Trial Outcomes & Findings for A Study to Determine the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of AG-348 in Adult Participants With Non-transfusion-dependent Thalassemia (NCT NCT03692052)
NCT ID: NCT03692052
Last Updated: 2026-01-29
Results Overview
HR was defined as a ≥1.0 gram per deciliter (g/dL) increase in Hb concentration from Baseline at 1 or more assessments between Week 4 and Week 12 (inclusive). A participant's Baseline Hb concentration was defined as the average of all the participant's available Hb concentrations during the screening period up to the first dose of study drug.
Recruitment status
ACTIVE_NOT_RECRUITING
Study phase
PHASE2
Target enrollment
20 participants
Primary outcome timeframe
Up to 12 weeks
Results posted on
2026-01-29
Participant Flow
Participants took part in the study at 4 investigative sites in the United States, Canada, and United Kingdom from 28 December 2018 to 30 September 2030. Results are reported for the primary and secondary outcome measures for the 24-week Core Period (data cut-off date: 20 August 2020). The Extension Period of this study is ongoing.
A total of 20 participants were enrolled in the Core Period of this study. The participants who completed the 24-week Core Period and achieved a hemoglobin (Hb) response or a delayed Hb response and had an acceptable safety profile were eligible to continue in the Extension Period.
Participant milestones
| Measure |
AG-348
Participants with alpha or beta thalassemia received AG-348 50 mg twice daily (BID), orally up to Week 6. Following Week 6, depending on the participants' safety and hemoglobin (Hb) concentrations, they could undergo one potential dose-level increase from 50 to 100 mg BID. After completion of the Core Period of 24 weeks, participants were eligible to continue to receive AG-348 in the Extension Period which is up to 10 years.
|
|---|---|
|
Core Period (Day 1 to Week 24)
STARTED
|
20
|
|
Core Period (Day 1 to Week 24)
COMPLETED
|
19
|
|
Core Period (Day 1 to Week 24)
NOT COMPLETED
|
1
|
|
Extension Period (Week 25 to 10 Years)
STARTED
|
19
|
|
Extension Period (Week 25 to 10 Years)
COMPLETED
|
0
|
|
Extension Period (Week 25 to 10 Years)
NOT COMPLETED
|
19
|
Reasons for withdrawal
| Measure |
AG-348
Participants with alpha or beta thalassemia received AG-348 50 mg twice daily (BID), orally up to Week 6. Following Week 6, depending on the participants' safety and hemoglobin (Hb) concentrations, they could undergo one potential dose-level increase from 50 to 100 mg BID. After completion of the Core Period of 24 weeks, participants were eligible to continue to receive AG-348 in the Extension Period which is up to 10 years.
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|---|---|
|
Core Period (Day 1 to Week 24)
Adverse Event
|
1
|
|
Extension Period (Week 25 to 10 Years)
Withdrawal of Consent
|
1
|
|
Extension Period (Week 25 to 10 Years)
Physician Decision
|
1
|
|
Extension Period (Week 25 to 10 Years)
Ongoing
|
17
|
Baseline Characteristics
A Study to Determine the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of AG-348 in Adult Participants With Non-transfusion-dependent Thalassemia
Baseline characteristics by cohort
| Measure |
AG-348
n=20 Participants
Participants with alpha or beta thalassemia received AG-348 50 mg BID, orally up to Week 6. Following Week 6, depending on the participants' safety and Hb concentrations, they could undergo one potential dose-level increase from 50 to 100 mg BID. After completion of the Core Period of 24 weeks, participants were eligible to continue to receive AG-348 in the Extension Period which is up to 10 years.
|
|---|---|
|
Age, Continuous
|
45.3 years
STANDARD_DEVIATION 11.81 • n=35 Participants
|
|
Sex: Female, Male
Female
|
15 Participants
n=35 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=35 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=35 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
19 Participants
n=35 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=35 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=35 Participants
|
|
Race (NIH/OMB)
Asian
|
10 Participants
n=35 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
1 Participants
n=35 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=35 Participants
|
|
Race (NIH/OMB)
White
|
4 Participants
n=35 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=35 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
4 Participants
n=35 Participants
|
PRIMARY outcome
Timeframe: Up to 12 weeksPopulation: FAS included all participants who received at least 1 dose of study treatment.
HR was defined as a ≥1.0 gram per deciliter (g/dL) increase in Hb concentration from Baseline at 1 or more assessments between Week 4 and Week 12 (inclusive). A participant's Baseline Hb concentration was defined as the average of all the participant's available Hb concentrations during the screening period up to the first dose of study drug.
Outcome measures
| Measure |
AG-348
n=20 Participants
Participants with alpha or beta thalassemia received AG-348 50 mg BID, orally up to Week 6. Following Week 6, depending on the participants' safety and Hb concentrations, they could undergo one potential dose-level increase from 50 to 100 mg BID. After completion of the Core Period of 24 weeks, participants were eligible to continue to receive AG-348 in the Extension Period which is up to 10 years.
|
|---|---|
|
Percentage of Participants Achieving a Hemoglobin Response (HR)
|
80.0 percentage of participants
Interval 59.9 to 92.86
|
SECONDARY outcome
Timeframe: Baseline, Week 12 to Week 24Population: FAS included all participants who received at least 1 dose of study treatment. Number analyzed is the number of participants with data available for analysis at the given time point.
A participant's Baseline Hb concentration was defined as the average of all the participant's available Hb concentrations during the screening period up to the first dose of study drug.
Outcome measures
| Measure |
AG-348
n=20 Participants
Participants with alpha or beta thalassemia received AG-348 50 mg BID, orally up to Week 6. Following Week 6, depending on the participants' safety and Hb concentrations, they could undergo one potential dose-level increase from 50 to 100 mg BID. After completion of the Core Period of 24 weeks, participants were eligible to continue to receive AG-348 in the Extension Period which is up to 10 years.
|
|---|---|
|
Average Change From Baseline in Hb Concentrations From Week 12 to Week 24
Baseline
|
79.44 grams per liter (g/L)
Standard Deviation 13.690
|
|
Average Change From Baseline in Hb Concentrations From Week 12 to Week 24
Average Change from Baseline: Week 12 to 24
|
13.01 grams per liter (g/L)
Standard Deviation 6.283
|
SECONDARY outcome
Timeframe: Week 12 to Week 24Population: FAS included all participants who received at least 1 dose of study treatment.
sHR was defined as achieving HR and achieving a ≥1.0 g/deciliter (dL) increase in Hb concentration at 2 or more evaluable Hb assessments out of the 4 scheduled assessments between the Week 12 visit and Week 24 visit.
Outcome measures
| Measure |
AG-348
n=20 Participants
Participants with alpha or beta thalassemia received AG-348 50 mg BID, orally up to Week 6. Following Week 6, depending on the participants' safety and Hb concentrations, they could undergo one potential dose-level increase from 50 to 100 mg BID. After completion of the Core Period of 24 weeks, participants were eligible to continue to receive AG-348 in the Extension Period which is up to 10 years.
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|---|---|
|
Percentage of Participants Achieving a Sustained Hb Response (sHR)
|
65.0 percentage of participants
Interval 44.2 to 82.27
|
SECONDARY outcome
Timeframe: Week 12 to Week 24Population: FAS included all participants who received at least 1 dose of study treatment.
Delayed Hb response was defined as not achieving HR and achieving a ≥1.0 g/dL increase in Hb concentration at 1 or more Hb assessments after Week 12.
Outcome measures
| Measure |
AG-348
n=20 Participants
Participants with alpha or beta thalassemia received AG-348 50 mg BID, orally up to Week 6. Following Week 6, depending on the participants' safety and Hb concentrations, they could undergo one potential dose-level increase from 50 to 100 mg BID. After completion of the Core Period of 24 weeks, participants were eligible to continue to receive AG-348 in the Extension Period which is up to 10 years.
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|---|---|
|
Percentage of Participants Achieving a Delayed Hb Response
|
10.0 percentage of participants
Interval 1.81 to 28.26
|
SECONDARY outcome
Timeframe: Baseline up to approximately 10.5 yearsOutcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to Week 24Population: Full Analysis Set (FAS) included all participants who received at least 1 dose of study treatment. Data is reported for the responders.
Outcome measures
| Measure |
AG-348
n=16 Participants
Participants with alpha or beta thalassemia received AG-348 50 mg BID, orally up to Week 6. Following Week 6, depending on the participants' safety and Hb concentrations, they could undergo one potential dose-level increase from 50 to 100 mg BID. After completion of the Core Period of 24 weeks, participants were eligible to continue to receive AG-348 in the Extension Period which is up to 10 years.
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|---|---|
|
Time to First ≥1.0 g/dL Increase in Hb Concentration
|
4.54 weeks
Standard Deviation 3.204
|
SECONDARY outcome
Timeframe: Up to approximately 10.5 yearsOutcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to approximately 10.5 yearsOutcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to approximately 10.5 yearsOutcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to approximately 10.5 yearsOutcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to approximately 10.5 yearsOutcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to approximately 10.5 yearsOutcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Up to approximately 10.5 yearsOutcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Predose (60 minutes) and 0.00 hour, 0.50 hour, 1 hour, 2 hours, 4 hours, and 8 hours postdose on Day 1 and Week 12Population: The Pharmacokinetic (PK) Analysis Set included all participants who were enrolled and received a dose of study medication (AG-348), with at least one non-zero plasma concentration of AG-348 at Day 1 or Week 12 (or the Unscheduled Visit where intensive PK samples were assessed). Number analyzed is the number of participants with data available for analysis at the given time point.
Outcome measures
| Measure |
AG-348
n=20 Participants
Participants with alpha or beta thalassemia received AG-348 50 mg BID, orally up to Week 6. Following Week 6, depending on the participants' safety and Hb concentrations, they could undergo one potential dose-level increase from 50 to 100 mg BID. After completion of the Core Period of 24 weeks, participants were eligible to continue to receive AG-348 in the Extension Period which is up to 10 years.
|
|---|---|
|
Drug Concentrations Over Time for AG-348
AG-348 50 mg: 0.00 Hour, Day 1
|
NA nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation NA
The geometric mean and geometric coefficient of variation were not estimable due to lower limit of quantitation.
|
|
Drug Concentrations Over Time for AG-348
AG-348 50 mg: 0.50 Hour, Day 1
|
NA nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation NA
The geometric mean and geometric coefficient of variation were not estimable due to lower limit of quantitation.
|
|
Drug Concentrations Over Time for AG-348
AG-348 50 mg: 1 Hour, Day 1
|
785.2 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 64.6
|
|
Drug Concentrations Over Time for AG-348
AG-348 50 mg: 2 Hour, Day 1
|
694.5 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 26.6
|
|
Drug Concentrations Over Time for AG-348
AG-348 50 mg: 4 Hour, Day 1
|
369.2 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 29.4
|
|
Drug Concentrations Over Time for AG-348
AG-348 50 mg: 8 Hour, Day 1
|
128.9 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 55.1
|
|
Drug Concentrations Over Time for AG-348
AG-348 100 mg: 0.00 Hour, Week 12
|
39.39 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 117.1
|
|
Drug Concentrations Over Time for AG-348
AG-348 100 mg: 0.50 Hour, Week 12
|
1030 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 137.7
|
|
Drug Concentrations Over Time for AG-348
AG-348 100 mg: 1 Hour, Week 12
|
1442 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 30.6
|
|
Drug Concentrations Over Time for AG-348
AG-348 100 mg: 2 Hour, Week 12
|
740.1 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 76.3
|
|
Drug Concentrations Over Time for AG-348
AG-348 100 mg: 4 Hour, Week 12
|
302.8 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 75.2
|
|
Drug Concentrations Over Time for AG-348
AG-348 100 mg: 8 Hour, Week 12
|
77.35 nanograms per milliliter (ng/mL)
Geometric Coefficient of Variation 48.2
|
SECONDARY outcome
Timeframe: Predose (60 minutes) and 30 minutes, 1 hour, 2 hours, 4 hours, and 8 hours postdose on Day 1 and Week 12Population: The PK Analysis Set included all participants who were enrolled and received a dose of study medication (AG-348), with at least one non-zero plasma concentration of AG-348 at Day 1 or Week 12 (or the Unscheduled Visit where intensive PK samples were assessed). Number analyzed is the number of participants with data available for analysis at the given time point.
Outcome measures
| Measure |
AG-348
n=20 Participants
Participants with alpha or beta thalassemia received AG-348 50 mg BID, orally up to Week 6. Following Week 6, depending on the participants' safety and Hb concentrations, they could undergo one potential dose-level increase from 50 to 100 mg BID. After completion of the Core Period of 24 weeks, participants were eligible to continue to receive AG-348 in the Extension Period which is up to 10 years.
|
|---|---|
|
AUC0-8h: Area Under the Plasma Concentration-time Curve From Time 0 to 8 Hours of AG-348
AG-348 50 mg: Day 1
|
3083.3 nanograms*hour per milliliter (ng*h/mL)
Geometric Coefficient of Variation 25.6
|
|
AUC0-8h: Area Under the Plasma Concentration-time Curve From Time 0 to 8 Hours of AG-348
AG-348 100 mg: Week 12
|
3384.4 nanograms*hour per milliliter (ng*h/mL)
Geometric Coefficient of Variation 65.7
|
SECONDARY outcome
Timeframe: Predose (60 minutes) and 30 minutes, 1 hour, 2 hours, 4 hours, and 8 hours postdose on Day 1 and Week 12Population: The PK Analysis Set included all participants who were enrolled and received a dose of study medication (AG-348), with at least one non-zero plasma concentration of AG-348 at Day 1 or Week 12 (or the Unscheduled Visit where intensive PK samples were assessed). Number analyzed is the number of participants with data available for analysis at the given time point.
Outcome measures
| Measure |
AG-348
n=20 Participants
Participants with alpha or beta thalassemia received AG-348 50 mg BID, orally up to Week 6. Following Week 6, depending on the participants' safety and Hb concentrations, they could undergo one potential dose-level increase from 50 to 100 mg BID. After completion of the Core Period of 24 weeks, participants were eligible to continue to receive AG-348 in the Extension Period which is up to 10 years.
|
|---|---|
|
AUC0-t: Area Under the Plasma Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration of AG-348
AG-348 50 mg: Day 1
|
3083.5 ng*h/mL
Geometric Coefficient of Variation 25.6
|
|
AUC0-t: Area Under the Plasma Concentration-time Curve From Time 0 to Time of the Last Quantifiable Concentration of AG-348
AG-348 100 mg: Week 12
|
3384.4 ng*h/mL
Geometric Coefficient of Variation 65.7
|
SECONDARY outcome
Timeframe: Predose (60 minutes) and 30 minutes, 1 hour, 2 hours, 4 hours, and 8 hours postdose on Day 1 and Week 12Population: The PK Analysis Set included all participants who were enrolled and received a dose of study medication (AG-348), with at least one non-zero plasma concentration of AG-348 at Day 1 or Week 12 (or the Unscheduled Visit where intensive PK samples were assessed). Number analyzed is the number of participants with data available for analysis at the given time point.
Outcome measures
| Measure |
AG-348
n=20 Participants
Participants with alpha or beta thalassemia received AG-348 50 mg BID, orally up to Week 6. Following Week 6, depending on the participants' safety and Hb concentrations, they could undergo one potential dose-level increase from 50 to 100 mg BID. After completion of the Core Period of 24 weeks, participants were eligible to continue to receive AG-348 in the Extension Period which is up to 10 years.
|
|---|---|
|
Cmax: Maximum Observed Plasma Concentration of AG-348
AG-348 50 mg: Day 1
|
968.9 ng/mL
Geometric Coefficient of Variation 38.1
|
|
Cmax: Maximum Observed Plasma Concentration of AG-348
AG-348 100 mg: Week 12
|
1476 ng/mL
Geometric Coefficient of Variation 93.5
|
SECONDARY outcome
Timeframe: Predose (60 minutes) and 30 minutes, 1 hour, 2 hours, 4 hours, and 8 hours postdose on Day 1 and Week 12Population: The PK Analysis Set included all participants who were enrolled and received a dose of study medication (AG-348), with at least one non-zero plasma concentration of AG-348 at Day 1 or Week 12 (or the Unscheduled Visit where intensive PK samples were assessed). Number analyzed is the number of participants with data available for analysis at the given time point.
Outcome measures
| Measure |
AG-348
n=20 Participants
Participants with alpha or beta thalassemia received AG-348 50 mg BID, orally up to Week 6. Following Week 6, depending on the participants' safety and Hb concentrations, they could undergo one potential dose-level increase from 50 to 100 mg BID. After completion of the Core Period of 24 weeks, participants were eligible to continue to receive AG-348 in the Extension Period which is up to 10 years.
|
|---|---|
|
Tmax: Time to Reach the Maximum Plasma Radioactivity Concentration (Cmax)
AG-348 50 mg: Day 1
|
1.07 hours
Interval 0.48 to 4.07
|
|
Tmax: Time to Reach the Maximum Plasma Radioactivity Concentration (Cmax)
AG-348 100 mg: Week 12
|
0.53 hours
Interval 0.43 to 2.03
|
SECONDARY outcome
Timeframe: Predose (60 minutes) and 30 minutes, 1 hour, 2 hours, 4 hours, and 8 hours postdose on Day 1 and Week 12Population: The PK Analysis Set included all participants who were enrolled and received a dose of study medication (AG-348), with at least one non-zero plasma concentration of AG-348 at Day 1 or Week 12 (or the Unscheduled Visit where intensive PK samples were assessed). Number analyzed is the number of participants with data available for analysis at the given time point.
Outcome measures
| Measure |
AG-348
n=20 Participants
Participants with alpha or beta thalassemia received AG-348 50 mg BID, orally up to Week 6. Following Week 6, depending on the participants' safety and Hb concentrations, they could undergo one potential dose-level increase from 50 to 100 mg BID. After completion of the Core Period of 24 weeks, participants were eligible to continue to receive AG-348 in the Extension Period which is up to 10 years.
|
|---|---|
|
Tlast: Time of the Last Quantifiable Concentration of AG-348
AG-348 50 mg: Day 1
|
7.60 hours
Interval 7.5 to 8.02
|
|
Tlast: Time of the Last Quantifiable Concentration of AG-348
AG-348 100 mg: Week 12
|
7.55 hours
Interval 7.5 to 7.95
|
SECONDARY outcome
Timeframe: Predose (60 minutes) and 30 minutes, 1 hour, 2 hours, 4 hours, and 8 hours postdose on Day 1 and Week 12Population: The PK Analysis Set included all participants who were enrolled and received a dose of study medication (AG-348), with at least one non-zero plasma concentration of AG-348 at Day 1 or Week 12 (or the Unscheduled Visit where intensive PK samples were assessed). Number analyzed is the number of participants with data available for analysis at the given time point.
Outcome measures
| Measure |
AG-348
n=20 Participants
Participants with alpha or beta thalassemia received AG-348 50 mg BID, orally up to Week 6. Following Week 6, depending on the participants' safety and Hb concentrations, they could undergo one potential dose-level increase from 50 to 100 mg BID. After completion of the Core Period of 24 weeks, participants were eligible to continue to receive AG-348 in the Extension Period which is up to 10 years.
|
|---|---|
|
Ctrough: Observed Plasma Concentration at the End of a Dosing Interval of AG-348
AG-348 100 mg: Week 12
|
37.34 ng/mL
Geometric Coefficient of Variation 117.7
|
SECONDARY outcome
Timeframe: From signing the inform consent form up to data cut-off date: 20 August 2020 (Up to approximately 19 months)Population: Safety Analysis Set included all participants who received at least 1 dose of study treatment.
An AE is any unfavorable and unintended sign, symptom, or disease, whether or not related to the investigational product. A TEAE was defined as any AE with onset post study drug treatment. An SAE was defined as any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is medically important. AESIs are predefined AEs that required close monitoring and prompt reporting to the sponsor. AESIs included protocol-specified transaminase increase.
Outcome measures
| Measure |
AG-348
n=20 Participants
Participants with alpha or beta thalassemia received AG-348 50 mg BID, orally up to Week 6. Following Week 6, depending on the participants' safety and Hb concentrations, they could undergo one potential dose-level increase from 50 to 100 mg BID. After completion of the Core Period of 24 weeks, participants were eligible to continue to receive AG-348 in the Extension Period which is up to 10 years.
|
|---|---|
|
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs), AEs of Special Interest (AESIs), and TEAEs Leading to Study Drug Dose Reduction, Study Drug Interruption, and Study Drug Discontinuation
TEAEs
|
85.0 percentage of participants
|
|
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs), AEs of Special Interest (AESIs), and TEAEs Leading to Study Drug Dose Reduction, Study Drug Interruption, and Study Drug Discontinuation
SAEs
|
5.0 percentage of participants
|
|
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs), AEs of Special Interest (AESIs), and TEAEs Leading to Study Drug Dose Reduction, Study Drug Interruption, and Study Drug Discontinuation
AESIs
|
5.0 percentage of participants
|
|
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs), AEs of Special Interest (AESIs), and TEAEs Leading to Study Drug Dose Reduction, Study Drug Interruption, and Study Drug Discontinuation
TEAEs Leading to Study Drug Dose Reduction
|
15.0 percentage of participants
|
|
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs), AEs of Special Interest (AESIs), and TEAEs Leading to Study Drug Dose Reduction, Study Drug Interruption, and Study Drug Discontinuation
TEAEs Leading to Study Drug Interruption
|
5.0 percentage of participants
|
|
Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs), AEs of Special Interest (AESIs), and TEAEs Leading to Study Drug Dose Reduction, Study Drug Interruption, and Study Drug Discontinuation
TEAEs Leading to Study Drug Discontinuation
|
5.0 percentage of participants
|
Adverse Events
AG-348
Serious events: 1 serious events
Other events: 17 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
AG-348
n=20 participants at risk
Participants with alpha or beta thalassemia received AG-348 50 mg BID, orally up to Week 6. Following Week 6, depending on the participants' safety and Hb concentrations, they could undergo one potential dose-level increase from 50 to 100 mg BID. After completion of the Core Period of 24 weeks, participants were eligible to continue to receive AG-348 in the Extension Period which is up to 10 years.
|
|---|---|
|
Renal and urinary disorders
Renal impairment
|
5.0%
1/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
Other adverse events
| Measure |
AG-348
n=20 participants at risk
Participants with alpha or beta thalassemia received AG-348 50 mg BID, orally up to Week 6. Following Week 6, depending on the participants' safety and Hb concentrations, they could undergo one potential dose-level increase from 50 to 100 mg BID. After completion of the Core Period of 24 weeks, participants were eligible to continue to receive AG-348 in the Extension Period which is up to 10 years.
|
|---|---|
|
General disorders
Oedema peripheral
|
5.0%
1/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Gastrointestinal disorders
Dyspepsia
|
20.0%
4/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
General disorders
Chest discomfort
|
10.0%
2/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
General disorders
Pyrexia
|
10.0%
2/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Psychiatric disorders
Initial insomnia
|
50.0%
10/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Psychiatric disorders
Anxiety
|
5.0%
1/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Psychiatric disorders
Middle insomnia
|
5.0%
1/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Psychiatric disorders
Restlessness
|
5.0%
1/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Psychiatric disorders
Terminal insomnia
|
5.0%
1/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Gastrointestinal disorders
Abdominal pain
|
15.0%
3/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Gastrointestinal disorders
Diarrhoea
|
15.0%
3/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Gastrointestinal disorders
Abdominal distension
|
15.0%
3/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Gastrointestinal disorders
Nausea
|
15.0%
3/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Gastrointestinal disorders
Abdominal pain upper
|
10.0%
2/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Gastrointestinal disorders
Vomiting
|
10.0%
2/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Gastrointestinal disorders
Constipation
|
5.0%
1/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Gastrointestinal disorders
Dry mouth
|
5.0%
1/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Gastrointestinal disorders
Gingival pain
|
5.0%
1/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Gastrointestinal disorders
Haemorrhoids
|
5.0%
1/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Gastrointestinal disorders
Oral pain
|
5.0%
1/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Gastrointestinal disorders
Flatulence
|
5.0%
1/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Nervous system disorders
Dizziness
|
30.0%
6/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Nervous system disorders
Headache
|
25.0%
5/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Nervous system disorders
Carotid arteriosclerosis
|
5.0%
1/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Nervous system disorders
Hypoaesthesia
|
5.0%
1/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Nervous system disorders
Nystagmus
|
5.0%
1/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Nervous system disorders
Presyncope
|
5.0%
1/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Nervous system disorders
Syncope
|
5.0%
1/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Nervous system disorders
Taste disorder
|
5.0%
1/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
General disorders
Fatigue
|
20.0%
4/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
General disorders
Pain
|
15.0%
3/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
General disorders
Non-cardiac chest pain
|
5.0%
1/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Skin and subcutaneous tissue disorders
Rash erythematous
|
10.0%
2/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Skin and subcutaneous tissue disorders
Rash
|
10.0%
2/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Skin and subcutaneous tissue disorders
Dermatitis contact
|
5.0%
1/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Skin and subcutaneous tissue disorders
Night sweats
|
5.0%
1/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
5.0%
1/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Skin and subcutaneous tissue disorders
Skin odour abnormal
|
5.0%
1/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Infections and infestations
Upper respiratory tract infection
|
20.0%
4/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Infections and infestations
Body tinea
|
5.0%
1/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Infections and infestations
Conjunctivitis
|
5.0%
1/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Infections and infestations
Oral herpes
|
5.0%
1/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Infections and infestations
Sinusitis
|
5.0%
1/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Infections and infestations
Viral upper respiratory tract infection
|
5.0%
1/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Infections and infestations
Herpes simplex
|
5.0%
1/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Infections and infestations
Suspected COVID-19
|
5.0%
1/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
15.0%
3/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
10.0%
2/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
5.0%
1/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Musculoskeletal and connective tissue disorders
Joint range of motion decreased
|
5.0%
1/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Musculoskeletal and connective tissue disorders
Joint swelling
|
5.0%
1/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Musculoskeletal and connective tissue disorders
Muscle spasms
|
5.0%
1/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Musculoskeletal and connective tissue disorders
Muscular weakness
|
5.0%
1/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Musculoskeletal and connective tissue disorders
Sjogren's syndrome
|
5.0%
1/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Musculoskeletal and connective tissue disorders
Temporomandibular joint syndrome
|
5.0%
1/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Musculoskeletal and connective tissue disorders
Tendonitis
|
5.0%
1/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
20.0%
4/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
20.0%
4/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
15.0%
3/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
5.0%
1/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Sneezing
|
5.0%
1/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Respiratory, thoracic and mediastinal disorders
Upper-airway cough syndrome
|
5.0%
1/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Renal and urinary disorders
Dysuria
|
5.0%
1/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Renal and urinary disorders
Polyuria
|
5.0%
1/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Renal and urinary disorders
Renal artery stenosis
|
5.0%
1/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Hepatobiliary disorders
Ocular icterus
|
15.0%
3/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Investigations
Aspartate aminotransferase increased
|
5.0%
1/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Investigations
Electrocardiogram QT prolonged
|
5.0%
1/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Investigations
Fibrin D dimer increased
|
5.0%
1/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Blood and lymphatic system disorders
Anaemia
|
5.0%
1/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Blood and lymphatic system disorders
Lymphadenopathy
|
5.0%
1/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Ear and labyrinth disorders
Vertigo positional
|
5.0%
1/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Ear and labyrinth disorders
Ear pain
|
5.0%
1/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Cardiac disorders
Palpitations
|
5.0%
1/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Cardiac disorders
Tachycardia
|
5.0%
1/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Vascular disorders
Hypotension
|
5.0%
1/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Vascular disorders
Hot flush
|
5.0%
1/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Injury, poisoning and procedural complications
Limb injury
|
5.0%
1/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Metabolism and nutrition disorders
Decreased appetite
|
5.0%
1/20 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
|
Reproductive system and breast disorders
Vulvovaginal pruritus
|
6.7%
1/15 • Up to completion of the Core Period data cut-off date: 20 August 2020 (Up to approximately 19 months)
Safety Analysis Set included all participants who received at least 1 dose of study treatment.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER