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

Age-related Macular Degeneration Clinical Trial

— EVEREST II  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01846273
• Other study ID #: CRFB002A2412
• Status: Completed
• Phase: Phase 4
• Start date: August 7, 2013
• Est. completion date: March 2, 2017

Study information

• Verified date: March 2019
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

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

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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Recruitment information / eligibility

• Status: Completed
• Enrollment: 321
• Est. completion date: March 2, 2017
• Est. primary completion date: March 11, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Age-related Macular Degeneration
• Macular Degeneration
• Polypoidal Choroidal Vasculopathy
• Vascular Diseases

Intervention

Drug:
• Ranibizumab
Intravitreal injection of 0.5 mg ranibizumab
• Verteporfin PDT
Infusion of 30 ml verteporfin in 5% dextrose solution followed by 83 sec of laser light (50J/cm2; 600mW/cm2; 689 nm)
• Sham PDT
Infusion of 30 ml 5% dextrose solution followed by 83 sec of laser light (50J/cm2; 600mW/cm2; 689 nm)

Locations

Country	Name	City	State
Hong Kong	Novartis Investigative Site	Hong Kong
Hong Kong	Novartis Investigative Site	Hongkong
Japan	Novartis Investigative Site	Amagasaki city	Hyogo
Japan	Novartis Investigative Site	Bunkyo ku	Tokyo
Japan	Novartis Investigative Site	Chiba
Japan	Novartis Investigative Site	Chiyoda-ku	Tokyo
Japan	Novartis Investigative Site	Fukuoka city	Fukuoka
Japan	Novartis Investigative Site	Fukushima-city	Fukushima
Japan	Novartis Investigative Site	Hirakata-city	Osaka
Japan	Novartis Investigative Site	Inashiki-gun	Ibaraki
Japan	Novartis Investigative Site	Kita-gun	Kagawa
Japan	Novartis Investigative Site	Kobe-city	Hyogo
Japan	Novartis Investigative Site	Kobe-shi	Hyogo
Japan	Novartis Investigative Site	Maebashi city	Gunma
Japan	Novartis Investigative Site	Mitaka-city	Tokyo
Japan	Novartis Investigative Site	Nagoya	Aichi
Japan	Novartis Investigative Site	Nagoya-city	Aichi
Japan	Novartis Investigative Site	Ohtsu-city	Shiga
Japan	Novartis Investigative Site	Okayama-city	Okayama
Japan	Novartis Investigative Site	Osaka-city	Osaka
Japan	Novartis Investigative Site	Osaka-city	Osaka
Japan	Novartis Investigative Site	Sakyo-ku	Kyoto
Japan	Novartis Investigative Site	Shinjuku ku	Tokyo
Japan	Novartis Investigative Site	Tsu-city	Mie
Korea, Republic of	Novartis Investigative Site	Seongnam-si	Gyeonggi-do
Korea, Republic of	Novartis Investigative Site	Seoul	Korea
Korea, Republic of	Novartis Investigative Site	Seoul	Seocho-gu
Korea, Republic of	Novartis Investigative Site	Seoul
Korea, Republic of	Novartis Investigative Site	Seoul
Malaysia	Novartis Investigative Site	Batu Caves	Selangor
Malaysia	Novartis Investigative Site	Petaling Jaya	Selangor Darul Ehsan
Singapore	Novartis Investigative Site	Singapore
Singapore	Novartis Investigative Site	Singapore
Singapore	Novartis Investigative Site	Singapore
Taiwan	Novartis Investigative Site	Changhua
Taiwan	Novartis Investigative Site	Kaohsiung
Taiwan	Novartis Investigative Site	Taipei
Taiwan	Novartis Investigative Site	Taipei
Taiwan	Novartis Investigative Site	Taipei	Taiwan, ROC
Taiwan	Novartis Investigative Site	Taoyuan
Thailand	Novartis Investigative Site	Bangkok
Thailand	Novartis Investigative Site	Songkla	Hat Yai

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

Hong Kong,  Japan,  Korea, Republic of,  Malaysia,  Singapore,  Taiwan,  Thailand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline, Month 12
Primary	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.	Baseline, Month 12
Secondary	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.	Baseline, Month 24
Secondary	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.	Baseline, Month 24
Secondary	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.	Month 3, Month 12, Month 24
Secondary	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.	Month 3, Month 12, Month 24
Secondary	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.	Month 6, Month 24
Secondary	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.	Month 6, Month 12 and Month 24
Secondary	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.	Baseline, Month 24
Secondary	Total Number of Ranibizumab Injections Received in the Study Eye Prior to Month 12		Baseline, Month 12
Secondary	Total Number of Verteporfin/Sham PDT Injections Received in the Study Eye Prior to Month 12		Baseline, Month 12
Secondary	Total Number of Ranibizumab Injections Received in the Study Eye Prior to Month 24		Baseline, Month 24
Secondary	Total Number of Verteporfin/Sham PDT Injections Received in the Study Eye Prior to Month 24		Baseline, Month 24
Secondary	Total Number of Ranibizumab Injections Received in the Study Eye From Month 3 to Month 12		Month 3, Month 12
Secondary	Total Number of Ranibizumab Injections Received in the Study Eye From Month 3 to Month 24		Month 3, Month 24
Secondary	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.	Baseline, Month 3, Month 12, Month 24
Secondary	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	Up to Month 24
Secondary	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	Up to Month 24