AnemiaPhase 1NCT02630927
A Safety and Tolerability Study of AG-519 in Healthy Subjects
A Phase 1 study testing AG-519 in people with Anemia, run by Agios Pharmaceuticals, Inc. at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Anemia
- What is being tested?
- AG-519
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 108 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Dec 2015to Dec 2016
- 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 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- 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.
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- 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.
- Clinically significant abnormal biochemistry, hematology or urinalysis as judged by the investigator.
- Positive drugs of abuse test result at screening or admission.
- Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) results.
- Subjects who are taking, or have taken, any prescribed or over-the-counter drug.
- Subjects who have used St. John's Wort within 28 days before the first dose of study drug.
- History of cardiovascular, renal, hepatic, chronic respiratory or GI disease, or hematologic, lymphatic, neurolologic, endocrine, psychiatric, musculoskeletal, genitourinary, immunologic, dermatologic or connective tissue disease or disorders, as judged by the investigator.
- Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients, including history of allergy to sulfonamides.
- Presence or history of clinically significant allergy requiring treatment, as judged by the investigator.
- Donation or loss of greater than 400 mL of blood within the previous 3 months.
- Failure to satisfy the investigator of fitness to participate for any other reason.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Quotient Clinical
Ruddington Fields, Nottingham, NG11 6JS
About this study
Official title: A Phase I Randomized, Double-blind, Five-Part Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Ascending Oral Doses of AG-519, the Relative Bioavailability of Prototype Tablet Formulations Compared With a Suspension Formulation, and to Evaluate the Pharmacokinetics of a Selected Tablet Formulation Under Fed and Fasted Conditions in Healthy Subjects
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
- Being tested
- AG-519, Placebo
- Keywords
- Safety and Tolerability, Pharmacokinetic Study, Healthy Volunteer, Pyruvate Kinase, Rare Genetic
- Medical subject headings
- Anemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AG-519Drug
AG519 will be tested.
PlaceboDrug
Placebo will be tested.
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: 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. Receives: 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. Receives: 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 Receives: 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. Receives: Drug: AG-519 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 14 days
Secondary outcomes (5)
Cmax of AG-519
Descriptive statistics will be used to summarize PK parameters of AG-519 for each dose group and, where appropriate, for the entire population. Standard non-compartmental PK parameters will be calculated from individual plasma concentration data.
Measured: 4 days (Parts 1, 3, & 4) 17 days (Parts 2 & 5)
Tmax of AG-519
Descriptive statistics will be used to summarize PK parameters of AG-519 for each dose group and, where appropriate, for the entire population. Standard non-compartmental PK parameters will be calculated from individual plasma concentration data.
Measured: 4 days (Parts 1, 3, & 4) 17 days (Parts 2 & 5)
AUC of AG-519
Descriptive statistics will be used to summarize PK parameters of AG-519 for each dose group and, where appropriate, for the entire population. Standard non-compartmental PK parameters will be calculated from individual plasma concentration data.
Measured: 4 days (Parts 1, 3, & 4) 17 days (Parts 2 & 5)
Change from baseline in whole blood concentration of adenosine triphosphate (ATP)
The potential relationship between AG-519 and metabolic biomarkers will be explored with descriptive and graphical methods.
Measured: 4 days (Parts 1 & 3) 17 days (Part 2)
Change from baseline in whole blood concentration of 2,3 - diphosphoglycerate (2,3-DPG)
The potential relationship between AG-519 and metabolic biomarkers will be explored with descriptive and graphical methods.
Measured: 4 days (Parts 1 & 3) 17 days (Part 2)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Dec 2015 (estimated)
- Study startDec 2015
- Primary completionDec 2016
- Study completionDec 2016
Why it stopped: Agios is no longer developing its second pyruvate kinase-R (PKR) activator, AG-519, and withdrew its investigational new drug (IND) application in December 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AnemiaStudies 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
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 108 participants (actual)
Sponsor and investigators
- Lead sponsor
- Agios Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Gary A Connor, RN, Study director, Agios Pharmaceuticals, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02630927
- Sponsor's protocol ID
- AG519-C-001
- Status last verified
- Jun 2017
- First submitted
- 8 Dec 2015
- Last updated
- 29 Jun 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Randomized, Double-blind, Five-Part Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Ascending Oral Doses of AG-519, the Relative Bioavailability of Prototype Tablet Formulations Compared With a Suspension Formulation, and to Evaluate the Pharmacokinetics of a Selected Tablet Formulation Under Fed and Fasted Conditions in Healthy Subjects
- ClinicalTrials.gov ID
- NCT02630927
- Acronym / sponsor ID
- AG519-C-001
- Conditions
- Anemia
- Keywords
- Safety and Tolerability, Pharmacokinetic Study, Healthy Volunteer, Pyruvate Kinase, Rare Genetic
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Agios is no longer developing its second pyruvate kinase-R (PKR) activator, AG-519, and withdrew its investigational new drug (IND) application in December 2016
- Enrolment
- 108 participants (actual)
- Lead sponsor
- Agios Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- Dec 2015
- Primary completion
- Dec 2016 (actual)
- Study completion
- Dec 2016 (actual)
- First posted
- 15 Dec 2015 (estimated)
- 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 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| Part 1 Single-Ascending (SAD Phase) | Placebo comparator | Drug: AG-519, Drug: PlaceboA 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). |
| Part 2 Multiple-Ascending (MAD Phase) | Placebo comparator | Drug: AG-519, Drug: PlaceboA 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. |
| Part 3 Bioavailability & Food Effect | Experimental | Drug: AG-519The 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. |
| Experimental Part 4 (Subjects of Japanese Origin) | Experimental | Drug: AG-519Two 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 |
| Experimental Part 5 Open-label Multiple-Ascending (MAD) | Experimental | Drug: AG-519Up 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. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- 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.
Key exclusion criteria (25 listed)
- 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).
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-519AG519 will be tested. | Drug | 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 |
| PlaceboPlacebo will be tested. | Drug | Part 1 Single-Ascending (SAD Phase), Part 2 Multiple-Ascending (MAD Phase) |
Primary outcome
Incidence of Treatment-Emergent Adverse Events
Time frame: 14 days
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
5 secondary outcomes
Cmax of AG-519
Time frame: 4 days (Parts 1, 3, & 4) 17 days (Parts 2 & 5)
Tmax of AG-519
Time frame: 4 days (Parts 1, 3, & 4) 17 days (Parts 2 & 5)
AUC of AG-519
Time frame: 4 days (Parts 1, 3, & 4) 17 days (Parts 2 & 5)
Change from baseline in whole blood concentration of adenosine triphosphate (ATP)
Time frame: 4 days (Parts 1 & 3) 17 days (Part 2)
Change from baseline in whole blood concentration of 2,3 - diphosphoglycerate (2,3-DPG)
Time frame: 4 days (Parts 1 & 3) 17 days (Part 2)
Results and safety
The study was stopped early (reason given: Agios is no longer developing its second pyruvate kinase-R (PKR) activator, AG-519, and withdrew its investigational new drug (IND) application in December 2016). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jun 2017.
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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.
Gary A Connor, RN study director
Agios Pharmaceuticals, Inc.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AG-519 in people with Anemia, run by Agios Pharmaceuticals, Inc. at 1 site in United Kingdom.
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 9 inclusion and 25 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: stopped early, as of the sponsor's last update on 29 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. 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. Some participants in this study may receive a placebo. 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 was stopped early (reason given: Agios is no longer developing its second pyruvate kinase-R (PKR) activator, AG-519, and withdrew its investigational new drug (IND) application in December 2016). Results are not available in the source record.
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?
Incidence of Treatment-Emergent Adverse Events (time frame: 14 days). 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 29 Jun 2017.