Trial · NCT04000165

A Dose-Finding Study of AG-348 in Sickle Cell Disease

NCT04000165, Early phase 1, Completed, National Institutes of Health Clinical Center (CC); results first posted 2022-07-12

3 sourcestrials-2026-11-12-0.5.0

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ConductScience Library. A Dose-Finding Study of AG-348 in Sickle Cell Disease. Trials, record NCT04000165. Release trials-2026-11-12-0.5.0, 12 Nov 2026. https://conductscience.org/library/trials/NCT04000165

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Trial

As registered on ClinicalTrials.gov, in the graph's capture of the registry.

Title: A Dose-Finding Study of AG-348 in Sickle Cell Disease
NCT number: NCT04000165
Status: Completed
Phases: Early phase 1
Enrollment: 17 participants, actual
Lead sponsor: National Institutes of Health Clinical Center (CC)
Conditions: Sickle Cell Disease
Interventions: AG-348
First posted: 2019-06-27
Last updated: 2022-07-12
Results first posted: 2022-07-12

Source ClinicalTrials.gov

Registered outcomes15

Each outcome the trial registered, primary first, in ClinicalTrials.gov's words.

List	Outcome	Time frame	Description
Primary	Number Participants With Most Common Reported Drug Related Adverse Events	14 weeks	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.
Primary	Number Participants With Serious Adverse Events That Were Possibly Drug-related Serious Adverse Events	14 weeks	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.
Primary	Number Participants With Increase of ≥ 1 g/dL in Hemoglobin	14 weeks	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.
Secondary	Change in Hemoglobin at Each Dose Level of AG-348	14 weeks	To assess change in hemoglobin in stable sickle cell disease participants at each dose level of AG-348
Secondary	Change in Lactic Acid Dehydrogenase (LDH) at Each Dose Level of AG-348	14 weeks	To assess change in lactic acid dehydrogenase (LDH) in stable sickle cell disease participants at each dose level of AG-348
Secondary	Change in Total Bilirubin at Each Dose Level of AG-348	14 weeks	To assess change in total bilirubin in stable sickle cell disease participants at each dose level of AG-348
Secondary	Change in Absolute Reticulocyte Count at Each Dose Level of AG-348	14 weeks	To assess change in absolute reticulocyte count in stable sickle cell disease participants at each dose level of AG-348
Secondary	Change in Aspartate Aminotransferase (AST) at Each Dose Level of AG-348	14 weeks	To assess change in aspartate aminotransferase (AST) in stable sickle cell disease participants at each dose level of AG-348
Secondary	Change in Mean Corpuscular Volume (MCV) at Each Dose Level of AG-348	14 weeks	To assess change in mean corpuscular volume (MCV) in stable sickle cell disease participants at each dose level of AG-348
Secondary	Change in Fetal Hemoglobin at Each Dose Level of AG-348	14 weeks	To assess the change in fetal hemoglobin (HbF) in stable sickle cell disease participants at each dose level of AG-348

1 to 10 of 15Source ClinicalTrials.gov

See all 15 registered outcomes

Outcomes15

Each outcome the trial posted results for, in ClinicalTrials.gov's words.

Type	Outcome	Time frame	Population	Units	Measured as
PRIMARY	Number Participants With Most Common Reported Drug Related Adverse Events	14 weeks		Participants	COUNT_OF_PARTICIPANTS
PRIMARY	Number Participants With Serious Adverse Events That Were Possibly Drug-related Serious Adverse Events	14 weeks		Participants	COUNT_OF_PARTICIPANTS
PRIMARY	Number Participants With Increase of ≥ 1 g/dL in Hemoglobin	14 weeks	One participant, withdrawn 3 days after starting the study for a pre-existing pulmonary embolus, was not evaluable for response. Intention to treat analysis.	Participants	COUNT_OF_PARTICIPANTS
SECONDARY	Change in Hemoglobin at Each Dose Level of AG-348	14 weeks	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.	g/dL	MEAN
SECONDARY	Change in Lactic Acid Dehydrogenase (LDH) at Each Dose Level of AG-348	14 weeks	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.	U/L	MEAN
SECONDARY	Change in Total Bilirubin at Each Dose Level of AG-348	14 weeks	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.	mg/dL	MEAN
SECONDARY	Change in Absolute Reticulocyte Count at Each Dose Level of AG-348	14 weeks	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.	K/mcL	MEAN
SECONDARY	Change in Aspartate Aminotransferase (AST) at Each Dose Level of AG-348	14 weeks	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.	U/L	MEAN
SECONDARY	Change in Mean Corpuscular Volume (MCV) at Each Dose Level of AG-348	14 weeks	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.	fL	MEAN
SECONDARY	Change in Fetal Hemoglobin at Each Dose Level of AG-348	14 weeks	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.	Percent HbF	MEAN

1 to 10 of 15Source ClinicalTrials.gov

See all 15 outcomes

Results by group84

Each measurement the trial posted, group by group, in the words and numbers it posted.

Outcome	Group	Category	Value	Spread	Units
Number Participants With Most Common Reported Drug Related Adverse Events	AG-348 in Participants With Sickle Cell Disease	Insomnia	6		Participants
Number Participants With Most Common Reported Drug Related Adverse Events	AG-348 in Participants With Sickle Cell Disease	Arthralgia	3		Participants
Number Participants With Most Common Reported Drug Related Adverse Events	AG-348 in Participants With Sickle Cell Disease	Hypertension	3		Participants
Number Participants With Serious Adverse Events That Were Possibly Drug-related Serious Adverse Events	AG-348 in Participants With Sickle Cell Disease		2		Participants
Number Participants With Increase of ≥ 1 g/dL in Hemoglobin	AG-348 in Participants With Sickle Cell Disease		9		Participants
Change in Hemoglobin at Each Dose Level of AG-348	AG-348 in Participants With Sickle Cell Disease	Baseline	8.73	Standard Error 0.51	g/dL
Change in Hemoglobin at Each Dose Level of AG-348	AG-348 in Participants With Sickle Cell Disease	5 mg dose of AG-348	0.34	Standard Error 0.22	g/dL
Change in Hemoglobin at Each Dose Level of AG-348	AG-348 in Participants With Sickle Cell Disease	20 mg dose AG-348	0.76	Standard Error 0.22	g/dL
Change in Hemoglobin at Each Dose Level of AG-348	AG-348 in Participants With Sickle Cell Disease	50 mg dose AG-348	1.19	Standard Error 0.22	g/dL
Change in Hemoglobin at Each Dose Level of AG-348	AG-348 in Participants With Sickle Cell Disease	100 mg dose AG-348	0.92	Standard Error 0.26	g/dL

1 to 10 of 84Source ClinicalTrials.gov

See all 84 results by group

Participant flow5

How many started, completed or left each group, period by period.

Period	Milestone	Group	Participants
Overall Study	STARTED	AG-348 in Participants With Sickle Cell Disease	17
Overall Study	Completed Study at 50 mg Dose	AG-348 in Participants With Sickle Cell Disease	7
Overall Study	Escalated to 100 mg	AG-348 in Participants With Sickle Cell Disease	10
Overall Study	COMPLETED	AG-348 in Participants With Sickle Cell Disease	15
Overall Study	NOT COMPLETED	AG-348 in Participants With Sickle Cell Disease	2

Source ClinicalTrials.gov

Adverse events66

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	Anemia	Blood and lymphatic system disorders	AG-348 in Participants With Sickle Cell Disease	3	17	3
other	Elevated C-Reactive Protein (CRP)	Blood and lymphatic system disorders	AG-348 in Participants With Sickle Cell Disease	1	17	1
other	Iron deficiency anemia	Blood and lymphatic system disorders	AG-348 in Participants With Sickle Cell Disease	1	17	1
other	Palpitations	Cardiac disorders	AG-348 in Participants With Sickle Cell Disease	1	17	1
other	Corneal scar	Eye disorders	AG-348 in Participants With Sickle Cell Disease	1	17	1
other	Red eye (bilateral)	Eye disorders	AG-348 in Participants With Sickle Cell Disease	1	17	2
other	Diarrhea	Gastrointestinal disorders	AG-348 in Participants With Sickle Cell Disease	2	17	2
other	Helicobacter Pylori	Gastrointestinal disorders	AG-348 in Participants With Sickle Cell Disease	2	17	2
other	Vomiting and diarrhea	Gastrointestinal disorders	AG-348 in Participants With Sickle Cell Disease	1	17	1
other	Gingival pain	Gastrointestinal disorders	AG-348 in Participants With Sickle Cell Disease	1	17	1

1 to 10 of 66Source ClinicalTrials.gov

See all 66 adverse events

Adverse event totals3

The totals the trial posted for each group.

Total	Group	Affected	At risk
Total, all-cause mortality	AG-348 in Participants With Sickle Cell Disease	0	17
Total, other adverse events	AG-348 in Participants With Sickle Cell Disease	16	17
Total, serious adverse events	AG-348 in Participants With Sickle Cell Disease	6	17

Source ClinicalTrials.gov

Papers3

The papers the trial lists on ClinicalTrials.gov.

PMID	Listed as	Source
35576529	DERIVED	PubMed
39265169	DERIVED	PubMed
41809202	DERIVED	PubMed

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.

ClinicalTrials.gov: 2026-11-12; ClinicalTrials.gov
Results, from AACT: 2026-03-23; AACT
NIH grant links: 2026-11-13; NIH RePORTER

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.

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