A Safety and Tolerability Study of AG-519 in Healthy Subjects

NCT02630927 | Terminated Phase 1

• 1 other identifier: AG519-C-001
• Study Type: interventional
• Target: 108
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to investigate a drug called AG-519, which is being developed for the treatment of a disease called pyruvate kinase deficiency (also known as PK deficiency) and other forms of anemia. This study is a 5 part study with Part 1 enrolling healthy volunteers into single ascending dose (SAD) groups, Part 2 enrolling healthy volunteers into multiple ascending dose (MAD) groups and Part 3 enrolling healthy volunteers to investigate how much of the study drug is taken up by the body and how food affects the uptake of a prototype formulation of AG-519, Part 4 enrolling healthy volunteers of Japanese origin to compare to the results of subjects of non-Japanese origin, and Part 5 a non-randomized, open-label, multiple dose study enrolling healthy volunteers to further investigate how much of the study drug is taken up by the body when dosed over 14 days.

Conditions

Anemia

Keywords

Safety and Tolerability; Pharmacokinetic Study; Healthy Volunteer; Pyruvate Kinase; Rare Genetic

Outcome Measures

Primary Outcomes (1)

• Incidence of Treatment-Emergent Adverse Events

  Incidence of adverse events and descriptive statistics for safety laboratory parameters, physical exam findings, vital signs and ECGs. This outcome applies to all Parts of the study

  14 days

Secondary Outcomes (5)

• Cmax of AG-519

  4 days (Parts 1, 3, & 4) 17 days (Parts 2 & 5)

• Tmax of AG-519

  4 days (Parts 1, 3, & 4) 17 days (Parts 2 & 5)

• AUC of AG-519

  4 days (Parts 1, 3, & 4) 17 days (Parts 2 & 5)

• Change from baseline in whole blood concentration of adenosine triphosphate (ATP)

  4 days (Parts 1 & 3) 17 days (Part 2)

• Change from baseline in whole blood concentration of 2,3 - diphosphoglycerate (2,3-DPG)

  4 days (Parts 1 & 3) 17 days (Part 2)

Study Arms (5)

Part 1 Single-Ascending (SAD Phase)

PLACEBO COMPARATOR

A range of doses of AG519 will be tested based on the assessment of safety and tolerability. A single dose of AG-519 will be administered by mouth (orally).

Drug: AG-519; Drug: Placebo

Part 2 Multiple-Ascending (MAD Phase)

PLACEBO COMPARATOR

A range of doses of AG519 will be tested based on the assessment of safety and tolerability. AG519 will be administered by mouth (orally) each day for a period up to 14 days.

Drug: AG-519; Drug: Placebo

Part 3 Bioavailability & Food Effect

EXPERIMENTAL

The dose to be assessed in Part 3 will be selected based on emerging safety, tolerability and PK/PD data from preceding cohorts in Part 1 and Part 2, which will be reviewed during a dose decision meeting.

Drug: AG-519

Experimental Part 4 (Subjects of Japanese Origin)

EXPERIMENTAL

Two dose levels of AG-519 will be tested based on the assessment of safety and tolerability in preceding cohorts in Part 1, Part 2, and Part 3

Drug: AG-519

Experimental Part 5 Open-label Multiple-Ascending (MAD)

EXPERIMENTAL

Up to two dose levels of AG-519 will be tested based on the assessment of safety and tolerability in preceding cohorts in Part 1, Part 2, and Part 3. AG519 will be administered by mouth (orally) each day for a period up to 14 days.

Drug: AG-519

Interventions

AG-519 DRUG

AG519 will be tested.

Experimental Part 4 (Subjects of Japanese Origin); Experimental Part 5 Open-label Multiple-Ascending (MAD); Part 1 Single-Ascending (SAD Phase); Part 2 Multiple-Ascending (MAD Phase); Part 3 Bioavailability & Food Effect

Placebo DRUG

Placebo will be tested.

Part 1 Single-Ascending (SAD Phase); Part 2 Multiple-Ascending (MAD Phase)

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy adult male or female subjects. Female subjects must be of non-childbearing potential.
• Age 18 to 60 years inclusive at time of consent.
• Body mass index (BMI) of ≥18.5 to ≤32.0 kg/m2 or, if outside the range, considered not clinically significant by the investigator.
• Good state of health (mentally and physically) as indicated by a comprehensive clinical assessment (detailed medical history and a complete physical examination), ECG and laboratory investigations.
• Subjects who are actively non-smokers and have not used other nicotine-containing products for at least 12 months prior to the screening assessment.
• Must be willing and able to communicate and participate in the whole study.
• Must provide written informed consent.
• Must agree to use an adequate method of contraception.
• Japanese subjects enrolled in Part 4 must be first generation: born in Japan, not having lived outside Japan for 5 to 10 years, able to trace maternal and paternal Japanese ancestry, with no significant change in lifestyle, including diet (at least one Japanese meal consumed per day), since leaving Japan.

You may not qualify if:

• Participation in a clinical research study within the previous 3 months.
• Subjects who are study site employees, or immediate family members of a study site or sponsor employee.
• Subjects who have previously been enrolled in this study.
• History of any drug or alcohol abuse in the past 2 years.
• Regular alcohol consumption in males \>21 units per week and females \>14 units per week (1 unit = ½ pint beer, 25 mL of 40% spirit or a 125 mL glass of wine).
• Current smokers and those who have smoked within the last 12 months. A breath carbon monoxide reading of greater than 10 ppm at screening.
• Any females of childbearing potential.
• Subjects who do not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator at screening.
• Subjects who, after 10 min of supine rest, have a systolic blood pressure (BP) ≥140 mmHg (≥150 mmHg in subjects \>45 years of age) or a diastolic BP of ≥90 mmHg.
• Male subjects with QTcF interval (Fridericia's correction factor) ECG \>450 msec, or female subjects with QTcF interval ECG \>470 msec on screening or Day 1 (pre dose) ECG.
• Subjects with a history of serious mental illness, that includes, but is not limited to schizophrenia, bipolar disorder, and major depression.
• Subjects with glucose-6-phosphate-dehydrogenase (G6PD) deficiency.
• Subjects with a history of any primary malignancy, including a history of melanoma or suspicious undiagnosed skin lesions.
• Subjects with any other medical or psychological condition, deemed by the investigator to be likely to interfere with a subject's ability to sign informed consent, cooperate, or participate in the study.
• Subjects who have undergone major surgery within 6 months prior to screening.

Sponsors & Collaborators

• Agios Pharmaceuticals, Inc.: lead

Study Sites (1)

Quotient Clinical

Ruddington Fields, Nottingham, NG11 6JS, United Kingdom

Location

MeSH Terms

Conditions

Anemia

Condition Hierarchy (Ancestors)

Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Gary A Connor, RN

  Agios Pharmaceuticals, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 8, 2015
• First Posted: December 15, 2015
• Study Start: December 1, 2015
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: June 29, 2017

Record last verified: 2017-06

Locations

GB (1)