Panuveitis, Uveitis, Uveitis, Anterior, Uveitis, Intermediate, Uveitis, Posterior
Conditions
Keywords
Uveitis, UME, Posterior Uveitis, Anterior Uveitis, Intermediate Uveitis, Panuveitis, Non-infectious Uveitis, Triamcinolone, Choroid, Choroidal Injection, Suprachoroidal, Microneedle, Microinjection, Triamcinolone acetonide
Brief summary
This study is a non-interventional, observational extension of the Parent study, CLS1001-301 (NCT02595398). The purpose of this study is to characterize the continued clinical benefit(s) regarding safety and efficacy of suprachoroidally administered CLS-TA, triamcinolone acetonide injectable suspension, for the treatment of macular edema associated with non-infectious uveitis.
Detailed description
This is a non-interventional, observation extension study of up to 6 months for subjects completing the Parent study, CLS1001-301 (NCT02595398). The Parent study is a Phase 3, multicenter study to assess the safety and efficacy of 4 mg of CLS-TA administered via suprachoroidal injection compared to a sham procedure in the treatment of subjects with macular edema associated with non-infectious uveitis. The design of the Extension study includes 4 clinic visits over a maximum of 24 weeks. Subject eligibility will be established at Visit 1 during the crossover day from the Parent study to the extension study (Day 0). Follow-up visits will be conducted every 6 weeks up to 24 weeks (Visit 4). At Visit 4, subjects will have a final evaluation conducted 24 weeks following study entry (48 weeks from Parent study randomization). This study was initiated prior to the completion of the parent study, therefore treatment assignment was masked prior to study entry.
Interventions
This drug was administered in the Parent study, CLS1001-301 (NCT02595398). No study treatments were administered during this observational extension study.
DRUGSham procedure
This drug was administered in the Parent study, CLS1001-301 (NCT02595398). No study treatments were administered during this observational extension study.
Sponsors
Clearside Biomedical, Inc.
Study design
Observational model
OTHER
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Enrolled in the Parent study, CLS1001-301, through Visit 8/Month 6 * Willing and able to provide written informed consent prior to any study procedures; willing to comply with the instructions and attend all scheduled study visits
Exclusion criteria
* Received additional therapy for the treatment of uveitis or prohibited medication * Require additional therapy for the treatment of uveitis or prohibited medication at the time of the Crossover visit
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to Additional Therapy for Uveitis | 6 months following completion of the Parent study CLS1001-301 (NCT02595398), for a total of up to 1 year | This time to event outcome was calculated as the number of days between the date of initiation of additional therapy for uveitis and the date of first treatment in the Parent study CLS1001-301 (NCT02595398). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events | 6 months following exit from Parent study | Number of participants with treatment emergent adverse events and serious adverse events reported during the extension study. |
| Mean Change From Baseline in Central Subfield Thickness | 6 months following exit from Parent study | Central subfield thickness (CST) is a diagnostic measurement used in identifying the presence of edema in the circular area 1 mm in diameter centered around the fovea. CST was measured using spectral domain optical coherence tomography (SD-OCT). A masked reading center graded the SD-OCT digital images. A negative change from baseline value represents a reduction in macular edema. |
| Mean Change From Baseline in Best Corrected Visual Acuity | 6 months following exit from Parent study | Best corrected visual acuity (BCVA) refers to the measurement of the best possible vision that can be achieved following refraction or correction. BCVA was assessed following the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol and was measured in the number of letters read correctly on an ETDRS eye chart. An increase from the pre-treatment state in BCVA of 15 letters or more represents a clinically meaningful improvement. |
Countries
India, United States
Participant flow
Recruitment details
Subjects enrolled into the Parent study CLS1001-301 (NCT02595398), and who completed the Parent study without receiving additional therapy for uveitis were eligible for enrollment into this non-interventional observation extension study. The Parent study was still masked when subjects started enrolling into this extension study, therefore, treatment assignment was unknown at study entry and during the study.
Pre-assignment details
Subjects enrolled into this non-interventional observational extension study successfully completed the Parent study CLS1001-301 (NCT02595398) without requiring additional therapy for uveitis. In the Parent study, subjects were randomized 3:2 to either 4 mg CLS-TA or a sham procedure in a masked fashion. Eligible and consenting subjects from selected sites were enrolled into the non-interventional extension study.
Participants by arm
| Arm | Count |
|---|---|
| 4 mg CLS-TA Suprachoriodal Injection Those subjects randomized to the CLS-TA 4 mg arm in CLS1001-301 (NCT02595398) and who completed participation in the Parent study without receiving additional therapy. No study drug was administered during this study.
4 mg CLS-TA Suprachoriodal Injection: This drug was administered in the Parent study, CLS1001-301 (NCT02595398). No study treatments were administered during this observational extension study. | 28 |
| Sham Procedure Those subjects randomized to the sham procedure arm in CLS1001-301 (NCT02595398) and who completed participation in the Parent study without receiving additional therapy. No study drug was administered during this study.
Sham procedure: This drug was administered in the Parent study, CLS1001-301 (NCT02595398). No study treatments were administered during this observational extension study. | 5 |
| Total | 33 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 0 |
| Overall Study | Due to Posterior Capsular Opacity | 1 | 0 |
| Overall Study | Prohibited therapy | 10 | 3 |
Baseline characteristics
| Characteristic | 4 mg CLS-TA Suprachoriodal Injection | Sham Procedure | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 1 Participants | 5 Participants |
| Age, Categorical Between 18 and 65 years | 24 Participants | 4 Participants | 28 Participants |
| Age, Continuous | 48.57 years STANDARD_DEVIATION 15.039 | 51.20 years STANDARD_DEVIATION 15.818 | 48.97 years STANDARD_DEVIATION 14.934 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 28 Participants | 5 Participants | 33 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 | 20 Participants | 2 Participants | 22 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 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 | 7 Participants | 2 Participants | 9 Participants |
| Region of Enrollment India | 20 participants | 2 participants | 22 participants |
| Region of Enrollment United States | 8 participants | 3 participants | 11 participants |
| Sex: Female, Male Female | 14 Participants | 1 Participants | 15 Participants |
| Sex: Female, Male Male | 14 Participants | 4 Participants | 18 Participants |
| Type of Uveitis Anterior uveitis | 10 Participants | 1 Participants | 11 Participants |
| Type of Uveitis Intermediate uveitis | 9 Participants | 0 Participants | 9 Participants |
| Type of Uveitis Panuveitis | 4 Participants | 3 Participants | 7 Participants |
| Type of Uveitis Posterior uveitis | 11 Participants | 1 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 28 | 0 / 5 |
| other Total, other adverse events | 16 / 28 | 3 / 5 |
| serious Total, serious adverse events | 1 / 28 | 0 / 5 |
Outcome results
Primary
Time to Additional Therapy for Uveitis
This time to event outcome was calculated as the number of days between the date of initiation of additional therapy for uveitis and the date of first treatment in the Parent study CLS1001-301 (NCT02595398).
Time frame: 6 months following completion of the Parent study CLS1001-301 (NCT02595398), for a total of up to 1 year
Population: The Safety population included all enrolled subjects who successfully completed the enrollment visit of the extension study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| 4 mg CLS-TA Suprachoriodal Injection | Time to Additional Therapy for Uveitis | 344.0 days |
| Sham Procedure | Time to Additional Therapy for Uveitis | 332.0 days |
Comparison: The null hypothesis of no difference in the survival time distributions was tested.p-value: 0.562Log-rank chi-square test
Secondary
Mean Change From Baseline in Best Corrected Visual Acuity
Best corrected visual acuity (BCVA) refers to the measurement of the best possible vision that can be achieved following refraction or correction. BCVA was assessed following the Early Treatment Diabetic Retinopathy Study (ETDRS) protocol and was measured in the number of letters read correctly on an ETDRS eye chart. An increase from the pre-treatment state in BCVA of 15 letters or more represents a clinically meaningful improvement.
Time frame: 6 months following exit from Parent study
Population: The Safety population included all enrolled subjects who successfully completed the enrollment visit of the extension study. Results include those subjects with non-missing BCVA values at follow-up week 24. Values for missing data were not imputed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 4 mg CLS-TA Suprachoriodal Injection | Mean Change From Baseline in Best Corrected Visual Acuity | 12.1 letters | Standard Deviation 13 |
| Sham Procedure | Mean Change From Baseline in Best Corrected Visual Acuity | 14.0 letters | Standard Deviation 15.56 |
Secondary
Mean Change From Baseline in Central Subfield Thickness
Central subfield thickness (CST) is a diagnostic measurement used in identifying the presence of edema in the circular area 1 mm in diameter centered around the fovea. CST was measured using spectral domain optical coherence tomography (SD-OCT). A masked reading center graded the SD-OCT digital images. A negative change from baseline value represents a reduction in macular edema.
Time frame: 6 months following exit from Parent study
Population: The Safety population included all enrolled subjects who successfully completed the enrollment visit of the extension study. Results include those subjects with gradable images at follow-up week 24. Values for missing data were not imputed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 4 mg CLS-TA Suprachoriodal Injection | Mean Change From Baseline in Central Subfield Thickness | -174.5 microns | Standard Deviation 145.7 |
| Sham Procedure | Mean Change From Baseline in Central Subfield Thickness | 19.5 microns | Standard Deviation 0.71 |
Secondary
Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events
Number of participants with treatment emergent adverse events and serious adverse events reported during the extension study.
Time frame: 6 months following exit from Parent study
Population: The Safety population included all enrolled subjects who successfully completed the enrollment visit of the extension study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| 4 mg CLS-TA Suprachoriodal Injection | Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events | Treatment-emergent adverse events | 16 Participants |
| 4 mg CLS-TA Suprachoriodal Injection | Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events | Serious adverse events | 1 Participants |
| Sham Procedure | Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events | Treatment-emergent adverse events | 3 Participants |
| Sham Procedure | Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events | Serious adverse events | 0 Participants |