Trial Outcomes & Findings for A Dose-Finding Study of AG-348 in Sickle Cell Disease (NCT NCT04000165)
NCT ID: NCT04000165
Last Updated: 2022-07-12
Results Overview
To assess the clinical safety and tolerability of multiple escalating doses of AG-348, an allosteric activator of the enzyme pyruvate kinase, in subjects with stable sickle cell disease (SCD). Safety and tolerability were assessed by frequency and severity of adverse events (AEs) using Common Terminology Criteria for Adverse Events (CTCAE) 5.0.
Recruitment status
COMPLETED
Study phase
EARLY_PHASE1
Target enrollment
17 participants
Primary outcome timeframe
14 weeks
Results posted on
2022-07-12
Participant Flow
Participants were enrolled at the National Institutes of Health in Bethesda, Maryland from July 2019 to June 2021.
Participant milestones
| Measure |
AG-348 in Participants With Sickle Cell Disease
Intra-patient dose escalating study, starting with 5 mg twice a day, increasing to 20 mg twice a day, to maximum 50 mg or 100 mg twice a day. Dosing period is every 2 weeks at each dose level. Dose taper will start on Day 42 (50 mg) or Day 56 (100 mg) with dose reduced over 12 to 15 days.
|
|---|---|
|
Overall Study
STARTED
|
17
|
|
Overall Study
Completed Study at 50 mg Dose
|
7
|
|
Overall Study
Escalated to 100 mg
|
10
|
|
Overall Study
COMPLETED
|
15
|
|
Overall Study
NOT COMPLETED
|
2
|
Reasons for withdrawal
| Measure |
AG-348 in Participants With Sickle Cell Disease
Intra-patient dose escalating study, starting with 5 mg twice a day, increasing to 20 mg twice a day, to maximum 50 mg or 100 mg twice a day. Dosing period is every 2 weeks at each dose level. Dose taper will start on Day 42 (50 mg) or Day 56 (100 mg) with dose reduced over 12 to 15 days.
|
|---|---|
|
Overall Study
Physician Decision
|
1
|
|
Overall Study
Withdrawal by Subject
|
1
|
Baseline Characteristics
A Dose-Finding Study of AG-348 in Sickle Cell Disease
Baseline characteristics by cohort
| Measure |
AG-348 in Participants With Sickle Cell Disease
n=17 Participants
Intra-patient dose escalating study, starting with 5 mg twice a day, increasing to 20 mg twice a day, to maximum 50 mg or 100 mg twice a day. Dosing period is every 2 weeks at each dose level. Dose taper will start on Day 42 (50 mg) or Day 56 (100 mg) with dose reduced over 12 to 15 days.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
17 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
11 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
17 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
17 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
17 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 14 weeksTo assess the clinical safety and tolerability of multiple escalating doses of AG-348, an allosteric activator of the enzyme pyruvate kinase, in subjects with stable sickle cell disease (SCD). Safety and tolerability were assessed by frequency and severity of adverse events (AEs) using Common Terminology Criteria for Adverse Events (CTCAE) 5.0.
Outcome measures
| Measure |
AG-348 in Participants With Sickle Cell Disease
n=17 Participants
Intra-patient dose escalating study, starting with 5 mg twice a day, increasing to 20 mg twice a day, to maximum 50 mg or 100 mg twice a day. Dosing period is every 2 weeks at each dose level. Dose taper will start on Day 42 (50 mg) or Day 56 (100 mg) with dose reduced over 12 to 15 days.
|
|---|---|
|
Number Participants With Most Common Reported Drug Related Adverse Events
Insomnia
|
6 Participants
|
|
Number Participants With Most Common Reported Drug Related Adverse Events
Arthralgia
|
3 Participants
|
|
Number Participants With Most Common Reported Drug Related Adverse Events
Hypertension
|
3 Participants
|
PRIMARY outcome
Timeframe: 14 weeksTo assess the clinical safety and tolerability of multiple escalating doses of AG-348, an allosteric activator of the enzyme pyruvate kinase, in subjects with stable sickle cell disease (SCD). Safety and tolerability were assessed by frequency and severity of adverse events (AEs) using Common Terminology Criteria for Adverse Events (CTCAE) 5.0.
Outcome measures
| Measure |
AG-348 in Participants With Sickle Cell Disease
n=17 Participants
Intra-patient dose escalating study, starting with 5 mg twice a day, increasing to 20 mg twice a day, to maximum 50 mg or 100 mg twice a day. Dosing period is every 2 weeks at each dose level. Dose taper will start on Day 42 (50 mg) or Day 56 (100 mg) with dose reduced over 12 to 15 days.
|
|---|---|
|
Number Participants With Serious Adverse Events That Were Possibly Drug-related Serious Adverse Events
|
2 Participants
|
PRIMARY outcome
Timeframe: 14 weeksPopulation: One participant, withdrawn 3 days after starting the study for a pre-existing pulmonary embolus, was not evaluable for response. Intention to treat analysis.
To assess the clinical safety and tolerability of multiple escalating doses of AG-348, an allosteric activator of the enzyme pyruvate kinase, in subjects with stable sickle cell disease (SCD). Safety and tolerability were assessed by defined as a ≥ 1 g/dL increase in hemoglobin at any dose level compared to baseline.
Outcome measures
| Measure |
AG-348 in Participants With Sickle Cell Disease
n=16 Participants
Intra-patient dose escalating study, starting with 5 mg twice a day, increasing to 20 mg twice a day, to maximum 50 mg or 100 mg twice a day. Dosing period is every 2 weeks at each dose level. Dose taper will start on Day 42 (50 mg) or Day 56 (100 mg) with dose reduced over 12 to 15 days.
|
|---|---|
|
Number Participants With Increase of ≥ 1 g/dL in Hemoglobin
|
9 Participants
|
SECONDARY outcome
Timeframe: 14 weeksPopulation: One participant, withdrawn 3 days after starting the study for a pre-existing pulmonary embolus, was not evaluable for response. 10 participants escalated to 100 mg dose with 1 participant self-discontinued 3 days after escalating to 100 mg dose. Intention to treat analysis.
To assess change in hemoglobin in stable sickle cell disease participants at each dose level of AG-348
Outcome measures
| Measure |
AG-348 in Participants With Sickle Cell Disease
n=16 Participants
Intra-patient dose escalating study, starting with 5 mg twice a day, increasing to 20 mg twice a day, to maximum 50 mg or 100 mg twice a day. Dosing period is every 2 weeks at each dose level. Dose taper will start on Day 42 (50 mg) or Day 56 (100 mg) with dose reduced over 12 to 15 days.
|
|---|---|
|
Change in Hemoglobin at Each Dose Level of AG-348
Baseline
|
8.73 g/dL
Standard Error 0.51
|
|
Change in Hemoglobin at Each Dose Level of AG-348
5 mg dose of AG-348
|
0.34 g/dL
Standard Error 0.22
|
|
Change in Hemoglobin at Each Dose Level of AG-348
20 mg dose AG-348
|
0.76 g/dL
Standard Error 0.22
|
|
Change in Hemoglobin at Each Dose Level of AG-348
50 mg dose AG-348
|
1.19 g/dL
Standard Error 0.22
|
|
Change in Hemoglobin at Each Dose Level of AG-348
100 mg dose AG-348
|
0.92 g/dL
Standard Error 0.26
|
|
Change in Hemoglobin at Each Dose Level of AG-348
End of Taper Dose AG-348
|
0.34 g/dL
Standard Error 0.22
|
|
Change in Hemoglobin at Each Dose Level of AG-348
End of Study AG-348
|
0.37 g/dL
Standard Error 0.22
|
SECONDARY outcome
Timeframe: 14 weeksPopulation: One participant, withdrawn 3 days after starting the study for a pre-existing pulmonary embolus, was not evaluable for response. 10 participants escalated to 100 mg dose with 1 participant self-discontinued 3 days after escalating to 100 mg dose. Intention to treat analysis.
To assess change in lactic acid dehydrogenase (LDH) in stable sickle cell disease participants at each dose level of AG-348
Outcome measures
| Measure |
AG-348 in Participants With Sickle Cell Disease
n=16 Participants
Intra-patient dose escalating study, starting with 5 mg twice a day, increasing to 20 mg twice a day, to maximum 50 mg or 100 mg twice a day. Dosing period is every 2 weeks at each dose level. Dose taper will start on Day 42 (50 mg) or Day 56 (100 mg) with dose reduced over 12 to 15 days.
|
|---|---|
|
Change in Lactic Acid Dehydrogenase (LDH) at Each Dose Level of AG-348
Baseline
|
348.4 U/L
Standard Error 51.21
|
|
Change in Lactic Acid Dehydrogenase (LDH) at Each Dose Level of AG-348
5 mg dose of AG-348
|
-7.81 U/L
Standard Error 27.81
|
|
Change in Lactic Acid Dehydrogenase (LDH) at Each Dose Level of AG-348
20 mg dose AG-348
|
-39.94 U/L
Standard Error 27.81
|
|
Change in Lactic Acid Dehydrogenase (LDH) at Each Dose Level of AG-348
50 mg dose AG-348
|
-25.31 U/L
Standard Error 27.81
|
|
Change in Lactic Acid Dehydrogenase (LDH) at Each Dose Level of AG-348
100 mg dose AG-348
|
-37.89 U/L
Standard Error 34.95
|
|
Change in Lactic Acid Dehydrogenase (LDH) at Each Dose Level of AG-348
End of Taper Dose AG-348
|
20.63 U/L
Standard Error 28.35
|
|
Change in Lactic Acid Dehydrogenase (LDH) at Each Dose Level of AG-348
End of Study AG-348
|
30.72 U/L
Standard Error 28.34
|
SECONDARY outcome
Timeframe: 14 weeksPopulation: One participant, withdrawn 3 days after starting the study for a pre-existing pulmonary embolus, was not evaluable for response. 10 participants escalated to 100 mg dose with 1 participant self-discontinued 3 days after escalating to 100 mg dose. Intention to treat analysis.
To assess change in total bilirubin in stable sickle cell disease participants at each dose level of AG-348
Outcome measures
| Measure |
AG-348 in Participants With Sickle Cell Disease
n=16 Participants
Intra-patient dose escalating study, starting with 5 mg twice a day, increasing to 20 mg twice a day, to maximum 50 mg or 100 mg twice a day. Dosing period is every 2 weeks at each dose level. Dose taper will start on Day 42 (50 mg) or Day 56 (100 mg) with dose reduced over 12 to 15 days.
|
|---|---|
|
Change in Total Bilirubin at Each Dose Level of AG-348
Baseline
|
1.82 mg/dL
Standard Error 0.28
|
|
Change in Total Bilirubin at Each Dose Level of AG-348
5 mg dose of AG-348
|
-0.19 mg/dL
Standard Error 0.17
|
|
Change in Total Bilirubin at Each Dose Level of AG-348
20 mg dose AG-348
|
-0.56 mg/dL
Standard Error 0.17
|
|
Change in Total Bilirubin at Each Dose Level of AG-348
100 mg dose AG-348
|
-0.87 mg/dL
Standard Error 0.2
|
|
Change in Total Bilirubin at Each Dose Level of AG-348
End Of Taper Dose AG-348
|
-0.19 mg/dL
Standard Error 0.17
|
|
Change in Total Bilirubin at Each Dose Level of AG-348
End of Study AG-348
|
0.1 mg/dL
Standard Error 0.17
|
|
Change in Total Bilirubin at Each Dose Level of AG-348
50 mg dose AG-348
|
-0.77 mg/dL
Standard Error 0.17
|
SECONDARY outcome
Timeframe: 14 weeksPopulation: One participant, withdrawn 3 days after starting the study for a pre-existing pulmonary embolus, was not evaluable for response. 10 participants escalated to 100 mg dose with 1 participant self-discontinued 3 days after escalating to 100 mg dose. Intention to treat analysis.
To assess change in absolute reticulocyte count in stable sickle cell disease participants at each dose level of AG-348
Outcome measures
| Measure |
AG-348 in Participants With Sickle Cell Disease
n=16 Participants
Intra-patient dose escalating study, starting with 5 mg twice a day, increasing to 20 mg twice a day, to maximum 50 mg or 100 mg twice a day. Dosing period is every 2 weeks at each dose level. Dose taper will start on Day 42 (50 mg) or Day 56 (100 mg) with dose reduced over 12 to 15 days.
|
|---|---|
|
Change in Absolute Reticulocyte Count at Each Dose Level of AG-348
Baseline
|
196.44 K/mcL
Standard Error 39.88
|
|
Change in Absolute Reticulocyte Count at Each Dose Level of AG-348
5 mg dose of AG-348
|
-20.97 K/mcL
Standard Error 13.95
|
|
Change in Absolute Reticulocyte Count at Each Dose Level of AG-348
20 mg dose AG-348
|
-20.72 K/mcL
Standard Error 13.95
|
|
Change in Absolute Reticulocyte Count at Each Dose Level of AG-348
50 mg dose AG-348
|
-44.99 K/mcL
Standard Error 13.95
|
|
Change in Absolute Reticulocyte Count at Each Dose Level of AG-348
100 mg dose AG-348
|
-34.1 K/mcL
Standard Error 16.82
|
|
Change in Absolute Reticulocyte Count at Each Dose Level of AG-348
End of Taper Dose AG-348
|
-13.77 K/mcL
Standard Error 14.22
|
|
Change in Absolute Reticulocyte Count at Each Dose Level of AG-348
End of Study AG-348
|
8.1 K/mcL
Standard Error 14.22
|
SECONDARY outcome
Timeframe: 14 weeksPopulation: One participant, withdrawn 3 days after starting the study for a pre-existing pulmonary embolus, was not evaluable for response. 10 participants escalated to 100 mg dose with 1 participant self-discontinued 3 days after escalating to 100 mg dose. Intention to treat analysis.
To assess change in aspartate aminotransferase (AST) in stable sickle cell disease participants at each dose level of AG-348
Outcome measures
| Measure |
AG-348 in Participants With Sickle Cell Disease
n=16 Participants
Intra-patient dose escalating study, starting with 5 mg twice a day, increasing to 20 mg twice a day, to maximum 50 mg or 100 mg twice a day. Dosing period is every 2 weeks at each dose level. Dose taper will start on Day 42 (50 mg) or Day 56 (100 mg) with dose reduced over 12 to 15 days.
|
|---|---|
|
Change in Aspartate Aminotransferase (AST) at Each Dose Level of AG-348
Baseline
|
33.88 U/L
Standard Error 5.94
|
|
Change in Aspartate Aminotransferase (AST) at Each Dose Level of AG-348
5 mg dose of AG-348
|
-3.31 U/L
Standard Error 3.43
|
|
Change in Aspartate Aminotransferase (AST) at Each Dose Level of AG-348
20 mg dose AG-348
|
-3.37 U/L
Standard Error 3.43
|
|
Change in Aspartate Aminotransferase (AST) at Each Dose Level of AG-348
50 mg dose AG-348
|
-2 U/L
Standard Error 3.43
|
|
Change in Aspartate Aminotransferase (AST) at Each Dose Level of AG-348
100 mg dose AG-348
|
-3.54 U/L
Standard Error 4.13
|
|
Change in Aspartate Aminotransferase (AST) at Each Dose Level of AG-348
End of Taper Dose AG-348
|
-2.49 U/L
Standard Error 3.49
|
|
Change in Aspartate Aminotransferase (AST) at Each Dose Level of AG-348
End of Study AG-348
|
3.02 U/L
Standard Error 3.49
|
SECONDARY outcome
Timeframe: 14 weeksPopulation: One participant, withdrawn 3 days after starting the study for a pre-existing pulmonary embolus, was not evaluable for response. 10 participants escalated to 100 mg dose with 1 participant self-discontinued 3 days after escalating to 100 mg dose. Intention to treat analysis.
To assess change in mean corpuscular volume (MCV) in stable sickle cell disease participants at each dose level of AG-348
Outcome measures
| Measure |
AG-348 in Participants With Sickle Cell Disease
n=16 Participants
Intra-patient dose escalating study, starting with 5 mg twice a day, increasing to 20 mg twice a day, to maximum 50 mg or 100 mg twice a day. Dosing period is every 2 weeks at each dose level. Dose taper will start on Day 42 (50 mg) or Day 56 (100 mg) with dose reduced over 12 to 15 days.
|
|---|---|
|
Change in Mean Corpuscular Volume (MCV) at Each Dose Level of AG-348
Baseline
|
103.32 fL
Standard Error 7.42
|
|
Change in Mean Corpuscular Volume (MCV) at Each Dose Level of AG-348
5 mg dose of AG-348
|
-0.5 fL
Standard Error 0.8
|
|
Change in Mean Corpuscular Volume (MCV) at Each Dose Level of AG-348
20 mg dose AG-348
|
0.52 fL
Standard Error 0.8
|
|
Change in Mean Corpuscular Volume (MCV) at Each Dose Level of AG-348
50 mg dose AG-348
|
0.42 fL
Standard Error 0.8
|
|
Change in Mean Corpuscular Volume (MCV) at Each Dose Level of AG-348
End of Taper Dose AG-348
|
-0.25 fL
Standard Error 0.84
|
|
Change in Mean Corpuscular Volume (MCV) at Each Dose Level of AG-348
End of Study AG-348
|
-0.64 fL
Standard Error 0.82
|
|
Change in Mean Corpuscular Volume (MCV) at Each Dose Level of AG-348
100 mg dose AG-348
|
1.98 fL
Standard Error 1.01
|
SECONDARY outcome
Timeframe: 14 weeksPopulation: One participant, withdrawn 3 days after starting the study for a pre-existing pulmonary embolus, was not evaluable for response. 10 participants escalated to 100 mg dose with 1 participant self-discontinued 3 days after escalating to 100 mg dose. Intention to treat analysis.
To assess the change in fetal hemoglobin (HbF) in stable sickle cell disease participants at each dose level of AG-348
Outcome measures
| Measure |
AG-348 in Participants With Sickle Cell Disease
n=16 Participants
Intra-patient dose escalating study, starting with 5 mg twice a day, increasing to 20 mg twice a day, to maximum 50 mg or 100 mg twice a day. Dosing period is every 2 weeks at each dose level. Dose taper will start on Day 42 (50 mg) or Day 56 (100 mg) with dose reduced over 12 to 15 days.
|
|---|---|
|
Change in Fetal Hemoglobin at Each Dose Level of AG-348
Baseline
|
20.39 Percent HbF
Standard Error 4.26
|
|
Change in Fetal Hemoglobin at Each Dose Level of AG-348
5 mg dose of AG-348
|
-0.42 Percent HbF
Standard Error 0.49
|
|
Change in Fetal Hemoglobin at Each Dose Level of AG-348
20 mg dose AG-348
|
-1.02 Percent HbF
Standard Error 0.49
|
|
Change in Fetal Hemoglobin at Each Dose Level of AG-348
50 mg dose AG-348
|
-1.31 Percent HbF
Standard Error 0.49
|
|
Change in Fetal Hemoglobin at Each Dose Level of AG-348
100 mg dose AG-348
|
-0.34 Percent HbF
Standard Error 0.56
|
|
Change in Fetal Hemoglobin at Each Dose Level of AG-348
End of Taper Dose AG-348
|
0.19 Percent HbF
Standard Error 0.47
|
|
Change in Fetal Hemoglobin at Each Dose Level of AG-348
End of Study AG-348
|
0.81 Percent HbF
Standard Error 0.47
|
SECONDARY outcome
Timeframe: 14 weeksPopulation: One participant, withdrawn 3 days after starting the study for a pre-existing pulmonary embolus, was not evaluable for response. 10 participants escalated to 100 mg dose with 1 participant self-discontinued 3 days after escalating to 100 mg dose. Intention to treat analysis.
To understand the mechanisms of action of AG- 348 on the glycolytic pathway in sickle cell disease through laboratory studies of specific pharmacodynamics of 2,3-DPG at each dose level of AG-348.
Outcome measures
| Measure |
AG-348 in Participants With Sickle Cell Disease
n=16 Participants
Intra-patient dose escalating study, starting with 5 mg twice a day, increasing to 20 mg twice a day, to maximum 50 mg or 100 mg twice a day. Dosing period is every 2 weeks at each dose level. Dose taper will start on Day 42 (50 mg) or Day 56 (100 mg) with dose reduced over 12 to 15 days.
|
|---|---|
|
Percent Change From Baseline of 2,3-DPG at Each Dose Level of AG-348
5 mg Dose AG-348
|
-3.74 percent change
Standard Error 3.65
|
|
Percent Change From Baseline of 2,3-DPG at Each Dose Level of AG-348
20 mg Dose AG-348
|
-16.08 percent change
Standard Error 3.65
|
|
Percent Change From Baseline of 2,3-DPG at Each Dose Level of AG-348
50 mg Dose AG-348
|
-23.49 percent change
Standard Error 3.65
|
|
Percent Change From Baseline of 2,3-DPG at Each Dose Level of AG-348
100 mg Dose AG-348
|
-24.13 percent change
Standard Error 4.12
|
|
Percent Change From Baseline of 2,3-DPG at Each Dose Level of AG-348
End of Taper Dose AG-348
|
1.97 percent change
Standard Error 3.68
|
|
Percent Change From Baseline of 2,3-DPG at Each Dose Level of AG-348
End of Study AG-348
|
9.11 percent change
Standard Error 3.68
|
SECONDARY outcome
Timeframe: 14 weeksPopulation: One participant, withdrawn 3 days after starting the study for a pre-existing pulmonary embolus, was not evaluable for response. 10 participants escalated to 100 mg dose with 1 participant self-discontinued 3 days after escalating to 100 mg dose. Intention to treat analysis.
To understand the mechanisms of action of AG- 348 on the glycolytic pathway in sickle cell disease through laboratory studies of specific pharmacodynamics of adenosine triphosphate (ATP) at each dose level of AG-348.
Outcome measures
| Measure |
AG-348 in Participants With Sickle Cell Disease
n=16 Participants
Intra-patient dose escalating study, starting with 5 mg twice a day, increasing to 20 mg twice a day, to maximum 50 mg or 100 mg twice a day. Dosing period is every 2 weeks at each dose level. Dose taper will start on Day 42 (50 mg) or Day 56 (100 mg) with dose reduced over 12 to 15 days.
|
|---|---|
|
Percent Change From Baseline of Adenosine Triphosphate (ATP) at Each Dose Level of AG-348
5 mg Dose AG-348
|
13.68 percent change
Standard Error 6.29
|
|
Percent Change From Baseline of Adenosine Triphosphate (ATP) at Each Dose Level of AG-348
20 mg Dose AG-348
|
26.95 percent change
Standard Error 6.29
|
|
Percent Change From Baseline of Adenosine Triphosphate (ATP) at Each Dose Level of AG-348
50 mg Dose AG-348
|
33.43 percent change
Standard Error 6.29
|
|
Percent Change From Baseline of Adenosine Triphosphate (ATP) at Each Dose Level of AG-348
100 mg Dose AG-348
|
39.84 percent change
Standard Error 6.74
|
|
Percent Change From Baseline of Adenosine Triphosphate (ATP) at Each Dose Level of AG-348
End of Taper Dose AG-348
|
15.51 percent change
Standard Error 6.31
|
|
Percent Change From Baseline of Adenosine Triphosphate (ATP) at Each Dose Level of AG-348
End of Study AG-348
|
12.03 percent change
Standard Error 6.31
|
SECONDARY outcome
Timeframe: 14 weeksPopulation: One participant, withdrawn 3 days after starting the study for a pre-existing pulmonary embolus, was not evaluable for response. 10 participants escalated to 100 mg dose with 1 participant self-discontinued 3 days after escalating to 100 mg dose. Intention to treat analysis.
Measure percent change from baseline in oxygen binding p50 value at each dose level of AG-348
Outcome measures
| Measure |
AG-348 in Participants With Sickle Cell Disease
n=16 Participants
Intra-patient dose escalating study, starting with 5 mg twice a day, increasing to 20 mg twice a day, to maximum 50 mg or 100 mg twice a day. Dosing period is every 2 weeks at each dose level. Dose taper will start on Day 42 (50 mg) or Day 56 (100 mg) with dose reduced over 12 to 15 days.
|
|---|---|
|
Percent Change From Baseline in Oxygen Binding p50 Value at Each Dose Level of AG-348
5 mg Dose AG-348
|
0.5 Percent Change
Standard Error 2.88
|
|
Percent Change From Baseline in Oxygen Binding p50 Value at Each Dose Level of AG-348
20 mg Dose AG-348
|
-2.09 Percent Change
Standard Error 3.01
|
|
Percent Change From Baseline in Oxygen Binding p50 Value at Each Dose Level of AG-348
50 mg Dose AG-348
|
-3.84 Percent Change
Standard Error 3.19
|
|
Percent Change From Baseline in Oxygen Binding p50 Value at Each Dose Level of AG-348
100 mg Dose AG-348
|
-4.88 Percent Change
Standard Error 3.9
|
|
Percent Change From Baseline in Oxygen Binding p50 Value at Each Dose Level of AG-348
End of Taper Dose AG-348
|
7.97 Percent Change
Standard Error 3.1
|
|
Percent Change From Baseline in Oxygen Binding p50 Value at Each Dose Level of AG-348
End of Study AG-348
|
10.79 Percent Change
Standard Error 3.39
|
SECONDARY outcome
Timeframe: 14 weeksPopulation: One participant, withdrawn 3 days after starting the study for a pre-existing pulmonary embolus, was not evaluable for response. 10 participants escalated to 100 mg dose with 1 participant self-discontinued 3 days after escalating to 100 mg dose. Intention to treat analysis.
Measure percent change in Time (mins) at which 50% of red blood cells are sickled (t50) Value at Each Dose Level of AG-348
Outcome measures
| Measure |
AG-348 in Participants With Sickle Cell Disease
n=16 Participants
Intra-patient dose escalating study, starting with 5 mg twice a day, increasing to 20 mg twice a day, to maximum 50 mg or 100 mg twice a day. Dosing period is every 2 weeks at each dose level. Dose taper will start on Day 42 (50 mg) or Day 56 (100 mg) with dose reduced over 12 to 15 days.
|
|---|---|
|
Percent Change in Time (Mins) at Which 50% of Red Blood Cells Are Sickled (t50) Value at Each Dose Level of AG-348
5 mg Dose AG-348
|
-0.46 percent change
Standard Error 9.68
|
|
Percent Change in Time (Mins) at Which 50% of Red Blood Cells Are Sickled (t50) Value at Each Dose Level of AG-348
20 mg Dose AG-348
|
10.19 percent change
Standard Error 9.75
|
|
Percent Change in Time (Mins) at Which 50% of Red Blood Cells Are Sickled (t50) Value at Each Dose Level of AG-348
50 mg Dose AG-348
|
7.11 percent change
Standard Error 9.84
|
|
Percent Change in Time (Mins) at Which 50% of Red Blood Cells Are Sickled (t50) Value at Each Dose Level of AG-348
100 mg Dose AG-348
|
13.98 percent change
Standard Error 12.44
|
|
Percent Change in Time (Mins) at Which 50% of Red Blood Cells Are Sickled (t50) Value at Each Dose Level of AG-348
End of Taper AG-348
|
-11.38 percent change
Standard Error 9.76
|
|
Percent Change in Time (Mins) at Which 50% of Red Blood Cells Are Sickled (t50) Value at Each Dose Level of AG-348
End of Study AG-348
|
1.67 percent change
Standard Error 10.13
|
SECONDARY outcome
Timeframe: 14 weeksPopulation: One participant, withdrawn 3 days after starting the study for a pre-existing pulmonary embolus, was not evaluable for response. 10 participants escalated to 100 mg dose with 1 participant self-discontinued 3 days after escalating to 100 mg dose. Intention to treat analysis.
To understand the mechanisms of action of AG- 348 on the glycolytic pathway in sickle cell disease through laboratory studies of specific pharmacodynamics of PK-R at each dose level of AG-348.
Outcome measures
| Measure |
AG-348 in Participants With Sickle Cell Disease
n=16 Participants
Intra-patient dose escalating study, starting with 5 mg twice a day, increasing to 20 mg twice a day, to maximum 50 mg or 100 mg twice a day. Dosing period is every 2 weeks at each dose level. Dose taper will start on Day 42 (50 mg) or Day 56 (100 mg) with dose reduced over 12 to 15 days.
|
|---|---|
|
Percent Change of PK-R at Each Dose Level of AG-348
5 mg Dose AG-348
|
-6.89 percent change
Standard Error 6.94
|
|
Percent Change of PK-R at Each Dose Level of AG-348
20 mg Dose AG-348
|
-2.82 percent change
Standard Error 6.94
|
|
Percent Change of PK-R at Each Dose Level of AG-348
50 mg Dose AG-348
|
-10.66 percent change
Standard Error 6.94
|
|
Percent Change of PK-R at Each Dose Level of AG-348
100 mg Dose AG-348
|
-28.99 percent change
Standard Error 7.7
|
|
Percent Change of PK-R at Each Dose Level of AG-348
End of Taper AG-348
|
-8.38 percent change
Standard Error 6.98
|
|
Percent Change of PK-R at Each Dose Level of AG-348
End of Study AG-348
|
-16.47 percent change
Standard Error 6.98
|
Adverse Events
AG-348 in Participants With Sickle Cell Disease
Serious events: 6 serious events
Other events: 16 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
AG-348 in Participants With Sickle Cell Disease
n=17 participants at risk
Intra-patient dose escalating, starting with 5 mg twice a day, increasing to 20 mg twice a day, to maximum 50 mg or 100 mg twice a day. Dosing period is every 2 weeks at each dose level. Dose taper will start on Day 42 (50 mg) or Day 56 (100 mg) with dose reduced over 12 to 15 days.
|
|---|---|
|
Congenital, familial and genetic disorders
Sickle cell anemia with crisis
|
23.5%
4/17 • Number of events 4 • 1 year
All Adverse Events (serious and non-serious) spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination, or other diagnostic procedures will be recorded. AE were pre-specified to be collected as a single Arm/Group irrespective of dose level.
|
|
General disorders
Pain
|
5.9%
1/17 • Number of events 1 • 1 year
All Adverse Events (serious and non-serious) spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination, or other diagnostic procedures will be recorded. AE were pre-specified to be collected as a single Arm/Group irrespective of dose level.
|
|
Vascular disorders
Thromboembolic event: Pulmonary embolism
|
5.9%
1/17 • Number of events 1 • 1 year
All Adverse Events (serious and non-serious) spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination, or other diagnostic procedures will be recorded. AE were pre-specified to be collected as a single Arm/Group irrespective of dose level.
|
Other adverse events
| Measure |
AG-348 in Participants With Sickle Cell Disease
n=17 participants at risk
Intra-patient dose escalating, starting with 5 mg twice a day, increasing to 20 mg twice a day, to maximum 50 mg or 100 mg twice a day. Dosing period is every 2 weeks at each dose level. Dose taper will start on Day 42 (50 mg) or Day 56 (100 mg) with dose reduced over 12 to 15 days.
|
|---|---|
|
Metabolism and nutrition disorders
Hyperkalemia
|
5.9%
1/17 • Number of events 1 • 1 year
All Adverse Events (serious and non-serious) spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination, or other diagnostic procedures will be recorded. AE were pre-specified to be collected as a single Arm/Group irrespective of dose level.
|
|
Metabolism and nutrition disorders
Hyperuricemia
|
17.6%
3/17 • Number of events 3 • 1 year
All Adverse Events (serious and non-serious) spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination, or other diagnostic procedures will be recorded. AE were pre-specified to be collected as a single Arm/Group irrespective of dose level.
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
5.9%
1/17 • Number of events 1 • 1 year
All Adverse Events (serious and non-serious) spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination, or other diagnostic procedures will be recorded. AE were pre-specified to be collected as a single Arm/Group irrespective of dose level.
|
|
Metabolism and nutrition disorders
Hypokalemia
|
5.9%
1/17 • Number of events 1 • 1 year
All Adverse Events (serious and non-serious) spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination, or other diagnostic procedures will be recorded. AE were pre-specified to be collected as a single Arm/Group irrespective of dose level.
|
|
Metabolism and nutrition disorders
Hyponatremia
|
17.6%
3/17 • Number of events 3 • 1 year
All Adverse Events (serious and non-serious) spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination, or other diagnostic procedures will be recorded. AE were pre-specified to be collected as a single Arm/Group irrespective of dose level.
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
5.9%
1/17 • Number of events 1 • 1 year
All Adverse Events (serious and non-serious) spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination, or other diagnostic procedures will be recorded. AE were pre-specified to be collected as a single Arm/Group irrespective of dose level.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
17.6%
3/17 • Number of events 3 • 1 year
All Adverse Events (serious and non-serious) spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination, or other diagnostic procedures will be recorded. AE were pre-specified to be collected as a single Arm/Group irrespective of dose level.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
11.8%
2/17 • Number of events 2 • 1 year
All Adverse Events (serious and non-serious) spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination, or other diagnostic procedures will be recorded. AE were pre-specified to be collected as a single Arm/Group irrespective of dose level.
|
|
Musculoskeletal and connective tissue disorders
Chest wall pain
|
5.9%
1/17 • Number of events 3 • 1 year
All Adverse Events (serious and non-serious) spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination, or other diagnostic procedures will be recorded. AE were pre-specified to be collected as a single Arm/Group irrespective of dose level.
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
5.9%
1/17 • Number of events 1 • 1 year
All Adverse Events (serious and non-serious) spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination, or other diagnostic procedures will be recorded. AE were pre-specified to be collected as a single Arm/Group irrespective of dose level.
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
5.9%
1/17 • Number of events 1 • 1 year
All Adverse Events (serious and non-serious) spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination, or other diagnostic procedures will be recorded. AE were pre-specified to be collected as a single Arm/Group irrespective of dose level.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
5.9%
1/17 • Number of events 1 • 1 year
All Adverse Events (serious and non-serious) spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination, or other diagnostic procedures will be recorded. AE were pre-specified to be collected as a single Arm/Group irrespective of dose level.
|
|
Nervous system disorders
Dizziness
|
5.9%
1/17 • Number of events 1 • 1 year
All Adverse Events (serious and non-serious) spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination, or other diagnostic procedures will be recorded. AE were pre-specified to be collected as a single Arm/Group irrespective of dose level.
|
|
Nervous system disorders
Dysesthesia
|
5.9%
1/17 • Number of events 1 • 1 year
All Adverse Events (serious and non-serious) spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination, or other diagnostic procedures will be recorded. AE were pre-specified to be collected as a single Arm/Group irrespective of dose level.
|
|
Nervous system disorders
Headache
|
17.6%
3/17 • Number of events 3 • 1 year
All Adverse Events (serious and non-serious) spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination, or other diagnostic procedures will be recorded. AE were pre-specified to be collected as a single Arm/Group irrespective of dose level.
|
|
Psychiatric disorders
Anxiety
|
5.9%
1/17 • Number of events 1 • 1 year
All Adverse Events (serious and non-serious) spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination, or other diagnostic procedures will be recorded. AE were pre-specified to be collected as a single Arm/Group irrespective of dose level.
|
|
Psychiatric disorders
Insomnia
|
41.2%
7/17 • Number of events 7 • 1 year
All Adverse Events (serious and non-serious) spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination, or other diagnostic procedures will be recorded. AE were pre-specified to be collected as a single Arm/Group irrespective of dose level.
|
|
Renal and urinary disorders
Hematuria
|
5.9%
1/17 • Number of events 1 • 1 year
All Adverse Events (serious and non-serious) spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination, or other diagnostic procedures will be recorded. AE were pre-specified to be collected as a single Arm/Group irrespective of dose level.
|
|
Renal and urinary disorders
Proteinuria
|
5.9%
1/17 • Number of events 1 • 1 year
All Adverse Events (serious and non-serious) spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination, or other diagnostic procedures will be recorded. AE were pre-specified to be collected as a single Arm/Group irrespective of dose level.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
5.9%
1/17 • Number of events 1 • 1 year
All Adverse Events (serious and non-serious) spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination, or other diagnostic procedures will be recorded. AE were pre-specified to be collected as a single Arm/Group irrespective of dose level.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
11.8%
2/17 • Number of events 2 • 1 year
All Adverse Events (serious and non-serious) spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination, or other diagnostic procedures will be recorded. AE were pre-specified to be collected as a single Arm/Group irrespective of dose level.
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
5.9%
1/17 • Number of events 1 • 1 year
All Adverse Events (serious and non-serious) spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination, or other diagnostic procedures will be recorded. AE were pre-specified to be collected as a single Arm/Group irrespective of dose level.
|
|
Respiratory, thoracic and mediastinal disorders
Lung crackles
|
5.9%
1/17 • Number of events 1 • 1 year
All Adverse Events (serious and non-serious) spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination, or other diagnostic procedures will be recorded. AE were pre-specified to be collected as a single Arm/Group irrespective of dose level.
|
|
Respiratory, thoracic and mediastinal disorders
Sneezing
|
5.9%
1/17 • Number of events 1 • 1 year
All Adverse Events (serious and non-serious) spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination, or other diagnostic procedures will be recorded. AE were pre-specified to be collected as a single Arm/Group irrespective of dose level.
|
|
Respiratory, thoracic and mediastinal disorders
Sore throat
|
11.8%
2/17 • Number of events 2 • 1 year
All Adverse Events (serious and non-serious) spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination, or other diagnostic procedures will be recorded. AE were pre-specified to be collected as a single Arm/Group irrespective of dose level.
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
5.9%
1/17 • Number of events 1 • 1 year
All Adverse Events (serious and non-serious) spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination, or other diagnostic procedures will be recorded. AE were pre-specified to be collected as a single Arm/Group irrespective of dose level.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
5.9%
1/17 • Number of events 1 • 1 year
All Adverse Events (serious and non-serious) spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination, or other diagnostic procedures will be recorded. AE were pre-specified to be collected as a single Arm/Group irrespective of dose level.
|
|
Skin and subcutaneous tissue disorders
Skin ulceration
|
11.8%
2/17 • Number of events 2 • 1 year
All Adverse Events (serious and non-serious) spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination, or other diagnostic procedures will be recorded. AE were pre-specified to be collected as a single Arm/Group irrespective of dose level.
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
5.9%
1/17 • Number of events 2 • 1 year
All Adverse Events (serious and non-serious) spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination, or other diagnostic procedures will be recorded. AE were pre-specified to be collected as a single Arm/Group irrespective of dose level.
|
|
Vascular disorders
Hypertension
|
17.6%
3/17 • Number of events 4 • 1 year
All Adverse Events (serious and non-serious) spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination, or other diagnostic procedures will be recorded. AE were pre-specified to be collected as a single Arm/Group irrespective of dose level.
|
|
Vascular disorders
Thromboembolic event: Pulmonary embolism
|
5.9%
1/17 • Number of events 1 • 1 year
All Adverse Events (serious and non-serious) spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination, or other diagnostic procedures will be recorded. AE were pre-specified to be collected as a single Arm/Group irrespective of dose level.
|
|
Blood and lymphatic system disorders
Anemia
|
17.6%
3/17 • Number of events 3 • 1 year
All Adverse Events (serious and non-serious) spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination, or other diagnostic procedures will be recorded. AE were pre-specified to be collected as a single Arm/Group irrespective of dose level.
|
|
Blood and lymphatic system disorders
Elevated C-Reactive Protein (CRP)
|
5.9%
1/17 • Number of events 1 • 1 year
All Adverse Events (serious and non-serious) spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination, or other diagnostic procedures will be recorded. AE were pre-specified to be collected as a single Arm/Group irrespective of dose level.
|
|
Blood and lymphatic system disorders
Iron deficiency anemia
|
5.9%
1/17 • Number of events 1 • 1 year
All Adverse Events (serious and non-serious) spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination, or other diagnostic procedures will be recorded. AE were pre-specified to be collected as a single Arm/Group irrespective of dose level.
|
|
Cardiac disorders
Palpitations
|
5.9%
1/17 • Number of events 1 • 1 year
All Adverse Events (serious and non-serious) spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination, or other diagnostic procedures will be recorded. AE were pre-specified to be collected as a single Arm/Group irrespective of dose level.
|
|
Eye disorders
Corneal scar
|
5.9%
1/17 • Number of events 1 • 1 year
All Adverse Events (serious and non-serious) spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination, or other diagnostic procedures will be recorded. AE were pre-specified to be collected as a single Arm/Group irrespective of dose level.
|
|
Eye disorders
Red eye (bilateral)
|
5.9%
1/17 • Number of events 2 • 1 year
All Adverse Events (serious and non-serious) spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination, or other diagnostic procedures will be recorded. AE were pre-specified to be collected as a single Arm/Group irrespective of dose level.
|
|
Gastrointestinal disorders
Diarrhea
|
11.8%
2/17 • Number of events 2 • 1 year
All Adverse Events (serious and non-serious) spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination, or other diagnostic procedures will be recorded. AE were pre-specified to be collected as a single Arm/Group irrespective of dose level.
|
|
Gastrointestinal disorders
Helicobacter Pylori
|
11.8%
2/17 • Number of events 2 • 1 year
All Adverse Events (serious and non-serious) spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination, or other diagnostic procedures will be recorded. AE were pre-specified to be collected as a single Arm/Group irrespective of dose level.
|
|
Gastrointestinal disorders
Vomiting and diarrhea
|
5.9%
1/17 • Number of events 1 • 1 year
All Adverse Events (serious and non-serious) spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination, or other diagnostic procedures will be recorded. AE were pre-specified to be collected as a single Arm/Group irrespective of dose level.
|
|
Gastrointestinal disorders
Gingival pain
|
5.9%
1/17 • Number of events 1 • 1 year
All Adverse Events (serious and non-serious) spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination, or other diagnostic procedures will be recorded. AE were pre-specified to be collected as a single Arm/Group irrespective of dose level.
|
|
General disorders
Chills
|
5.9%
1/17 • Number of events 1 • 1 year
All Adverse Events (serious and non-serious) spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination, or other diagnostic procedures will be recorded. AE were pre-specified to be collected as a single Arm/Group irrespective of dose level.
|
|
General disorders
Edema limbs
|
5.9%
1/17 • Number of events 1 • 1 year
All Adverse Events (serious and non-serious) spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination, or other diagnostic procedures will be recorded. AE were pre-specified to be collected as a single Arm/Group irrespective of dose level.
|
|
General disorders
Fatigue
|
5.9%
1/17 • Number of events 3 • 1 year
All Adverse Events (serious and non-serious) spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination, or other diagnostic procedures will be recorded. AE were pre-specified to be collected as a single Arm/Group irrespective of dose level.
|
|
General disorders
Fever
|
5.9%
1/17 • Number of events 1 • 1 year
All Adverse Events (serious and non-serious) spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination, or other diagnostic procedures will be recorded. AE were pre-specified to be collected as a single Arm/Group irrespective of dose level.
|
|
General disorders
Non-cardiac chest pain
|
5.9%
1/17 • Number of events 1 • 1 year
All Adverse Events (serious and non-serious) spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination, or other diagnostic procedures will be recorded. AE were pre-specified to be collected as a single Arm/Group irrespective of dose level.
|
|
General disorders
Pain
|
23.5%
4/17 • Number of events 4 • 1 year
All Adverse Events (serious and non-serious) spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination, or other diagnostic procedures will be recorded. AE were pre-specified to be collected as a single Arm/Group irrespective of dose level.
|
|
Infections and infestations
Upper respiratory infection
|
11.8%
2/17 • Number of events 2 • 1 year
All Adverse Events (serious and non-serious) spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination, or other diagnostic procedures will be recorded. AE were pre-specified to be collected as a single Arm/Group irrespective of dose level.
|
|
Injury, poisoning and procedural complications
Fall
|
5.9%
1/17 • Number of events 1 • 1 year
All Adverse Events (serious and non-serious) spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination, or other diagnostic procedures will be recorded. AE were pre-specified to be collected as a single Arm/Group irrespective of dose level.
|
|
Injury, poisoning and procedural complications
Finger laceration
|
5.9%
1/17 • Number of events 1 • 1 year
All Adverse Events (serious and non-serious) spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination, or other diagnostic procedures will be recorded. AE were pre-specified to be collected as a single Arm/Group irrespective of dose level.
|
|
Investigations
Aspartate aminotransferase increased
|
17.6%
3/17 • Number of events 3 • 1 year
All Adverse Events (serious and non-serious) spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination, or other diagnostic procedures will be recorded. AE were pre-specified to be collected as a single Arm/Group irrespective of dose level.
|
|
Investigations
Blood bicarbonate decreased
|
11.8%
2/17 • Number of events 2 • 1 year
All Adverse Events (serious and non-serious) spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination, or other diagnostic procedures will be recorded. AE were pre-specified to be collected as a single Arm/Group irrespective of dose level.
|
|
Investigations
Blood bilirubin increased
|
11.8%
2/17 • Number of events 3 • 1 year
All Adverse Events (serious and non-serious) spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination, or other diagnostic procedures will be recorded. AE were pre-specified to be collected as a single Arm/Group irrespective of dose level.
|
|
Investigations
CPK increased
|
23.5%
4/17 • Number of events 4 • 1 year
All Adverse Events (serious and non-serious) spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination, or other diagnostic procedures will be recorded. AE were pre-specified to be collected as a single Arm/Group irrespective of dose level.
|
|
Investigations
Creatinine increased
|
5.9%
1/17 • Number of events 1 • 1 year
All Adverse Events (serious and non-serious) spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination, or other diagnostic procedures will be recorded. AE were pre-specified to be collected as a single Arm/Group irrespective of dose level.
|
|
Investigations
Blood urea nitrogen increased
|
5.9%
1/17 • Number of events 1 • 1 year
All Adverse Events (serious and non-serious) spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination, or other diagnostic procedures will be recorded. AE were pre-specified to be collected as a single Arm/Group irrespective of dose level.
|
|
Investigations
Chloride increased
|
5.9%
1/17 • Number of events 1 • 1 year
All Adverse Events (serious and non-serious) spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination, or other diagnostic procedures will be recorded. AE were pre-specified to be collected as a single Arm/Group irrespective of dose level.
|
|
Investigations
Heart rate increased
|
17.6%
3/17 • Number of events 3 • 1 year
All Adverse Events (serious and non-serious) spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination, or other diagnostic procedures will be recorded. AE were pre-specified to be collected as a single Arm/Group irrespective of dose level.
|
|
Investigations
Urine urobilinogen increased
|
5.9%
1/17 • Number of events 1 • 1 year
All Adverse Events (serious and non-serious) spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination, or other diagnostic procedures will be recorded. AE were pre-specified to be collected as a single Arm/Group irrespective of dose level.
|
|
Investigations
White blood cell increased
|
5.9%
1/17 • Number of events 1 • 1 year
All Adverse Events (serious and non-serious) spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination, or other diagnostic procedures will be recorded. AE were pre-specified to be collected as a single Arm/Group irrespective of dose level.
|
|
Investigations
Lymphocyte count increased
|
5.9%
1/17 • Number of events 1 • 1 year
All Adverse Events (serious and non-serious) spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination, or other diagnostic procedures will be recorded. AE were pre-specified to be collected as a single Arm/Group irrespective of dose level.
|
|
Investigations
Neutrophil count decreased
|
5.9%
1/17 • Number of events 1 • 1 year
All Adverse Events (serious and non-serious) spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination, or other diagnostic procedures will be recorded. AE were pre-specified to be collected as a single Arm/Group irrespective of dose level.
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
29.4%
5/17 • Number of events 6 • 1 year
All Adverse Events (serious and non-serious) spontaneously reported by the subject and/or in response to an open question from study personnel or revealed by observation, physical examination, or other diagnostic procedures will be recorded. AE were pre-specified to be collected as a single Arm/Group irrespective of dose level.
|
Additional Information
Dr. Swee Lay Thein, Chief of Sickle Cell Branch
The National Institutes of Health / The National Heart, Lung, and Blood Institute
Phone: 301.402.6699
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place