Non-Infectious Uveitis of the Posterior Segment of the Eye
Conditions
Brief summary
The objective of this extension study is to evaluate the long-term safety of treatment with DE-109 (440 μg) in subjects with non-infectious uveitis of the posterior segment of the eye who have participated in the SAKURA development program.
Detailed description
This is a multicenter, open-label, extension study of intravitreal injections of the 440 μg dose of DE-109 in subjects with non-infectious uveitis of the posterior segment who received any dose of DE-109 and exited the SAKURA program under Santen Protocol 32-007, Amendment 05. Subjects who were randomized and received at least two injections of DE-109 during the first five months of the SAKURA program and obtained clinical benefit from the study medication, as determined by the Investigator, may be considered for entry in this 12-month extension study. The minimum time lag from last injection in the SAKURA program to entry into the current protocol is 60 days.
Interventions
DRUGDE-109 440 μg
Medium Dose
Sponsors
Santen Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Participated in the SAKURA study 2. Received clinical benefit from treatment in the SAKURA study 3. Ability to sign informed consent and attend all study visits
Exclusion criteria
1. Uveitis of infectious etiology 2. Implanted device 3. Suspected or confirmed central nervous system or ocular lymphoma 4. Uncontrolled glaucoma 5. Significant ocular disease 6. Intravitreal injections in the past 60 days 7. Intraocular surgery or treatment 8. Ocular or periocular infection 9. History of herpetic infection 10. Toxoplasmosis or toxoplasmosis scar 11. Ocular malignancy 12. Vitrectomy 13. Allergy or hypersensitivity to study drug 14. Participation in other uveitis device clinical trials within 30 days 15. Any recent systemic condition/infection 16. Immunosuppressive therapy or immunocomprimised 17. Cytomegalovirus infection 18. Malignancy in remission 19. Females who are pregnant or lactating and who are not using adequate contraceptive 20. Medical marijuana or illegal drug use 21. Systemic saroidosis 22. Therapeutic radiation to the head or neck
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Mean Change From Baseline in Intraocular Pressure at Month 12 in the Study Eye | Day 1 (Baseline) and Month 12 or early termination visit | Intraocular pressure (IOP), the fluid pressure inside the eye, was measured by applanation tonometry in millimeters mercury (mmHg) with one decimal point. |
| Change From Baseline in Best Corrected Visual Acuity (BCVA) at Month 12 in the Study Eye | Day 1 (Baseline) and Month 12 or early termination visit | Best Corrected Visual Acuity (BCVA) measures the acuteness or clearness of best-corrected vision in ETDRS (Early Treatment of Diabetic Retinopathy Study) letters. An increase in BCVA indicates improvement in the best-corrected vision. A BCVA score of 85 ETDRS letters is equivalent to 20/20 vision, which is considered normal vision. |
| Number of Subjects With a Shift in Choroid Status at Month 12 in the Study Eye. | Day 1 (Baseline) and Month 12 or early termination visit | Ophthalmoscopy findings were reported as normal or abnormal. |
| Changes From Baseline in Vitreous Haze (VH) Scores at Month 12 | Day 1 (Baseline) and Month 12 or early termination visit | Vitreous Haze (VH) scores were measured using the modified Standardized Uveitis Nomenclature Photographic Scale (SUN) : 0 No inflammation 0.5+ Trace Inflammation (slight blurring of the optic disc margins and or loss of nerve fiber layer reflex) 1. Mild blurring of the retinal vessels and optic nerve 1.5+ Optic nerve head and posterior retina view obstruction greater than 1+ but less than 2+ 2. Moderate blurring of the optic nerve head 3. Marked blurring of the optic nerve head 4. Optic Nerve head not visible |
| Number of Subjects Who Receive Rescue Therapy. | By Month12 | Rescue therapy was defined as any treatment that would have a therapeutic effect on the uveitis in the posterior segment (e.g., systemic treatment with an immunosuppressant agent, or a corticosteroid injection in the study eye) other than intravitreal DE-109 determined by the Investigator. |
| Number of Subjects With a Shift in Macula Status at Month 12 in the Study Eye. | Day 1 (Baseline) and Month 12 or early termination visit | Ophthalmoscopy findings were reported as normal or abnormal. |
| Number of Subjects With a Shift in Optic Nerve Status at Month 12 in the Study Eye. | Day 1 (Baseline) and Month 12 or early termination visit | Ophthalmoscopy findings were reported as normal or abnormal. |
| Number of Subjects With a Shift in Retina Status at Month 12 in the Study Eye. | Day 1 (Baseline) and Month 12 or early termination visit | Ophthalmoscopy findings were reported as normal or abnormal. |
Countries
Austria, France, India, Italy, Turkey (Türkiye), United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| DE-109 440 μg Medium dose of DE-109 | 60 |
| Total | 60 |
Baseline characteristics
| Characteristic | DE-109 440 μg |
|---|---|
| Age, Continuous | 43.31 years STANDARD_DEVIATION 15.092 |
| Geographic Region Europe, the Middle East and Africa | 10 Participants |
| Geographic Region India | 17 Participants |
| Geographic Region United States | 33 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 10 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 47 Participants |
| Race/Ethnicity, Customized Not reported | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 21 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants |
| Race (NIH/OMB) White | 30 Participants |
| Sex: Female, Male Female | 31 Participants |
| Sex: Female, Male Male | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 60 |
| other Total, other adverse events | 35 / 60 |
| serious Total, serious adverse events | 8 / 60 |
Outcome results
Primary
Change From Baseline in Best Corrected Visual Acuity (BCVA) at Month 12 in the Study Eye
Best Corrected Visual Acuity (BCVA) measures the acuteness or clearness of best-corrected vision in ETDRS (Early Treatment of Diabetic Retinopathy Study) letters. An increase in BCVA indicates improvement in the best-corrected vision. A BCVA score of 85 ETDRS letters is equivalent to 20/20 vision, which is considered normal vision.
Time frame: Day 1 (Baseline) and Month 12 or early termination visit
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DE-109 440 μg | Change From Baseline in Best Corrected Visual Acuity (BCVA) at Month 12 in the Study Eye | 2.1 ETDRS Letters | Standard Deviation 11.35 |
Primary
Changes From Baseline in Vitreous Haze (VH) Scores at Month 12
Vitreous Haze (VH) scores were measured using the modified Standardized Uveitis Nomenclature Photographic Scale (SUN) : 0 No inflammation 0.5+ Trace Inflammation (slight blurring of the optic disc margins and or loss of nerve fiber layer reflex) 1. Mild blurring of the retinal vessels and optic nerve 1.5+ Optic nerve head and posterior retina view obstruction greater than 1+ but less than 2+ 2. Moderate blurring of the optic nerve head 3. Marked blurring of the optic nerve head 4. Optic Nerve head not visible
Time frame: Day 1 (Baseline) and Month 12 or early termination visit
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DE-109 440 μg | Changes From Baseline in Vitreous Haze (VH) Scores at Month 12 | -0.09 score on a scale | Standard Deviation 0.847 |
Primary
Mean Change From Baseline in Intraocular Pressure at Month 12 in the Study Eye
Intraocular pressure (IOP), the fluid pressure inside the eye, was measured by applanation tonometry in millimeters mercury (mmHg) with one decimal point.
Time frame: Day 1 (Baseline) and Month 12 or early termination visit
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| DE-109 440 μg | Mean Change From Baseline in Intraocular Pressure at Month 12 in the Study Eye | 0.3 mmHg | Standard Deviation 4.16 |
Primary
Number of Subjects Who Receive Rescue Therapy.
Rescue therapy was defined as any treatment that would have a therapeutic effect on the uveitis in the posterior segment (e.g., systemic treatment with an immunosuppressant agent, or a corticosteroid injection in the study eye) other than intravitreal DE-109 determined by the Investigator.
Time frame: By Month12
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| DE-109 440 μg | Number of Subjects Who Receive Rescue Therapy. | 9 Participants |
Primary
Number of Subjects With a Shift in Choroid Status at Month 12 in the Study Eye.
Ophthalmoscopy findings were reported as normal or abnormal.
Time frame: Day 1 (Baseline) and Month 12 or early termination visit
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DE-109 440 μg | Number of Subjects With a Shift in Choroid Status at Month 12 in the Study Eye. | Normal to Abnormal | 0 Subjects |
| DE-109 440 μg | Number of Subjects With a Shift in Choroid Status at Month 12 in the Study Eye. | Normal to Normal | 36 Subjects |
| DE-109 440 μg | Number of Subjects With a Shift in Choroid Status at Month 12 in the Study Eye. | Abnormal to Normal | 4 Subjects |
| DE-109 440 μg | Number of Subjects With a Shift in Choroid Status at Month 12 in the Study Eye. | Abnormal to Abnormal | 3 Subjects |
Primary
Number of Subjects With a Shift in Macula Status at Month 12 in the Study Eye.
Ophthalmoscopy findings were reported as normal or abnormal.
Time frame: Day 1 (Baseline) and Month 12 or early termination visit
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DE-109 440 μg | Number of Subjects With a Shift in Macula Status at Month 12 in the Study Eye. | Normal to Normal | 20 Subjects |
| DE-109 440 μg | Number of Subjects With a Shift in Macula Status at Month 12 in the Study Eye. | Normal to Abnormal | 2 Subjects |
| DE-109 440 μg | Number of Subjects With a Shift in Macula Status at Month 12 in the Study Eye. | Abnormal to Normal | 6 Subjects |
| DE-109 440 μg | Number of Subjects With a Shift in Macula Status at Month 12 in the Study Eye. | Abnormal to Abnormal | 15 Subjects |
Primary
Number of Subjects With a Shift in Optic Nerve Status at Month 12 in the Study Eye.
Ophthalmoscopy findings were reported as normal or abnormal.
Time frame: Day 1 (Baseline) and Month 12 or early termination visit
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DE-109 440 μg | Number of Subjects With a Shift in Optic Nerve Status at Month 12 in the Study Eye. | Normal to Normal | 39 Subjects |
| DE-109 440 μg | Number of Subjects With a Shift in Optic Nerve Status at Month 12 in the Study Eye. | Normal to Abnormal | 2 Subjects |
| DE-109 440 μg | Number of Subjects With a Shift in Optic Nerve Status at Month 12 in the Study Eye. | Abnormal to Normal | 0 Subjects |
| DE-109 440 μg | Number of Subjects With a Shift in Optic Nerve Status at Month 12 in the Study Eye. | Abnormal to Abnormal | 2 Subjects |
Primary
Number of Subjects With a Shift in Retina Status at Month 12 in the Study Eye.
Ophthalmoscopy findings were reported as normal or abnormal.
Time frame: Day 1 (Baseline) and Month 12 or early termination visit
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| DE-109 440 μg | Number of Subjects With a Shift in Retina Status at Month 12 in the Study Eye. | Normal to Normal | 34 Subjects |
| DE-109 440 μg | Number of Subjects With a Shift in Retina Status at Month 12 in the Study Eye. | Normal to Abnormal | 2 Subjects |
| DE-109 440 μg | Number of Subjects With a Shift in Retina Status at Month 12 in the Study Eye. | Abnormal to Normal | 1 Subjects |
| DE-109 440 μg | Number of Subjects With a Shift in Retina Status at Month 12 in the Study Eye. | Abnormal to Abnormal | 6 Subjects |