0.97 to 2.03)
1.97
(1.00 to 2.08)
Day 15: AG-348 Number Analyzed 5 participants 5 participants
1.00
(0.97 to 1.90)
1.00
(0.42 to 2.00)
Day 1: AGI-8702 Number Analyzed 5 participants 7 participants
2.00
(1.92 to 2.03)
1.97
(1.00 to 2.13)
Day 15: AGI-8702 Number Analyzed 5 participants 5 participants
2.00
(1.95 to 4.00)
1.00
(0.93 to 4.00)
17.Secondary Outcome
Title Apparent Clearance at Steady-State (Clss/F) for AG-348 and Its Metabolite AGI-8702
Hide Description Pre-dose pharmacokinetic concentrations, if any, were excluded from the pharmacokinetic analyses.
Time Frame pre-dose, 0.5, 1, 2, 4, 8 hours post-dose Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title AG-348 50 mg BID AG-348 300 mg BID
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 5 7
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: liter per hour (L/hr)
Day 15: AG-348 Number Analyzed 5 participants 5 participants
12.27
(40.3%)
25.31
(11.7%)
Day 15: AGI-8702 Number Analyzed 3 participants 3 participants
91.50
(31.0%)
128.2
(18.8%)
18.Secondary Outcome
Title Maximum Change From Baseline Response Value Over 12 Hours Post-dose (BRmax) for Adenosine Triphosphate (ATP)
Hide Description Pre-dose concentration observed on Day 1 was used as Baseline for calculation of change from baseline.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
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. Number analyzed is the number of participants with evaluable data at the given time-point.
Arm/Group Title AG-348 50 mg BID AG-348 300 mg BID
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 5 7
Mean (Standard Deviation)
Unit of Measure: µg/mL
Change at Day 1 Number Analyzed 4 participants 6 participants
16.50  (11.790) 20.67  (6.8896)
Change at Day 15 Number Analyzed 4 participants 4 participants
1.500  (31.032) 45.50  (60.995)
19.Secondary Outcome
Title Maximum Change From Baseline Response Value Over 12 Hours Post-dose (BRmax) for 2,3 - Diphosphoglycerate (2,3-DPG)
Hide Description Pre-dose concentration observed on Day 1 was used as Baseline for calculation of change from baseline.
Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
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. Number analyzed is the number of participants with evaluable data at the given time-point.
Arm/Group Title AG-348 50 mg BID AG-348 300 mg BID
Hide Arm/Group Description:
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.
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.
Overall Number of Participants Analyzed 5 7
Mean (Standard Deviation)
Unit of Measure: microgram per milliliter (µg/mL)
Change at Day 1 Number Analyzed 4 participants 7 participants
42.25  (38.836) 59.57  (58.569)
Change at Day 15 Number Analyzed 4 participants 5 participants
-65.50  (69.745) 8.200  (195.13)
Time Frame Up to Week 24
Adverse Event Reporting Description The Safety Analysis Set included all participants who had received at least one dose of study drug.
 
Arm/Group Title AG-348 50 mg BID AG-348 300 mg BID
Hide Arm/Group Description 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. 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.
All-Cause Mortality
AG-348 50 mg BID AG-348 300 mg BID
Affected / at Risk (%) Affected / at Risk (%)
Total   0/27 (0.00%)   0/25 (0.00%) 
Hide Serious Adverse Events
AG-348 50 mg BID AG-348 300 mg BID
Affected / at Risk (%) Affected / at Risk (%)
Total   5/27 (18.52%)   3/25 (12.00%) 
Blood and lymphatic system disorders     
Haemolytic anaemia  1  1/27 (3.70%)  1/25 (4.00%) 
Haemolysis  1  0/27 (0.00%)  1/25 (4.00%) 
Hepatobiliary disorders     
Cholelithiasis  1  1/27 (3.70%)  0/25 (0.00%) 
Infections and infestations     
Pharyngitis  1  1/27 (3.70%)  1/25 (4.00%) 
Influenza  1  1/27 (3.70%)  0/25 (0.00%) 
Metabolism and nutrition disorders     
Hypertriglyceridaemia  1  0/27 (0.00%)  1/25 (4.00%) 
Musculoskeletal and connective tissue disorders     
Osteoporosis  1  1/27 (3.70%)  0/25 (0.00%) 
1
Term from vocabulary, MedDRA 19.0
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
AG-348 50 mg BID AG-348 300 mg BID
Affected / at Risk (%) Affected / at Risk (%)
Total   26/27 (96.30%)   25/25 (100.00%) 
Cardiac disorders     
Palpitations  1  1/27 (3.70%)  2/25 (8.00%) 
Gastrointestinal disorders     
Nausea  1  10/27 (37.04%)  10/25 (40.00%) 
Vomiting  1  2/27 (7.41%)  5/25 (20.00%) 
Diarrhoea  1  3/27 (11.11%)  3/25 (12.00%) 
Dyspepsia  1  2/27 (7.41%)  2/25 (8.00%) 
Abdominal pain  1  0/27 (0.00%)  3/25 (12.00%) 
Abdominal pain upper  1  0/27 (0.00%)  3/25 (12.00%) 
General disorders     
Fatigue  1  4/27 (14.81%)  4/25 (16.00%) 
Pyrexia  1  1/27 (3.70%)  5/25 (20.00%) 
Chest discomfort  1  1/27 (3.70%)  4/25 (16.00%) 
Asthenia  1  3/27 (11.11%)  1/25 (4.00%) 
Non-cardiac chest pain  1  0/27 (0.00%)  3/25 (12.00%) 
Infections and infestations     
Viral upper respiratory tract infection  1  7/27 (25.93%)  2/25 (8.00%) 
Influenza  1  6/27 (22.22%)  1/25 (4.00%) 
Gastroenteritis  1  3/27 (11.11%)  1/25 (4.00%) 
Sinusitis  1  2/27 (7.41%)  1/25 (4.00%) 
Upper respiratory tract infection  1  2/27 (7.41%)  1/25 (4.00%) 
Metabolism and nutrition disorders     
Hypertriglyceridaemia  1  1/27 (3.70%)  4/25 (16.00%) 
Decreased appetite  1  1/27 (3.70%)  2/25 (8.00%) 
Musculoskeletal and connective tissue disorders     
Arthralgia  1  5/27 (18.52%)  3/25 (12.00%) 
Back pain  1  4/27 (14.81%)  3/25 (12.00%) 
Pain in extremity  1  2/27 (7.41%)  2/25 (8.00%) 
Musculoskeletal chest pain  1  1/27 (3.70%)  2/25 (8.00%) 
Musculoskeletal pain  1  1/27 (3.70%)  2/25 (8.00%) 
Nervous system disorders     
Headache  1  9/27 (33.33%)  14/25 (56.00%) 
Dizziness  1  5/27 (18.52%)  2/25 (8.00%) 
Dysgeusia  1  0/27 (0.00%)  3/25 (12.00%) 
Psychiatric disorders     
Insomnia  1  5/27 (18.52%)  16/25 (64.00%) 
Reproductive system and breast disorders     
Dysmenorrhoea  1  3/27 (11.11%)  4/25 (16.00%) 
Respiratory, thoracic and mediastinal disorders     
Cough  1  4/27 (14.81%)  4/25 (16.00%) 
Oropharyngeal pain  1  3/27 (11.11%)  4/25 (16.00%) 
Nasal congestion  1  3/27 (11.11%)  2/25 (8.00%) 
Dyspnoea  1  1/27 (3.70%)  3/25 (12.00%) 
Epistaxis  1  2/27 (7.41%)  1/25 (4.00%) 
Skin and subcutaneous tissue disorders     
Night sweats  1  0/27 (0.00%)  4/25 (16.00%) 
Rash  1  1/27 (3.70%)  3/25 (12.00%) 
Pruritus generalised  1  1/27 (3.70%)  2/25 (8.00%) 
Skin ulcer  1  0/27 (0.00%)  3/25 (12.00%) 
Vascular disorders     
Hot flush  1  2/27 (7.41%)  7/25 (28.00%) 
Flushing  1  2/27 (7.41%)  2/25 (8.00%) 
1
Term from vocabulary, MedDRA 20.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The information obtained from the clinical study will be used towards the development of AG-348 and may be disclosed to regulatory authority(ies), other Investigators, corporate partners, or consultants as required.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Affairs
Organization: Agios Pharmaceuticals, Inc.
Phone: 833-228-8474
EMail: medinfo@agios.com
Layout table for additonal information
Responsible Party: Agios Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT02476916    
Other Study ID Numbers: AG348-C-003
2015-000484-13 ( EudraCT Number )
First Submitted: June 10, 2015
First Posted: June 22, 2015
Results First Submitted: May 21, 2020
Results First Posted: June 11, 2020
Last Update Posted: June 8, 2021