Classic GalactosemiaPhase 1/2NCT04117711
Safety and Pharmacokinetics of AT-007 in Healthy Subjects and in Adult Subjects With Classic Galactosemia
A Phase 1/2 study testing AT-007 in people with Classic Galactosemia, run by Applied Therapeutics, Inc. at 4 sites in United States.
Trial summary
This study is a first-in-human, randomized, placebo-controlled, 4-Part, single ascending dose (SAD) and multiple ascending dose (MAD) study in healthy adult subjects and adult subjects with Classic Galactosemia. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Classic Galactosemia
- What is being tested?
- AT-007
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 114 participants
- Where
- 4 sitesUnited States
- Study dates
- 21 Jun 2019to 14 Dec 2021
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Diagnosis of Classic Galactosemia confirmed by evidence of absent or significantly decreased (<1%) GALT activity in red blood cells and by GALT gene analysis
- Urine galactitol >100 mmol/mol creatinine
- Galactose-restricted diet
Who cannot join
- Complications of CG resulting in disability that, in the opinion of the Investigator, may prevent the subject from completing all study requirements (e.g., severe neurological deficits, severe cognitive impairment, or severe language difficulty).
- Renal disease (eGFR < 90 mL/min/1.73 m2 or albuminuria).
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Anaheim Clinical Trials, LLC
Anaheim, California, 92801
Atlanta Center for Medical Research
Atlanta, Georgia, 30331
Brigham and Women's Hospital
Boston, Massachusetts, 02115
ICON Clinical Research
San Antonio, Texas, 78209
About this study
Official title: A Phase 1-2, Dose-Escalating, 4-Part Study to Evaluate the Safety and Pharmacokinetics of Single and Multiple Doses of AT-007 in Healthy Adult Subjects and Adult Subjects With Classic Galactosemia
This study is a first-in-human, randomized, placebo-controlled, 4-Part, single ascending dose (SAD) and multiple ascending dose (MAD) study in healthy adult subjects and adult subjects with Classic Galactosemia.
Read the detailed description
The study is designed to assess the safety and PK of AT-007 in healthy subjects and subjects with Classic Galactosemia as well as the effect of AT-007 on biomarkers of galactose metabolism (galactose, galactitol, and other galactose metabolites) in subjects with Classic Galactosemia.
This study consists of 4 parts:
- Part A (SAD) in 32 healthy subjects. Once daily oral escalating dose (6 active, 2 placebo).
- Part B and C (MAD for 7 days) in 36 healthy subjects. Once daily multiple daily dosing (8 active, 2 placebo per each dose cohort).
- Part D (SAD followed by MAD for 27 days) in 18 subjects with Classic Galactosemia. Once daily followed by multiple daily oral dosing (6 active, 2 placebo for each dose cohort).
- Conditions
- Classic Galactosemia
- Being tested
- AT-007, Placebo
- Keywords
- Classic Galactosemia, Aldose Reductase Inhibition, Galactose, Galactitol
- Medical subject headings
- Galactosemias
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AT-007Drug
Also called Govorestat
AT-007 will be administered once daily before breakfast. Up to 4 different dose cohorts in part A; up to 4 dose cohorts in part B, up to 2 dose cohorts for part C, and up to 3 dose cohorts for part D will be enrolled in the study. The starting dose in Part A will be 0.5 mg/kg as a single dose. Subsequent doses in Part A and all doses in Parts B, C, and D will be based on the results of previous cohorts and/or previous parts of the study. Part B will start after all subjects in Part A have completed the study. Cohort C1 will be conducted simultaneously with Cohort B3 and using the same dose as Cohort B2. The dose for Cohort D1 will not be higher than the dose for Cohort B2. The second and third cohorts in Part D (D2 and D3) will not start until after all subjects in Cohorts B3 and B4, respectively, have completed the study and the dose levels will not be higher than those for Cohorts B3 and B4, respectively.
PlaceboDrug
Matching placebo will be administered once in the morning before breakfast
| Study group | Role | What they receive |
|---|---|---|
| AT-007 | Experimental | AT-007 is a CNS and retina penetrant aldose reductase inhibitor. Receives: Drug: AT-007 |
| Placebo Comparator | Placebo comparator | Placebo is used as a comparator to the experimental arm. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Treatment-emergent Adverse Events
To evaluate the safety and tolerability of AT-007 after administration to healthy subjects, including clinically-significant changes in clinical laboratory test results, physical examination findings, vital sign evaluations, and electrocardiogram results.
Measured: Events after 1 day of administration.
Number of Participants With Treatment-emergent Adverse Events
To evaluate the safety and tolerability of AT-007 after multiple ascending doses are administered to healthy subjects, including clinically-significant changes in clinical laboratory test results, physical examination findings, vital sign evaluations, and electrocardiogram results. Part B and Part C are combined.
Measured: 7 Days after Dosing
Number of Participants With Treatment-emergent Adverse Events
To evaluate the safety and tolerability of AT-007 after multiple doses administered to Classic Galactosemia Patients, including clinically-significant changes in clinical laboratory test results, physical examination findings, vital sign evaluations, and electrocardiogram results.
Measured: 28 Days of Dosing
Number of Participants With Treatment-emergent Adverse Events
To evaluate the safety and tolerability of AT-007 administered to Classic Galactosemia Patients, including clinically-significant changes in clinical laboratory test results, physical examination findings, vital sign evaluations, and electrocardiogram results.
Measured: 90 Days after Dosing
Secondary outcomes (8)
Cmax of AT-007
Maximum (peak) plasma drug concentration
Measured: Part A: Sampling- predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs Parts B, C, D: Day of Last Dose for each Part- predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs D Extension: Day 30, 60, 90- predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs
Tmax of AT-007
Time to reach maximum (peak) plasma drug concentration
Measured: Part A: Sampling- predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs Parts B, C, D: Day of Last Dose for each Part- predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs D Extension: Day 30, 60, 90- predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs
t1/2 of AT-007
Terminal elimination half life
Measured: Part A: Sequential sampling at predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours. Parts B, C, D: Determined using Day of Last Dose for the respective Part; predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours.
AUClast of AT-007
Area under the plasma concentration-time curve from time zero to time of last quantifiable concentration
Measured: Part A: Sequential sampling at predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours. Parts B, C, D: Determined using Day of Last Dose for the respective Part at predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours.
AUCinf of AT-007
Area under the plasma concentration-time curve from time zero extrapolated to infinity
Measured: Part A: Sequential sampling at predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours. Part D: Determined using Day 1 with sampling at predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours.
Maximal Galactitol Reduction in Plasma
Disease-Specific Biomarker in Classic Galactosemia Patients
Measured: Part D: Samples at predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours on days 1, 12, 32. Part D Extension: Samples at predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours on days 1, 30, 60, & 90.
Galactose Concentration in Plasma
Disease-Specific Biomarker in Classic Galactosemia Patients
Measured: Part D: Day 32. Part D Extension: Days 30, 60, & 90.
Galactose-1-Phosphate (Gal-1p) Concentration in Plasma
Disease-Specific Biomarker in Classic Galactosemia Patients
Measured: Part D: Day 32. Part D Extension: Days 30, 60, & 90.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Oct 2019
- Study start21 Jun 2019
- Primary completion14 Dec 2021
- Study completion14 Dec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Classic GalactosemiaStudies of the same condition, open and under way.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 114 participants (actual)
Sponsor and investigators
- Lead sponsor
- Applied Therapeutics, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Robert Green, MD, MPH, Principal investigator, Brigham and Women's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04117711
- Sponsor's protocol ID
- AT-007-1001
- Status last verified
- May 2024
- First submitted
- 23 Aug 2019
- Last updated
- 30 May 2024
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Perfetti R, Bailey E, Wang S, Mills R, Mohanlal R, Shendelman S. Safety, Pharmacokinetics, and Pharmacodynamics of the New Aldose Reductase Inhibitor Govorestat (AT-007) After a Single and Multiple Doses in Participants in a Phase 1/2 Study. J Clin Pharmacol. 2024 Nov;64(11):1397-1406. doi: 10.1002/jcph.2495. Epub 2024 Jul 10.
PubMed 38988185
Study at a glance
From the registry record, last updated by the sponsor on 30 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1-2, Dose-Escalating, 4-Part Study to Evaluate the Safety and Pharmacokinetics of Single and Multiple Doses of AT-007 in Healthy Adult Subjects and Adult Subjects With Classic Galactosemia
- ClinicalTrials.gov ID
- NCT04117711
- Acronym / sponsor ID
- AT-007-1001
- Conditions
- Classic Galactosemia
- Keywords
- Classic Galactosemia, Aldose Reductase Inhibition, Galactose, Galactitol
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 114 participants (actual)
- Lead sponsor
- Applied Therapeutics, Inc.Industry (pharma, biotech, devices)
- Study start
- 21 Jun 2019 (actual)
- Primary completion
- 14 Dec 2021 (actual)
- Study completion
- 14 Dec 2021 (actual)
- First posted
- 7 Oct 2019 (actual)
- Results
- Posted 30 May 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is a first-in-human, randomized, placebo-controlled, 4-Part, single ascending dose (SAD) and multiple ascending dose (MAD) study in healthy adult subjects and adult subjects with Classic Galactosemia.
Detailed description
The study is designed to assess the safety and PK of AT-007 in healthy subjects and subjects with Classic Galactosemia as well as the effect of AT-007 on biomarkers of galactose metabolism (galactose, galactitol, and other galactose metabolites) in subjects with Classic Galactosemia.
This study consists of 4 parts:
- Part A (SAD) in 32 healthy subjects. Once daily oral escalating dose (6 active, 2 placebo).
- Part B and C (MAD for 7 days) in 36 healthy subjects. Once daily multiple daily dosing (8 active, 2 placebo per each dose cohort).
- Part D (SAD followed by MAD for 27 days) in 18 subjects with Classic Galactosemia. Once daily followed by multiple daily oral dosing (6 active, 2 placebo for each dose cohort).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| AT-007 | Experimental | Drug: AT-007AT-007 is a CNS and retina penetrant aldose reductase inhibitor. |
| Placebo Comparator | Placebo comparator | Drug: PlaceboPlacebo is used as a comparator to the experimental arm. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Diagnosis of Classic Galactosemia confirmed by evidence of absent or significantly decreased (<1%) GALT activity in red blood cells and by GALT gene analysis
- Urine galactitol >100 mmol/mol creatinine
- Galactose-restricted diet
Key exclusion criteria (2 listed)
- Complications of CG resulting in disability that, in the opinion of the Investigator, may prevent the subject from completing all study requirements (e.g., severe neurological deficits, severe cognitive impairment, or severe language difficulty).
- Renal disease (eGFR < 90 mL/min/1.73 m2 or albuminuria).
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 |
|---|---|---|
| AT-007Also: GovorestatAT-007 will be administered once daily before breakfast. Up to 4 different dose cohorts in part A; up to 4 dose cohorts in part B, up to 2 dose cohorts for part C, and up to 3 dose cohorts for part D will be enrolled in the study. The starting dose in Part A will be 0.5 mg/kg as a single dose. Subsequent doses in Part A and all doses in Parts B, C, and D will be based on the results of previous cohorts and/or previous parts of the study. Part B will start after all subjects in Part A have completed the study. Cohort C1 will be conducted simultaneously with Cohort B3 and using the same dose as Cohort B2. The dose for Cohort D1 will not be higher than the dose for Cohort B2. The second and third cohorts in Part D (D2 and D3) will not start until after all subjects in Cohorts B3 and B4, respectively, have completed the study and the dose levels will not be higher than those for Cohorts B3 and B4, respectively. | Drug | AT-007 |
| PlaceboMatching placebo will be administered once in the morning before breakfast | Drug | Placebo Comparator |
Primary outcome
Number of Participants With Treatment-emergent Adverse Events
Time frame: Events after 1 day of administration.
To evaluate the safety and tolerability of AT-007 after administration to healthy subjects, including clinically-significant changes in clinical laboratory test results, physical examination findings, vital sign evaluations, and electrocardiogram results.
Number of Participants With Treatment-emergent Adverse Events
Time frame: 7 Days after Dosing
To evaluate the safety and tolerability of AT-007 after multiple ascending doses are administered to healthy subjects, including clinically-significant changes in clinical laboratory test results, physical examination findings, vital sign evaluations, and electrocardiogram results. Part B and Part C are combined.
Number of Participants With Treatment-emergent Adverse Events
Time frame: 28 Days of Dosing
To evaluate the safety and tolerability of AT-007 after multiple doses administered to Classic Galactosemia Patients, including clinically-significant changes in clinical laboratory test results, physical examination findings, vital sign evaluations, and electrocardiogram results.
Number of Participants With Treatment-emergent Adverse Events
Time frame: 90 Days after Dosing
To evaluate the safety and tolerability of AT-007 administered to Classic Galactosemia Patients, including clinically-significant changes in clinical laboratory test results, physical examination findings, vital sign evaluations, and electrocardiogram results.
8 secondary outcomes
Cmax of AT-007
Time frame: Part A: Sampling- predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs Parts B, C, D: Day of Last Dose for each Part- predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs D Extension: Day 30, 60, 90- predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs
Tmax of AT-007
Time frame: Part A: Sampling- predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs Parts B, C, D: Day of Last Dose for each Part- predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs D Extension: Day 30, 60, 90- predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, 48 hrs
t1/2 of AT-007
Time frame: Part A: Sequential sampling at predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours. Parts B, C, D: Determined using Day of Last Dose for the respective Part; predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours.
AUClast of AT-007
Time frame: Part A: Sequential sampling at predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours. Parts B, C, D: Determined using Day of Last Dose for the respective Part at predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours.
AUCinf of AT-007
Time frame: Part A: Sequential sampling at predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours. Part D: Determined using Day 1 with sampling at predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours.
Maximal Galactitol Reduction in Plasma
Time frame: Part D: Samples at predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours on days 1, 12, 32. Part D Extension: Samples at predose, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, 36, and 48 hours on days 1, 30, 60, & 90.
Galactose Concentration in Plasma
Time frame: Part D: Day 32. Part D Extension: Days 30, 60, & 90.
Galactose-1-Phosphate (Gal-1p) Concentration in Plasma
Time frame: Part D: Day 32. Part D Extension: Days 30, 60, & 90.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 May 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 38988185Perfetti R, Bailey E, Wang S, Mills R, Mohanlal R, Shendelman S. Safety, Pharmacokinetics, and Pharmacodynamics of the New Aldose Reductase Inhibitor Govorestat (AT-007) After a Single and Multiple Doses in Participants in a Phase 1/2 Study. J Clin Pharmacol. 2024 Nov;64(11):1397-1406. doi: 10.1002/jcph.2495. Epub 2024 Jul 10.
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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.
Robert Green, MD, MPH principal investigator
Brigham and Women's Hospital
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing AT-007 in people with Classic Galactosemia, run by Applied Therapeutics, Inc. at 4 sites in United States.
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 3 inclusion and 2 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 30 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 30 May 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Participants With Treatment-emergent Adverse Events (time frame: Events after 1 day of administration.). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04117711, which also lists 1 linked publication.
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 30 May 2024.