Trial Outcomes & Findings for Suprachoroidal Injection of Triamcinolone Acetonide With IVT Anti-VEGF in Subjects With Macular Edema Following RVO (NCT NCT03203447)

NCT ID: NCT03203447

Last Updated: 2021-04-23

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE3

Target enrollment

325 participants

Primary outcome timeframe

2 months

Results posted on

2021-04-23

Participant Flow

Participant milestones

Participant milestones
Measure	Active Lucentis (0.5 mg/0.05 mL), IVT injection + CLS-TA (4 mg/0.10 mL), SC injection or Avastin (1.25 mg/0.05 mL), IVT injection + CLS-TA (4 mg/0.10 mL), SC injection suprachoroidal CLS-TA: suprachoroidal injection of CLS-TA Lucentis or Avastin: IVT anti-VEGF agent. Either a 0.5 mg intravitreal injection of Lucentis or 1.25 mg intravitreal injection of Avastin	Control Lucentis (0.5 mg/0.05 mL), IVT injection + sham SC procedure or Avastin (1.25 mg/0.05 mL), IVT injection + sham SC procedure suprachoroidal sham: sham suprachoroidal procedure Lucentis or Avastin: IVT anti-VEGF agent. Either a 0.5 mg intravitreal injection of Lucentis or 1.25 mg intravitreal injection of Avastin
Overall Study STARTED	162	163
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	162	163

Reasons for withdrawal

Reasons for withdrawal
Measure	Active Lucentis (0.5 mg/0.05 mL), IVT injection + CLS-TA (4 mg/0.10 mL), SC injection or Avastin (1.25 mg/0.05 mL), IVT injection + CLS-TA (4 mg/0.10 mL), SC injection suprachoroidal CLS-TA: suprachoroidal injection of CLS-TA Lucentis or Avastin: IVT anti-VEGF agent. Either a 0.5 mg intravitreal injection of Lucentis or 1.25 mg intravitreal injection of Avastin	Control Lucentis (0.5 mg/0.05 mL), IVT injection + sham SC procedure or Avastin (1.25 mg/0.05 mL), IVT injection + sham SC procedure suprachoroidal sham: sham suprachoroidal procedure Lucentis or Avastin: IVT anti-VEGF agent. Either a 0.5 mg intravitreal injection of Lucentis or 1.25 mg intravitreal injection of Avastin
Overall Study Withdrawal by Subject	2	1
Overall Study Lost to Follow-up	1	10
Overall Study Includes premature discontinuation due to study termination and unknown	159	152

Baseline Characteristics

Suprachoroidal Injection of Triamcinolone Acetonide With IVT Anti-VEGF in Subjects With Macular Edema Following RVO

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Active n=160 Participants Lucentis (0.5 mg/0.05 mL), IVT injection + CLS-TA (4 mg/0.10 mL), SC injection or Avastin (1.25 mg/0.05 mL), IVT injection + CLS-TA (4 mg/0.10 mL), SC injection suprachoroidal CLS-TA: suprachoroidal injection of CLS-TA Lucentis or Avastin: IVT anti-VEGF agent. Either a 0.5 mg intravitreal injection of Lucentis or 1.25 mg intravitreal injection of Avastin	Control n=162 Participants Lucentis (0.5 mg/0.05 mL), IVT injection + sham SC procedure or Avastin (1.25 mg/0.05 mL), IVT injection + sham SC procedure suprachoroidal sham: sham suprachoroidal procedure Lucentis or Avastin: IVT anti-VEGF agent. Either a 0.5 mg intravitreal injection of Lucentis or 1.25 mg intravitreal injection of Avastin	Total n=322 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	75 Participants n=5 Participants	91 Participants n=7 Participants	166 Participants n=5 Participants
Age, Categorical >=65 years	85 Participants n=5 Participants	71 Participants n=7 Participants	156 Participants n=5 Participants
Age, Continuous	63.8 years STANDARD_DEVIATION 13.07 • n=5 Participants	62.6 years STANDARD_DEVIATION 12.26 • n=7 Participants	63.2 years STANDARD_DEVIATION 12.66 • n=5 Participants
Sex: Female, Male Female	79 Participants n=5 Participants	93 Participants n=7 Participants	172 Participants n=5 Participants
Sex: Female, Male Male	81 Participants n=5 Participants	69 Participants n=7 Participants	150 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	72 Participants n=5 Participants	70 Participants n=7 Participants	142 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Black or African American	6 Participants n=5 Participants	3 Participants n=7 Participants	9 Participants n=5 Participants
Race (NIH/OMB) White	77 Participants n=5 Participants	84 Participants n=7 Participants	161 Participants n=5 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	1 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Region of Enrollment Hungary	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment United States	96 Participants n=5 Participants	98 Participants n=7 Participants	194 Participants n=5 Participants
Region of Enrollment Australia	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Region of Enrollment India	60 Participants n=5 Participants	61 Participants n=7 Participants	121 Participants n=5 Participants
Type of Retinal Vein Occlusion Branch retinal vein occlusion	90 Participants n=5 Participants	93 Participants n=7 Participants	183 Participants n=5 Participants
Type of Retinal Vein Occlusion Central retinal vein occlusion	70 Participants n=5 Participants	69 Participants n=7 Participants	139 Participants n=5 Participants

PRIMARY outcome

Timeframe: 2 months

Population: The Intent-to-treat population included all randomized patients. Values for missing data were imputed using last observation carried forward.

Outcome measures

Outcome measures
Measure	Active n=162 Participants Lucentis (0.5 mg/0.05 mL), IVT injection + CLS-TA (4 mg/0.10 mL), SC injection or Avastin (1.25 mg/0.05 mL), IVT injection + CLS-TA (4 mg/0.10 mL), SC injection suprachoroidal CLS-TA: suprachoroidal injection of CLS-TA Lucentis or Avastin: IVT anti-VEGF agent. Either a 0.5 mg intravitreal injection of Lucentis or 1.25 mg intravitreal injection of Avastin	Control n=163 Participants Lucentis (0.5 mg/0.05 mL), IVT injection + sham SC procedure or Avastin (1.25 mg/0.05 mL), IVT injection + sham SC procedure suprachoroidal sham: sham suprachoroidal procedure Lucentis or Avastin: IVT anti-VEGF agent. Either a 0.5 mg intravitreal injection of Lucentis or 1.25 mg intravitreal injection of Avastin
Proportion of Subjects Demonstrating ≥ 15 Letter Improvement From Baseline in Early Treatment of Diabetic Retinopathy Study (ETDRS)	64 Participants	76 Participants

SECONDARY outcome

Timeframe: 6 months

Population: The Intent-to-treat population included all randomized subjects who received at least one study treatment. Values for missing data were not imputed.

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. A positive change from baseline value represents an improvement in vision.

Outcome measures

Outcome measures
Measure	Active n=160 Participants Lucentis (0.5 mg/0.05 mL), IVT injection + CLS-TA (4 mg/0.10 mL), SC injection or Avastin (1.25 mg/0.05 mL), IVT injection + CLS-TA (4 mg/0.10 mL), SC injection suprachoroidal CLS-TA: suprachoroidal injection of CLS-TA Lucentis or Avastin: IVT anti-VEGF agent. Either a 0.5 mg intravitreal injection of Lucentis or 1.25 mg intravitreal injection of Avastin	Control n=159 Participants Lucentis (0.5 mg/0.05 mL), IVT injection + sham SC procedure or Avastin (1.25 mg/0.05 mL), IVT injection + sham SC procedure suprachoroidal sham: sham suprachoroidal procedure Lucentis or Avastin: IVT anti-VEGF agent. Either a 0.5 mg intravitreal injection of Lucentis or 1.25 mg intravitreal injection of Avastin
Mean Change From Baseline in Best Corrected Visual Acuity	13.8 letters Standard Error 1.96	20.7 letters Standard Error 1.91

SECONDARY outcome

Timeframe: 6 months

Population: The Intent-to-treat population included all randomized subjects who received at least one study treatment. Values for missing data were not imputed.

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.

Outcome measures

Outcome measures
Measure	Active n=162 Participants Lucentis (0.5 mg/0.05 mL), IVT injection + CLS-TA (4 mg/0.10 mL), SC injection or Avastin (1.25 mg/0.05 mL), IVT injection + CLS-TA (4 mg/0.10 mL), SC injection suprachoroidal CLS-TA: suprachoroidal injection of CLS-TA Lucentis or Avastin: IVT anti-VEGF agent. Either a 0.5 mg intravitreal injection of Lucentis or 1.25 mg intravitreal injection of Avastin	Control n=159 Participants Lucentis (0.5 mg/0.05 mL), IVT injection + sham SC procedure or Avastin (1.25 mg/0.05 mL), IVT injection + sham SC procedure suprachoroidal sham: sham suprachoroidal procedure Lucentis or Avastin: IVT anti-VEGF agent. Either a 0.5 mg intravitreal injection of Lucentis or 1.25 mg intravitreal injection of Avastin
Mean Change From Baseline in Central Subfield Thickness	-353.6 microns Standard Error 19.60	-374.7 microns Standard Error 19.12

Adverse Events

Active

Serious events: 1 serious events

Other events: 11 other events

Deaths: 0 deaths

Control

Serious events: 3 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Active n=160 participants at risk Lucentis (0.5 mg/0.05 mL), IVT injection + CLS-TA (4 mg/0.10 mL), SC injection or Avastin (1.25 mg/0.05 mL), IVT injection + CLS-TA (4 mg/0.10 mL), SC injection suprachoroidal CLS-TA: suprachoroidal injection of CLS-TA Lucentis or Avastin: IVT anti-VEGF agent. Either a 0.5 mg intravitreal injection of Lucentis or 1.25 mg intravitreal injection of Avastin	Control n=162 participants at risk Lucentis (0.5 mg/0.05 mL), IVT injection + sham SC procedure or Avastin (1.25 mg/0.05 mL), IVT injection + sham SC procedure suprachoroidal sham: sham suprachoroidal procedure Lucentis or Avastin: IVT anti-VEGF agent. Either a 0.5 mg intravitreal injection of Lucentis or 1.25 mg intravitreal injection of Avastin
Cardiac disorders Cardiac failure congestive	0.62% 1/160 • Number of events 1 • Adverse events were collected through follow-up and study completion, approximately 6 months.	0.00% 0/162 • Adverse events were collected through follow-up and study completion, approximately 6 months.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/160 • Adverse events were collected through follow-up and study completion, approximately 6 months.	0.62% 1/162 • Number of events 1 • Adverse events were collected through follow-up and study completion, approximately 6 months.
Infections and infestations Urinary tract infection	0.00% 0/160 • Adverse events were collected through follow-up and study completion, approximately 6 months.	0.62% 1/162 • Number of events 1 • Adverse events were collected through follow-up and study completion, approximately 6 months.
Metabolism and nutrition disorders Hyperglycaemia	0.00% 0/160 • Adverse events were collected through follow-up and study completion, approximately 6 months.	0.62% 1/162 • Number of events 1 • Adverse events were collected through follow-up and study completion, approximately 6 months.
Psychiatric disorders Mental status changes	0.00% 0/160 • Adverse events were collected through follow-up and study completion, approximately 6 months.	0.62% 1/162 • Number of events 1 • Adverse events were collected through follow-up and study completion, approximately 6 months.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.00% 0/160 • Adverse events were collected through follow-up and study completion, approximately 6 months.	0.62% 1/162 • Number of events 1 • Adverse events were collected through follow-up and study completion, approximately 6 months.
Respiratory, thoracic and mediastinal disorders Respiratory failure	0.62% 1/160 • Number of events 1 • Adverse events were collected through follow-up and study completion, approximately 6 months.	0.00% 0/162 • Adverse events were collected through follow-up and study completion, approximately 6 months.
Vascular disorders Deep vein thrombosis	0.00% 0/160 • Adverse events were collected through follow-up and study completion, approximately 6 months.	0.62% 1/162 • Number of events 1 • Adverse events were collected through follow-up and study completion, approximately 6 months.

Other adverse events

Other adverse events
Measure	Active n=160 participants at risk Lucentis (0.5 mg/0.05 mL), IVT injection + CLS-TA (4 mg/0.10 mL), SC injection or Avastin (1.25 mg/0.05 mL), IVT injection + CLS-TA (4 mg/0.10 mL), SC injection suprachoroidal CLS-TA: suprachoroidal injection of CLS-TA Lucentis or Avastin: IVT anti-VEGF agent. Either a 0.5 mg intravitreal injection of Lucentis or 1.25 mg intravitreal injection of Avastin	Control n=162 participants at risk Lucentis (0.5 mg/0.05 mL), IVT injection + sham SC procedure or Avastin (1.25 mg/0.05 mL), IVT injection + sham SC procedure suprachoroidal sham: sham suprachoroidal procedure Lucentis or Avastin: IVT anti-VEGF agent. Either a 0.5 mg intravitreal injection of Lucentis or 1.25 mg intravitreal injection of Avastin
Investigations Intraocular pressure increased	6.9% 11/160 • Number of events 14 • Adverse events were collected through follow-up and study completion, approximately 6 months.	0.62% 1/162 • Number of events 1 • Adverse events were collected through follow-up and study completion, approximately 6 months.

Additional Information

Thomas Ciulla, MD MBA

Clearside Biomedical, Inc.

Phone: (678) 392-2318

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The institutions and Investigators participating in this study shall have no right to publish or present the results of this study without the prior written consent of Clearside Biomedical, Inc.
Publication restrictions are in place

Restriction type: OTHER