Clinical trial NCT01846273: Visual Outcome in Patients With Symptomatic Macular Polypoidal Choroidal Vasculopathy (PCV) Treated With Either Ranibizumab as Monotherapy or Combined With Verteporfin Photodynamic Therapy (vPDT)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Age-related Macular Degeneration
Polypoidal Choroidal Vasculopathy
Keywords: Polypoidal choroidal vasculopathy
Visual acuity
Ranibizumab
Verteporfin PDT
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2013-05-03
Enrollment: 321
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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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Eligibility 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

Primary outcomes:
measure: Mean Change From Baseline in Best Corrected Visual Acuity (BCVA) at Month 12 - Study Eye
timeFrame: Baseline, Month 12
measure: Number of Patients With Complete Polyp Regression From Baseline at Month 12 - Study Eye
timeFrame: Baseline, Month 12
Secondary outcomes:
measure: Mean Change From Baseline in Best-Corrected Visual Acuity (BCVA) at Month 24 - Study Eye
timeFrame: Baseline, Month 24
measure: Percentage of Patients With BCVA (Letters) Change From Baseline at Month 24 - Study Eye
timeFrame: Baseline, Month 24
measure: Maintenance of BCVA (Within 5 Letter Change) at Month 12 and 24 Compared to BCVA at the Time Point of First Ranibizumab Treatment Interruption
timeFrame: Month 3, Month 12, Month 24
measure: Change in BCVA at Month 12 and 24 Compared to the Time Point of First Ranibizumab Treatment Interruption
timeFrame: Month 3, Month 12, Month 24
measure: Percentage of Patients With Complete Polyp Regression at Months 6 and 24 - Study Eye
timeFrame: Month 6, Month 24
measure: Percentage of Patients With Presence of Leakage at Month 6, Month 12 and Month 24 - Study Eye
timeFrame: Month 6, Month 12 and Month 24
measure: Mean Change From Baseline in Investigator-Assessed Central Subfield Retinal Thickness (CSFT) at Month 24 - Study Eye
timeFrame: Baseline, Month 24
measure: Total Number of Ranibizumab Injections Received in the Study Eye Prior to Month 12
timeFrame: Baseline, Month 12
measure: Total Number of Verteporfin/Sham PDT Injections Received in the Study Eye Prior to Month 12
timeFrame: Baseline, Month 12
measure: Total Number of Ranibizumab Injections Received in the Study Eye Prior to Month 24
timeFrame: Baseline, Month 24
measure: Total Number of Verteporfin/Sham PDT Injections Received in the Study Eye Prior to Month 24
timeFrame: Baseline, Month 24
measure: Total Number of Ranibizumab Injections Received in the Study Eye From Month 3 to Month 12
timeFrame: Month 3, Month 12
measure: Total Number of Ranibizumab Injections Received in the Study Eye From Month 3 to Month 24
timeFrame: Month 3, Month 24
measure: Mean Change From Baseline in Composite Scores, National Eye Institute Visual Functioning Questionnaire (NEI-VFQ-25) at Months 3, 12 and 24
timeFrame: Baseline, Month 3, Month 12, Month 24
measure: Number of Ocular Adverse Events of the Study Eye Regardless of Study Drug Relationship up to Month 24, Any Primary System Organ Class
timeFrame: Up to Month 24
measure: Number of Non-Ocular Adverse Events of the Study Eye Regardless of Study Drug Relationship up to Month 24, Any Primary System Organ Class
timeFrame: Up to Month 24
Other outcomes:
Locations:
city: Hong Kong
country: Hong Kong
facility: Novartis Investigative Site
city: Hongkong
country: Hong Kong
facility: Novartis Investigative Site
city: Nagoya-city
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Nagoya
country: Japan
facility: Novartis Investigative Site
state: Aichi
city: Fukuoka city
country: Japan
facility: Novartis Investigative Site
state: Fukuoka
city: Fukushima-city
country: Japan
facility: Novartis Investigative Site
state: Fukushima
city: Maebashi city
country: Japan
facility: Novartis Investigative Site
state: Gunma
city: Amagasaki city
country: Japan
facility: Novartis Investigative Site
state: Hyogo
city: Kobe-city
country: Japan
facility: Novartis Investigative Site
state: Hyogo
city: Kobe-shi
country: Japan
facility: Novartis Investigative Site
state: Hyogo
city: Inashiki-gun
country: Japan
facility: Novartis Investigative Site
state: Ibaraki
city: Kita-gun
country: Japan
facility: Novartis Investigative Site
state: Kagawa
city: Sakyo-ku
country: Japan
facility: Novartis Investigative Site
state: Kyoto
city: Tsu-city
country: Japan
facility: Novartis Investigative Site
state: Mie
city: Okayama-city
country: Japan
facility: Novartis Investigative Site
state: Okayama
city: Hirakata-city
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Osaka-city
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Osaka-city
country: Japan
facility: Novartis Investigative Site
state: Osaka
city: Ohtsu-city
country: Japan
facility: Novartis Investigative Site
state: Shiga
city: Bunkyo ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Chiyoda-ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Mitaka-city
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Shinjuku ku
country: Japan
facility: Novartis Investigative Site
state: Tokyo
city: Chiba
country: Japan
facility: Novartis Investigative Site
city: Seongnam-si
country: Korea, Republic of
facility: Novartis Investigative Site
state: Gyeonggi-do
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Korea
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
state: Seocho-gu
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Seoul
country: Korea, Republic of
facility: Novartis Investigative Site
city: Petaling Jaya
country: Malaysia
facility: Novartis Investigative Site
state: Selangor Darul Ehsan
city: Batu Caves
country: Malaysia
facility: Novartis Investigative Site
state: Selangor
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Singapore
country: Singapore
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
state: Taiwan, ROC
city: Changhua
country: Taiwan
facility: Novartis Investigative Site
city: Kaohsiung
country: Taiwan
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Taipei
country: Taiwan
facility: Novartis Investigative Site
city: Taoyuan
country: Taiwan
facility: Novartis Investigative Site
city: Songkla
country: Thailand
facility: Novartis Investigative Site
state: Hat Yai
city: Bangkok
country: Thailand
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.