Trial · NCT03548220
A Study to Evaluate Efficacy and Safety of AG-348 in Not Regularly Transfused Adult Participants With Pyruvate Kinase Deficiency (PKD)
NCT03548220, Phase 3, Completed, Agios Pharmaceuticals, Inc.; results first posted 2022-05-24
3 sourcestrials-2026-11-12-0.5.0
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ConductScience Library. A Study to Evaluate Efficacy and Safety of AG-348 in Not Regularly Transfused Adult Participants With Pyruvate Kinase Deficiency (PKD). Trials, record NCT03548220. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT03548220
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Trial
As registered on ClinicalTrials.gov, in the graph's capture of the registry.
- Title
- A Study to Evaluate Efficacy and Safety of AG-348 in Not Regularly Transfused Adult Participants With Pyruvate Kinase Deficiency (PKD)
- NCT number
- NCT03548220
- Status
- Completed
- Phases
- Phase 3
- Enrollment
- 80 participants, actual
- Lead sponsor
- Agios Pharmaceuticals, Inc.
- Conditions
- Pyruvate Kinase Deficiency, Anemia, Hemolytic
- Interventions
- Placebo, AG-348
- First posted
- 2018-06-07
- Last updated
- 2022-05-24
- Results first posted
- 2022-05-24
Source ClinicalTrials.gov
Registered outcomes20
Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.
| List | Outcome | Time frame | Description |
|---|---|---|---|
| Primary | Percentage of Participants Achieving a Hemoglobin (Hb) Response (HR) | Baseline, Weeks 16, 20, 24 | Hemoglobin response (HR) is defined as a ≥1.5 g/dL (0.93 mmol/L) increase in Hb concentration from baseline that is sustained at 2 or more scheduled assessments at Weeks 16, 20, and 24. The baseline Hb concentration is the average of all available Hb concentrations for a participant during the Screening Period up to the first dose of study treatment. As pre-specified in the protocol, the data for this outcome measure is summarized between the active arm vs the placebo arm (AG-348 5 mg, 20 mg and 50 mg arms are analyzed and reported together in comparison to Placebo). |
| Secondary | Average Change From Baseline in Hb Concentration at Weeks 16, 20 and 24 | Baseline, Weeks 16, 20, 24 | This is the change in Hb concentration at Weeks 16, 20 and 24 compared to baseline. Data presented represents the value of the change from baseline averaged over Weeks 16, 20 and 24. Baseline was defined as the average of all screening assessments within 45 (42+3) days before randomization for participants randomized and not dosed or before start of study treatment for participants randomized and dosed. As pre-specified in the protocol, the data for this outcome measure is summarized between the active arm vs the placebo arm (AG-348 5 mg, 20 mg and 50 mg arms are analyzed and reported together in comparison to Placebo). |
| Secondary | Maximum Change From Baseline in Hb Concentration | Baseline, up to Week 24 | This is the maximum change from baseline in Hb concentration up to Week 24. As pre-specified in the protocol, the data for this outcome measure is summarized between the active arm vs the placebo arm (AG-348 5 mg, 20 mg and 50 mg arms are analyzed and reported together in comparison to Placebo). |
| Secondary | Time to Achieve an Increase in Hb Concentration of 1.5 g/dL or More | Baseline, up to Week 24 | This is the time taken to first achieve an increase of hemoglobin concentration of 1.5 g/dL or more from baseline. As pre-specified in the protocol, the data for this outcome measure is summarized between the active arm vs the placebo arm (AG-348 5 mg, 20 mg and 50 mg arms are analyzed and reported together in comparison to Placebo). |
| Secondary | Average Change From Baseline in Indirect Bilirubin at Weeks 16, 20 and 24 | Baseline, Weeks 16, 20, 24 | The change from baseline in indirect bilirubin levels was summarized. Indirect bilirubin is a marker for hemolysis. Data presented represents the value of the change from baseline averaged over Weeks 16, 20 and 24. Baseline was defined as the average of all screening assessments within 45 (42+3) days before randomization for participants randomized and not dosed or before the start of study treatment for participants randomized and dosed. As pre-specified in the protocol, the data for this outcome measure is summarized between the active arm vs the placebo arm (AG-348 5 mg, 20 mg and 50 mg arms are analyzed and reported together in comparison to Placebo). |
| Secondary | Average Change From Baseline in Lactic Acid Dehydrogenase (LDH) at Weeks 16, 20 and 24 | Baseline, Weeks 16, 20, 24 | The change from baseline in LDH levels was summarized. LDH is a marker for hemolysis. Data presented represents the value of the change from baseline averaged over Weeks 16, 20 and 24. Baseline was defined as the average of all screening assessments within 45 (42+3) days before randomization for participants randomized and not dosed or before the start of study treatment for participants randomized and dosed. As pre-specified in the protocol, the data for this outcome measure is summarized between the active arm vs the placebo arm (AG-348 5 mg, 20 mg and 50 mg arms are analyzed and reported together in comparison to Placebo). |
| Secondary | Average Change From Baseline in Haptoglobin at Weeks 16, 20 and 24 | Baseline, Weeks 16, 20, 24 | The change from baseline in haptoglobin levels was summarized. Haptoglobin levels are markers for hemolysis. Data presented represents the value of the change from baseline averaged over Weeks 16, 20 and 24. Baseline was defined as the average of all screening assessments within 45 (42+3) days before randomization for participants randomized and not dosed or before the start of study treatment for participants randomized and dosed. As pre-specified in the protocol, the data for this outcome measure is summarized between the active arm vs the placebo arm (AG-348 5 mg, 20 mg and 50 mg arms are analyzed and reported together in comparison to Placebo). |
| Secondary | Average Change From Baseline in Reticulocyte Percentages at Weeks 16, 20 and 24 | Baseline, Weeks 16, 20, 24 | The change from baseline in reticulocyte percentage was summarized. Reticulocyte levels are markers for hematopoietic activity. Data presented represents the value of the change from baseline averaged over Weeks 16, 20 and 24. Baseline was defined as the average of all screening assessments within 45 (42+3) days before randomization for participants randomized and not dosed or before the start of study treatment for participants randomized and dosed. As pre-specified in the protocol, the data for this outcome measure is summarized between the active arm vs the placebo arm (AG-348 5 mg, 20 mg and 50 mg arms are analyzed and reported together in comparison to Placebo). |
| Secondary | Change From Baseline in Pyruvate Kinase Deficiency Diary (PKDD) Score at Week 24 | Baseline, Week 24 | The PKDD is a 7-item patient reported outcome (PRO) measure of the core signs and symptoms associated with PK deficiency in adults. Participants rate their experience with symptoms of PK deficiency on the present day. The symptoms include those associated with tiredness, jaundice, bone pain, shortness of breath, and energy level. The score ranges from 25 to 76, with higher scores indicating a higher disease burden. The change from baseline in PKDD weekly scores was evaluated. A negative change from baseline indicates a lower disease burden. As pre-specified in the protocol, the data for this outcome measure is summarized between the active arm vs the placebo arm (AG-348 5 mg, 20 mg and 50 mg arms are analyzed and reported together in comparison to Placebo). |
| Secondary | Change From Baseline in Pyruvate Kinase Deficiency Impact Assessment (PKDIA) Score at Week 24 | Baseline, Week 24 | The PKDIA is a 12-item patient reported outcome (PRO) measure of the common impacts of PK deficiency on activities of daily living. Participants rate how PK deficiency has impacted aspects of daily living in the past 7 days, including impacts on relationships; perceived appearance; work performance; and leisure, social, mental, and physical activities. The score range is 30 to 76, with higher scores indicating a higher disease burden. The change from baseline in PKDIA scores was evaluated. A negative change from baseline indicates a lower disease burden. As pre-specified in the protocol, the data for this outcome measure is summarized between the active arm vs the placebo arm (AG-348 5 mg, 20 mg and 50 mg arms are analyzed and reported together in comparison to Placebo). |
1 to 10 of 20Source ClinicalTrials.gov
See all 20 registered outcomesOutcomes20
Each outcome the trial posted results for, in ClinicalTrials.gov's words.
| Type | Outcome | Time frame | Population | Units | Measured as |
|---|---|---|---|---|---|
| PRIMARY | Percentage of Participants Achieving a Hemoglobin (Hb) Response (HR) | Baseline, Weeks 16, 20, 24 | Full analysis set included all participants who were randomized. | percentage of participants | NUMBER |
| SECONDARY | Average Change From Baseline in Hb Concentration at Weeks 16, 20 and 24 | Baseline, Weeks 16, 20, 24 | Full analysis set included all participants who were randomized. | grams per liter (g/L) | LEAST_SQUARES_MEAN |
| SECONDARY | Maximum Change From Baseline in Hb Concentration | Baseline, up to Week 24 | Full analysis set included all participants who were randomized. Overall number of participants analyzed is the number of participants evaluated for the outcome measure. | g/L | MEAN |
| SECONDARY | Time to Achieve an Increase in Hb Concentration of 1.5 g/dL or More | Baseline, up to Week 24 | Full analysis set included all participants who were randomized. Overall number of participants analyzed is the number of participants evaluated for the outcome measure. | weeks | MEAN |
| SECONDARY | Average Change From Baseline in Indirect Bilirubin at Weeks 16, 20 and 24 | Baseline, Weeks 16, 20, 24 | Full analysis set included all participants who were randomized. Overall number of participants analyzed is the number of participants evaluated for the outcome measure. | micromoles per liter (μmol/L) | LEAST_SQUARES_MEAN |
| SECONDARY | Average Change From Baseline in Lactic Acid Dehydrogenase (LDH) at Weeks 16, 20 and 24 | Baseline, Weeks 16, 20, 24 | Full analysis set included all participants who were randomized. Overall number of participants analyzed is the number of participants evaluated for the outcome measure. | units per litre (U/L) | LEAST_SQUARES_MEAN |
| SECONDARY | Average Change From Baseline in Haptoglobin at Weeks 16, 20 and 24 | Baseline, Weeks 16, 20, 24 | Full analysis set included all participants who were randomized. | g/L | LEAST_SQUARES_MEAN |
| SECONDARY | Average Change From Baseline in Reticulocyte Percentages at Weeks 16, 20 and 24 | Baseline, Weeks 16, 20, 24 | Full analysis set included all participants who were randomized. | Reticulocyte percentages | LEAST_SQUARES_MEAN |
| SECONDARY | Change From Baseline in Pyruvate Kinase Deficiency Diary (PKDD) Score at Week 24 | Baseline, Week 24 | Full analysis set included all participants who were randomized. Overall number of participants analyzed is the number of participants evaluated for the outcome measure. | score on a scale | LEAST_SQUARES_MEAN |
| SECONDARY | Change From Baseline in Pyruvate Kinase Deficiency Impact Assessment (PKDIA) Score at Week 24 | Baseline, Week 24 | Full analysis set included all participants who were randomized. Overall number of participants analyzed is the number of participants evaluated for the outcome measure. | score on a scale | LEAST_SQUARES_MEAN |
1 to 10 of 20Source ClinicalTrials.gov
See all 20 outcomesResults by group47
Each measurement the trial posted, group by group, in the words and numbers it posted.
| Outcome | Group | Category | Value | Spread | Units |
|---|---|---|---|---|---|
| Percentage of Participants Achieving a Hemoglobin (Hb) Response (HR) | Placebo Comparator: Placebo | 0 | percentage of participants | ||
| Percentage of Participants Achieving a Hemoglobin (Hb) Response (HR) | Experimental: AG-348 | 40.0 | percentage of participants | ||
| Average Change From Baseline in Hb Concentration at Weeks 16, 20 and 24 | Placebo Comparator: Placebo | -1.48 | Standard Error 2.082 | grams per liter (g/L) | |
| Average Change From Baseline in Hb Concentration at Weeks 16, 20 and 24 | Experimental: AG-348 | 16.73 | Standard Error 2.075 | grams per liter (g/L) | |
| Maximum Change From Baseline in Hb Concentration | Placebo Comparator: Placebo | 4.76 | Standard Deviation 4.217 | g/L | |
| Maximum Change From Baseline in Hb Concentration | Experimental: AG-348 | 23.94 | Standard Deviation 21.367 | g/L | |
| Time to Achieve an Increase in Hb Concentration of 1.5 g/dL or More | Experimental: AG-348 | 7.66 | Standard Deviation 4.050 | weeks | |
| Average Change From Baseline in Indirect Bilirubin at Weeks 16, 20 and 24 | Placebo Comparator: Placebo | 5.10 | Standard Error 4.061 | micromoles per liter (μmol/L) | |
| Average Change From Baseline in Indirect Bilirubin at Weeks 16, 20 and 24 | Experimental: AG-348 | -21.16 | Standard Error 4.228 | micromoles per liter (μmol/L) | |
| Average Change From Baseline in Lactic Acid Dehydrogenase (LDH) at Weeks 16, 20 and 24 | Placebo Comparator: Placebo | -21.18 | Standard Error 16.040 | units per litre (U/L) |
1 to 10 of 47Source ClinicalTrials.gov
See all 47 results by groupParticipant flow12
How many started, completed or left each group, period by period.
| Period | Milestone | Group | Participants | Units counted |
|---|---|---|---|---|
| Overall Study | STARTED | Placebo Comparator: Placebo | 40 | |
| Overall Study | STARTED | Experimental: AG-348 5 mg | 2 | |
| Overall Study | STARTED | Experimental: AG-348, 20 mg | 3 | |
| Overall Study | STARTED | Experimental: AG-348, 50 mg | 35 | |
| Overall Study | COMPLETED | Placebo Comparator: Placebo | 39 | |
| Overall Study | COMPLETED | Experimental: AG-348 5 mg | 2 | |
| Overall Study | COMPLETED | Experimental: AG-348, 20 mg | 3 | |
| Overall Study | COMPLETED | Experimental: AG-348, 50 mg | 35 | |
| Overall Study | NOT COMPLETED | Placebo Comparator: Placebo | 1 | |
| Overall Study | NOT COMPLETED | Experimental: AG-348 5 mg | 0 |
1 to 10 of 12Source ClinicalTrials.gov
See all 12 participant flowAdverse events204
Each adverse event the trial posted, group by group: the participants affected out of those at risk.
| Type | Event | Organ system | Group | Affected | At risk | Events |
|---|---|---|---|---|---|---|
| other | Nausea | Gastrointestinal disorders | Placebo Comparator: Placebo | 9 | 39 | |
| other | Nausea | Gastrointestinal disorders | Experimental: AG-348, 5 mg | 0 | 2 | |
| other | Nausea | Gastrointestinal disorders | Experimental: AG-348, 20 mg | 2 | 3 | |
| other | Nausea | Gastrointestinal disorders | Experimental: AG-348, 50 mg | 5 | 35 | |
| other | Diarrhoea | Gastrointestinal disorders | Placebo Comparator: Placebo | 7 | 39 | |
| other | Diarrhoea | Gastrointestinal disorders | Experimental: AG-348, 5 mg | 0 | 2 | |
| other | Diarrhoea | Gastrointestinal disorders | Experimental: AG-348, 20 mg | 2 | 3 | |
| other | Diarrhoea | Gastrointestinal disorders | Experimental: AG-348, 50 mg | 2 | 35 | |
| other | Abdominal pain | Gastrointestinal disorders | Placebo Comparator: Placebo | 2 | 39 | |
| other | Abdominal pain | Gastrointestinal disorders | Experimental: AG-348, 5 mg | 0 | 2 |
1 to 10 of 204Source ClinicalTrials.gov
See all 204 adverse eventsAdverse event totals12
The totals the trial posted for each group.
| Total | Group | Affected | At risk |
|---|---|---|---|
| Total, all-cause mortality | Placebo Comparator: Placebo | 0 | 39 |
| Total, all-cause mortality | Experimental: AG-348, 5 mg | 0 | 2 |
| Total, all-cause mortality | Experimental: AG-348, 20 mg | 0 | 3 |
| Total, all-cause mortality | Experimental: AG-348, 50 mg | 0 | 35 |
| Total, other adverse events | Placebo Comparator: Placebo | 35 | 39 |
| Total, other adverse events | Experimental: AG-348, 5 mg | 1 | 2 |
| Total, other adverse events | Experimental: AG-348, 20 mg | 3 | 3 |
| Total, other adverse events | Experimental: AG-348, 50 mg | 31 | 35 |
| Total, serious adverse events | Placebo Comparator: Placebo | 2 | 39 |
| Total, serious adverse events | Experimental: AG-348, 5 mg | 0 | 2 |
1 to 10 of 12Source ClinicalTrials.gov
See all 12 adverse event totalsPapers5
The papers the trial lists on ClinicalTrials.gov.
Grants0
The grants NIH RePORTER links to the trial, newest funded first: NIH's, and some of AHRQ's, CDC's, FDA's and VA's. Each shows its title, principal investigators, organization and funder in its newest year.
None in this release.
Trial comparisons0
Comparisons of the trial's two groups, calculated by ConductScience from the counts it posted.
None in this release.
Tests0
The ConductCognition tests this trial's registered outcomes name, as ScienceGraph matched them in trial-tests-2026-11-12-0.2.1.
None in this release.
Data dates
The day each source was copied for this release.
Sources 3
- ClinicalTrials.gov's posted results, through CTTI's AACTFreely available. Acknowledgement requested
- ClinicalTrials.govNo license stated
- NIH RePORTER's clinical studies and project filesPublic domain
Each source's terms
- ClinicalTrials.gov's posted results, through CTTI's AACTClinicalTrials.gov data via Aggregate Analysis of ClinicalTrials.gov (AACT), CTTI. CTTI makes its materials freely available and requests acknowledgement. https://aact.ctti-clinicaltrials.org/documentation/299
- ClinicalTrials.govnone stated
- NIH RePORTER's clinical studies and project filesPublic domain (NIH RePORTER)
ClinicalTrials.gov's data carry an international copyright outside the United States: https://clinicaltrials.gov/about-site/terms-conditions.
For software
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The record and each of its lists are JSON, twenty rows a page. No key.
GET https://conductscience.org/api/trials/v1/NCT03548220
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