Clinical Trial: Pharmacogenomic Study on Anti-VEGF Medicine in Treatment of Macular Neovascular Diseases

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational

Official Title: Pharmacogenomic Study on Anti-VEGF Medicine in Treatment of Macular Neovascular Diseases

Brief Summary:

Macular neovascular diseases including age-related macular degeneration (AMD), polypoidal choroidal vasculopathy (PCV), pathological myopia (PM) and etc. can cause severe vision loss. It has become the focus of World Health Organization's blindness- prevention cause. A new anti—VEGF drug conbercept has been approved and showed good efficacy and safety in clinical trials. But the exact therapeutic regimen and the efficacy in the real world still needs to be further studied, the reasons are as follows:

  1. The efficacy and safety data of conbercept are collected from rigorous random controlled trials (RCT) , it can not fully reflect the clinical application of conbercept in the real world . Therefore, the knowledge of the therapeutic regimen, safety and efficacy of conbercept is still limited.
  2. Conbercept has been approved for wet-AMD only, but in clinical practice, some doctors applied other "off-label use" of conbercept. These "off-label use" has become a common phenomenon all over the world for the instruction book of drugs usually lag behind scientific researches. There is no specific law or regulatory document of drug off-label use in China until now.
  3. Anti-VEGF drugs are expensive and often require multiple treatments, and some patients have poor or even no response to the drugs. This resulted enormous waste of medical resources. So, how to accurately find out those patients who have good response, how to develop individualized therapeutic regimen, and the response of patients in the real world need to be urgently investigated in the aspect of pharmacogenomics, and pharmacometabolomics.

Therefore, the investigators plan to carry out real-world researches of conbercept on treating macular neov

Detailed Summary:

Research Background

Macular neovascular disease, is a group of diseases with subfoveal choroidal neovascularization, including age-related macular degeneration (AMD), polypoidal choroidal vasculopathy (PCV), pathological myopia (PM) and etc. Due to the high permeability of immature blood vessel wall, consequent bleeding, and scarring，macular neovascularization often leads to severe vision loss. It has become the focus of World Health Organization's blindness- prevention cause [1]. Currently, the vascular endothelial growth factor (VEGF) has been widely recognized as an important promoter for neovascularization. And a series of large-scale clinical studies revealed that anti- VEGF drug is the only effective way for macular neovascular disease [2], Anti-VEGF drug has been awarded as one of the top ten scientific and technological progress by Nature magazine.

Conbercept is an anti-VEGF drug developed independently by Chinese researchers in recent years, it competitively prevents the binding of VEGF to its receptor and inhibits the downstream pathway activation, and has a higher binding affinity to VEGFA than other widely used anti-VEGF drugs. Many multicenter double blind random controlled study showed that conbercept has good efficacy and safety in treating macular neovascular diseases. In 2013, conbercept has been approved by the State Food and Drug Regulatory Administration of China and now has been widely used and recognized.

Clinical trial results showed that the conbercept has good efficacy and safety in treating macular neovascular diseases [3], but the exact therapeutic regimen and the efficacy in the real world still needs to be further studied, the reasons are as follows:

  1. The eff
    Sponsor: Xun Xu

    Current Primary Outcome: visual improvement after intravitreal injection of conbercept [ Time Frame: Feb. 2017—Dec.2018 ]

    The efficacy was graded as significantly effective (visual improvement ≥15 letters in EDTRS )，effective (visual improvement ≥5 letters and ＜15 letters in EDTRS），invalid（visual improvement ＜5 letters and visual reduction＜5 letters in EDTRS， deterioration （visual reduction≥5 letters in EDTRS. The number and ratio of the above-mentioned grade are to be analyzed.


    Original Primary Outcome: Same as current

    Current Secondary Outcome:

    • The off-label use of conbercept in real world. [ Time Frame: Feb. 2017—Dec.2018 ]
      Calculate the number of cases and percentage of off-label use（%）in real world.
    • The application of off-label use on targeted diseases [ Time Frame: Feb. 2017—Dec.2018 ]
      Record the name of diseases when off-label use is applied.
    • The number and percentage（%）of each target diseases in off-label use. [ Time Frame: Feb. 2017—Dec.2018 ]
      Calculate the the number and percentage（%）of each target diseases in off-label use respectively.
    • The improvement of retinal edema after using conbercept [ Time Frame: Feb. 2017—Dec.2018 ]
      The improvement of retinal edema after using conbercept and compare the difference between central foveal retinal thickness (CRT in μm) and the baseline after 1 month, 3 months, 6 months, and 12 months.
    • The different therapeutic regimens [ Time Frame: Feb. 2017—Dec.2018 ]
      The different therapeutic regimens when conbercept is applied on different diseases in real world, including number of treatments, frequency of injection（times per year), interval time(months).
    • Dropout rate of the study. [ Time Frame: Feb. 2017—Dec.2018 ]
      Calculate the dropout rate（%) of each follow-up time and during the whole follow-up.
    • Predict patients' response to conbercept on treating macular neovascular diseases by analyzing macular leakage area [ Time Frame: Feb. 2017—Dec.2018 ]
      After 3 months treatment, compare the macular leakage area (mm2) to baseline in Fluorescein Fundus Angiography (FFA) on patients who response to conbercept treatment and patients with no response, to further analyze the potential relationship with the response / non-response.
    • Predict patients' response to conbercept on treating macular neovascular diseases by analyzing CNV area [ Time Frame: Feb. 2017—Dec.2018 ]
      After 3 months treatment, compare the CNV area (mm2) to baseline in FFA on patients who response to conbercept treatment and patients with no response, to further analyze the potential relationship with the response / non-response.


    Original Secondary Outcome: Same as current

    Information By: Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine

    Dates:
    Date Received: March 9, 2017
    Date Started: February 28, 2017
    Date Completion: December 31, 2018
    Last Updated: April 20, 2017
    Last Verified: April 2017