Proliferative Diabetic Retinopathy
Conditions
Brief summary
To evaluate the effects of oral emixustat hydrochloride (emixustat) on aqueous humor biomarkers associated with proliferative diabetic retinopathy (PDR) from baseline to week 12.
Detailed description
This is a multicenter, randomized, double-masked, placebo-controlled study to evaluate the effects of emixustat in subjects with PDR. Subjects will be randomly assigned to either emixustat or placebo arms and treated once daily (QD) for 12 weeks. Doses of emixustat will be doubled on a weekly basis until week 4 after which all subjects will be held at a stable dose for the remainder of the 12-week dosing regimen. Subjects in the placebo group will be mock-titrated on the same schedule as those in the emixustat arm.
Interventions
Tablet for oral administration
OTHERPlacebo
Placebo tablets for oral administration contain only inactive ingredients
Sponsors
Kubota Vision Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Able and willing to provide written informed consent * Documented diagnosis of type 1 or type 2 diabetes mellitus * Meets specific ocular criteria for the study eye including but not limited to, the presence of PDR with or without diabetic macular edema in study eye for which treatment can be deferred for at least 4 weeks after Day 1 visit * Media clarity, pupillary dilation, and subject cooperation sufficient to obtain adequate assessments
Exclusion criteria
* Any condition that would preclude participation in the study (e.g., unstable medical status including blood pressure, cardiovascular disease or glycemic control) * History of myocardial infarction or other acute cardiac event * History of chronic renal failure requiring dialysis or kidney transplant * Prior participation in any clinical study of emixustat * Treatment with any investigational study drug within 30 days of screening * Known allergy to fluorescein sodium for injection in angiography * Treatment with specific prohibited medications or therapy beginning 4 weeks prior to screening and throughout the duration of the study * History of systemic anti-VEGF or pro-VEGF treatment within 4 months prior to randomization * Pre-specified laboratory abnormalities at screening * Specific ocular characteristics in the study eye * Male subjects who are not surgically sterile and are not willing to practice a medically accepted method of birth control with their female partner of childbearing potential from screening through 30 days following completion of the study * Female subjects of childbearing potential who are not willing to practice a medically accepted method of birth control with their non-surgically sterile male sexual partner from screening through 30 days following completion of the study * Female subjects who are pregnant or lactating
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Aqueous Humor Concentration of the Following Biomarkers:IL-6, IL-8, IP-10, PDGF-AA, TGFβ-1, MCP-1, IL-1β, and VEGF, to be Reported in pg/mL Values | Baseline and 12 weeks | All values for IL-1β were below the lower limit of detection and were recorded as zero. Tests for IP-10 and MCP-1 failed accuracy and stability testing during assay development and were dropped from the study. The assay for PDGF-AA could not be developed.and results were not reported. |
Countries
United States
Participant flow
Recruitment details
Subjects were enrolled from May 2016 through July 2017 at 8 sites in the United States
Participants by arm
| Arm | Count |
|---|---|
| Emixustat Hydrochloride Week 1- Four tablets (2 placebo, 2 emixustat HCl Strength A)
Week 2- Four tablets (2 placebo, 2 emixustat HCl Strength B)
Week 3- Four tablets (2 placebo, 2 emixustat HCl Strength C)
Week 4- Four emixustat HCl tablets (Strength C)
All tablets are administered orally once daily. After week 4, all subjects will be held at a stable dose for the remainder of the 12-week dosing regimen.
emixustat hydrochloride: Tablet for oral administration
Placebo: Placebo tablets for oral administration contain only inactive ingredients | 12 |
| Placebo Four placebo tablets are administered orally once daily for 12 weeks; Subjects in the placebo group will be mock-titrated on the same schedule as those in the active arm.
Placebo: Placebo tablets for oral administration contain only inactive ingredients | 12 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 0 |
| Overall Study | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | Emixustat Hydrochloride | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 52.1 years STANDARD_DEVIATION 7.06 | 49.8 years STANDARD_DEVIATION 9.52 | 47.4 years STANDARD_DEVIATION 11.29 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants | 16 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 8 Participants | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 11 Participants | 21 Participants | 10 Participants |
| Region of Enrollment United States | 12 participants | 24 participants | 12 participants |
| Sex: Female, Male Female | 7 Participants | 12 Participants | 5 Participants |
| Sex: Female, Male Male | 5 Participants | 12 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 11 |
| other Total, other adverse events | 12 / 12 | 9 / 11 |
| serious Total, serious adverse events | 0 / 12 | 2 / 11 |
Outcome results
Primary
Change in Aqueous Humor Concentration of the Following Biomarkers:IL-6, IL-8, IP-10, PDGF-AA, TGFβ-1, MCP-1, IL-1β, and VEGF, to be Reported in pg/mL Values
All values for IL-1β were below the lower limit of detection and were recorded as zero. Tests for IP-10 and MCP-1 failed accuracy and stability testing during assay development and were dropped from the study. The assay for PDGF-AA could not be developed.and results were not reported.
Time frame: Baseline and 12 weeks
Population: Not all subjects had primary endpoint end-of-treatment data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Emixustat Hydrochloride | Change in Aqueous Humor Concentration of the Following Biomarkers:IL-6, IL-8, IP-10, PDGF-AA, TGFβ-1, MCP-1, IL-1β, and VEGF, to be Reported in pg/mL Values | IL-6, change from baseline | 45.6 pg/ml | Standard Deviation 137.1 |
| Emixustat Hydrochloride | Change in Aqueous Humor Concentration of the Following Biomarkers:IL-6, IL-8, IP-10, PDGF-AA, TGFβ-1, MCP-1, IL-1β, and VEGF, to be Reported in pg/mL Values | IL-8, change from baseline | 4.2 pg/ml | Standard Deviation 5.1 |
| Emixustat Hydrochloride | Change in Aqueous Humor Concentration of the Following Biomarkers:IL-6, IL-8, IP-10, PDGF-AA, TGFβ-1, MCP-1, IL-1β, and VEGF, to be Reported in pg/mL Values | TGFβ-1, change from baseline | -19.9 pg/ml | Standard Deviation 32.4 |
| Emixustat Hydrochloride | Change in Aqueous Humor Concentration of the Following Biomarkers:IL-6, IL-8, IP-10, PDGF-AA, TGFβ-1, MCP-1, IL-1β, and VEGF, to be Reported in pg/mL Values | VEGF, change from baseline | -38.0 pg/ml | Standard Deviation 115.1 |
| Placebo | Change in Aqueous Humor Concentration of the Following Biomarkers:IL-6, IL-8, IP-10, PDGF-AA, TGFβ-1, MCP-1, IL-1β, and VEGF, to be Reported in pg/mL Values | VEGF, change from baseline | -24.8 pg/ml | Standard Deviation 277.2 |
| Placebo | Change in Aqueous Humor Concentration of the Following Biomarkers:IL-6, IL-8, IP-10, PDGF-AA, TGFβ-1, MCP-1, IL-1β, and VEGF, to be Reported in pg/mL Values | IL-6, change from baseline | 4.9 pg/ml | Standard Deviation 12.6 |
| Placebo | Change in Aqueous Humor Concentration of the Following Biomarkers:IL-6, IL-8, IP-10, PDGF-AA, TGFβ-1, MCP-1, IL-1β, and VEGF, to be Reported in pg/mL Values | TGFβ-1, change from baseline | -17.5 pg/ml | Standard Deviation 43.7 |
| Placebo | Change in Aqueous Humor Concentration of the Following Biomarkers:IL-6, IL-8, IP-10, PDGF-AA, TGFβ-1, MCP-1, IL-1β, and VEGF, to be Reported in pg/mL Values | IL-8, change from baseline | 2.6 pg/ml | Standard Deviation 4.6 |