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

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ClinicalTrials.gov Identifier: NCT01846273
Recruitment Status : Completed
First Posted : May 3, 2013
Results First Posted : June 7, 2019
Last Update Posted : June 7, 2019
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief 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). The results of this study provided long-term safety and efficacy data used to generate further guidance on the management of patients with PCV.

Condition or disease Intervention/treatment Phase
Age-related Macular Degeneration Polypoidal Choroidal Vasculopathy Drug: Ranibizumab Drug: Verteporfin PDT Drug: Sham PDT Phase 4

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).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 321 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : August 7, 2013
Actual Primary Completion Date : March 11, 2016
Actual Study Completion Date : March 2, 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Ranibizumab + vPDT
Treatment 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
Drug: Ranibizumab
Intravitreal injection of 0.5 mg ranibizumab
Other Name: Lucentis

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

Active Comparator: Ranibizumab monotherapy
Treatment 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
Drug: Ranibizumab
Intravitreal injection of 0.5 mg ranibizumab
Other Name: Lucentis

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




Primary Outcome Measures :
  1. Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) at Month 12 - Study Eye [ Time Frame: Baseline, Month 12 ]
    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.

  2. Number of Patients With Complete Polyp Regression From Baseline at Month 12 - Study Eye [ Time Frame: Baseline, Month 12 ]
    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.


Secondary Outcome Measures :
  1. Mean Change From Baseline in Best-Corrected Visual Acuity (BCVA) at Month 24 - Study Eye [ Time Frame: Baseline, Month 24 ]
    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.

  2. Percentage of Patients With BCVA (Letters) Change From Baseline at Month 24 - Study Eye [ Time Frame: Baseline, Month 24 ]
    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.

  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 [ Time Frame: Month 3, Month 12, Month 24 ]
    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.

  4. Change in BCVA at Month 12 and 24 Compared to the Time Point of First Ranibizumab Treatment Interruption [ Time Frame: Month 3, Month 12, Month 24 ]
    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.

  5. Percentage of Patients With Complete Polyp Regression at Months 6 and 24 - Study Eye [ Time Frame: Month 6, Month 24 ]
    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.

  6. Percentage of Patients With Presence of Leakage at Month 6, Month 12 and Month 24 - Study Eye [ Time Frame: Month 6, Month 12 and Month 24 ]
    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.

  7. Mean Change From Baseline in Investigator-Assessed Central Subfield Retinal Thickness (CSFT) at Month 24 - Study Eye [ Time Frame: Baseline, Month 24 ]
    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.

  8. Total Number of Ranibizumab Injections Received in the Study Eye Prior to Month 12 [ Time Frame: Baseline, Month 12 ]
  9. Total Number of Verteporfin/Sham PDT Injections Received in the Study Eye Prior to Month 12 [ Time Frame: Baseline, Month 12 ]
  10. Total Number of Ranibizumab Injections Received in the Study Eye Prior to Month 24 [ Time Frame: Baseline, Month 24 ]
  11. Total Number of Verteporfin/Sham PDT Injections Received in the Study Eye Prior to Month 24 [ Time Frame: Baseline, Month 24 ]
  12. Total Number of Ranibizumab Injections Received in the Study Eye From Month 3 to Month 12 [ Time Frame: Month 3, Month 12 ]
  13. Total Number of Ranibizumab Injections Received in the Study Eye From Month 3 to Month 24 [ Time Frame: 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 [ Time Frame: Baseline, Month 3, Month 12, Month 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.

  15. Number of Ocular Adverse Events of the Study Eye Regardless of Study Drug Relationship up to Month 24, Any Primary System Organ Class [ Time Frame: Up to Month 24 ]
    Reported categorically: Mild, Moderate, Severe

  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 [ Time Frame: Up to Month 24 ]
    Reported categorically: Mild, Moderate, Severe



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01846273


Locations
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Hong Kong
Novartis Investigative Site
Hong Kong, Hong Kong
Novartis Investigative Site
Hongkong, Hong Kong
Japan
Novartis Investigative Site
Nagoya-city, Aichi, Japan, 462-0825
Novartis Investigative Site
Nagoya, Aichi, Japan, 466 8560
Novartis Investigative Site
Fukuoka city, Fukuoka, Japan, 812-8582
Novartis Investigative Site
Fukushima-city, Fukushima, Japan, 960-1295
Novartis Investigative Site
Maebashi city, Gunma, Japan, 371 8511
Novartis Investigative Site
Amagasaki city, Hyogo, Japan, 660 8550
Novartis Investigative Site
Kobe-city, Hyogo, Japan, 650-0047
Novartis Investigative Site
Kobe-shi, Hyogo, Japan, 650-0017
Novartis Investigative Site
Inashiki-gun, Ibaraki, Japan, 300-0395
Novartis Investigative Site
Kita-gun, Kagawa, Japan, 761-0793
Novartis Investigative Site
Sakyo-ku, Kyoto, Japan, 606 8507
Novartis Investigative Site
Tsu-city, Mie, Japan, 514-8507
Novartis Investigative Site
Okayama-city, Okayama, Japan, 700-8558
Novartis Investigative Site
Hirakata-city, Osaka, Japan, 573-1191
Novartis Investigative Site
Osaka-city, Osaka, Japan, 545-8586
Novartis Investigative Site
Osaka-city, Osaka, Japan, 550-0024
Novartis Investigative Site
Ohtsu-city, Shiga, Japan, 520-2192
Novartis Investigative Site
Bunkyo ku, Tokyo, Japan, 113 8655
Novartis Investigative Site
Chiyoda-ku, Tokyo, Japan, 101-8309
Novartis Investigative Site
Mitaka-city, Tokyo, Japan, 181-8611
Novartis Investigative Site
Shinjuku ku, Tokyo, Japan, 162 8666
Novartis Investigative Site
Chiba, Japan, 260-8677
Korea, Republic of
Novartis Investigative Site
Seongnam-si, Gyeonggi-do, Korea, Republic of, 13620
Novartis Investigative Site
Seoul, Korea, Korea, Republic of, 02447
Novartis Investigative Site
Seoul, Seocho-gu, Korea, Republic of, 06591
Novartis Investigative Site
Seoul, Korea, Republic of, 07301
Novartis Investigative Site
Seoul, Korea, Republic of, 150-950
Malaysia
Novartis Investigative Site
Petaling Jaya, Selangor Darul Ehsan, Malaysia, 46150
Novartis Investigative Site
Batu Caves, Selangor, Malaysia, 68100
Singapore
Novartis Investigative Site
Singapore, Singapore, 119074
Novartis Investigative Site
Singapore, Singapore, 168751
Novartis Investigative Site
Singapore, Singapore, 308433
Taiwan
Novartis Investigative Site
Taipei, Taiwan, ROC, Taiwan, 11217
Novartis Investigative Site
Changhua, Taiwan, 50006
Novartis Investigative Site
Kaohsiung, Taiwan, 81346
Novartis Investigative Site
Taipei, Taiwan, 10002
Novartis Investigative Site
Taipei, Taiwan, 10449
Novartis Investigative Site
Taoyuan, Taiwan, 33305
Thailand
Novartis Investigative Site
Songkla, Hat Yai, Thailand, 90110
Novartis Investigative Site
Bangkok, Thailand, 10400
Sponsors and Collaborators
Novartis Pharmaceuticals
Investigators
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Study Director: Novartis Pharmaceuticals Novartis Pharmaceuticals
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01846273    
Other Study ID Numbers: CRFB002A2412
First Posted: May 3, 2013    Key Record Dates
Results First Posted: June 7, 2019
Last Update Posted: June 7, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Polypoidal choroidal vasculopathy
Visual acuity
Ranibizumab
Verteporfin PDT
Additional relevant MeSH terms:
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Macular Degeneration
Vascular Diseases
Retinal Degeneration
Retinal Diseases
Eye Diseases
Cardiovascular Diseases
Ranibizumab
Verteporfin
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents
Photosensitizing Agents
Dermatologic Agents