Prospective Trial of Treat and Extend Aflibercept for Macular Edema Secondary to Branch Retinal Vein Occlusion

Branch Retinal Vein Occlusion With Macular Edema Clinical Trial

Official title:

Prospective Trial of Treat and Extend Aflibercept for Macular Edema Secondary to Branch Retinal Vein Occlusion: the PLATON Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03405376
• Other study ID #: YUMC2017-07-056-003
• Status: Recruiting
• Phase: Phase 4
• Start date: January 25, 2018
• Est. completion date: September 30, 2020

Study information

• Verified date: January 2019
• Source: Yeungnam University College of Medicine
• Contact: Min Sagong, MD
• Phone: 82-53-620-3443
• Email: msagong[@]ynu.ac.kr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to evaluate the efficacy and safety of the treat-and-extend regimen extending to 4 months by intervals of 4 weeks using intravitreal aflivercept injection for treatment of macular edema secondary to BRVO.

Description:

Retinal vein occlusion (RVO) includes central RVO (CRVO) and branch RVO (BRVO). A highly prevalent retinal vascular disease, RVO is second only to diabetic retinopathy. In CRVO, hemorrhages and edema develop throughout the retina, whereas in BRVO the pathology is more sectoral, involving the portions of the retina drained by the obstructed branch vein. This suggests that increased intraluminal pressure behind the obstruction may lead to transudation of blood cells and plasma into the retina. However, recent studies have demonstrated that although increased venous pressure may be the precipitating event for hemorrhages and edema, increased production of vascular endothelial growth factor (VEGF) occurs early in RVO and is a major contributor to their evolution and persistence. In addition, the high levels of VEGF contribute to progression of retinal nonperfusion and hence retinal ischemia, which may in turn increase production of VEGF, and may explain why some eyes enter a vicious cycle of worsening disease often referred to as conversion to an ischemic RVO.

Treat-and-extend intravitreal anti-VEGF with age related macular degeneration and diabetic macular edema has been reported to offer the opportunity to individual management while minimizing treatment burden and similar visual and anatomical outcomes to those with fixed montly dosing.

Also, small retrospective treat-and-extend intravitreal bevacizumab injection for treatment of BRVO associated macular edema demonstrated similar visual outcomes and number of intravitreal injections as did pro-re-nata treatment with ranibizumab conducted in phase 3 trials but with fewer visits and lower annual medical costs.

The effects of afilbercept have been reported to persist for over 8 weeks in DME and AMD studies. In addition, VIBRANT study also demonstrated that bi-monthly injection of aflibercept showed significant visual improvement in BRVO patients.

In the treat-and-extend studies of RVO, ranibizumab has been extended for up to 4 months at intervals of 2 weeks. But, to our knowledge, there was no prospective study of treat-and-extend regiments with intravitreal aflibercept in treatment naïve patients in BRVO.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 49
• Est. completion date: September 30, 2020
• Est. primary completion date: March 31, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Center-involved macular edema secondary to BRVO for no longer than 3 months (at the screening visit it should be ensured that the subjects will comply with the criterion of = 3 months since onset of macular edema at their scheduled baseline visit).

• Adult subjects diagnosed with macular edema secondary to BRVO who are scheduled to be treated with intravitreal aflibercept as per investigator's routine treatment practice with the intent to use a T&E regimen after initial treatment.

• Treatment-naïve subjects for macular edema secondary to BRVO.

• Both ischemic and non-ischemic BRVO, which are confirmed by FA at baselin, week 24 and week 72.

• Men and women = 18 years of age.

• Documented BCVA of ETDRS letter score of 73 to 24 letters (Snellen equivalent of 20/40 to 20/320) in the study eye.

Exclusion Criteria:

• Previous PRP or macular laser photocoagulation in the study eye.

• Any prior or concomitant ocular treatment (e.g. anti-VEGF therapy, corticosteroids) in the study eye for macular edema secondary to BRVO, except dietary supplements or vitamins prior to inclusion in the study. Intraocular anti-VEGF treatment is permitted for the treatment of diseases of fellow eye except for those that are specifically excluded.

• Prior systemic anti-VEGF or corticosteroid therapy, investigational or approved, within the last 3 months before the first dose in the study.

• Previous use of intraocular corticosteroids in the study eye at any time or use of periocular corticosteroids in the study eye within 12 months prior to Day 1.

• Any active intraocular, extraocular, and periocular inflammation or infection in either eye within 4 weeks of screening.

• Any history of allergy to povidone iodine.

• Known serious allergy to the fluorescein sodium for injection in angiography.

• Presence of any contraindications indicated in the EU commission/locally approved label for intravitreal aflibercept: hypersensitivity to the active substance intravitreal aflibercept or to any of the excipients; active or suspected ocular or periocular infection; active severe intraocular inflammation.

Related Conditions & MeSH terms

• Branch Retinal Vein Occlusion With Macular Edema
• Edema
• Macular Edema
• Retinal Vein Occlusion

Intervention

Drug:
• Intravitreal aflibercept injection
Aflibercept 2mg is injected into the vitreous cavity through the pars plana using 30G needle-attached syringe for branch retinal vein occlusion.

Locations

Country	Name	City	State
Korea, Republic of	Dong-A University Hospital	Busan
Korea, Republic of	Maryknoll Medical Center	Busan
Korea, Republic of	Min Sagong	Daegu	Deagu
Korea, Republic of	Chungnam National University Hospital	Daejeon
Korea, Republic of	Chonnam National University Hospital	Gwangju

Sponsors (1)

Lead Sponsor	Collaborator
Yeungnam University College of Medicine

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean change of best corrected visual acuity	The mean change of best corrected visual acuity from baseline to Week 72 in early treatment diabetic retinopathy letter score	From baseline to Week 72
Secondary	Mean change of best corrected visual acuity	The change in mean best corrected visual acuity at baseline as measured by the early treatment diabetic retinopathy letter score	From baseline to Week 24, 52
Secondary	mean change in central macular thickness	The mean change in central macular thickness	From baseline to Weeks 24, 52, and 72
Secondary	mean treatment interval between injections	The mean treatment interval between injections	From baseline to Week 72
Secondary	gain = 15 letters in best corrected visual acuity	The proportion of subjects who gain = 15 letters in best corrected visual acuity on the early treatment diabetic retinopathy chart	Compared with baseline at Week 24, 52 and 72
Secondary	mean treatment interval between injections of = 12 or 16 weeks	The proportion of subjects with a mean treatment interval between injections of = 12 or 16 weeks	From the last actual visit of the initiation phase to Week 72
Secondary	who reach 16 weeks treatment interval at any time point	The proportion of subjects who reach 16 weeks treatment interval at any time point	up to 72 weeks