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

NCT ID: NCT01846273

Last Updated: 2019-06-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 321 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-08-07
• Study Completion Date: 2017-03-02

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).

.

Conditions

Age-related Macular Degeneration; Polypoidal Choroidal Vasculopathy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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

Group Type: EXPERIMENTAL

Ranibizumab

Intervention Type: DRUG

Intravitreal injection of 0.5 mg ranibizumab

Verteporfin PDT

Intervention Type: DRUG

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

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

Group Type: ACTIVE_COMPARATOR

Ranibizumab

Intervention Type: DRUG

Intravitreal injection of 0.5 mg ranibizumab

Sham PDT

Intervention Type: DRUG

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

Interventions

Ranibizumab

Intravitreal injection of 0.5 mg ranibizumab

Intervention Type: 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)

Intervention Type: DRUG

Sham PDT

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

Intervention Type: DRUG

Other Intervention Names

Lucentis

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Novartis Investigative Site

Hong Kong, , Hong Kong

Novartis Investigative Site

Nagoya, Aichi-ken, Japan

Novartis Investigative Site

Nagoya, Aichi-ken, Japan

Novartis Investigative Site

Fukuoka, Fukuoka, Japan

Novartis Investigative Site

Fukushima, Fukushima, Japan

Novartis Investigative Site

Maebashi, Gunma, Japan

Novartis Investigative Site

Amagasaki, Hyōgo, Japan

Novartis Investigative Site

Kobe, Hyōgo, Japan

Novartis Investigative Site

Kobe, Hyōgo, Japan

Novartis Investigative Site

Inashiki-gun, Ibaraki, Japan

Novartis Investigative Site

Kita-gun, Kagawa-ken, Japan

Novartis Investigative Site

Sakyo-ku, Kyoto, Japan

Novartis Investigative Site

Tsu, Mie-ken, Japan

Novartis Investigative Site

Okayama, Okayama-ken, Japan

Novartis Investigative Site

Hirakata, Osaka, Japan

Novartis Investigative Site

Osaka, Osaka, Japan

Novartis Investigative Site

Osaka, Osaka, Japan

Novartis Investigative Site

Ohtsu-city, Shiga, Japan

Novartis Investigative Site

Bunkyo Ku, Tokyo, Japan

Novartis Investigative Site

Chiyoda-ku, Tokyo, Japan

Novartis Investigative Site

Mitaka, Tokyo, Japan

Novartis Investigative Site

Shinjuku Ku, Tokyo, Japan

Novartis Investigative Site

Chiba, , Japan

Novartis Investigative Site

Batu Caves, Selangor, Malaysia

Novartis Investigative Site

Petaling Jaya, Selangor, Malaysia

Novartis Investigative Site

Singapore, , Singapore

Novartis Investigative Site

Singapore, , Singapore

Novartis Investigative Site

Singapore, , Singapore

Novartis Investigative Site

Seongnam-si, Gyeonggi-do, South Korea

Novartis Investigative Site

Seoul, Korea, South Korea

Novartis Investigative Site

Seoul, Seocho-gu, South Korea

Novartis Investigative Site

Seoul, , South Korea

Novartis Investigative Site

Seoul, , South Korea

Novartis Investigative Site

Taipei, Taiwan, ROC, Taiwan

Novartis Investigative Site

Changhua, , Taiwan

Novartis Investigative Site

Kaohsiung City, , Taiwan

Novartis Investigative Site

Taipei, , Taiwan

Novartis Investigative Site

Taipei, , Taiwan

Novartis Investigative Site

Taoyuan District, , Taiwan

Novartis Investigative Site

Songkhla, Hat Yai, Thailand

Novartis Investigative Site

Bangkok, , Thailand

Countries

Hong Kong; Japan; Malaysia; Singapore; South Korea; Taiwan; Thailand

References

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 Jun 12. doi: 10.1007/s10384-025-01228-w. Online ahead of print.

Reference Type: DERIVED

PMID: 40504425 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 38308746 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32672800 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 28983556 (View on PubMed)

Other Identifiers

CRFB002A2412

Identifier Type: -

Identifier Source: org_study_id