Healthy VolunteersPhase 1NCT04536792
A Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AG-946 in Healthy Volunteers and in Participants With Sickle Cell Disease
A Phase 1 study testing AG-946 in people with Healthy Volunteers and Anemia, Sickle Cell, run by Agios Pharmaceuticals, Inc. at 10 sites in 3 countries.
Trial summary
The purpose of the study is to assess the safety and tolerability of AG-946 in healthy volunteers after oral administration of single ascending doses (SAD) and multiple ascending doses (MAD) of AG-946 over 14 or up to 28 days of dosing, and to identify a range of doses that are safe and pharmacologically active in… Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteers, Anemia, Sickle Cell
- What is being tested?
- AG-946
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 122 participants
- Where
- 10 sitesin 3 countries
- Study dates
- 10 Jul 2020to 19 Dec 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- SAD and MAD
- Participant is a healthy male or a female of nonchildbearing potential aged 18 to 55 years inclusive at the time of consent;
- Participant is able to understand and provide informed consent before the conduct of any protocol-specific screening procedures;
- Participant is willing and able to complete all study assessments and procedures;
- Participant has a bodyweight ≥50 kilograms (kg) and body mass index ≥18.5 and ≤32 kilograms per square meter (kg/m^2) at screening;
- Participant is in good general health with no clinically significant deviations from normal in screening medical history, physical examination, vital signs, or electrocardiogram (ECGs);
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- Male participants must agree to be abstinent as part of their usual lifestyle or use contraception up to 90 days after last dose of study treatment;
- Participant is a non-smoker and has not used nicotine-containing products for at least 3 months prior to screening;
- Participant is willing to refrain from caffeine- or xanthene-containing products (eg, coffee, tea, cola, chocolate) for 48 hours before the first dose of study treatment through 7 days after the last dose of study treatment;
- Participant is willing to refrain from marijuana- or cannabinol-containing products for 7 days before admission through the final visit;
- Participant is willing to refrain from strenuous exercise starting 72 hours before admission through the final visit;
- Participant is willing to refrain from use of alcohol starting 7 days prior to admission through final visit;
- Participant agrees not to donate blood products for duration of study participation;
- Male participants must agree not to donate sperm for duration of study and for 90 days after the last dose.
- SCD
- Participant is a male or female aged 18 to 70 years inclusive at the time of consent;
- Participant has documented sickle cell anemia;
- Provided informed consent before the conduct of any protocol-specific screening procedures;
- If the participant is taking hydroxyurea (HU), L-glutamine, and/or crizanlizumab, the dose(s) must have been stable for at least 3 months before the first dose of AG-946;
- Participant must start or continue to take folic acid in the equivalent of at least 0.8 milligrams per day (mg/day) orally for the duration of the study, unless the Investigator considers dietary folic acid intake to be adequate;
- Participant has adequate organ function;
- Female participants who are of childbearing potential, must have negative pregnancy test during screening;
- Female participants who are of childbearing potential and male participants who have partners who are females of childbearing potential, must agree to be abstinent as part of their usual lifestyle or agree to use contraception from the time of providing informed consent to 28 days for women and 90 days for men after the last dose of AG-946;
- Participant must be willing to comply with all study procedures for the duration of the study.
Who cannot join
- SAD and MAD
- Participant has previously enrolled in this study or has received an investigational drug with 3 months or 5 half-lives of the drug, whichever is longer, before the first dose of study treatment;
- Participant has previously received AG-946, except for participants who are dosing in the fed portion of the food-effect group;
- Participant has a heart rate-corrected QT interval (QTc) interval using Fridericia correction method (QTcF) >450 milliseconds (ms) at screening;
- Participant has used over-the-counter medication (excluding routine vitamins) within 7 days of the first dose of study treatment, unless agreed as not clinically relevant;
- Participant has used acetaminophen greater than 2 grams (g) in any 24-hour period up to 48 hours before the first dose of study treatment;
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- Participants has clinically relevant screening laboratory tests results outside the normal range;
- Participant has a history of any relevant cardiovascular, renal, hepatic, chronic respiratory, or gastrointestinal disease; or hematologic, lymphatic, neurologic, endocrine, psychiatric, musculoskeletal, genitourinary, immunologic, dermatologic, or connective tissue disease or disorders;
- Participant has a history of serious mental illness, that includes, but is not limited to schizophrenia, bipolar disorder, or major depression;
- Participant has a history of any primary malignancy, except for basal cell or squamous cell carcinomas of the skin or cervical carcinoma in situ or other malignancies that have been curatively treated and with no evidence of disease for at least 5 years before screening;
- Participant has had surgery within 6 months before the first dose of study treatment;
- Participant has a preexisting condition that interferes with normal gastrointestinal anatomy or motility, and/or hepatic and/or renal function that could interfere with the absorption, metabolism, and/or excretion of the study treatment or has previously undergone cholecystectomy;
- Participant has systolic blood pressure (BP) ≥140 mm Hg or a diastolic BP of ≥90 mm Hg after 10 minutes rest at screening or before the first dosing of study treatment;
- Participant has medical or psychological condition deemed by the Investigator to be likely to interfere with the volunteer's ability to provide informed consent, cooperate, and/or participate in the study;
- Participant has a known allergy to any of the excipients or components of the study treatment;
- Participant tests positive for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibody (Ab), or human immunodeficiency virus (HIV) infection -1 or -2 Ab;
- Participant has donated blood, had blood loss of more than 500 milliliters (mL), or has received transfusion of blood or plasma within 3 months before screening;
- Participant has a history of illicit drug abuse or alcoholism within the last 1 year before screening;
- Participant has consumed more than 21 units of alcohol a week within the last 1 year before screening;
- Participant has used prescription drugs within 2 weeks or 5 half-lives (whichever is longer) before the first dose of study treatment;
- Participant has a positive screen for drugs of abuse or urinary cotinine >200 nanograms per milliliter (ng/mL) at screening or admission; or a positive screen for alcohol (via urine analysis) at admission;
- Participant cannot communicate reliably with the Investigator;
- Participant cannot or is unlikely to cooperate with the requirements of the study;
- Participant has any conditions that, in the judgment of the Investigator, would make the volunteer unsuitable for enrollment or could interfere with the volunteer's participation in, or completion of, the study;
- Participant has known glucose-6-phosphate dehydrogenase (G6PD) deficiency or G6PD activity below the lower limit of the normal range at the screening visit.
- SCD
- Participant is a candidate for potentially curative treatment with bone marrow transplantation, and for whom participation in this study would delay or preclude such definitive treatment;
- Participant has documented history of pyruvate kinase deficiency (PKD) or red blood cell-specific form of pyruvate kinase (PKLR) mutation;
- Participant has had more than 6 vaso-occlusive crisis (VOCs) within the past 12 months that required a hospital, emergency room, or clinic visit;
- Participant is receiving regularly scheduled red blood cell (RBC) transfusion therapy, and/or has received a transfusion within the past 3 months before the first dose of AG-946;
- Participant is currently receiving treatment with voxelotor or any other agent intended to increase hemoglobin (Hb)-oxygen affinity;
- Participant has a significant medical condition that confers an unacceptable risk to participating in the study, and/or that could confound the interpretation of the study data as follows:
- Poorly controlled hypertension (defined as systolic BP >150 millimeters of mercury (mm Hg) or diastolic BP >90 mm Hg) refractory to medical management
- Any history of congestive heart failure; myocardial infarction; unstable angina pectoris; hemorrhagic, embolic, or thrombotic stroke; or recent venous thrombosis or pulmonary or arterial embolism
- Cardiac dysrhythmias judged as clinically significant by the Investigator
- QTcF >450 milliseconds (ms), unless related to right or left bundle branch block
- Clinically symptomatic cholelithiasis or cholecystitis
- History of drug-induced cholestatic hepatitis
- Iron overload sufficiently severe to result in a clinical diagnosis by the Investigator of cardiac, hepatic, or pancreatic dysfunction
- Have a diagnosis of any other congenital or acquired blood disorder, or any other hemolytic process as defined by a positive direct antiglobulin test, except for mild alloimmunization as a consequence of transfusion therapy
- Positive test for HBsAg, or positive test for HCV Ab with evidence of active virus infection
- Positive test for HIV-1 or -2 Ab
- Active infection requiring the use of parenteral antimicrobial agents or Grade ≥3 in severity
- Diabetes mellitus judged to be under poor control by the Investigator or requiring >2 antidiabetic agents, including insulin
- History of any primary malignancy, except for curatively treated nonmelanoma skin cancer, cervical or breast carcinoma in situ, prostate cancer, or other primary tumor treated with curative intent, no known active disease present, and no treatment administered during the last 3 years before Screening
- Unstable extramedullary hematopoiesis that could pose a risk of imminent neurologic compromise
- Current or recent history of a psychiatric disorder
- Participant is currently enrolled in another therapeutic clinical trial involving ongoing therapy with any investigational or marketed product or placebo;
- Participant has had exposure to any investigational drug within 3 months or 5 half-lives of the drug, whichever is longer, before the first dose of AG-946;
- Participant has had exposure to any investigational device or invasive procedure within 3 months before the first dose of AG-946;
- Participant has a history of major surgery within 6 months of providing informed consent;
- Participant has had a prior bone marrow or stem cell transplant;
- Participant is currently pregnant or breastfeeding;
- Participant has received medications that are strong inhibitors of permeability-glycoprotein (P-gp) within 5 days or a time frame equivalent to 5 half-lives (whichever is longer) before the first dose of AG-946;
- Participant has received hematopoietic stimulating agents within 28 days before the first dose of AG-946;
- Participant has a known allergy to any of the excipients found in AG-946.
Trial locations and contacts
10 sites in 3 countries.
10 sites in 3 countries
United States8 sites
PPD Development, LP
Austin, Texas, 78744
Massachusetts General Hospital
Boston, Massachusetts, 02114
Boston Medical Center
Boston, Massachusetts, 02118
Texas Oncology-Baylor Charles A. Sammons Cancer Center - USOR
Dallas, Texas, 75246
University of Texas Health Science Center of Houston
Houston, Texas, 77030
University of California San Diego
La Jolla, California, 92037
New York Presbyterian Hospital - Weill Cornell Medicine
New York, New York, 10065
University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania, 15213
About this study
Official title: A Phase 1 Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AG-946 in Healthy Volunteers and in Subjects With Sickle Cell Disease
The purpose of the study is to assess the safety and tolerability of AG-946 in healthy volunteers after oral administration of single ascending doses (SAD) and multiple ascending doses (MAD) of AG-946 over 14 or up to 28 days of dosing, and to identify a range of doses that are safe and pharmacologically active in participants with sickle cell disease. The SAD and MAD parts of the study will be randomized and double-blinded, and will assess the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of AG-946 as well as the effect of food (SAD only) on the pharmacokinetics (PK) of AG-946. The sickle cell disease (SCD) part of the study will be non-randomized and open-label, and is designed to identify 1 or more safe and tolerable dose(s) of AG-946 with potential activity in the treatment of participants with sickle cell disease (SCD).
- Conditions
- Healthy Volunteers, Anemia, Sickle Cell
- Being tested
- AG-946, AG-946 Matched Placebo
- Keywords
- Sickle Cell Disease, Healthy
- Medical subject headings
- Anemia, Sickle Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AG-946Drug
AG-946, oral encapsulated coated-granules or tablets.
AG-946 Matched PlaceboDrug
AG-946 matched-placebo, oral encapsulated sugar spheres or tablets.
| Study group | Role | What they receive |
|---|---|---|
| Part 1: Single Ascending Dose (SAD) Phase | Experimental | Participants will receive a range of doses of AG-946 or placebo, orally, once on Day 1. AG-946 will be given under fasted or fed conditions. Receives: Drug: AG-946; Drug: AG-946 Matched Placebo |
| Part 2: Multiple Ascending Dose (MAD) Phase | Experimental | Participants will receive a range of doses of AG-946 or placebo, orally, once daily (QD) for 14 days or using an alternative dosing regimen for up to 28 days under fasted conditions. Receives: Drug: AG-946; Drug: AG-946 Matched Placebo |
| Part 3: Sickle Cell Disease (SCD) Phase | Experimental | Participants will receive a range of selected ascending doses of AG-946, orally, QD or using an alternative dosing regimen for 28 days. Receives: Drug: AG-946 |
What is being measured
The primary outcome is the main question the study is designed to answer.
SAD and MAD: Number of Participants Who Experienced at Least One Adverse Event (AE), by Severity
Measured: SAD: Up to Day 13; MAD: Up to Day 49
SAD and MAD: Number of Participants Who Experienced at Least One AE Related to the Study Drug
Measured: SAD: Up to Day 13; MAD: Up to Day 49
SAD and MAD: Number of Participants Who Experienced at Least One Serious Adverse Event (SAE)
Measured: SAD: Up to Day 13; MAD: Up to Day 49
SAD and MAD: Number of Participants With Clinically Significant Laboratory Abnormalities, by Severity
Measured: SAD: Up to Day 13; MAD: Up to Day 49
SAD and MAD: Number of Participants With Clinically Significant Changes in Vital Signs and in Electrocardiogram (ECG) Parameters
Measured: SAD: Up to Day 13; MAD: Up to Day 49
SCD: Number of Participants Who Experienced at Least One AE, by Severity
Measured: Up to Day 56
SCD: Number of Participants Who Experienced at Least One AE Related to the Study Drug
Measured: Up to Day 56
SCD: Number of Participants Who Experienced at Least One SAE
Measured: Up to Day 56
SCD: Number of Participants With Clinically Significant Laboratory Abnormalities, by Severity
Measured: Up to Day 56
SCD: Number of Participants With Clinically Significant Changes in Vital Signs and in ECG Parameters
Measured: Up to Day 56
Secondary outcomes (17)
Maximum Observed Concentration (Cmax) of AG-946
Cmax will be determined under fasted and fed conditions in SAD and under fasted conditions only in MAD and SCD.
Measured: SAD: Up to Day 8; MAD: Up to Day 49; SCD: Up to Day 56
Time to Reach Maximum Observed Concentration (Tmax) of AG-946
Tmax will be determined under fasted and fed conditions in SAD and under fasted conditions only in MAD and SCD.
Measured: SAD: Up to Day 8; MAD: Up to Day 49; SCD: Up to Day 56
Area Under the Plasma Concentration-Time Curve from Time Zero to Last Quantifiable Concentration (AUC0-t), Time Curve from Time Zero to Infinity (AUC0-∞), and Time Curve from Time Zero to Time tau Over the Dosing Interval (AUC0-τ) for AG-946
AUC0-t, AUC0-∞, and AUC0-τ will be determined under fasted and fed conditions in SAD and under fasted conditions only in MAD and SCD.
Measured: SAD: Up to Day 8; MAD: Up to Day 49; SCD: Up to Day 56
SAD: Apparent Clearance (CL/F) for AG-946
CL/F will be determined under fasted and fed conditions.
Measured: SAD: Up to Day 8
SAD: Apparent Volume of Distribution (Vd/F) for AG-946
V/F will be determined under fasted and fed conditions.
Measured: SAD: Up to Day 8
SAD: Total Amount of Drug Excreted in Urine from Time 0 to Time T (Aet) and from Time t1 to Time t2 (Aet1-t2) for AG-946 Under Fasted and Fed Conditions
Measured: Up to Day 3
SAD: Percentage Dose of Drug Excreted in Urine from Time 0 to Time t (fet) and from Time t1 to Time t2 (fet1-t2) for AG-946 Under Fasted and Fed Conditions
Measured: Up to Day 3
SAD: Renal Clearance (CLr) for AG-946 Under Fasted and Fed Conditions
Measured: Up to Day 3
Changes in the Concentration of 2,3-diphosphoglycerate (2,3-DPG) and Adenosine Triphosphate (ATP) in Whole Blood
Measured: SAD: Up to Day 13; MAD: Up to Day 49; SCD: Up to Day 56
Area Under the Effect Curve (AUEC) from Time zero to t for 2,3-DPG and ATP
Measured: SAD: Up to Day 13; MAD: Up to Day 49; SCD: Up to Day 56
SAD: Relative Bioavailability Comparing Fasted to Fed Conditions Determined from the PK Parameters of AG-946
Measured: SAD: Up to Day 8
SCD: Change From Baseline in Hemoglobin (Hb)
Measured: Up to Day 56
SCD: Change From Baseline in Direct Bilirubin
Measured: Up to Day 56
SCD: Change From Baseline in Lactate Dehydrogenase (LDH)
Measured: Up to Day 56
SCD: Change From Baseline in Haptoglobin
Measured: Up to Day 56
SCD: Change From Baseline in Reticulocytes
Measured: Up to Day 56
SCD: Change From Baseline in Erythropoietin
Measured: Up to Day 56
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Sep 2020
- Study start10 Jul 2020
- Primary completion19 Dec 2023
- Study completion19 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Healthy VolunteersStudies of the same condition, open and under way.
- More trials run by Agios Pharmaceuticals, Inc.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 122 participants (actual)
Sponsor and investigators
- Lead sponsor
- Agios Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04536792
- Sponsor's protocol ID
- AG946-C-001
- Other IDs
- 2020-000691-38
- Status last verified
- Apr 2024
- First submitted
- 15 Jul 2020
- Last updated
- 16 Apr 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AG-946 in Healthy Volunteers and in Subjects With Sickle Cell Disease
- ClinicalTrials.gov ID
- NCT04536792
- Acronym / sponsor ID
- AG946-C-001
- Conditions
- Healthy Volunteers, Anemia, Sickle Cell
- Keywords
- Sickle Cell Disease, Healthy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 122 participants (actual)
- Lead sponsor
- Agios Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 10 Jul 2020 (actual)
- Primary completion
- 19 Dec 2023 (actual)
- Study completion
- 19 Dec 2023 (actual)
- First posted
- 3 Sep 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of the study is to assess the safety and tolerability of AG-946 in healthy volunteers after oral administration of single ascending doses (SAD) and multiple ascending doses (MAD) of AG-946 over 14 or up to 28 days of dosing, and to identify a range of doses that are safe and pharmacologically active in participants with sickle cell disease. The SAD and MAD parts of the study will be randomized and double-blinded, and will assess the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of AG-946 as well as the effect of food (SAD only) on the pharmacokinetics (PK) of AG-946. The sickle cell disease (SCD) part of the study will be non-randomized and open-label, and is designed to identify 1 or more safe and tolerable dose(s) of AG-946 with potential activity in the treatment of participants with sickle cell disease (SCD).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Part 1: Single Ascending Dose (SAD) Phase | Experimental | Drug: AG-946, Drug: AG-946 Matched PlaceboParticipants will receive a range of doses of AG-946 or placebo, orally, once on Day 1. AG-946 will be given under fasted or fed conditions. |
| Part 2: Multiple Ascending Dose (MAD) Phase | Experimental | Drug: AG-946, Drug: AG-946 Matched PlaceboParticipants will receive a range of doses of AG-946 or placebo, orally, once daily (QD) for 14 days or using an alternative dosing regimen for up to 28 days under fasted conditions. |
| Part 3: Sickle Cell Disease (SCD) Phase | Experimental | Drug: AG-946Participants will receive a range of selected ascending doses of AG-946, orally, QD or using an alternative dosing regimen for 28 days. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (24 listed)
- SAD and MAD
- Participant is a healthy male or a female of nonchildbearing potential aged 18 to 55 years inclusive at the time of consent;
- Participant is able to understand and provide informed consent before the conduct of any protocol-specific screening procedures;
- Participant is willing and able to complete all study assessments and procedures;
- Participant has a bodyweight ≥50 kilograms (kg) and body mass index ≥18.5 and ≤32 kilograms per square meter (kg/m^2) at screening;
Key exclusion criteria (56 listed)
- SAD and MAD
- Participant has previously enrolled in this study or has received an investigational drug with 3 months or 5 half-lives of the drug, whichever is longer, before the first dose of study treatment;
- Participant has previously received AG-946, except for participants who are dosing in the fed portion of the food-effect group;
- Participant has a heart rate-corrected QT interval (QTc) interval using Fridericia correction method (QTcF) >450 milliseconds (ms) at screening;
- Participant has used over-the-counter medication (excluding routine vitamins) within 7 days of the first dose of study treatment, unless agreed as not clinically relevant;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AG-946AG-946, oral encapsulated coated-granules or tablets. | Drug | Part 1: Single Ascending Dose (SAD) Phase, Part 2: Multiple Ascending Dose (MAD) Phase, Part 3: Sickle Cell Disease (SCD) Phase |
| AG-946 Matched PlaceboAG-946 matched-placebo, oral encapsulated sugar spheres or tablets. | Drug | Part 1: Single Ascending Dose (SAD) Phase, Part 2: Multiple Ascending Dose (MAD) Phase |
Primary outcome
SAD and MAD: Number of Participants Who Experienced at Least One Adverse Event (AE), by Severity
Time frame: SAD: Up to Day 13; MAD: Up to Day 49
SAD and MAD: Number of Participants Who Experienced at Least One AE Related to the Study Drug
Time frame: SAD: Up to Day 13; MAD: Up to Day 49
SAD and MAD: Number of Participants Who Experienced at Least One Serious Adverse Event (SAE)
Time frame: SAD: Up to Day 13; MAD: Up to Day 49
SAD and MAD: Number of Participants With Clinically Significant Laboratory Abnormalities, by Severity
Time frame: SAD: Up to Day 13; MAD: Up to Day 49
SAD and MAD: Number of Participants With Clinically Significant Changes in Vital Signs and in Electrocardiogram (ECG) Parameters
Time frame: SAD: Up to Day 13; MAD: Up to Day 49
SCD: Number of Participants Who Experienced at Least One AE, by Severity
Time frame: Up to Day 56
SCD: Number of Participants Who Experienced at Least One AE Related to the Study Drug
Time frame: Up to Day 56
SCD: Number of Participants Who Experienced at Least One SAE
Time frame: Up to Day 56
SCD: Number of Participants With Clinically Significant Laboratory Abnormalities, by Severity
Time frame: Up to Day 56
SCD: Number of Participants With Clinically Significant Changes in Vital Signs and in ECG Parameters
Time frame: Up to Day 56
17 secondary outcomes
Maximum Observed Concentration (Cmax) of AG-946
Time frame: SAD: Up to Day 8; MAD: Up to Day 49; SCD: Up to Day 56
Time to Reach Maximum Observed Concentration (Tmax) of AG-946
Time frame: SAD: Up to Day 8; MAD: Up to Day 49; SCD: Up to Day 56
Area Under the Plasma Concentration-Time Curve from Time Zero to Last Quantifiable Concentration (AUC0-t), Time Curve from Time Zero to Infinity (AUC0-∞), and Time Curve from Time Zero to Time tau Over the Dosing Interval (AUC0-τ) for AG-946
Time frame: SAD: Up to Day 8; MAD: Up to Day 49; SCD: Up to Day 56
SAD: Apparent Clearance (CL/F) for AG-946
Time frame: SAD: Up to Day 8
SAD: Apparent Volume of Distribution (Vd/F) for AG-946
Time frame: SAD: Up to Day 8
SAD: Total Amount of Drug Excreted in Urine from Time 0 to Time T (Aet) and from Time t1 to Time t2 (Aet1-t2) for AG-946 Under Fasted and Fed Conditions
Time frame: Up to Day 3
SAD: Percentage Dose of Drug Excreted in Urine from Time 0 to Time t (fet) and from Time t1 to Time t2 (fet1-t2) for AG-946 Under Fasted and Fed Conditions
Time frame: Up to Day 3
SAD: Renal Clearance (CLr) for AG-946 Under Fasted and Fed Conditions
Time frame: Up to Day 3
Changes in the Concentration of 2,3-diphosphoglycerate (2,3-DPG) and Adenosine Triphosphate (ATP) in Whole Blood
Time frame: SAD: Up to Day 13; MAD: Up to Day 49; SCD: Up to Day 56
Area Under the Effect Curve (AUEC) from Time zero to t for 2,3-DPG and ATP
Time frame: SAD: Up to Day 13; MAD: Up to Day 49; SCD: Up to Day 56
SAD: Relative Bioavailability Comparing Fasted to Fed Conditions Determined from the PK Parameters of AG-946
Time frame: SAD: Up to Day 8
SCD: Change From Baseline in Hemoglobin (Hb)
Time frame: Up to Day 56
SCD: Change From Baseline in Direct Bilirubin
Time frame: Up to Day 56
SCD: Change From Baseline in Lactate Dehydrogenase (LDH)
Time frame: Up to Day 56
SCD: Change From Baseline in Haptoglobin
Time frame: Up to Day 56
SCD: Change From Baseline in Reticulocytes
Time frame: Up to Day 56
SCD: Change From Baseline in Erythropoietin
Time frame: Up to Day 56
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Apr 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
10 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AG-946 in people with Healthy Volunteers and Anemia, Sickle Cell, run by Agios Pharmaceuticals, Inc. at 10 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 24 inclusion and 56 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States, Denmark, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
SAD and MAD: Number of Participants Who Experienced at Least One Adverse Event (AE), by Severity (time frame: SAD: Up to Day 13; MAD: Up to Day 49). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Apr 2024.