Aflibercept in Polypoidal Choroidal Vasculopathy (PLANET)

A Randomized, Double-masked, Sham-controlled Phase 3b/4 Study of the Efficacy, Safety, and Tolerability of Intravitreal Aflibercept Monotherapy Compared to Aflibercept With Adjunctive Photodynamic Therapy as Indicated in Subjects With Polypoidal Choroidal Vasculopathy

To collect data reflecting the efficacy and safety of aflibercept with and without photodynamic therapy in subjects diagnosed with the polypoidal choroidal vasculopathy subtype of wet age-related macular degeneration

Study Overview

• Status: Completed
• Conditions: Neovascular Macular Degeneration
• Intervention / Treatment: Drug: Aflibercept (Eylea, VEGF Trap-Eye, BAY86-5321); Other: Visudyne

• Study Type: Interventional
• Enrollment (Actual): 333
• Phase: Phase 4

Contacts and Locations

Study Locations

• Australia
  • Parramatta, Australia, 2150
  • New South Wales
    • Liverpool, New South Wales, Australia, 2170
    • Strathfield, New South Wales, Australia, 2135
    • Westmead, New South Wales, Australia, 2145
  • Victoria
    • East Melbourne, Victoria, Australia, 3002
• Germany
  • München, Germany, 80336
• Hong Kong
  • Hong Kong, Hong Kong
  • Kowloon, Hong Kong
• Hungary
  • Budapest, Hungary, 1082
  • Budapest, Hungary, 1106
  • Budapest, Hungary, 1133
  • Debrecen, Hungary, 4032
• Japan
  • Akita, Japan, 010-8543
  • Aomori, Japan, 030-8553
  • Chiba, Japan, 260-8677
  • Fukuoka, Japan, 812-8582
  • Fukuoka, Japan, 812-0011
  • Fukushima, Japan, 960-1295
  • Kumamoto, Japan, 860-0027
  • Kyoto, Japan, 606-8507
  • Kyoto, Japan, 602-0841
  • Nagasaki, Japan, 852-8511
  • Okayama, Japan, 700-8558
  • Osaka, Japan, 545-8586
  • Tokushima, Japan, 770-8503
  • Wakayama, Japan, 641-8510
  • Aichi
    • Nagoya, Aichi, Japan, 466-8560
  • Chiba
    • Urayasu, Chiba, Japan, 279-0021
  • Gifu
    • Ogaki, Gifu, Japan, 503-0015
  • Gunma
    • Maebashi, Gunma, Japan, 371-8511
  • Hokkaido
    • Asahikawa, Hokkaido, Japan, 078-8510
    • Sapporo, Hokkaido, Japan, 060-8604
  • Hyogo
    • Amagasaki, Hyogo, Japan, 660-8550
    • Kobe, Hyogo, Japan, 650-0017
  • Kagawa
    • Kita, Kagawa, Japan, 761-0793
  • Mie
    • Tsu, Mie, Japan, 514-8507
  • Nara
    • Kashihara, Nara, Japan, 634-8522
  • Osaka
    • Hirakata, Osaka, Japan, 573-1191
    • Suita, Osaka, Japan, 565-0871
  • Shiga
    • Otsu, Shiga, Japan, 520-2192
  • Shizuoka
    • Hamamatsu, Shizuoka, Japan, 430-8558
  • Tochigi
    • Shimotsuke, Tochigi, Japan, 329-0498
  • Tokyo
    • Bunkyo-ku, Tokyo, Japan, 113-8655
    • Chiyoda-ku, Tokyo, Japan, 101-8309
    • Meguro-ku, Tokyo, Japan, 152-8902
    • Mitaka, Tokyo, Japan, 181-8611
    • Shinjuku-ku, Tokyo, Japan, 162-8666
    • Shinjuku-ku, Tokyo, Japan, 160-8582
• Korea, Republic of
  • Seoul, Korea, Republic of, 137-701
  • Seoul, Korea, Republic of, 03080
  • Seoul, Korea, Republic of, 135-710
  • Seoul, Korea, Republic of, 05505
  • Seoul, Korea, Republic of, 153-950
  • Gyeonggido
    • Seongnam-si, Gyeonggido, Korea, Republic of, 463-707
• Singapore
  • Singapore, Singapore, 119074
  • Singapore, Singapore, 168751
• Taiwan
  • Kaohsiung, Taiwan, 81362
  • Taipei, Taiwan, 11217
  • Taipei, Taiwan, 10002
  • Taipei, Taiwan, 10449
  • Taipei City, Taiwan
  • Changhua
    • Changhua City, Changhua, Taiwan, 500

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Signed informed consent
• Men and women ≥50 years of age
• Diagnosis of symptomatic macular Polypoidal Choroidal Vasculopathy (PCV) in the study eye established by Indocyanine Green Angiography(ICGA) at the study center
• Greatest linear dimension of the lesion of < 5400 mm (approximately, 9 Macular Photocoagulation Study disk areas), assessed by ICGA.
• An Early treatment diabetic retinopathy study (ETDRS) BCVA of 73 to 24 letters in the study eye.

Exclusion Criteria:

• Prior use of intravitreal or sub-tenon corticosteroids in the study eye within 3 months prior to study entry
• Any prior use of intraocular anti Vascular Endothelial Growth Factor (anti-VEGF)agents in the study eye, or systemic use of anti VEGF products within 3 months prior to study entry
• Prior macular laser treatment in the study eye including Photodynamic Therapy (PDT)
• History of allergy to fluorescein used in fluorescein angiography, iodine and/or indocyanine green.
• History of allergy to aflibercept, verteporfin, or their excipients.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Aflibercept + Sham PDT; Participants received 2 milligram (mg) Intravitreal aflibercept injection (IAI) (Eylea, VEGF Trap-Eye, BAY86-5321) every month for the first 3 months (run-in period). At Week 12, subjects were randomized to receive Aflibercept injection plus sham photodynamic therapy (only in subjects qualifying for rescue therapy)	Drug: Aflibercept (Eylea, VEGF Trap-Eye, BAY86-5321); Eylea is administered as an intravitreal injection
Experimental: Aflibercept + Active PDT; Participants received 2 mg Intravitreal aflibercept injection (IAI) (Eylea, VEGF Trap-Eye, BAY86-5321) every month for the first 3 months (run-in period). At Week 12, subjects were randomized to receive Aflibercept injection plus active photodynamic therapy (only in subjects qualifying for rescue therapy)	Drug: Aflibercept (Eylea, VEGF Trap-Eye, BAY86-5321); Eylea is administered as an intravitreal injection; Other: Visudyne; Photodynamic therapy is a combined therapy of drug (Visudyne) applied to reinforce the action of a device (laser)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change in Best Corrected Visual Acuity (BCVA) as Measured by Early Treatment of Diabetic Retinopathy Study (ETDRS) Letter Scores From Baseline to Week 52 - Last Observation Carried Forward (LOCF)	Visual function of the study eye and fellow eye was assessed at each study visit according to the standard procedure developed for the ETDRS adapted for Age Related Eye Disease Study (AREDS), using 70 letter charts at a starting distance of 4 meters. Participants were challenged with reading letters on lines of an eye chart (5 letters per line). Lines became smaller as participants progressed from the top to the bottom of the chart. Participants read down the chart until they reached a row where a minimum of three letters on a line could be read, and were scored by how many letters could be correctly identified.	From Baseline to Week 52

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects Who Avoided at Least 15 Letters Loss in ETDRS at Week 52	Visual function of the study eye and fellow eye was assessed at each study visit according to the standard procedure developed for the ETDRS adapted for Age Related Eye Disease Study (AREDS), using 70 letter charts at a starting distance of 4 meters. Participants were challenged with reading letters on lines of an eye chart (5 letters per line). Lines became smaller as participants progressed from the top to the bottom of the chart. Participants read down the chart until they reached a row where a minimum of three letters on a line could be read, and were scored by how many letters could be correctly identified.	At Week 52

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Subjects Who Never Need Rescue Therapy in the First Year	Evaluations for qualification for rescue were conducted at each visit from Week 12 to Week 52. Intensified aflibercept treatment plus active or sham PDT treatments were given at any of these visits if treatment criteria were met. Qualification for rescue was based upon insufficient gain of BCVA, leakage, and presence of active polyps.	Baseline to Week 52
Number of PDT Treatments in the Study Eye Before Week 52		Baseline to Week 52
Number of Aflibercept Treatments in the Study Eye (After Randomization) Before Week 52		Baseline to Week 52
Time to First Administration of PDT in the Study Eye Before Week 52		Baseline to Week 52
Change of Visual Acuity (Letters) From Baseline Over Time (Week) in the Study Eye	Visual function of the study eye and fellow eye was assessed at each study visit according to the standard procedure developed for the ETDRS adapted for Age Related Eye Disease Study (AREDS), using 70 letter charts at a starting distance of 4 meters. Participants were challenged with reading letters on lines of an eye chart (5 letters per line). Lines became smaller as participants progressed from the top to the bottom of the chart. Participants read down the chart until they reached a row where a minimum of three letters on a line could be read, and were scored by how many letters could be correctly identified.	Baseline to Week 52
Percentage of Subjects Who Gained ≥5, 10, or 15 Letters at Week 52	Visual function of the study eye and fellow eye was assessed at each study visit according to the standard procedure developed for the ETDRS adapted for Age Related Eye Disease Study (AREDS), using 70 letter charts at a starting distance of 4 meters. Participants were challenged with reading letters on lines of an eye chart (5 letters per line). Lines became smaller as participants progressed from the top to the bottom of the chart. Participants read down the chart until they reached a row where a minimum of three letters on a line could be read, and were scored by how many letters could be correctly identified.	Baseline to Week 52
Percentage of Subjects Who Lost ≥5, 10, or 15 Letters at Week 52	Visual function of the study eye and fellow eye was assessed at each study visit according to the standard procedure developed for the ETDRS adapted for Age Related Eye Disease Study (AREDS), using 70 letter charts at a starting distance of 4 meters. Participants were challenged with reading letters on lines of an eye chart (5 letters per line). Lines became smaller as participants progressed from the top to the bottom of the chart. Participants read down the chart until they reached a row where a minimum of three letters on a line could be read, and were scored by how many letters could be correctly identified.	Baseline to Week 52
Percentage of Subjects With Complete Polyp Regression at Week 52	Complete polyp regression was defined as absent or indeterminate visual polyps on Indocyanine green angiography (ICGA) in the study eye.	Baseline to Week 52
Change of Leakage Area in Fluorescein Angiography (FA) in the Study Eye at Week 52	Leakage is the release of fluorescein dye from diseased retinal vessels. Leakage area is defined as the area showing presence of fluorescein dye in the late stages of fluorescein angiography.	Baseline to Week 52
Change of Central Subfield Thickness (CST) on Optical Coherence Tomography (OCT) From Baseline to Week 52	Retinal and lesion characteristics, such as central retinal thickness (CRT), were evaluated by OCT in both eyes at every study visit. CRT was measured using optical coherence tomography to determine the average thickness of the retina in a circle with 1 millimeter of diameter centered on the fovea. This value is reported by some OCT devices as central subfield thickness (CST).	Baseline to Week 52
Change in National Eye Institute 25-item Visual Function Questionnaire (NEI VFQ-25) Total Score From Baseline to Week 52	The NEI VFQ-25 total score ranges from 0-100 with a score of 0 being the worst outcome and 100 being the best outcome. The NEI VFQ questionnaire is organized as a collection of subscales which are all scored from 0-100. To reach the overall composite score, each sub-scale score is averaged in order to give each sub-scale equal weight.	Baseline to Week 52
Percentage of Subjects for Whom Rescue Therapy is Indicated Over the Course Till Week 52	Evaluations for qualification for rescue were conducted at each visit from Week 12 to Week 52. Intensified aflibercept treatment plus active or sham PDT treatments were given at any of these visits if treatment criteria were met. Qualification for rescue was based upon insufficient gain of BCVA, leakage, and presence of active polyps.	Baseline to Week 52

Collaborators and Investigators

• Sponsor: Bayer
• Collaborators: Regeneron Pharmaceuticals

Publications and helpful links

General Publications

• Lee WK, Iida T, Ogura Y, Chen SJ, Wong TY, Mitchell P, Cheung GCM, Zhang Z, Leal S, Ishibashi T; PLANET Investigators. Efficacy and Safety of Intravitreal Aflibercept for Polypoidal Choroidal Vasculopathy in the PLANET Study: A Randomized Clinical Trial. JAMA Ophthalmol. 2018 Jul 1;136(7):786-793. doi: 10.1001/jamaophthalmol.2018.1804. Erratum In: JAMA Ophthalmol. 2018 Jul 1;136(7):840.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): May 29, 2014
• Primary Completion (Actual): August 12, 2016
• Study Completion (Actual): July 7, 2017

Study Registration Dates

• First Submitted: April 10, 2014
• First Submitted That Met QC Criteria: April 22, 2014
• First Posted (Estimate): April 23, 2014

Study Record Updates

• Last Update Posted (Actual): December 2, 2020
• Last Update Submitted That Met QC Criteria: November 17, 2020
• Last Verified: November 1, 2020

More Information

Terms related to this study

• Keywords: PCV
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Photosensitizing Agents; Dermatologic Agents; Verteporfin; Aflibercept
• Other Study ID Numbers: 16995; 2013-004464-54 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No