A Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of AG-946 in Healthy Volunteers and in Participants With Sickle Cell Disease

Completed · Phase 1 · Has a placebo group

Conditions studied: Healthy Volunteers, Anemia, Sickle Cell

In brief

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).

Key facts

Study ID

NCT04536792

Run by

Agios Pharmaceuticals, Inc.

People needed

122

Starts

2020-07-10

Expected to finish

2023-12-19

Last updated by the study team

2024-04-16

Who can join

Age: 18 and older, up to 70. Sex: any. Healthy volunteers: accepted.

You may qualify if…

• 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);
• 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.

You may not qualify if…

• 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;
• 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.

Where it is running

• University of California San Diego — La Jolla, California, United States
• Massachusetts General Hospital — Boston, Massachusetts, United States
• Boston Medical Center — Boston, Massachusetts, United States
• New York Presbyterian Hospital - Weill Cornell Medicine — New York, New York, United States
• University of Pittsburgh Medical Center — Pittsburgh, Pennsylvania, United States
• PPD Development, LP — Austin, Texas, United States
• Texas Oncology-Baylor Charles A. Sammons Cancer Center - USOR — Dallas, Texas, United States
• University of Texas Health Science Center of Houston — Houston, Texas, United States
• Rigshospitalet, Department of Hematology — Copenhagen, Denmark
• Hospital Universitario Vall d'Hebron - PPDS — Barcelona, Spain

Full record on ClinicalTrials.gov

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