Trial Outcomes & Findings for Suprachoroidal CLS-TA With Intravitreal Aflibercept Versus Aflibercept Alone in Subject With Diabetic Macular Edema (NCT NCT03126786)

Last Updated: 2021-05-13

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

COMPLETED

Study phase

PHASE2

Target enrollment

71 participants

Primary outcome timeframe

Baseline, 6 months

Results posted on

2021-05-13

Participant Flow

Participant milestones

Participant milestones
Measure	Active Treatment will consist of IVT injection of Aflibercept followed by an SC injection of CLS-TA IVT aflibercept: IVT aflibercept \[2 mg (0.05 mL)\] SC CLS-TA: SC CLS-TA \[40 mg/mL\]	Control Treatment will consist of IVT aflibercept injection followed by a sham SC procedure IVT aflibercept: IVT aflibercept \[2 mg (0.05 mL)\] Sham SC: sham SC
Overall Study STARTED	36	35
Overall Study COMPLETED	30	33
Overall Study NOT COMPLETED	6	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Active Treatment will consist of IVT injection of Aflibercept followed by an SC injection of CLS-TA IVT aflibercept: IVT aflibercept \[2 mg (0.05 mL)\] SC CLS-TA: SC CLS-TA \[40 mg/mL\]	Control Treatment will consist of IVT aflibercept injection followed by a sham SC procedure IVT aflibercept: IVT aflibercept \[2 mg (0.05 mL)\] Sham SC: sham SC
Overall Study Adverse Event	3	0
Overall Study Lost to Follow-up	0	1
Overall Study Withdrawal by Subject	3	1

Baseline Characteristics

Suprachoroidal CLS-TA With Intravitreal Aflibercept Versus Aflibercept Alone in Subject With Diabetic Macular Edema

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Active n=36 Participants Treatment will consist of IVT injection of Aflibercept followed by an SC injection of CLS-TA IVT aflibercept: IVT aflibercept \[2 mg (0.05 mL)\] SC CLS-TA: SC CLS-TA \[40 mg/mL\]	Control n=35 Participants Treatment will consist of IVT aflibercept injection followed by a sham SC procedure IVT aflibercept: IVT aflibercept \[2 mg (0.05 mL)\] Sham SC: sham SC	Total n=71 Participants Total of all reporting groups
Best corrected visual acuity	57.1 letters STANDARD_DEVIATION 13.00 • n=5 Participants	58.1 letters STANDARD_DEVIATION 11.33 • n=7 Participants	57.6 letters STANDARD_DEVIATION 12.13 • n=5 Participants
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	25 Participants n=5 Participants	23 Participants n=7 Participants	48 Participants n=5 Participants
Age, Categorical >=65 years	11 Participants n=5 Participants	12 Participants n=7 Participants	23 Participants n=5 Participants
Age, Continuous	59.8 years STANDARD_DEVIATION 10.16 • n=5 Participants	59.2 years STANDARD_DEVIATION 12.89 • n=7 Participants	59.5 years STANDARD_DEVIATION 11.51 • n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants	11 Participants n=7 Participants	21 Participants n=5 Participants
Sex: Female, Male Male	26 Participants n=5 Participants	24 Participants n=7 Participants	50 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	12 Participants n=5 Participants	9 Participants n=7 Participants	21 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	24 Participants n=5 Participants	26 Participants n=7 Participants	50 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) White	31 Participants n=5 Participants	32 Participants n=7 Participants	63 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	36 participants n=5 Participants	35 participants n=7 Participants	71 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, 6 months

Population: The Intent-to-treat population included all randomized subjects who received at least 1 study treatment

Outcome measures

Outcome measures
Measure	Active n=36 Participants Treatment will consist of IVT injection of Aflibercept followed by an SC injection of CLS-TA IVT aflibercept: IVT aflibercept \[2 mg (0.05 mL)\] SC CLS-TA: SC CLS-TA \[40 mg/mL\]	Control n=35 Participants Treatment will consist of IVT aflibercept injection followed by a sham SC procedure IVT aflibercept: IVT aflibercept \[2 mg (0.05 mL)\] Sham SC: sham SC
Mean Change From Baseline in Best Corrected Visual Acuity Letter Score	11.4 letters Standard Error 1.63	13.8 letters Standard Error 1.59

SECONDARY outcome

Timeframe: Baseline, 6 months

Population: The Intent-to-treat population included all randomized subjects who received at least 1 study treatment

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=36 Participants Treatment will consist of IVT injection of Aflibercept followed by an SC injection of CLS-TA IVT aflibercept: IVT aflibercept \[2 mg (0.05 mL)\] SC CLS-TA: SC CLS-TA \[40 mg/mL\]	Control n=35 Participants Treatment will consist of IVT aflibercept injection followed by a sham SC procedure IVT aflibercept: IVT aflibercept \[2 mg (0.05 mL)\] Sham SC: sham SC
Mean Change From Baseline in Central Subfield Thickness	-212.1 microns Standard Error 13.83	-178.6 microns Standard Error 13.61

Adverse Events

Active

Serious events: 6 serious events

Other events: 10 other events

Deaths: 2 deaths

Control

Serious events: 4 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Active n=36 participants at risk Treatment will consist of IVT injection of Aflibercept followed by an SC injection of CLS-TA IVT aflibercept: IVT aflibercept \[2 mg (0.05 mL)\] SC CLS-TA: SC CLS-TA \[40 mg/mL\]	Control n=35 participants at risk Treatment will consist of IVT aflibercept injection followed by a sham SC procedure IVT aflibercept: IVT aflibercept \[2 mg (0.05 mL)\] Sham SC: sham SC
Blood and lymphatic system disorders Anaemia	2.8% 1/36 • Number of events 2 • Adverse events were collected over 24 weeks of follow-up.	0.00% 0/35 • Adverse events were collected over 24 weeks of follow-up.
Cardiac disorders Acute left ventricular failure	0.00% 0/36 • Adverse events were collected over 24 weeks of follow-up.	2.9% 1/35 • Number of events 1 • Adverse events were collected over 24 weeks of follow-up.
Cardiac disorders Acute myocardial infarction	0.00% 0/36 • Adverse events were collected over 24 weeks of follow-up.	2.9% 1/35 • Number of events 1 • Adverse events were collected over 24 weeks of follow-up.
Cardiac disorders Cardiac arrest	2.8% 1/36 • Number of events 1 • Adverse events were collected over 24 weeks of follow-up.	0.00% 0/35 • Adverse events were collected over 24 weeks of follow-up.
Hepatobiliary disorders Hepatorenal syndrome	2.8% 1/36 • Number of events 1 • Adverse events were collected over 24 weeks of follow-up.	0.00% 0/35 • Adverse events were collected over 24 weeks of follow-up.
Infections and infestations Osteomyelitis	0.00% 0/36 • Adverse events were collected over 24 weeks of follow-up.	2.9% 1/35 • Number of events 1 • Adverse events were collected over 24 weeks of follow-up.
Infections and infestations Pneumonia	5.6% 2/36 • Number of events 2 • Adverse events were collected over 24 weeks of follow-up.	0.00% 0/35 • Adverse events were collected over 24 weeks of follow-up.
Infections and infestations Pneumonia staphylococcal	2.8% 1/36 • Number of events 1 • Adverse events were collected over 24 weeks of follow-up.	0.00% 0/35 • Adverse events were collected over 24 weeks of follow-up.
Injury, poisoning and procedural complications Femur fracture	2.8% 1/36 • Number of events 1 • Adverse events were collected over 24 weeks of follow-up.	0.00% 0/35 • Adverse events were collected over 24 weeks of follow-up.
Injury, poisoning and procedural complications Hip fracture	2.8% 1/36 • Number of events 1 • Adverse events were collected over 24 weeks of follow-up.	0.00% 0/35 • Adverse events were collected over 24 weeks of follow-up.
Metabolism and nutrition disorders Diabetes mellitus	2.8% 1/36 • Number of events 1 • Adverse events were collected over 24 weeks of follow-up.	0.00% 0/35 • Adverse events were collected over 24 weeks of follow-up.
Renal and urinary disorders Chronic kidney disease	2.8% 1/36 • Number of events 1 • Adverse events were collected over 24 weeks of follow-up.	0.00% 0/35 • Adverse events were collected over 24 weeks of follow-up.
Skin and subcutaneous tissue disorders Diabetic neuropathic ulcer	0.00% 0/36 • Adverse events were collected over 24 weeks of follow-up.	2.9% 1/35 • Number of events 1 • Adverse events were collected over 24 weeks of follow-up.
Vascular disorders Orthostatic hypotension	2.8% 1/36 • Number of events 1 • Adverse events were collected over 24 weeks of follow-up.	0.00% 0/35 • Adverse events were collected over 24 weeks of follow-up.

Other adverse events

Other adverse events
Measure	Active n=36 participants at risk Treatment will consist of IVT injection of Aflibercept followed by an SC injection of CLS-TA IVT aflibercept: IVT aflibercept \[2 mg (0.05 mL)\] SC CLS-TA: SC CLS-TA \[40 mg/mL\]	Control n=35 participants at risk Treatment will consist of IVT aflibercept injection followed by a sham SC procedure IVT aflibercept: IVT aflibercept \[2 mg (0.05 mL)\] Sham SC: sham SC
Psychiatric disorders Anxiety	5.6% 2/36 • Number of events 2 • Adverse events were collected over 24 weeks of follow-up.	0.00% 0/35 • Adverse events were collected over 24 weeks of follow-up.
Eye disorders Conjunctival haemorrhage	5.6% 2/36 • Number of events 2 • Adverse events were collected over 24 weeks of follow-up.	2.9% 1/35 • Number of events 1 • Adverse events were collected over 24 weeks of follow-up.
Eye disorders Eye pain	0.00% 0/36 • Adverse events were collected over 24 weeks of follow-up.	5.7% 2/35 • Number of events 2 • Adverse events were collected over 24 weeks of follow-up.
Vascular disorders Hypertension	8.3% 3/36 • Number of events 3 • Adverse events were collected over 24 weeks of follow-up.	11.4% 4/35 • Number of events 4 • Adverse events were collected over 24 weeks of follow-up.
Eye disorders Intraocular pressure increased	8.3% 3/36 • Number of events 4 • Adverse events were collected over 24 weeks of follow-up.	2.9% 1/35 • Number of events 1 • Adverse events were collected over 24 weeks of follow-up.
Infections and infestations Nasopharyngitis	0.00% 0/36 • Adverse events were collected over 24 weeks of follow-up.	8.6% 3/35 • Number of events 5 • Adverse events were collected over 24 weeks of follow-up.
Eye disorders Retinal exudates	0.00% 0/36 • Adverse events were collected over 24 weeks of follow-up.	5.7% 2/35 • Number of events 2 • Adverse events were collected over 24 weeks of follow-up.

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