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AzTrials

Age-related Macular DegenerationPhase 4EVEREST IINCT01846273

Visual Outcome in Patients With Symptomatic Macular Polypoidal Choroidal Vasculopathy (PCV) Treated With Either Ranibizumab as Monotherapy or Combined With Verteporfin Photodynamic Therapy (vPDT)

A Phase 4 study testing Ranibizumab and Verteporfin PDT in people with Age-related Macular Degeneration and Polypoidal Choroidal Vasculopathy, run by Novartis Pharmaceuticals at 41 sites in 7 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This study compared the effect of ranibizumab administered as monotherapy versus ranibizumab administered in combination with verteporfin photodynamic therapy (PDT) on visual acuity in patients with symptomatic macular polypoidal choroidal vasculopathy (PCV). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Ranibizumab and Verteporfin PDT
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
321 participants
Where
41 sitesin 7 countries
Study dates
7 Aug 2013to 2 Mar 2017
Phase
Phase 4
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Confirmed diagnosis of symptomatic macular PCV in the study eye
  • A qualifying vision score at study entry
  • A qualifying lesion size in the study eye at study entry

Who cannot join

  • Active inflammation or infection in the study eye
  • Uncontrolled intraocular pressure in the stuy eye
  • Ocular condition in the study eye which may impact vision and confound study outcomes
  • Prior treatment of the study eye with anti-VEGF therapy, verteporfin PDT, other laser and surgical interventions, intraocular corticosteroids

Trial locations and contacts

41 sites in 7 countries.

41 sites in 7 countries

Japan22 sites

  • Novartis Investigative Site

    Amagasaki, Hyōgo, 660 8550

  • Novartis Investigative Site

    Bunkyo Ku, Tokyo, 113 8655

  • Novartis Investigative Site

    Chiba, 260-8677

  • Novartis Investigative Site

    Chiyoda-ku, Tokyo, 101-8309

  • Novartis Investigative Site

    Fukuoka, Fukuoka, 812-8582

  • Novartis Investigative Site

    Fukushima, Fukushima, 960-1295

  • Novartis Investigative Site

    Hirakata, Osaka, 573-1191

  • Novartis Investigative Site

    Inashiki-gun, Ibaraki, 300-0395

  • Novartis Investigative Site

    Kita-gun, Kagawa-ken, 761-0793

  • Novartis Investigative Site

    Kobe, Hyōgo, 650-0017

  • Novartis Investigative Site

    Kobe, Hyōgo, 650-0047

  • Novartis Investigative Site

    Maebashi, Gunma, 371 8511

  • Novartis Investigative Site

    Mitaka, Tokyo, 181-8611

  • Novartis Investigative Site

    Nagoya, Aichi-ken, 462-0825

  • Novartis Investigative Site

    Nagoya, Aichi-ken, 466 8560

  • Novartis Investigative Site

    Ohtsu-city, Shiga, 520-2192

  • Novartis Investigative Site

    Okayama, Okayama-ken, 700-8558

  • Novartis Investigative Site

    Osaka, Osaka, 545-8586

  • Novartis Investigative Site

    Osaka, Osaka, 550-0024

  • Novartis Investigative Site

    Sakyo-ku, Kyoto, 606 8507

  • Novartis Investigative Site

    Shinjuku Ku, Tokyo, 162 8666

  • Novartis Investigative Site

    Tsu, Mie-ken, 514-8507

Other trials in Japan

Taiwan6 sites

  • Novartis Investigative Site

    Changhua, 50006

  • Novartis Investigative Site

    Kaohsiung City, 81346

  • Novartis Investigative Site

    Taipei, Taiwan, ROC, 11217

  • Novartis Investigative Site

    Taipei, 10002

  • Novartis Investigative Site

    Taipei, 10449

  • Novartis Investigative Site

    Taoyuan, 33305

Other trials in Taiwan

South Korea5 sites

  • Novartis Investigative Site

    Seongnam-si, Gyeonggi-do, 13620

  • Novartis Investigative Site

    Seoul, Korea, 02447

  • Novartis Investigative Site

    Seoul, Seocho-gu, 06591

  • Novartis Investigative Site

    Seoul, 07301

  • Novartis Investigative Site

    Seoul, 150-950

Other trials in South Korea

Singapore3 sites

  • Novartis Investigative Site

    Singapore, 119074

  • Novartis Investigative Site

    Singapore, 168751

  • Novartis Investigative Site

    Singapore, 308433

Other trials in Singapore

Malaysia2 sites

  • Novartis Investigative Site

    Batu Caves, Selangor, 68100

  • Novartis Investigative Site

    Petaling Jaya, Selangor, 46150

Other trials in Malaysia

Thailand2 sites

  • Novartis Investigative Site

    Bangkok, 10400

  • Novartis Investigative Site

    Songkhla, Hat Yai, 90110

Other trials in Thailand

Hong Kong1 site

  • Novartis Investigative Site

    Hong Kong

Other trials in Hong Kong

About this study

Official title: A 24-month, Phase IV, Randomized, Double Masked, Multi-center Study of Ranibizumab Monotherapy or Ranibizumab in Combination With Verteporfin Photodynamic Therapy on Visual Outcome in Patients With Symptomatic Macular Polypoidal Choroidal Vasculopathy

This study compared the effect of ranibizumab administered as monotherapy versus ranibizumab administered in combination with verteporfin photodynamic therapy (PDT) on visual acuity in patients with symptomatic macular polypoidal choroidal vasculopathy (PCV). The results of this study provided long-term safety and efficacy data used to generate further guidance on the management of patients with PCV.

Read the detailed description

Patients were randomized to the study in 2 treatment groups: ranibizumab + vPDT combination therapy, and ranibizumab monotherapy. Based on the results of the primary analysis at Month 12, patients still in the ranibizumab monotherapy group at the time of the switch cut-off time point were switched to the ranibizumab + vPDT combination therapy group until study exit. A total of 168 and 154 patients were included in the ranibizumab + vPDT combined therapy and ranibizumab monotherapy groups, respectively for the FAS (Month 12 analysis). However, the safety set included 172 and 149 patients, respectively. Four patients in the combination therapy group never took vPDT . Among them, 1 patient actually received verteporfin injection but no laser injection. Thus a total of 3 patients (4-1) in the combination therapy group did not take the actual full vPDT treatment. Additionally, 7 patients in the monotherapy group received vPDT and 1 patient from the monotherapy group did not receive ranibizumab treatment. Considering the above numbers, safety set included 172 patients (i.e., 168-3+7) in the ranibizumab + vPDT combination therapy group and 149 patients (i.e., 154-7+3-1) in the ranibizumab monotherapy group for Month 12 analysis. For the Month 24 safety analysis, the 14 patients in the ranibizumab monotherapy group who were switched to ranibizumab +vPDT combination therapy group were analyzed as a separate group, ie, ranibizumab 0.5 mg + vPDT (switched).

.

Being tested
Ranibizumab, Verteporfin PDT, Sham PDT
Keywords
Polypoidal choroidal vasculopathy, Visual acuity, Ranibizumab, Verteporfin PDT
Medical subject headings
Macular Degeneration, Polypoidal Choroidal Vasculopathy

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • RanibizumabDrug

    Also called Lucentis

    Intravitreal injection of 0.5 mg ranibizumab

  • Verteporfin PDTDrug

    Infusion of 30 ml verteporfin in 5% dextrose solution followed by 83 sec of laser light (50J/cm2; 600mW/cm2; 689 nm)

  • Sham PDTDrug

    Infusion of 30 ml 5% dextrose solution followed by 83 sec of laser light (50J/cm2; 600mW/cm2; 689 nm)

Study groups in NCT01846273
Study groupRoleWhat they receive
Ranibizumab + vPDTExperimentalTreatment initiation with Ranibizumab and verteporfin PDT (vPDT), with re-treatment need (either Ranibizumab alone or combined with vPDT) determined at monthly visits based on defined retreatment criteria
Receives: Drug: Ranibizumab; Drug: Verteporfin PDT
Ranibizumab monotherapyActive comparatorTreatment initiation with Ranibizumab and Sham PDT, with re-treatment need (either Ranibizumab alone or combined with Sham PDT) determined at monthly visits based on defined retreatment criteria
Receives: Drug: Ranibizumab; Drug: Sham PDT

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) at Month 12 - Study Eye

    Best Corrected Visual Acuity (BCVA) was assessed during all study visits using best correction determined from protocol refraction at a starting test distance of 4 meters. VA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts. The BCVA score is the number of letters read correctly by the patient, hence an increase in score indicates improvement in acuity.

    Measured: Baseline, Month 12

  2. Number of Patients With Complete Polyp Regression From Baseline at Month 12 - Study Eye

    Polyp regression was based on the Indocyanine green angiography (ICGA) assessment by the Central Reading Center (CRC). A patient was considered to have complete polyp regression if the presence of polyps, as assessed by CRC, had value "No." Polyp regression which may lead to disease stabilization and consequently better vision.

    Measured: Baseline, Month 12

Secondary outcomes (16)

  1. Mean Change From Baseline in Best-Corrected Visual Acuity (BCVA) at Month 24 - Study Eye

    Best Corrected Visual Acuity (BCVA) was assessed during all study visits using best correction determined from protocol refraction at a starting test distance of 4 meters. VA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at a starting test distance of 4 meters. The BCVA score is the number of letters read correctly by the patient, hence an increase in score indicates improvement in acuity.

    Measured: Baseline, Month 24

  2. Percentage of Patients With BCVA (Letters) Change From Baseline at Month 24 - Study Eye

    BCVA score was based on the number of letters read correctly on the Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity chart assessed at a starting distance of 4 meters. An ETDRS visual acuity score of 85 is approximately 20/20.

    Measured: Baseline, Month 24

  3. Maintenance of BCVA (Within 5 Letter Change) at Month 12 and 24 Compared to BCVA at the Time Point of First Ranibizumab Treatment Interruption

    Best Corrected Visual Acuity (BCVA) was assessed using best correction determined from protocol refraction at a starting test distance of 4 meters. VA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at a starting test distance of 4 meters.

    Measured: Month 3, Month 12, Month 24

  4. Change in BCVA at Month 12 and 24 Compared to the Time Point of First Ranibizumab Treatment Interruption

    Best Corrected Visual Acuity (BCVA) was assessed using best correction determined from protocol refraction at a starting test distance of 4 meters. VA measurements were taken in a sitting position using Early Treatment Diabetic Retinopathy Study (ETDRS)-like visual acuity testing charts at a starting test distance of 4 meters.

    Measured: Month 3, Month 12, Month 24

  5. Percentage of Patients With Complete Polyp Regression at Months 6 and 24 - Study Eye

    Polyp regression was based on the Indocyanine green angiography (ICGA) assessment by the Central Reading Center (CRC). A patient was considered to have complete polyp regression if the presence of polyps, as assessed by CRC, had value "No." Polyp regression which may lead to disease stabilization and consequently better vision.

    Measured: Month 6, Month 24

  6. Percentage of Patients With Presence of Leakage at Month 6, Month 12 and Month 24 - Study Eye

    Presence of lesion leakage was based on Fluorescein Angiography (FA) as assessed by the Central Reading Center (CRC). The presence of leakage may lead to disease progression and worsening vision.

    Measured: Month 6, Month 12 and Month 24

  7. Mean Change From Baseline in Investigator-Assessed Central Subfield Retinal Thickness (CSFT) at Month 24 - Study Eye

    The thickness of the retina was measured using Spectral Domain (SD) optical coherence tomography (OCT) equipment (SD-OCT) and reported as a difference, in micrometers. A negative number indicates a reduction in thickness, whereas a positive number indicates an increase. An increase in thickness may indicate a progression of the underlying disease.

    Measured: Baseline, Month 24

  8. Total Number of Ranibizumab Injections Received in the Study Eye Prior to Month 12

    Measured: Baseline, Month 12

  9. Total Number of Verteporfin/Sham PDT Injections Received in the Study Eye Prior to Month 12

    Measured: Baseline, Month 12

  10. Total Number of Ranibizumab Injections Received in the Study Eye Prior to Month 24

    Measured: Baseline, Month 24

  11. Total Number of Verteporfin/Sham PDT Injections Received in the Study Eye Prior to Month 24

    Measured: Baseline, Month 24

  12. Total Number of Ranibizumab Injections Received in the Study Eye From Month 3 to Month 12

    Measured: Month 3, Month 12

  13. Total Number of Ranibizumab Injections Received in the Study Eye From Month 3 to Month 24

    Measured: Month 3, Month 24

  14. Mean Change From Baseline in Composite Scores, National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25) at Months 3, 12 and 24

    The National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) was used to measure a patient's subjective assessment of vision-related quality of life at Months 3, 12 and 24. The 12 subscales in the VFQ-25 are general health, general vision, ocular pain, near activities, distance activities, social function, mental health, role difficulties, dependency, driving, color vision, and peripheral vision. The scores on the subscales were added together for a total score, which ranged from 0 to 100. A higher score indicated poorer function.

    Measured: Baseline, Month 3, Month 12, Month 24

  15. Number of Ocular Adverse Events of the Study Eye Regardless of Study Drug Relationship up to Month 24, Any Primary System Organ Class

    Reported categorically: Mild, Moderate, Severe

    Measured: Up to Month 24

  16. Number of Non-Ocular Adverse Events of the Study Eye Regardless of Study Drug Relationship up to Month 24, Any Primary System Organ Class

    Reported categorically: Mild, Moderate, Severe

    Measured: Up to Month 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 May 2013 (estimated)
  2. Study start7 Aug 2013
  3. Primary completion11 Mar 2016
  4. Study completion2 Mar 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
321 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01846273
Sponsor's protocol ID
CRFB002A2412
Acronym
EVEREST II
Status last verified
Mar 2019
First submitted
29 Apr 2013
Last updated
7 Jun 2019
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Yanagi Y, Mori R, Teo KYC, Park KH, Ngah NF, Chen SJ, Ruamviboonsuk P, Kondo N, Lee WK, Rajagopalan R, Obata R, Wong IYH, Chee C, Terasaki H, Sekiryu T, Chen SC, Lai TYY, Cheung G, Honda S. Six-year findings of polypoidal choroidal vasculopathy in the EVEREST II study: Japanese subgroup analysis. Jpn J Ophthalmol. 2025 Nov;69(6):894-901. doi: 10.1007/s10384-025-01228-w. Epub 2025 Jun 12.

    PubMed 40504425

  • Teo KYC, Park KH, Ngah NF, Chen SJ, Ruamviboonsuk P, Mori R, Kondo N, Lee WK, Rajagopalan R, Obata R, Wong IYH, Chee C, Terasaki H, Sekiryu T, Chen SC, Yanagi Y, Honda S, Lai TYY, Cheung CMG. Six-Year Outcomes in Subjects with Polypoidal Choroidal Vasculopathy in the EVEREST II Study. Ophthalmol Ther. 2024 Apr;13(4):935-954. doi: 10.1007/s40123-024-00888-0. Epub 2024 Feb 3.

    PubMed 38308746

  • Lim TH, Lai TYY, Takahashi K, Wong TY, Chen LJ, Ruamviboonsuk P, Tan CS, Lee WK, Cheung CMG, Ngah NF, Patalauskaite R, Margaron P, Koh A; EVEREST II Study Group. Comparison of Ranibizumab With or Without Verteporfin Photodynamic Therapy for Polypoidal Choroidal Vasculopathy: The EVEREST II Randomized Clinical Trial. JAMA Ophthalmol. 2020 Sep 1;138(9):935-942. doi: 10.1001/jamaophthalmol.2020.2443.

    PubMed 32672800

  • Koh A, Lai TYY, Takahashi K, Wong TY, Chen LJ, Ruamviboonsuk P, Tan CS, Feller C, Margaron P, Lim TH, Lee WK; EVEREST II study group. Efficacy and Safety of Ranibizumab With or Without Verteporfin Photodynamic Therapy for Polypoidal Choroidal Vasculopathy: A Randomized Clinical Trial. JAMA Ophthalmol. 2017 Nov 1;135(11):1206-1213. doi: 10.1001/jamaophthalmol.2017.4030.

    PubMed 28983556

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Ranibizumab and Verteporfin PDT in people with Age-related Macular Degeneration and Polypoidal Choroidal Vasculopathy, run by Novartis Pharmaceuticals at 41 sites in 7 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 7 Jun 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 41 sites in Japan, Taiwan, South Korea, Singapore, Malaysia and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Jun 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) at Month 12 - Study Eye (time frame: Baseline, Month 12). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01846273, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jun 2019.

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