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Trial record 5 of 25 for:    AG-348

A Study to Evaluate Efficacy and Safety of AG-348 in Not Regularly Transfused Adult Participants With Pyruvate Kinase Deficiency (PKD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03548220
Recruitment Status : Completed
First Posted : June 7, 2018
Results First Posted : May 24, 2022
Last Update Posted : May 24, 2022
Sponsor:
Information provided by (Responsible Party):
Agios Pharmaceuticals, Inc.

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Triple (Participant, Care Provider, Investigator);   Primary Purpose: Treatment
Conditions Pyruvate Kinase Deficiency
Anemia, Hemolytic
Interventions Drug: Placebo
Drug: AG-348
Enrollment 80
Recruitment Details A total of 80 participants were randomized in the study, which was conducted across multiple sites in 14 countries: Brazil, Canada, Denmark, France, Germany, Italy, Japan, Republic of Korea, Netherlands, Spain, Switzerland, Turkey, United Kingdom, and United States. The study was conducted from 9 August 2018 to 9 October 2020.
Pre-assignment Details Screening was done for a period of 42 days after the participant provided the informed consent. Investigators determined if the participants met all the inclusion criteria and none of the exclusion criteria to receive AG-348 or placebo to determine the optimized dose to be received for 12 weeks as fixed-dose.
Arm/Group Title Placebo Comparator: Placebo Experimental: AG-348 5 mg Experimental: AG-348, 20 mg Experimental: AG-348, 50 mg
Hide Arm/Group Description Participants received a matching placebo to AG-348 tablets, for a period of 12 weeks as an optimized dose. This was followed by matching placebo further, for a period of 12 weeks as a fixed-dose. Participants received AG-348 tablets, 5 milligrams (mg) twice daily (BID), administered orally, for 4 weeks as a starting dose, followed by two potential sequential dose level increases to 20 mg and 50 mg BID at Weeks 4 and 8 respectively as determined by the investigator based on safety and efficacy. The optimized dose for each participant was determined as 5 mg BID at Week 12, and participants then received that optimized dose for a period of 12 weeks as a fixed dose. Participants received AG-348 tablets, 5 mg BID, administered orally, for 4 weeks as a starting dose, followed by two potential sequential dose level increases to 20 mg and 50 mg BID at Weeks 4 and 8 respectively as determined by the investigator based on safety and efficacy. The optimized dose for each participant was determined as 20 mg BID at Week 12, and participants then received that optimized dose for a period of 12 weeks as a fixed dose. Participants received AG-348 tablets, 5 mg BID, administered orally, for 4 weeks as a starting dose, followed by two potential sequential dose level increases to 20 mg and 50 mg BID at Weeks 4 and 8 respectively as determined by the investigator based on safety and efficacy. The optimized dose for each participant was determined as 50 mg BID at Week 12, and participants then received that optimized dose for a period of 12 weeks as a fixed dose.
Period Title: Overall Study
Started 40 2 3 35
Completed 39 2 3 35
Not Completed 1 0 0 0
Reason Not Completed
Lost to Follow-up             1             0             0             0
Arm/Group Title Placebo Comparator: Placebo Experimental: AG-348, 5 mg Experimental: AG-348, 20 mg Experimental: AG-348, 50 mg Total
Hide Arm/Group Description Participants received a matching placebo to AG-348 tablets, for a period of 12 weeks as an optimized dose. This was followed by matching placebo further, for a period of 12 weeks as a fixed-dose. Participants received AG-348 tablets, 5 mg BID, administered orally, for 4 weeks as a starting dose, followed by two potential sequential dose level increases to 20 mg and 50 mg BID at Weeks 4 and 8 respectively as determined by the investigator based on safety and efficacy. The optimized dose for each participant was determined as 5 mg BID at Week 12, and participants then received that optimized dose for a period of 12 weeks as a fixed dose. Participants received AG-348 tablets, 5 mg BID, administered orally, for 4 weeks as a starting dose, followed by two potential sequential dose level increases to 20 mg and 50 mg BID at Weeks 4 and 8 respectively as determined by the investigator based on safety and efficacy. The optimized dose for each participant was determined as 20 mg BID at Week 12, and participants then received that optimized dose for a period of 12 weeks as a fixed dose. Participants received AG-348 tablets, 5 mg BID, administered orally, for 4 weeks as a starting dose, followed by two potential sequential dose level increases to 20 mg and 50 mg BID at Weeks 4 and 8 respectively as determined by the investigator based on safety and efficacy. The optimized dose for each participant was determined as 50 mg BID at Week 12, and participants then received that optimized dose for a period of 12 weeks as a fixed dose. Total of all reporting groups
Overall Number of Baseline Participants 40 2 3 35 80
Hide Baseline Analysis Population Description
Full analysis set included all participants who were randomized.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 40 participants 2 participants 3 participants 35 participants 80 participants
37.2  (15.92) 21.5  (4.95) 48.0  (26.21) 35.8  (14.07) 36.6  (15.47)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 40 participants 2 participants 3 participants 35 participants 80 participants
Female
24
  60.0%
0
   0.0%
2
  66.7%
22
  62.9%
48
  60.0%
Male
16
  40.0%
2
 100.0%
1
  33.3%
13
  37.1%
32
  40.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 40 participants 2 participants 3 participants 35 participants 80 participants
Hispanic or Latino
1
   2.5%
0
   0.0%
0
   0.0%
2
   5.7%
3
   3.8%
Not Hispanic or Latino
34
  85.0%
1
  50.0%
2
  66.7%
25
  71.4%
62
  77.5%
Unknown or Not Reported
5
  12.5%
1
  50.0%
1
  33.3%
8
  22.9%
15
  18.8%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 40 participants 2 participants 3 participants 35 participants 80 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
3
   7.5%
0
   0.0%
0
   0.0%
5
  14.3%
8
  10.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
1
   2.9%
1
   1.3%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
White
32
  80.0%
2
 100.0%
3
 100.0%
23
  65.7%
60
  75.0%
More than one race
1
   2.5%
0
   0.0%
0
   0.0%
0
   0.0%
1
   1.3%
Unknown or Not Reported
4
  10.0%
0
   0.0%
0
   0.0%
6
  17.1%
10
  12.5%
1.Primary Outcome
Title Percentage of Participants Achieving a Hemoglobin (Hb) Response (HR)
Hide Description Hemoglobin response (HR) is defined as a ≥1.5 g/dL (0.93 mmol/L) increase in Hb concentration from baseline that is sustained at 2 or more scheduled assessments at Weeks 16, 20, and 24. The baseline Hb concentration is the average of all available Hb concentrations for a participant during the Screening Period up to the first dose of study treatment. As pre-specified in the protocol, the data for this outcome measure is summarized between the active arm vs the placebo arm (AG-348 5 mg, 20 mg and 50 mg arms are analyzed and reported together in comparison to Placebo).
Time Frame Baseline, Weeks 16, 20, 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all participants who were randomized.
Arm/Group Title Placebo Comparator: Placebo Experimental: AG-348
Hide Arm/Group Description:
Participants received matching placebo to AG-348 tablets, for a period of 12 weeks as an optimized dose. This was followed by matching placebo further, for a period of 12 weeks as a fixed-dose.
Participants received AG-348 tablets, 5 mg for 4 weeks followed by the respective optimized dose of 5 mg or 20 mg or 50 mg BID as determined by the investigator, administered orally, up to Weeks 8 and 12 respectively, as an optimized dose and continued to receive the same dose for a period of 12 weeks as a fixed-dose.
Overall Number of Participants Analyzed 40 40
Measure Type: Number
Unit of Measure: percentage of participants
0 40
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Comparator: Placebo, Experimental: AG-348
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments 2-sided p-value
Method Exact Cochran-Mantel-Haenszel
Comments [Not Specified]
2.Secondary Outcome
Title Average Change From Baseline in Hb Concentration at Weeks 16, 20 and 24
Hide Description This is the change in Hb concentration at Weeks 16, 20 and 24 compared to baseline. Data presented represents the value of the change from baseline averaged over Weeks 16, 20 and 24. Baseline was defined as the average of all screening assessments within 45 (42+3) days before randomization for participants randomized and not dosed or before start of study treatment for participants randomized and dosed. As pre-specified in the protocol, the data for this outcome measure is summarized between the active arm vs the placebo arm (AG-348 5 mg, 20 mg and 50 mg arms are analyzed and reported together in comparison to Placebo).
Time Frame Baseline, Weeks 16, 20, 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all participants who were randomized.
Arm/Group Title Placebo Comparator: Placebo Experimental: AG-348
Hide Arm/Group Description:
Participants received matching placebo to AG-348 tablets, for a period of 12 weeks as an optimized dose. This was followed by matching placebo further, for a period of 12 weeks as a fixed dose.
Participants received AG-348 tablets, 5 mg for 4 weeks followed by the respective optimized dose of 5 mg or 20 mg or 50 mg BID as determined by the investigator, administered orally, up to Weeks 8 and 12 respectively, as an optimized dose and continued to receive the same dose for a period of 12 weeks as a fixed-dose.
Overall Number of Participants Analyzed 40 40
Least Squares Mean (Standard Error)
Unit of Measure: grams per liter (g/L)
-1.48  (2.082) 16.73  (2.075)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Comparator: Placebo, Experimental: AG-348
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed-effect Model Repeated Measure
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 18.21
Confidence Interval (2-Sided) 95%
12.41 to 24.01
Estimation Comments Standard error = 2.913
3.Secondary Outcome
Title Maximum Change From Baseline in Hb Concentration
Hide Description This is the maximum change from baseline in Hb concentration up to Week 24. As pre-specified in the protocol, the data for this outcome measure is summarized between the active arm vs the placebo arm (AG-348 5 mg, 20 mg and 50 mg arms are analyzed and reported together in comparison to Placebo).
Time Frame Baseline, up to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all participants who were randomized. Overall number of participants analyzed is the number of participants evaluated for the outcome measure.
Arm/Group Title Placebo Comparator: Placebo Experimental: AG-348
Hide Arm/Group Description:
Participants received matching placebo to AG-348 tablets, for a period of 12 weeks as an optimized dose. This was followed by matching placebo further, for a period of 12 weeks as a fixed dose.
Participants received AG-348 tablets, 5 mg for 4 weeks followed by the respective optimized dose of 5 mg or 20 mg or 50 mg BID as determined by the investigator, administered orally, up to Weeks 8 and 12 respectively, as an optimized dose and continued to receive the same dose for a period of 12 weeks as a fixed-dose.
Overall Number of Participants Analyzed 39 39
Mean (Standard Deviation)
Unit of Measure: g/L
4.76  (4.217) 23.94  (21.367)
4.Secondary Outcome
Title Time to Achieve an Increase in Hb Concentration of 1.5 g/dL or More
Hide Description This is the time taken to first achieve an increase of hemoglobin concentration of 1.5 g/dL or more from baseline. As pre-specified in the protocol, the data for this outcome measure is summarized between the active arm vs the placebo arm (AG-348 5 mg, 20 mg and 50 mg arms are analyzed and reported together in comparison to Placebo).
Time Frame Baseline, up to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all participants who were randomized. Overall number of participants analyzed is the number of participants evaluated for the outcome measure.
Arm/Group Title Placebo Comparator: Placebo Experimental: AG-348
Hide Arm/Group Description:
Participants received matching placebo to AG-348 tablets, for a period of 12 weeks as an optimized dose. This was followed by matching placebo further, for a period of 12 weeks as a fixed dose.
Participants received AG-348 tablets, 5 mg for 4 weeks followed by the respective optimized dose of 5 mg or 20 mg or 50 mg BID as determined by the investigator, administered orally, up to Weeks 8 and 12 respectively, as an optimized dose and continued to receive the same dose for a period of 12 weeks as a fixed-dose.
Overall Number of Participants Analyzed 0 17
Mean (Standard Deviation)
Unit of Measure: weeks
7.66  (4.050)
5.Secondary Outcome
Title Average Change From Baseline in Indirect Bilirubin at Weeks 16, 20 and 24
Hide Description The change from baseline in indirect bilirubin levels was summarized. Indirect bilirubin is a marker for hemolysis. Data presented represents the value of the change from baseline averaged over Weeks 16, 20 and 24. Baseline was defined as the average of all screening assessments within 45 (42+3) days before randomization for participants randomized and not dosed or before the start of study treatment for participants randomized and dosed. As pre-specified in the protocol, the data for this outcome measure is summarized between the active arm vs the placebo arm (AG-348 5 mg, 20 mg and 50 mg arms are analyzed and reported together in comparison to Placebo).
Time Frame Baseline, Weeks 16, 20, 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all participants who were randomized. Overall number of participants analyzed is the number of participants evaluated for the outcome measure.
Arm/Group Title Placebo Comparator: Placebo Experimental: AG-348
Hide Arm/Group Description:
Participants received matching placebo to AG-348 tablets, for a period of 12 weeks as an optimized dose. This was followed by matching placebo further, for a period of 12 weeks as a fixed dose.
Participants received AG-348 tablets, 5 mg for 4 weeks followed by the respective optimized dose of 5 mg or 20 mg or 50 mg BID as determined by the investigator, administered orally, up to Weeks 8 and 12 respectively, as an optimized dose and continued to receive the same dose for a period of 12 weeks as a fixed-dose.
Overall Number of Participants Analyzed 39 37
Least Squares Mean (Standard Error)
Unit of Measure: micromoles per liter (μmol/L)
5.10  (4.061) -21.16  (4.228)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Comparator: Placebo, Experimental: AG-348
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed-effect Model Repeated Measure
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -26.26
Confidence Interval (2-Sided) 95%
-37.82 to -14.70
Estimation Comments Standard error = 5.788
6.Secondary Outcome
Title Average Change From Baseline in Lactic Acid Dehydrogenase (LDH) at Weeks 16, 20 and 24
Hide Description The change from baseline in LDH levels was summarized. LDH is a marker for hemolysis. Data presented represents the value of the change from baseline averaged over Weeks 16, 20 and 24. Baseline was defined as the average of all screening assessments within 45 (42+3) days before randomization for participants randomized and not dosed or before the start of study treatment for participants randomized and dosed. As pre-specified in the protocol, the data for this outcome measure is summarized between the active arm vs the placebo arm (AG-348 5 mg, 20 mg and 50 mg arms are analyzed and reported together in comparison to Placebo).
Time Frame Baseline, Weeks 16, 20, 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all participants who were randomized. Overall number of participants analyzed is the number of participants evaluated for the outcome measure.
Arm/Group Title Placebo Comparator: Placebo Experimental: AG-348
Hide Arm/Group Description:
Participants received matching placebo to AG-348 tablets, for a period of 12 weeks as an optimized dose. This was followed by matching placebo further, for a period of 12 weeks as a fixed dose.
Participants received AG-348 tablets, 5 mg for 4 weeks followed by the respective optimized dose of 5 mg or 20 mg or 50 mg BID as determined by the investigator, administered orally, up to Weeks 8 and 12 respectively, as an optimized dose and continued to receive the same dose for a period of 12 weeks as a fixed-dose.
Overall Number of Participants Analyzed 40 39
Least Squares Mean (Standard Error)
Unit of Measure: units per litre (U/L)
-21.18  (16.040) -91.99  (16.222)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Comparator: Placebo, Experimental: AG-348
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0027
Comments [Not Specified]
Method Mixed-effect Model Repeated Measure
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -70.81
Confidence Interval (2-Sided) 95%
-115.88 to -25.74
Estimation Comments Standard error = 22.488
7.Secondary Outcome
Title Average Change From Baseline in Haptoglobin at Weeks 16, 20 and 24
Hide Description The change from baseline in haptoglobin levels was summarized. Haptoglobin levels are markers for hemolysis. Data presented represents the value of the change from baseline averaged over Weeks 16, 20 and 24. Baseline was defined as the average of all screening assessments within 45 (42+3) days before randomization for participants randomized and not dosed or before the start of study treatment for participants randomized and dosed. As pre-specified in the protocol, the data for this outcome measure is summarized between the active arm vs the placebo arm (AG-348 5 mg, 20 mg and 50 mg arms are analyzed and reported together in comparison to Placebo).
Time Frame Baseline, Weeks 16, 20, 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all participants who were randomized.
Arm/Group Title Placebo Comparator: Placebo Experimental: AG-348
Hide Arm/Group Description:
Participants received matching placebo to AG-348 tablets, for a period of 12 weeks as an optimized dose. This was followed by matching placebo further, for a period of 12 weeks as a fixed dose.
Participants received AG-348 tablets, 5 mg for 4 weeks followed by the respective optimized dose of 5 mg or 20 mg or 50 mg BID as determined by the investigator, administered orally, up to Weeks 8 and 12 respectively, as an optimized dose and continued to receive the same dose for a period of 12 weeks as a fixed-dose.
Overall Number of Participants Analyzed 40 40
Least Squares Mean (Standard Error)
Unit of Measure: g/L
0.012  (0.0412) 0.169  (0.0408)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Comparator: Placebo, Experimental: AG-348
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0079
Comments [Not Specified]
Method Mixed-effect Model Repeated Measure
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value 0.158
Confidence Interval (2-Sided) 95%
0.043 to 0.273
Estimation Comments Standard error = 0.0578
8.Secondary Outcome
Title Average Change From Baseline in Reticulocyte Percentages at Weeks 16, 20 and 24
Hide Description The change from baseline in reticulocyte percentage was summarized. Reticulocyte levels are markers for hematopoietic activity. Data presented represents the value of the change from baseline averaged over Weeks 16, 20 and 24. Baseline was defined as the average of all screening assessments within 45 (42+3) days before randomization for participants randomized and not dosed or before the start of study treatment for participants randomized and dosed. As pre-specified in the protocol, the data for this outcome measure is summarized between the active arm vs the placebo arm (AG-348 5 mg, 20 mg and 50 mg arms are analyzed and reported together in comparison to Placebo).
Time Frame Baseline, Weeks 16, 20, 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all participants who were randomized.
Arm/Group Title Placebo Comparator: Placebo Experimental: AG-348
Hide Arm/Group Description:
Participants received matching placebo to AG-348 tablets, for a period of 12 weeks as an optimized dose. This was followed by matching placebo further, for a period of 12 weeks as a fixed dose.
Participants received AG-348 tablets, 5 mg for 4 weeks followed by the respective optimized dose of 5 mg or 20 mg or 50 mg BID as determined by the investigator, administered orally, up to Weeks 8 and 12 respectively, as an optimized dose and continued to receive the same dose for a period of 12 weeks as a fixed-dose.
Overall Number of Participants Analyzed 40 40
Least Squares Mean (Standard Error)
Unit of Measure: Reticulocyte percentages
0.0038  (0.01390) -0.0973  (0.01401)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Comparator: Placebo, Experimental: AG-348
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Mixed-effect Model Repeated Measure
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -0.1011
Confidence Interval (2-Sided) 95%
-0.1391 to -0.0632
Estimation Comments Standard error = 0.01904
9.Secondary Outcome
Title Change From Baseline in Pyruvate Kinase Deficiency Diary (PKDD) Score at Week 24
Hide Description The PKDD is a 7-item patient reported outcome (PRO) measure of the core signs and symptoms associated with PK deficiency in adults. Participants rate their experience with symptoms of PK deficiency on the present day. The symptoms include those associated with tiredness, jaundice, bone pain, shortness of breath, and energy level. The score ranges from 25 to 76, with higher scores indicating a higher disease burden. The change from baseline in PKDD weekly scores was evaluated. A negative change from baseline indicates a lower disease burden. As pre-specified in the protocol, the data for this outcome measure is summarized between the active arm vs the placebo arm (AG-348 5 mg, 20 mg and 50 mg arms are analyzed and reported together in comparison to Placebo).
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all participants who were randomized. Overall number of participants analyzed is the number of participants evaluated for the outcome measure.
Arm/Group Title Placebo Comparator: Placebo Experimental: AG-348
Hide Arm/Group Description:
Participants received matching placebo to AG-348 tablets, for a period of 12 weeks as an optimized dose. This was followed by matching placebo further, for a period of 12 weeks as a fixed dose.
Participants received AG-348 tablets, 5 mg for 4 weeks followed by the respective optimized dose of 5 mg or 20 mg or 50 mg BID as determined by the investigator, administered orally, up to Weeks 8 and 12 respectively, as an optimized dose and continued to receive the same dose for a period of 12 weeks as a fixed-dose.
Overall Number of Participants Analyzed 36 37
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
-2.05  (0.976) -5.16  (0.955)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Comparator: Placebo, Experimental: AG-348
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0247
Comments [Not Specified]
Method Mixed-effect Model Repeated Measure
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -3.11
Confidence Interval (2-Sided) 95%
-5.80 to -0.41
Estimation Comments Standard error = 1.352
10.Secondary Outcome
Title Change From Baseline in Pyruvate Kinase Deficiency Impact Assessment (PKDIA) Score at Week 24
Hide Description The PKDIA is a 12-item patient reported outcome (PRO) measure of the common impacts of PK deficiency on activities of daily living. Participants rate how PK deficiency has impacted aspects of daily living in the past 7 days, including impacts on relationships; perceived appearance; work performance; and leisure, social, mental, and physical activities. The score range is 30 to 76, with higher scores indicating a higher disease burden. The change from baseline in PKDIA scores was evaluated. A negative change from baseline indicates a lower disease burden. As pre-specified in the protocol, the data for this outcome measure is summarized between the active arm vs the placebo arm (AG-348 5 mg, 20 mg and 50 mg arms are analyzed and reported together in comparison to Placebo).
Time Frame Baseline, Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set included all participants who were randomized. Overall number of participants analyzed is the number of participants evaluated for the outcome measure.
Arm/Group Title Placebo Comparator: Placebo Experimental: AG-348
Hide Arm/Group Description:
Participants received matching placebo to AG-348 tablets, for a period of 12 weeks as an optimized dose. This was followed by matching placebo further, for a period of 12 weeks as a fixed dose.
Participants received AG-348 tablets, 5 mg for 4 weeks followed by the respective optimized dose of 5 mg or 20 mg or 50 mg BID as determined by the investigator, administered orally, up to Weeks 8 and 12 respectively, as an optimized dose and continued to receive the same dose for a period of 12 weeks as a fixed-dose.
Overall Number of Participants Analyzed 39 39
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
-1.39  (1.157) -4.65  (1.123)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo Comparator: Placebo, Experimental: AG-348
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0421
Comments [Not Specified]
Method Mixed-effect Model Repeated Measure
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean Difference
Estimated Value -3.25
Confidence Interval (2-Sided) 95%
-6.39 to -0.12
Estimation Comments Standard error = 1.574
11.Secondary Outcome
Title Percentage of Participants With Adverse Events
Hide Description An AE is any untoward medical occurrence in a participant or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the study treatment. An AE can, therefore, be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product.
Time Frame From signing of informed consent form to the end of study, including follow-up (up to Day 197)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set included all participants who received at least 1 dose of study treatment.
Arm/Group Title Placebo Comparator: Placebo Experimental: AG-348 5 mg Experimental: AG-348 20 mg Experimental: AG-348 50 mg
Hide Arm/Group Description:
Participants received matching placebo to AG-348 tablets, for a period of 12 weeks as an optimized dose. This was followed by matching placebo further, for a period of 12 weeks as a fixed dose.
Participants received AG-348 tablets, 5 mg BID, administered orally, for 4 weeks as a starting dose, followed by two potential sequential dose level increases to 20 mg and 50 mg BID at Weeks 4 and 8 respectively as determined by the investigator based on safety and efficacy. The optimized dose for each participant was determined as 5 mg BID at Week 12, and participants then received that optimized dose for a period of 12 weeks as a fixed dose
Participants received AG-348 tablets, 5 mg BID, administered orally, for 4 weeks as a starting dose, followed by two potential sequential dose level increases to 20 mg and 50 mg BID at Weeks 4 and 8 respectively as determined by the investigator based on safety and efficacy. The optimized dose for each participant was determined as 20 mg BID at Week 12, and participants then received that optimized dose for a period of 12 weeks as a fixed dose.
Participants received AG-348 tablets, 5 mg BID, administered orally, for 4 weeks as a starting dose, followed by two potential sequential dose level increases to 20 mg and 50 mg BID at Weeks 4 and 8 respectively as determined by the investigator based on safety and efficacy. The optimized dose for each participant was determined as 50 mg BID at Week 12, and participants then received that optimized dose for a period of 12 weeks as a fixed dose.
Overall Number of Participants Analyzed 39 2 3 35
Measure Type: Number
Unit of Measure: percentage of participants
89.7 50.0 100 88.6
12.Secondary Outcome
Title Area Under the Curve From Time 0 to the Last Quantifiable Concentration [AUC(0-last)] for AG-348 at Week 12
Hide Description [Not Specified]
Time Frame Pre-dose, 30 minutes and 1, 2, 4 and 8 hours post-dose on Day 85 (Week 12)
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacokinetic analysis population consisted of all participants who were enrolled and received a dose of study medication (mitapivat) with at least 1 non-zero pharmacokinetic plasma concentration of mitapivat at the Week 12 visit. Overall number of participants analyzed is the number of participants evaluated for the outcome measure.
Arm/Group Title AG-348, 5mg AG-348, 20 mg AG-348, 50mg
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Participants received 5mg AG-348 tablets BID at Week 12.
Participants received 20mg AG-348 tablets BID at Week 12.
Participants received 50mg AG-348 tablets BID at Week 12.
Overall Number of Participants Analyzed 2 3 24
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: h*ng/mL
565.9 [1] 
(NA%)
1481.2
(26.9%)
2973.3
(35.6%)
[1]
Data was not reported due to small size of sample.
13.Secondary Outcome
Title Maximum Plasma Concentration (Cmax) for AG-348
Hide Description [Not Specified]
Time Frame Pre-dose, 30 minutes and 1, 2, 4 and 8 hours post-dose on Day 85 (Week 12)
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Hide Analysis Population Description
Pharmacokinetic analysis population consisted of all participants who were enrolled and received a dose of study medication (mitapivat) with at least 1 non-zero pharmacokinetic plasma concentration of mitapivat at the Week 12 visit. Overall number of participants analyzed is the number of participants evaluated for the outcome measure.
Arm/Group Title AG-348, 5mg AG-348, 20 mg AG-348, 50mg
Hide Arm/Group Description:
Participants received 5mg AG-348 tablets BID at Week 12.
Participants received 20mg AG-348 tablets BID at Week 12.
Participants received 50mg AG-348 tablets BID at Week 12.
Overall Number of Participants Analyzed 2 3 26
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: Nanograms per milliliter (ng/mL)
156.9 [1] 
(NA%)
373.1
(13.6%)
1033
(31.2%)
[1]
Data not reported due to small size of sample.
14.Secondary Outcome
Title Time to Cmax (Tmax) for AG-348
Hide Description [Not Specified]
Time Frame Pre-dose, 30 minutes and 1, 2, 4 and 8 hours post-dose on Day 85 (Week 12)
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Pharmacokinetic analysis population consisted of all participants who were enrolled and received a dose of study medication (mitapivat) with at least 1 non-zero pharmacokinetic plasma concentration of mitapivat at the Week 12 visit. Overall number of participants analyzed is the number of participants evaluated for the outcome measure.
Arm/Group Title AG-348, 5mg AG-348, 20mg AG-348, 50mg
Hide Arm/Group Description:
Participants received 5mg AG-348 tablets BID at Week 12.
Participants received 20mg AG-348 tablets BID at Week 12.
Participants received 50mg AG-348 tablets BID at Week 12.
Overall Number of Participants Analyzed 2 3 26
Median (Full Range)
Unit of Measure: hours (h)
0.75
(0.50 to 1.00)
1.02
(0.92 to 2.17)
0.50
(0.42 to 1.92)
15.Secondary Outcome
Title Time to Last Measurable Concentration (Tlast) for AG-348
Hide Description [Not Specified]
Time Frame Pre-dose, 30 minutes and 1, 2, 4 and 8 hours post-dose on Day 85 (Week 12)
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Pharmacokinetic analysis population consisted of all participants who were enrolled and received a dose of study medication (mitapivat) with at least 1 non-zero pharmacokinetic plasma concentration of mitapivat at the Week 12 visit. Overall number of participants analyzed is the number of participants evaluated for the outcome measure.
Arm/Group Title AG-348, 5mg AG-348, 20mg AG-346, 50mg
Hide Arm/Group Description:
Participants received 5mg AG-348 tablets BID at Week 12.
Participants received 20mg AG-348 tablets BID at Week 12.
Participants received 50mg AG-348 tablets BID at Week 12.
Overall Number of Participants Analyzed 2 3 24
Geometric Mean (Geometric Coefficient of Variation)
Unit of Measure: hours (h)
7.787 [1] 
(NA%)
7.809
(4.2%)
7.162
(28.0%)
[1]
Data not reported due to small size of sample.
16.Secondary Outcome
Title Exposure-Response Relationship of Adverse Event (Hot Flush) and AG-348 Concentration and Relevant AG-348 Pharmacokinetic Parameters
Hide Description Predicted probability of experiencing all grade hot flush at the doses of 5, 20, and 50 mg mitapivat BID based on exposure-response model.
Time Frame From first dose of mitapivat to the end of study, including follow-up (up to Day 197)
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Safety Set: Participants who were administered the study drug. Participants who received mitapivat in studies: study AG348-C-003 (NCT02476916): 52 participants; study AG348-C-006 (NCT03548220): 40 participants; study AG348-C-007 (NCT03559699): 27 participants; and study AG348-C-011 (NCT03853798): 36 participants, were pooled for the analysis of this outcome measure.
Arm/Group Title Experimental: AG-348 5 mg Experimental: AG-348 20 mg Experimental: AG-348 50 mg
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Participants received AG-348 tablets, 5 mg BID, administered orally, for 4 weeks as a starting dose, participants continued to receive the same dose as determined by the investigator based on safety and efficacy up to Week 12, followed by the same optimized dose of 5 mg BID, for a period of 12 weeks as a fixed-dose.
Participants received AG-348 tablets, starting dose of 5 mg BID for 4 weeks, the dose was uptitrated to 20 mg BID, administered orally, up to Week 12 as an optimized dose as determined by the investigator based on safety and efficacy, followed by the same optimized dose of 20 mg BID further for a period of 12 weeks as a fixed-dose.
Participants received AG-348 tablets, starting dose of 5 mg BID for 4 weeks, the dose was uptitrated to 20 mg BID, administered orally, up to Week 8 followed by dose up titration to 50 mg BID up to Week 12 as an optimized dose, followed by the same optimized dose of 50 mg BID, as determined by the investigator based on safety and efficacy, further for a period of 12 weeks as a fixed-dose.
Overall Number of Participants Analyzed 2 3 150
Mean (95% Confidence Interval)
Unit of Measure: Percent probability
3.37
(1.22 to 7.35)
4.03
(1.61 to 8.36)
5.5
(2.48 to 10.5)
17.Secondary Outcome
Title Exposure-Response Relationship Between Safety Parameters (Sex Hormone in Male Subjects) and AG-348 Concentration and Relevant AG-348 Pharmacokinetic Parameters
Hide Description Predicted percent change from baseline at Week 24 in the sex hormone measures (total testosterone, free testosterone, and estrone) at the doses of 5, 20, and 50 mg mitapivat BID in male participants.
Time Frame Baseline, Week 24
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Safety Set: Participants who were administered the study drug. Male participants who received mitapivat in studies: study AG348-C-003 (NCT02476916): 32 participants; study AG348-C-006 (NCT03548220):15 participants; study AG348-C-007 (NCT03559699): 7 participants; and study AG348-C-011 (NCT03853798): 14 participants were pooled for analysis of this outcome measure.
Arm/Group Title Experimental: AG-348 5 mg Experimental: AG-348 20 mg Experimental: AG-348 50 mg
Hide Arm/Group Description:
Participants received AG-348 tablets, 5 mg BID, administered orally, for 4 weeks as a starting dose, participants continued to receive the same dose as determined by the investigator based on safety and efficacy up to Week 12, followed by the same optimized dose of 5 mg BID, for a period of 12 weeks as a fixed-dose.
Participants received AG-348 tablets, starting dose of 5 mg BID for 4 weeks, the dose was uptitrated to 20 mg BID, administered orally, up to Week 12 as an optimized dose as determined by the investigator based on safety and efficacy, followed by the same optimized dose of 20 mg BID further for a period of 12 weeks as a fixed-dose.
Participants received AG-348 tablets, starting dose of 5 mg BID for 4 weeks, the dose was uptitrated to 20 mg BID, administered orally, up to Week 8 followed by dose up titration to 50 mg BID up to Week 12 as an optimized dose, followed by the same optimized dose of 50 mg BID, as determined by the investigator based on safety and efficacy, further for a period of 12 weeks as a fixed-dose.
Overall Number of Participants Analyzed 2 3 63
Mean (95% Confidence Interval)
Unit of Measure: Percent change
Total Testosterone
0.877
(0.41 to 1.43)
3.18
(1.49 to 5.4)
7.59
(3.29 to 13.7)
Free Testosterone
6.01
(1.66 to 13.2)
14.1
(4 to 27.5)
26
(7.14 to 55.1)
Estrone
-31.5
(-51 to -21.1)
-56.5
(-67.3 to -48.4)
-68.2
(-74.5 to -62.6)
18.Other Pre-specified Outcome
Title Percentage of Participants With Adverse Events of Special Interest (AESI)
Hide Description An AE is any untoward medical occurrence in a participant or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the study treatment. An AE can, therefore, be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AESI can be serious or non-serious.
Time Frame Through 4 weeks after last dose (approximately Week 31)
Outcome Measure Data Not Reported
19.Other Pre-specified Outcome
Title Change From Baseline in Bone Mineral Density Z-Score at Week 24
Hide Description [Not Specified]
Time Frame Baseline, Week 24
Outcome Measure Data Not Reported
20.Other Pre-specified Outcome
Title Change From Baseline in Bone Mineral Density T-Score at Week 24
Hide Description [Not Specified]
Time Frame Baseline, Week 24
Outcome Measure Data Not Reported
Time Frame From time of signing of informed consent form to end of study, including follow-up (up to Day 197)
Adverse Event Reporting Description The placebo arm includes AEs that occurred in participants who received at least 1 dose of AG-348 matching placebo during the study. As pre-specified in SAP, AEs that occurred in AG-348 arms for participants who received AG-348 treatment during the study are reported based on the fixed dose treatment received. The safety analysis set included all participants who received at least 1 dose of study treatment.
 
Arm/Group Title Placebo Comparator: Placebo Experimental: AG-348, 5 mg Experimental: AG-348, 20 mg Experimental: AG-348, 50 mg
Hide Arm/Group Description Participants received a matching placebo to AG-348 tablets, for a period of 12 weeks as an optimized dose. This was followed by matching placebo further, for a period of 12 weeks as a fixed-dose. Participants received AG-348 tablets, 5 mg BID, administered orally, for 4 weeks as a starting dose, followed by two potential sequential dose level increases to 20 mg and 50 mg BID at Weeks 4 and 8 respectively as determined by the investigator based on safety and efficacy. The optimized dose for each participant was determined as 5 mg BID at Week 12, and participants then received that optimized dose for a period of 12 weeks as a fixed dose. Participants received AG-348 tablets, 5 mg BID, administered orally, for 4 weeks as a starting dose, followed by two potential sequential dose level increases to 20 mg and 50 mg BID at Weeks 4 and 8 respectively as determined by the investigator based on safety and efficacy. The optimized dose for each participant was determined as 20 mg BID at Week 12, and participants then received that optimized dose for a period of 12 weeks as a fixed dose. Participants received AG-348 tablets, 5 mg BID, administered orally, for 4 weeks as a starting dose, followed by two potential sequential dose level increases to 20 mg and 50 mg BID at Weeks 4 and 8 respectively as determined by the investigator based on safety and efficacy. The optimized dose for each participant was determined as 50 mg BID at Week 12, and participants then received that optimized dose for a period of 12 weeks as a fixed dose.
All-Cause Mortality
Placebo Comparator: Placebo Experimental: AG-348, 5 mg Experimental: AG-348, 20 mg Experimental: AG-348, 50 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/39 (0.00%)   0/2 (0.00%)   0/3 (0.00%)   0/35 (0.00%) 
Hide Serious Adverse Events
Placebo Comparator: Placebo Experimental: AG-348, 5 mg Experimental: AG-348, 20 mg Experimental: AG-348, 50 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   2/39 (5.13%)   0/2 (0.00%)   1/3 (33.33%)   3/35 (8.57%) 
Cardiac disorders         
Atrial fibrillation  1  0/39 (0.00%)  0/2 (0.00%)  0/3 (0.00%)  1/35 (2.86%) 
Gastrointestinal disorders         
Obstructive pancreatitis  1  1/39 (2.56%)  0/2 (0.00%)  0/3 (0.00%)  0/35 (0.00%) 
Infections and infestations         
Gastroenteritis  1  0/39 (0.00%)  0/2 (0.00%)  0/3 (0.00%)  1/35 (2.86%) 
Metapneumovirus infection  1  1/39 (2.56%)  0/2 (0.00%)  0/3 (0.00%)  0/35 (0.00%) 
Injury, poisoning and procedural complications         
Rib fracture  1  0/39 (0.00%)  0/2 (0.00%)  0/3 (0.00%)  1/35 (2.86%) 
Musculoskeletal and connective tissue disorders         
Musculoskeletal pain  1  0/39 (0.00%)  0/2 (0.00%)  1/3 (33.33%)  0/35 (0.00%) 
1
Term from vocabulary, MedDRA 23.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Placebo Comparator: Placebo Experimental: AG-348, 5 mg Experimental: AG-348, 20 mg Experimental: AG-348, 50 mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   35/39 (89.74%)   1/2 (50.00%)   3/3 (100.00%)   31/35 (88.57%) 
Blood and lymphatic system disorders         
Anaemia  1  2/39 (5.13%)  0/2 (0.00%)  0/3 (0.00%)  0/35 (0.00%) 
Gastrointestinal disorders         
Nausea  1  9/39 (23.08%)  0/2 (0.00%)  2/3 (66.67%)  5/35 (14.29%) 
Diarrhoea  1  7/39 (17.95%)  0/2 (0.00%)  2/3 (66.67%)  2/35 (5.71%) 
Abdominal pain  1  2/39 (5.13%)  0/2 (0.00%)  0/3 (0.00%)  4/35 (11.43%) 
Abdominal distension  1  0/39 (0.00%)  0/2 (0.00%)  0/3 (0.00%)  2/35 (5.71%) 
Constipation  1  0/39 (0.00%)  0/2 (0.00%)  0/3 (0.00%)  2/35 (5.71%) 
Dyspepsia  1  2/39 (5.13%)  0/2 (0.00%)  1/3 (33.33%)  0/35 (0.00%) 
Abdominal pain upper  1  3/39 (7.69%)  0/2 (0.00%)  0/3 (0.00%)  0/35 (0.00%) 
General disorders         
Fatigue  1  4/39 (10.26%)  0/2 (0.00%)  1/3 (33.33%)  4/35 (11.43%) 
Influenza like illness  1  0/39 (0.00%)  0/2 (0.00%)  0/3 (0.00%)  2/35 (5.71%) 
Pyrexia  1  2/39 (5.13%)  0/2 (0.00%)  0/3 (0.00%)  0/35 (0.00%) 
Infections and infestations         
Nasopharyngitis  1  6/39 (15.38%)  0/2 (0.00%)  2/3 (66.67%)  3/35 (8.57%) 
Gastroenteritis  1  0/39 (0.00%)  1/2 (50.00%)  0/3 (0.00%)  2/35 (5.71%) 
Urinary tract infection  1  3/39 (7.69%)  0/2 (0.00%)  0/3 (0.00%)  1/35 (2.86%) 
Upper respiratory tract infection  1  4/39 (10.26%)  0/2 (0.00%)  0/3 (0.00%)  0/35 (0.00%) 
Oral herpes  1  2/39 (5.13%)  0/2 (0.00%)  0/3 (0.00%)  0/35 (0.00%) 
Injury, poisoning and procedural complications         
Contusion  1  1/39 (2.56%)  0/2 (0.00%)  0/3 (0.00%)  2/35 (5.71%) 
Investigations         
Alanine aminotransferase increased  1  6/39 (15.38%)  0/2 (0.00%)  0/3 (0.00%)  1/35 (2.86%) 
Aspartate aminotransferase increased  1  3/39 (7.69%)  0/2 (0.00%)  0/3 (0.00%)  1/35 (2.86%) 
Metabolism and nutrition disorders         
Hypertriglyceridaemia  1  0/39 (0.00%)  0/2 (0.00%)  0/3 (0.00%)  3/35 (8.57%) 
Musculoskeletal and connective tissue disorders         
Back pain  1  3/39 (7.69%)  0/2 (0.00%)  0/3 (0.00%)  5/35 (14.29%) 
Arthralgia  1  2/39 (5.13%)  0/2 (0.00%)  2/3 (66.67%)  2/35 (5.71%) 
Pain in extremity  1  3/39 (7.69%)  0/2 (0.00%)  0/3 (0.00%)  2/35 (5.71%) 
Neck pain  1  2/39 (5.13%)  0/2 (0.00%)  0/3 (0.00%)  0/35 (0.00%) 
Nervous system disorders         
Headache  1  13/39 (33.33%)  0/2 (0.00%)  1/3 (33.33%)  5/35 (14.29%) 
Dizziness  1  3/39 (7.69%)  0/2 (0.00%)  0/3 (0.00%)  4/35 (11.43%) 
Presyncope  1  1/39 (2.56%)  0/2 (0.00%)  0/3 (0.00%)  2/35 (5.71%) 
Paraesthesia  1  0/39 (0.00%)  0/2 (0.00%)  0/3 (0.00%)  2/35 (5.71%) 
Psychiatric disorders         
Middle insomnia  1  3/39 (7.69%)  0/2 (0.00%)  0/3 (0.00%)  3/35 (8.57%) 
Insomnia  1  0/39 (0.00%)  0/2 (0.00%)  0/3 (0.00%)  2/35 (5.71%) 
Initial insomnia  1  4/39 (10.26%)  0/2 (0.00%)  0/3 (0.00%)  1/35 (2.86%) 
Stress  1  2/39 (5.13%)  0/2 (0.00%)  0/3 (0.00%)  0/35 (0.00%) 
Reproductive system and breast disorders         
Breast discomfort  1  0/39 (0.00%)  0/2 (0.00%)  0/3 (0.00%)  2/35 (5.71%) 
Dysmenorrhoea  1  3/39 (7.69%)  0/2 (0.00%)  0/3 (0.00%)  1/35 (2.86%) 
Respiratory, thoracic and mediastinal disorders         
Dyspnoea  1  4/39 (10.26%)  0/2 (0.00%)  1/3 (33.33%)  2/35 (5.71%) 
Cough  1  2/39 (5.13%)  0/2 (0.00%)  0/3 (0.00%)  3/35 (8.57%) 
Oropharyngeal pain  1  2/39 (5.13%)  0/2 (0.00%)  0/3 (0.00%)  3/35 (8.57%) 
Nasal congestion  1  3/39 (7.69%)  0/2 (0.00%)  0/3 (0.00%)  2/35 (5.71%) 
Rhinitis allergic  1  3/39 (7.69%)  0/2 (0.00%)  0/3 (0.00%)  1/35 (2.86%) 
Epistaxis  1  2/39 (5.13%)  0/2 (0.00%)  0/3 (0.00%)  1/35 (2.86%) 
Skin and subcutaneous tissue disorders         
Dry skin  1  1/39 (2.56%)  0/2 (0.00%)  0/3 (0.00%)  2/35 (5.71%) 
Rash  1  3/39 (7.69%)  0/2 (0.00%)  0/3 (0.00%)  0/35 (0.00%) 
Dermatitis acneiform  1  2/39 (5.13%)  0/2 (0.00%)  0/3 (0.00%)  0/35 (0.00%) 
Vascular disorders         
Hot flush  1  0/39 (0.00%)  0/2 (0.00%)  0/3 (0.00%)  3/35 (8.57%) 
Hypertension  1  0/39 (0.00%)  0/2 (0.00%)  1/3 (33.33%)  1/35 (2.86%) 
1
Term from vocabulary, MedDRA 23.1
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
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Responsible Party: Agios Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT03548220    
Other Study ID Numbers: AG348-C-006
First Submitted: May 24, 2018
First Posted: June 7, 2018
Results First Submitted: October 8, 2021
Results First Posted: May 24, 2022
Last Update Posted: May 24, 2022