MAGNOLIA: Extension Study of Patients With Non-infectious Uveitis Who Participated in CLS1001-301
Sponsor
Clearside Biomedical, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT02952001
Collaborator
(none)
33
16
5.3
2.1
0.4
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
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.
Study Design
Study Type:
Observational
Actual Enrollment
:
33 participants
Observational Model:
Other
Time Perspective:
Prospective
Official Title:
MAGNOLIA: Multi-Center, Non-Interventional Extension Study of the Safety and Efficacy of CLS-TA for the Treatment of Macular Edema Associated With Non-Infectious Uveitis
Actual Study Start Date
:
Dec 13, 2017
Actual Primary Completion Date
:
May 22, 2018
Actual Study Completion Date
:
May 22, 2018
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| 4 mg CLS-TA Suprachoriodal Injection Those subjects randomized to the CLS-TA 4 mg arm in CLS1001-301 (NCT02595398) and who completed participation without receiving additional therapy. No study drug was administered during this study. |
Drug: 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.
Other Names:
|
| Sham procedure Those subjects randomized to the sham procedure arm in CLS1001-301 (NCT02595398) and who completed participation without receiving additional therapy. No study drug was administered during this study. |
Drug: Sham procedure
This drug was administered in the Parent study, CLS1001-301 (NCT02595398). No study treatments were administered during this observational extension study.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- 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 Outcome Measures
- 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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts 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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Retinal Consultants of Arizona | Phoenix | Arizona | United States | 85014 |
| 2 | Northern California Retina Vitreous Associates Medical Group, Inc. | Mountain View | California | United States | 94040 |
| 3 | Retina Group of Florida | Fort Lauderdale | Florida | United States | 33308 |
| 4 | Marietta Eye Clinic | Marietta | Georgia | United States | 30060 |
| 5 | Valley Eye Physicians and Surgeons, PC | Ayer | Massachusetts | United States | 01432 |
| 6 | Bergstrom Eye Research | Fargo | North Dakota | United States | 58103 |
| 7 | Oregon Health & Science University Casey Eye Institute | Portland | Oregon | United States | 97239 |
| 8 | University of Pittsburgh Medical Center Eye Center | Pittsburgh | Pennsylvania | United States | 15213 |
| 9 | Texas Retina Associates | Dallas | Texas | United States | 75231 |
| 10 | Retina Consultants of Houston | The Woodlands | Texas | United States | 77384 |
| 11 | Sri Sankaradeva Nethralaya | Guwahati | Assam | India | 781028 |
| 12 | JSS Hospital | Mysore | Karnataka | India | 570 004 |
| 13 | Sankara Eye Hospital | Coimbatore | Tamil Nadu | India | 641035 |
| 14 | King George's Medical University | Lucknow | Uttar Pradesh | India | 226003 |
| 15 | Disha Eye Hospitals Pvt. Ltd. | Kolkata | India | 700120 | |
| 16 | Dr Rajendra Prasad Centre for Ophthalmic Sciences | New Delhi | India | 110029 |
Sponsors and Collaborators
- Clearside Biomedical, Inc.
Investigators
- Study Director: Thomas Ciulla, MD, Clearside Biomedical, Inc.
Study Documents (Full-Text)
More Information
Publications
None provided.Responsible Party:
Clearside Biomedical, Inc.
ClinicalTrials.gov Identifier:
NCT02952001
Other Study ID Numbers:
- CLS1001-303
First Posted:
Nov 1, 2016
Last Update Posted:
Jun 2, 2021
Last Verified:
May 1, 2021
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Clearside Biomedical, Inc.
Additional relevant MeSH terms:
Study Results
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 Detail | 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. |
| Arm/Group Title | 4 mg CLS-TA Suprachoriodal Injection | Sham Procedure |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Period Title: Overall Study | ||
| STARTED | 28 | 5 |
| COMPLETED | 14 | 2 |
| NOT COMPLETED | 14 | 3 |
Baseline Characteristics
| Arm/Group Title | 4 mg CLS-TA Suprachoriodal Injection | Sham Procedure | Total |
|---|---|---|---|
| Arm/Group Description | 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. | 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. | Total of all reporting groups |
| Overall Participants | 28 | 5 | 33 |
| Age (Count of Participants) | |||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
24
85.7%
|
4
80%
|
28
84.8%
|
| >=65 years |
4
14.3%
|
1
20%
|
5
15.2%
|
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
48.57
(15.039)
|
51.20
(15.818)
|
48.97
(14.934)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
14
50%
|
1
20%
|
15
45.5%
|
| Male |
14
50%
|
4
80%
|
18
54.5%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||
| Hispanic or Latino |
0
0%
|
0
0%
|
0
0%
|
| Not Hispanic or Latino |
28
100%
|
5
100%
|
33
100%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Race (NIH/OMB) (Count of Participants) | |||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
| Asian |
20
71.4%
|
2
40%
|
22
66.7%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
| Black or African American |
1
3.6%
|
1
20%
|
2
6.1%
|
| White |
7
25%
|
2
40%
|
9
27.3%
|
| More than one race |
0
0%
|
0
0%
|
0
0%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
8
28.6%
|
3
60%
|
11
33.3%
|
| India |
20
71.4%
|
2
40%
|
22
66.7%
|
| Type of Uveitis (Count of Participants) | |||
| Anterior uveitis |
10
35.7%
|
1
20%
|
11
33.3%
|
| Intermediate uveitis |
9
32.1%
|
0
0%
|
9
27.3%
|
| Posterior uveitis |
11
39.3%
|
1
20%
|
12
36.4%
|
| Panuveitis |
4
14.3%
|
3
60%
|
7
21.2%
|
Outcome Measures
| Title | Time to Additional Therapy for Uveitis |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Safety population included all enrolled subjects who successfully completed the enrollment visit of the extension study. |
| Arm/Group Title | 4 mg CLS-TA Suprachoriodal Injection | Sham Procedure |
|---|---|---|
| Arm/Group Description | Those subjects randomized to the CLS-TA 4 mg arm in CLS1001-301 (NCT02595398) and who completed participation i 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. | 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. |
| Measure Participants | 28 | 5 |
| Median (95% Confidence Interval) [days] |
344.0
|
332.0
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | 4 mg CLS-TA Suprachoriodal Injection, Sham Procedure |
|---|---|---|
| Comments | The null hypothesis of no difference in the survival time distributions was tested. | |
| Type of Statistical Test | Superiority | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.562 |
| Comments | The a priori threshold for statistical significance was 0.050. No adjustments made or required for multiplicity. | |
| Method | Log-rank chi-square test | |
| Comments | ||
| Title | Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Safety population included all enrolled subjects who successfully completed the enrollment visit of the extension study. |
| Arm/Group Title | 4 mg CLS-TA Suprachoriodal Injection | Sham Procedure |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 28 | 5 |
| Treatment-emergent adverse events |
16
57.1%
|
3
60%
|
| Serious adverse events |
1
3.6%
|
0
0%
|
| Title | Mean Change From Baseline in Central Subfield Thickness |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | 4 mg CLS-TA Suprachoriodal Injection | Sham Procedure |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 13 | 2 |
| Mean (Standard Deviation) [microns] |
-174.5
(145.70)
|
19.5
(0.71)
|
| Title | Mean Change From Baseline in Best Corrected Visual Acuity |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| 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/Group Title | 4 mg CLS-TA Suprachoriodal Injection | Sham Procedure |
|---|---|---|
| Arm/Group Description | 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. | 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. |
| Measure Participants | 14 | 2 |
| Mean (Standard Deviation) [letters] |
12.1
(13.00)
|
14.0
(15.56)
|
Adverse Events
| Time Frame | 6 months following completion of the Parent study CLS1001-301 (NCT02595398), for a total of up to 1 year. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | Treatment-emergent adverse events and SAEs initiating or worsening in severity relative to the date of enrollment into the extension study (day 0) were summarized. | |||
| Arm/Group Title | 4 mg CLS-TA Suprachoriodal Injection | Sham Procedure | ||
| Arm/Group Description | 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. | 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. | ||
All Cause Mortality |
||||
| 4 mg CLS-TA Suprachoriodal Injection | Sham Procedure | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/28 (0%) | 0/5 (0%) | ||
Serious Adverse Events |
||||
| 4 mg CLS-TA Suprachoriodal Injection | Sham Procedure | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/28 (3.6%) | 0/5 (0%) | ||
| Gastrointestinal disorders | ||||
| Oesophageal achalasia | 1/28 (3.6%) | 1 | 0/5 (0%) | 0 |
| Infections and infestations | ||||
| Pneumonia | 1/28 (3.6%) | 2 | 0/5 (0%) | 0 |
| Septic shock | 1/28 (3.6%) | 1 | 0/5 (0%) | 0 |
| Renal and urinary disorders | ||||
| Acute kidney injury | 1/28 (3.6%) | 1 | 0/5 (0%) | 0 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Acute respiratory failure | 1/28 (3.6%) | 3 | 0/5 (0%) | 0 |
| Pneumonia aspiration | 1/28 (3.6%) | 2 | 0/5 (0%) | 0 |
Other (Not Including Serious) Adverse Events |
||||
| 4 mg CLS-TA Suprachoriodal Injection | Sham Procedure | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 16/28 (57.1%) | 3/5 (60%) | ||
| Eye disorders | ||||
| Cataract | 2/28 (7.1%) | 2 | 0/5 (0%) | 0 |
| Cataract cortical | 0/28 (0%) | 0 | 1/5 (20%) | 1 |
| Cataract subcapsular | 5/28 (17.9%) | 5 | 0/5 (0%) | 0 |
| Macular fibrosis | 0/28 (0%) | 0 | 1/5 (20%) | 1 |
| Macular oedema | 1/28 (3.6%) | 1 | 1/5 (20%) | 1 |
| Uveitis | 3/28 (10.7%) | 3 | 1/5 (20%) | 1 |
| Cataract cortical | 0/28 (0%) | 0 | 1/5 (20%) | 1 |
| Eye pain | 2/28 (7.1%) | 2 | 0/5 (0%) | 0 |
| Uveitis | 2/28 (7.1%) | 3 | 0/5 (0%) | 0 |
| Infections and infestations | ||||
| Infection parasitic | 0/28 (0%) | 0 | 1/5 (20%) | 1 |
| Investigations | ||||
| Eosinophil count increased | 0/28 (0%) | 0 | 1/5 (20%) | 1 |
| Intraocular pressure increased | 3/28 (10.7%) | 3 | 0/5 (0%) | 0 |
Limitations/Caveats
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 enrolled into this extension study, therefore, treatment assignment was unknown at study entry and remained masked until completion of the Parent study which occurred prior to the completion of this study.
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The institution and investigators participating in this trial shall have no right to publish or present the results of this study without the prior written consent of Clearside Biomedical.
Results Point of Contact
| Name/Title | Thomas Ciulla, MD MBA |
|---|---|
| Organization | Clearside Biomedical, Inc. |
| Phone | (678) 392-2318 |
| thomas.ciulla@clearsidebio.com |
Responsible Party:
Clearside Biomedical, Inc.
ClinicalTrials.gov Identifier:
NCT02952001
Other Study ID Numbers:
- CLS1001-303
First Posted:
Nov 1, 2016
Last Update Posted:
Jun 2, 2021
Last Verified:
May 1, 2021