An Open Label-study to Compare the Efficacy of Aflibercept Monotherapy for Polypoidal Choroidal Vasculopathy

NCT03117634 | Completed Phase 4 Results DMC

• 1 other identifier: R1448/31/2017
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

Polypoidal choroidal neovasculopathy (PCV) is a subtype of wet age related macula degeneration (AMD) occuring more commonly in the Asian population. Besides the phenotypic differences, PCV is thought to have a lesser response to anti VEGF therapy which is the mainstay of treatment for other typical wet AMD. Recent trial data suggest that a combination with photodynamic therapy may help in the visual and anatomical outcome of PCV, and emerging evidence shows favourable outcomes the newer anti VEGF agent, aflibercept 2mg monotherapy. These trials however, have assessed aflibercept in a strict 2mg every 8 weekly regime. In the clinical setting, a significant an unmet need in the management of PCV is a tailored treatment regime. Here we propose a treatment regimen based on disease activity for PCV with aflibercept mono therapy. A limitation of the 2q8 regime is that it is fixed and does not vary regardless of polyp closure or anatomical outcome at the first time point of assessment (month 3). We hypothesize that after the initial 3 monthly injections of aflibercept, about 50% of PCV will close and become quiescent, and in the remaining 50%, a further 3 monthly injections will increase overall polyp closure rate. After a loadings phase of either 3 or 6 months, all eyes will start on a treat and extend regime (T\&E), with a minimum period of 8 weeks and a maximum of 12 weeks between treatments with 2 week increments if PCV remains quiescent. The proposed study aims to evaluate the efficacy of a modified treat and extend regime based on disease activity with aflibercept monotherapy for PCV.

Conditions

Age Related Macular Degeneration; Polypoidal Choroidal Vasculopathy

Keywords

anti vegf; aflibercept; treat and extend

Outcome Measures

Primary Outcomes (1)

• Mean Change in Best Corrected Visual Acuity (BCVA)

  Mean Change in Best corrected visual acuity (BCVA) from baseline to week 52 for personalized and fixed regimen. it is a Non-inferiority of personalized to fixed regimen for mean change in BCVA from baseline to week 52 (Non-inferiority is considered as -5 ETDRS Letters difference )

  From Baseline to Week 52

Secondary Outcomes (3)

• Mean Change in Central Sub Field Thickness

  From Baseline to Week 52

• Number of Participants With Complete Polypoidal Lesion Closure

  At Week 52

• Number of Injections

  From Baseline to Week 52

Study Arms (2)

Fixed dosing group (2Q8)

ACTIVE COMPARATOR

Fixed Dosing with Aflibercept 2mg will be administered at a fixed regime at 8 week intervals through to week 52.

Drug: Fixed Dosing with Aflibercept 2mg

Treat and Extend group (T&E)

EXPERIMENTAL

Reassessment at week 12 (month 3) by repeat examination for disease activity by OCT and indocyanine green angiography (ICGA). Subsequent treatment regime of Treat and Extend with Aflibercept 2mg will depend on disease activity at this point.

Drug: Treat and Extend with Aflibercept 2mg

Interventions

Treat and Extend with Aflibercept 2mg DRUG

Drug treatment regime which allows extension of treatment interval based on disease activity

Also known as: T&E

Treat and Extend group (T&E)

Fixed Dosing with Aflibercept 2mg DRUG

Fixed 8 weekly dosing regime throughout the study duration

Also known as: 2Q8

Fixed dosing group (2Q8)

Eligibility Criteria

• Age: 45 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female study participants, age \>=45 years of age at the time of informed consent.
• Best corrected ETDRS visual acuity score \<= 78 (ie 20/32 or worse)
• Diagnosis of PCV based on ICGA
• Presence of intra retinal or subretinal fluid/blood at the fovea as seen on OCT
• Treatment naïve
• Media clarity, pupillary dilation and individual cooperation sufficient for study procedure including fundus photography.
• Able and willing to provide informed consent.

You may not qualify if:

• Medical condition that, in the opinion of the investigator, would preclude participation in the study (e.g.unstable medical status including blood pressure, cardiovascular disease, and glycemic control).
• Participation in an investigational trial within 30 days of enrolment which involves treatment with unapproved investigational drug
• Known allergy to any component of the study drug.
• Blood pressure \> 180/110 (systolic above 180 OR diastolic above 110 on repeated measurements). If blood pressure is brought below 180/110 by anti-hypertensive treatment, individual can become eligible.
• Myocardial infarction, other acute cardiac event requiring hospitalization, stroke, transient ischemic attack, or treatment for acute congestive heart failure within 4 months prior to randomization.
• Systemic anti-VEGF or pro-VEGF treatment within four months prior to randomization or anticipated use during the study.
• Study Eye
• Eye with intra retinal or subretinal fluid due to other causes than PCV
• An ocular condition is present (other than PCV) that, in the opinion of the investigator, might affect intra or sub retinal fluid or alter visual acuity during the course of the study (e.g., diabetic macula edema (DME), vein occlusion, uveitis or other ocular inflammatory disease, neovascular glaucoma, etc.)
• Substantial cataract that, in the opinion of the investigator, is likely to be decreasing visual acuity by more than three lines (i.e., cataract would be reducing acuity to worse than 20/40 if eye was otherwise normal).
• Any intraocular surgery within 3 months of enrollment
• Treatment with intra vitreal corticosteroids
• History of retinal detachment or surgery for retinal detachment
• History of vitrectomy
• History of macular hole

Sponsors & Collaborators

• Singapore National Eye Centre: lead
• Bayer: collaborator

Study Sites (1)

Singapore National Eye Centre

Singapore, Singpore, 168751, Singapore

Location

Related Publications (1)

• Teo KYC, Jordan-Yu JM, Tan ACS, Yeo IYS, Mathur R, Chan CM, Wong TY, Chakravarthy U, Cheung CMG. Efficacy of a novel personalised aflibercept monotherapy regimen based on polypoidal lesion closure in participants with polypoidal choroidal vasculopathy. Br J Ophthalmol. 2022 Jul;106(7):987-993. doi: 10.1136/bjophthalmol-2020-318354. Epub 2021 Feb 11.

  PMID: 33574033 DERIVED

MeSH Terms

Conditions

Macular Degeneration; Polypoidal Choroidal Vasculopathy

Interventions

Coal Tar; aflibercept

Condition Hierarchy (Ancestors)

Retinal Degeneration; Retinal Diseases; Eye Diseases; Choroidal Neovascularization; Choroid Diseases; Uveal Diseases; Neovascularization, Pathologic; Metaplasia; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Tars; Complex Mixtures

Limitations and Caveats

More participants in the personalised group(3:1)increased the power to detect outcomes. 52 week study duration may not fully demonstrate the advantages of a TNE regimen,PL closure. Study not powered to detect the difference in PL closure at month 3.

Results Point of Contact

• Title: Gemmy Cheung, Principal Investigator
• Organization: Singapore National Eye Center

gemmy.cheung.c.m@singhealth.com.sg

+65 6322 8335

Study Officials

• Gemmy Cheung

  SNEC

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: Prospective, 2-arm, Non-inferiority, interventional study

Study Record Dates

• First Submitted: April 6, 2017
• First Posted: April 18, 2017
• Study Start: December 1, 2017
• Primary Completion: June 30, 2020
• Study Completion: January 31, 2021
• Last Updated: August 18, 2021
• Results First Posted: August 18, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

SG (1)