Intermediate Uveitis, Noninfectious Uveitis, Panuveitis, Posterior Uveitis, Uveitis
Conditions
Keywords
uveitis, intermediate uveitis, posterior uveitis, panuveitis, noninfectious uveitis, microneedle, suprachoroidal space, SCS, inflammation, ocular inflammatory conditions, triamcinolone acetonide, TA, Triesence, injection, IVT, intravitreal, corticosteroid, sympathetic ophthalmia, temporal arteritis, vitreous haze
Brief summary
This study is designed to determine the safety and tolerability of a single microinjection of triamcinolone acetonide (TRIESENCE®) into the suprachoroidal space (SCS) of patients who have non-infectious uveitis.
Detailed description
This is a Phase 1/2, open-label study designed to evaluate the safety, tolerability and procedure of a microneedle injection of triamcinolone acetonide (TA) into the SCS. The subjects enrolled in this study will be chosen from subjects with non-infectious intermediate, posterior and pan-uveitis. The injection will only be administered to a single eye via the Clearside Biomedical proprietary microneedle into the SCS. The dose of TA to be injected is 4 mg of currently approved TRIESENCE® (triamcinolone acetonide injectable suspension 40 mg/mL). The study design includes 10 clinic visits over 27 weeks. Subjects will be followed for 26 weeks following treatment with TRIESENCE®.
Interventions
DRUGtriamcinolone acetonide (Triesence®)
4 mg of TRIESENCE® (triamcinolone acetonide injectable suspension 40 mg/mL) administered as a single injection to the suprachoroidal space
Sponsors
Clearside Biomedical, 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
* diagnosis of non-infectious intermediate, posterior or pan-uveitis
Exclusion criteria
* any ocular trauma within the past 6 months in the study eye * any injection of intraocular corticosteroids or steroid implant or the Ozurdex® implant in the 6 months prior to the study treatment, or any prior use of Retisert™ in the study eye * any uncontrolled systemic disease that would preclude participation in the study or put the subject at risk due to study treatment or procedures * have a known HIV infection or other immunodeficiency disease for which corticosteroid therapy would be contraindicated * are monocular * have ocular hypertension * history of any intraocular surgery in the study eye * presence of an anterior staphyloma in the study eye
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Intraocular Pressure (IOP) | Change from baseline in IOP at 8 weeks | Intraocular pressure is the fluid pressure inside the eye. Intraocular pressure change from baseline at week 8 was measured by Goldmann applanation tonometry. Tonometry is the method eye care professionals use to determine this pressure. Intraocular pressure is typically measured in millimeters of mercury. A higher pressure inside the eye can be a risk factor for developing glaucoma or glaucoma progression leading to optic nerve damage. A negative change indicates a reduction in intraocular pressure. |
| Best Corrected Visual Acuity | Change from baseline at 8 weeks and 26 weeks. | Visual acuity (VA) rates a person's ability to recognize small details with precision. Best corrected VA refers to this measurement when the best vision has be achieved following refraction. Visual acuity change from baseline at 8 and 26 weeks was measured following the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol using standardized lighting and lanes and an ETDRS eye chart. This eye chart comprises rows of letters, with 5 letters per row, and with the letter size from line to line varying logarithmically and is used to estimate visual acuity. Visual acuity is scored with reference to the logarithm of the minimum angle of resolution or logMAR. Zero logMAR indicates standard vision, positive values indicate poor vision and negative values indicate good vision. A negative changes indicates an improvement in visual acuity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Central Subfield Thickness Using Optical Coherence Tomography (OCT) | Change from baseline at 8 weeks and 26 weeks. | Central subfield thickness (CST) is a measure of the thickness of the retina in the 1 mm diameter circle centered on the fovea or center of the macular where eyesight is the sharpest. CST change from baseline at 8 and 26 weeks was measured using optical coherence tomography (OCT). OCT is a diagnostic imaging technique used to capture 2 and 3 dimensional images within biological tissue, e.g., for determining the amount of edema contained in the retina. CST is typically measured in microns. A negative change represents a reduction in retinal thickness and an improvement in cases of retinal edema. |
| Vitreous Haze Grade | Change from baseline at 8 weeks and 26 weeks | Vitreous haze scale (Nussenblatt 1985 as modified in Lowder 2011). Scores include value 0 (no inflammation), +0.5 (trace inflammation), +1 (mild blurring of the retinal vessels and optic nerve), +1.5 (optic nerve head and posterior retina view obscuration greater than +1 but less than +2), +2 (moderate blurring of the optic nerve head), +3 (marked blurring of the optic nerve head), and +4 (optic nerve head not visible) A higher score indicates a worse outcome. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Triamcinolone Acetonide (Triesence®) TRIESENCE® (triamcinolone acetonide injectable suspension 40 mg/mL) in a total volume of 100 uL administered via microneedle directly to the suprachoroidal space (SCS)
triamcinolone acetonide (Triesence®): 4 mg of TRIESENCE® (triamcinolone acetonide injectable suspension 40 mg/mL) administered as a single injection to the suprachoroidal space | 11 |
| Total | 11 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Re-enrolled into study | 1 |
Baseline characteristics
| Characteristic | Triamcinolone Acetonide (Triesence®) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 10 Participants |
| Age, Continuous | 57.3 years STANDARD_DEVIATION 9.47 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 4 Participants |
| Region of Enrollment United States | 11 participants |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 11 |
| other Total, other adverse events | 11 / 11 |
| serious Total, serious adverse events | 1 / 11 |
Outcome results
Primary
Best Corrected Visual Acuity
Visual acuity (VA) rates a person's ability to recognize small details with precision. Best corrected VA refers to this measurement when the best vision has be achieved following refraction. Visual acuity change from baseline at 8 and 26 weeks was measured following the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol using standardized lighting and lanes and an ETDRS eye chart. This eye chart comprises rows of letters, with 5 letters per row, and with the letter size from line to line varying logarithmically and is used to estimate visual acuity. Visual acuity is scored with reference to the logarithm of the minimum angle of resolution or logMAR. Zero logMAR indicates standard vision, positive values indicate poor vision and negative values indicate good vision. A negative changes indicates an improvement in visual acuity.
Time frame: Change from baseline at 8 weeks and 26 weeks.
Population: Per protocol population including all subjects who received at least one attempted dose of study drug. Data post-rescue was excluded.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Triamcinolone Acetonide (Triesence®) | Best Corrected Visual Acuity | Week 8 | -0.25 logMAR | Standard Deviation 0.107 |
| Triamcinolone Acetonide (Triesence®) | Best Corrected Visual Acuity | Week 26 | -0.28 logMAR | Standard Deviation 0.096 |
Primary
Change in Intraocular Pressure (IOP)
Intraocular pressure is the fluid pressure inside the eye. Intraocular pressure change from baseline at week 8 was measured by Goldmann applanation tonometry. Tonometry is the method eye care professionals use to determine this pressure. Intraocular pressure is typically measured in millimeters of mercury. A higher pressure inside the eye can be a risk factor for developing glaucoma or glaucoma progression leading to optic nerve damage. A negative change indicates a reduction in intraocular pressure.
Time frame: Change from baseline in IOP at 8 weeks
Population: Safety population including all subjects who received at least one attempted dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Triamcinolone Acetonide (Triesence®) | Change in Intraocular Pressure (IOP) | -0.1 mm Hg | Standard Deviation 3.21 |
Secondary
Central Subfield Thickness Using Optical Coherence Tomography (OCT)
Central subfield thickness (CST) is a measure of the thickness of the retina in the 1 mm diameter circle centered on the fovea or center of the macular where eyesight is the sharpest. CST change from baseline at 8 and 26 weeks was measured using optical coherence tomography (OCT). OCT is a diagnostic imaging technique used to capture 2 and 3 dimensional images within biological tissue, e.g., for determining the amount of edema contained in the retina. CST is typically measured in microns. A negative change represents a reduction in retinal thickness and an improvement in cases of retinal edema.
Time frame: Change from baseline at 8 weeks and 26 weeks.
Population: Per protocol population including all subjects who received at least one attempted dose of study drug. Data post-rescue was excluded.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Triamcinolone Acetonide (Triesence®) | Central Subfield Thickness Using Optical Coherence Tomography (OCT) | Week 8 | -153.7 Microns | Standard Deviation 109.45 |
| Triamcinolone Acetonide (Triesence®) | Central Subfield Thickness Using Optical Coherence Tomography (OCT) | Week 26 | -107.0 Microns | Standard Deviation 86.95 |
Secondary
Vitreous Haze Grade
Vitreous haze scale (Nussenblatt 1985 as modified in Lowder 2011). Scores include value 0 (no inflammation), +0.5 (trace inflammation), +1 (mild blurring of the retinal vessels and optic nerve), +1.5 (optic nerve head and posterior retina view obscuration greater than +1 but less than +2), +2 (moderate blurring of the optic nerve head), +3 (marked blurring of the optic nerve head), and +4 (optic nerve head not visible) A higher score indicates a worse outcome.
Time frame: Change from baseline at 8 weeks and 26 weeks
Population: Per protocol population including all subjects who received at least one attempted dose of study drug. Data post-rescue was excluded.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Triamcinolone Acetonide (Triesence®) | Vitreous Haze Grade | Week 8 | -0.75 score on a scale | Standard Deviation 0.463 |
| Triamcinolone Acetonide (Triesence®) | Vitreous Haze Grade | Week 26 | -0.75 score on a scale | Standard Deviation 0.289 |