Macular Atrophy, Stargardt Disease
Conditions
Brief summary
This is a pharmacodynamics study of emixustat hydrochloride in subjects with macular atrophy secondary to Stargardt disease.
Detailed description
This is a multicenter, randomized, masked study to characterize the pharmacodynamics, safety and tolerability of emixustat in subjects with macular atrophy secondary to Stargardt disease.
Interventions
DRUGEmixustat
Once daily, tablet for oral administration
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 No maximum
Healthy volunteers
No
Inclusion criteria
, including, but not limited to: * Clinical diagnosis of macular atrophy (MA) secondary to Stargardt disease (STGD) in one or both eyes * At least 2 pathogenic mutations of the ABCA4 gene * Early Treatment Diabetic Retinopathy Study BCVA of ≥ 20 letters (approximately ≥ 20/400 Snellen) in the study eye * Adequate clarity of ocular media and adequate pupillary dilation to permit good quality imaging of MA in the study eye * Able and willing to provide written informed consent before undergoing any study-related procedures * Able to reliably administer oral medication by self or with available assistance
Exclusion criteria
, including, but not limited to: * Macular atrophy associated with a condition other than STGD in either eye. * Presence in either eye of an active ocular disease that in the opinion of the Investigator compromises or confounds visual function. * History of any intraocular or ocular surface surgery in either eye within 3 months of screening. * Current or previous participation in an interventional study to treat STGD using gene therapy or stem cell therapy at any time, or participation in an interventional study of a vitamin A derivative ≤3 months prior to screening. * Pre-specified laboratory abnormalities at screening * Presence of other medical or ophthalmic disease, physical examination finding, or clinical laboratory finding that in the opinion of the Investigator may contraindicate the use of an investigational drug and place the subject at risk * Current or history of cancer (except for adequately treated basal cell or squamous cell carcinoma of the skin) within 1 year of screening * History of myocardial infarction, stroke, unstable ischemic heart disease, uncontrolled cardiac arrhythmia, or hospitalization for congestive heart failure within 6 months of screening. * Anticipated hospitalization for a medical/surgical procedure(s) that could result in interruption/premature cessation of study treatment or participation. * Electrocardiogram with a clinically significant abnormal finding * Female subjects who are pregnant or lactating * Female subjects of childbearing potential or male subjects who are not surgically sterile who are not willing to practice a medically accepted method of birth control with their sexual partner from screening through 30 days after the final dose of study drug
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Electrical Response of the Retina to a Flash of Light, as Measured by Electroretinogram | Baseline and 1 month | Percent suppression compared to baseline of rod b-wave amplitude recovery after a photobleaching light. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With Adverse Events, by Severity and Seriousness | 1 month | Assessment of safety profile |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited at 6 sites in the United States from January to September 2017
Participants by arm
| Arm | Count |
|---|---|
| Emixustat Dose 1 lowest dose of once-daily oral emixustat
Emixustat: Once daily, tablet for oral administration | 7 |
| Emixustat Dose 2 middle dose of once-daily oral emixustat
Emixustat: Once daily, tablet for oral administration | 9 |
| Emixustat Dose 3 highest dose of once-daily oral emixustat
Emixustat: Once daily, tablet for oral administration | 7 |
| Total | 23 |
Baseline characteristics
| Characteristic | Emixustat Dose 1 | Emixustat Dose 2 | Emixustat Dose 3 | Total |
|---|---|---|---|---|
| Age, Continuous | 53.6 years | 54.3 years | 46.3 years | 51.6 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 9 Participants | 7 Participants | 22 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Number of ABCA4 gene mutations One mutation | 1 Participants | 2 Participants | 2 Participants | 5 Participants |
| Number of ABCA4 gene mutations Two mutations | 6 Participants | 7 Participants | 5 Participants | 18 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 1 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 7 Participants | 6 Participants | 18 Participants |
| Region of Enrollment United States | 7 participants | 9 participants | 7 participants | 23 participants |
| Sex: Female, Male Female | 4 Participants | 1 Participants | 3 Participants | 8 Participants |
| Sex: Female, Male Male | 3 Participants | 8 Participants | 4 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 7 | 0 / 9 | 0 / 7 |
| other Total, other adverse events | 6 / 7 | 8 / 9 | 7 / 7 |
| serious Total, serious adverse events | 0 / 7 | 0 / 9 | 0 / 7 |
Outcome results
Primary
Change in Electrical Response of the Retina to a Flash of Light, as Measured by Electroretinogram
Percent suppression compared to baseline of rod b-wave amplitude recovery after a photobleaching light.
Time frame: Baseline and 1 month
Population: Subjects with evaluable ERGs at both Baseline and Month 1
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Emixustat Dose 1 | Change in Electrical Response of the Retina to a Flash of Light, as Measured by Electroretinogram | -12.23 percent suppression |
| Emixustat Dose 2 | Change in Electrical Response of the Retina to a Flash of Light, as Measured by Electroretinogram | 68.00 percent suppression |
| Emixustat Dose 3 | Change in Electrical Response of the Retina to a Flash of Light, as Measured by Electroretinogram | 96.69 percent suppression |
Secondary
Percentage of Subjects With Adverse Events, by Severity and Seriousness
Assessment of safety profile
Time frame: 1 month
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Emixustat Dose 1 | Percentage of Subjects With Adverse Events, by Severity and Seriousness | Subjects with 1 or more severe adverse events | 0 Participants |
| Emixustat Dose 1 | Percentage of Subjects With Adverse Events, by Severity and Seriousness | Subjects with 1 or more moderate adverse events | 1 Participants |
| Emixustat Dose 1 | Percentage of Subjects With Adverse Events, by Severity and Seriousness | Subjects with 1 or more adverse events | 6 Participants |
| Emixustat Dose 1 | Percentage of Subjects With Adverse Events, by Severity and Seriousness | Subjects with 1 or more mild adverse events | 5 Participants |
| Emixustat Dose 1 | Percentage of Subjects With Adverse Events, by Severity and Seriousness | Subjects with 1 or more serious adverse events | 0 Participants |
| Emixustat Dose 2 | Percentage of Subjects With Adverse Events, by Severity and Seriousness | Subjects with 1 or more moderate adverse events | 2 Participants |
| Emixustat Dose 2 | Percentage of Subjects With Adverse Events, by Severity and Seriousness | Subjects with 1 or more adverse events | 8 Participants |
| Emixustat Dose 2 | Percentage of Subjects With Adverse Events, by Severity and Seriousness | Subjects with 1 or more mild adverse events | 5 Participants |
| Emixustat Dose 2 | Percentage of Subjects With Adverse Events, by Severity and Seriousness | Subjects with 1 or more severe adverse events | 1 Participants |
| Emixustat Dose 2 | Percentage of Subjects With Adverse Events, by Severity and Seriousness | Subjects with 1 or more serious adverse events | 0 Participants |
| Emixustat Dose 3 | Percentage of Subjects With Adverse Events, by Severity and Seriousness | Subjects with 1 or more serious adverse events | 0 Participants |
| Emixustat Dose 3 | Percentage of Subjects With Adverse Events, by Severity and Seriousness | Subjects with 1 or more severe adverse events | 1 Participants |
| Emixustat Dose 3 | Percentage of Subjects With Adverse Events, by Severity and Seriousness | Subjects with 1 or more adverse events | 6 Participants |
| Emixustat Dose 3 | Percentage of Subjects With Adverse Events, by Severity and Seriousness | Subjects with 1 or more moderate adverse events | 2 Participants |
| Emixustat Dose 3 | Percentage of Subjects With Adverse Events, by Severity and Seriousness | Subjects with 1 or more mild adverse events | 4 Participants |