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EXTEND II: An Open-Label Phase III Multicentre Study to Evaluate Efficacy and Safety of Ranibizumab in Chinese Patients with Subfoveal Choroidal Neovascularization Secondary to Age-Related Macular Degeneration

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Abstract

Purpose

To evaluate the efficacy and safety of monthly ranibizumab 0.5 mg in Chinese patients with subfoveal choroidal neovascularization (CNV) secondary to neovascular age-related macular degeneration (nAMD).

Methods

A 12-month open-label single-arm multicenter phase III study that included treatment-naïve (study eye) patients with primary/recurrent subfoveal CNV secondary to AMD. Patients (N = 114) aged ≥50 years with best-corrected visual acuity (BCVA) of 73–24 letters were treated with monthly ranibizumab for 12 months. Main outcomes were mean BCVA change from baseline to month 4 (primary endpoint) and over time to month 12, effects of ranibizumab treatment on retinal structure (months 4 and 12), and safety.

Results

Ranibizumab led to significant improvements in mean BCVA ± standard error (SE) at both months 4 and 12 versus baseline (+9.5 ± 1.10 letters, 95 % confidence interval [CI] 7.3–11.7, and +12.7 ± 1.14 letters, 95 % CI 10.4–14.9, respectively, both P < 0.0001). Ranibizumab prevented loss of vision (≥0 letters BCVA gain) in 91.2 % of patients. Mean central retinal thickness ± SE reduced from baseline to month 12 (−119.9 ± 12.97 µm, 95 % CI −145.59 to −94.20, P < 0.0001). No new safety findings were reported in this study.

Conclusion

Ranibizumab administered monthly over 12 months was effective in improving BCVA and was well-tolerated in Chinese nAMD patients.

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Acknowledgments

A list of study team members for each of the seven medical centers appears in Appendix 1. The coauthors from each medical center contributed equally to the work. The authors thank Srividdya Agoram (for medical writing support), Ruchika Srinivasan (for her contribution towards various drafts of this manuscript), and Mayuri Shinde (for her editorial contribution) from Medical Communications, Novartis Healthcare Pvt. Ltd., India. Writing and editorial support was funded by Novartis.

Disclosure

The results from this study were presented in part at APAO 2012 and EURETINA 2012. Jialiang Zhao, Xiaoxin Li, Shibo Tang, Gezhi Xu, Xun Xu, Feng Zhang, and Meixia Zhang have no financial disclosures to make. Stefan Pilz, Jila Shamsazar, and Annette Nieweg are full-time employees of Novartis Pharma AG, Basel, Switzerland.

Funding

Novartis Pharma AG, Switzerland sponsored the study and was involved in the study conception and design, protocol writing, study drug provision, study coordination, data collection, data analysis, and interpretation. At all stages, the authors have had control over the content of this manuscript, for which they have given final approval and take full responsibility. Novartis Pharma AG enforces a ‘no ghost-writing’ policy. As funding sponsors, they have had the opportunity to review the manuscript but do not have authority to change any aspect of the manuscript. All authors (Jialiang Zhao, Xiaoxin Li, Shibo Tang, Gezhi Xu, Xun Xu, Feng Zhang, Meixia Zhang, Jila Shamsazar, Stefan Pilz, and Annette Nieweg) contributed to the conception, design, and conduct of the study, data collection, analysis, and interpretation; critical revision and final approval of the article.

Conflicts of interest

Stefan Pilz, Jila Shamsazar, and Annette Nieweg are full-time employees of Novartis Pharma AG, Basel, Switzerland.

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Correspondence to Jialiang Zhao.

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Appendix 1

Appendix 1

List of principal investigators and other important participants

Prof. Jialiang Zhao, Dr Junjie Ye, Dr Weiwei Wang, Dr Qi Zhou, Dr Ting Zhang, Ms Yajun Chen, Dr Ying YU, Dr Xiao Zhang, Prof. Fangtian Dong, Dr Shuran Wang, Prof. Youxin Chen, Ms Xiaoli Liu (Peking Union Medical College Hospital, Beijing China.)

Dr Xiaoxin Li, Dr Mingwei Zhao, Dr Yan Li, Dr Tong Qian, Ms Bin Liu, Dr Hong Yin, Dr Yi Chen, Ms Hongyan Li, Dr Huijun Qi (People's Hospital, Peking University, Beijing China.)

Prof. Feng Zhang, Dr Ying Xiong, Dr Liqin Gao, Dr Xuan Jiao, Dr Yu Mao (Beijing Tongren Hospital, Beijing China.)

Prof. Gezhi Xu, Prof. Qing Chang, Dr Lei Li, Dr Jia Yu, Dr Ling Wang, Prof. Yongjing Zhang, Dr. Wei Liu, Dr Rui Jiang (Eye Ear Nose and Throat Hospital of Fudan University, Shanghai China.)

Prof. Xun Xu, Dr Weiran Niu, Associate Prof. Bilian Ke, Ms Ping Zhu, Dr Weijun Wang, Ms Qian Li (Shanghai 1st People's Hospital, Jiao Tong University, Shanghai China.)

Prof. Shibo Tang, Mr Hongxing Diao, Ms Meifeng He, Dr Honghua Yu, Ms Jianying Pan, Dr Jie Hu, Dr Qingyun Liu, Dr Xiaobo Zhu, Mr Guohong Feng, Ms Shaofen Lin, Dr Xiaoyan Ding, Dr Andina Hu, Dr Wei Ma, Dr Xuting Hu, Dr Tao Li (Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou China.)

Associate Prof. Meixia Zhang, Prof. Junjun Zhang, Dr Bi Yang, Ms Ronghai Wang, Dr Fang Lu, Dr Ming Zou (West China Hospital of Sichuan University, Chengdu Sichuan China.)

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Zhao, J., Li, X., Tang, S. et al. EXTEND II: An Open-Label Phase III Multicentre Study to Evaluate Efficacy and Safety of Ranibizumab in Chinese Patients with Subfoveal Choroidal Neovascularization Secondary to Age-Related Macular Degeneration. BioDrugs 28, 527–536 (2014). https://doi.org/10.1007/s40259-014-0106-1

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  • DOI: https://doi.org/10.1007/s40259-014-0106-1

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