Age-Related Macular Degeneration Clinical Trial
Official title:
Pharmacogenomic Study on Anti-VEGF Medicine in Treatment of Macular Neovascular Diseases
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 neovascular diseases has significance and urgency.
The investigators intended to conduct a nationwide, non-intrusive, prospective,
observational, and multicenter registration study to investigate the efficacy of conbercept
in the real-world. And this study will explore the pharmacogenomics and pharmacometabolomics
of conbercept, relationships of phenotype and the effectiveness of the drug, optimize the
therapeutic regimen, then reduce the financial burden of patients and save the limited
medical resources to achieve the purpose of accurate treatment.
For three unanswered questions raised in the background, the researchers carried out the
following purposes:
1. Investigate the safety and efficacy of conbercept in treating neovascular macular
disease in the real world.
2. Find out whether the "off-label use" of conbercept on PCV and PM have good efficacy.
3. Explore the pharmacogenomics and pharmacometabolomics of conbercept through
large-sample registration study.
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 efficacy and safety data of conbercept are collected from rigorous random
controlled trials (RCT), it cannot 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, besides, 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 neovascular diseases has significance and urgency.
Scientific assumptions
The investigators intended to conduct a nationwide, non-intrusive, prospective,
observational, and multicenter registration study to investigate the efficacy of conbercept
in the real-world. And this study will explore the pharmacogenomics and pharmacometabolomics
of conbercept, relationships of phenotype and the effectiveness of the drug, optimize the
therapeutic regimen, then reduce the financial burden of patients and save the limited
medical resources to achieve the purpose of accurate treatment.
For three unanswered questions raised in the background, the researchers carried out the
following purposes:
1. Investigate the safety and efficacy of conbercept in treating neovascular macular
disease in the real world.
2. Find out whether the "off-label use" of conbercept on PCV and PM have good efficacy.
3. Explore the pharmacogenomics and pharmacometabolomics of conbercept through
large-sample registration study.
Research Plan
Program schedule: Total 2 years (1 year on enrollment, 1-year on observation) Start time:
February of 2017 (FPFV, First Time Patient First Visit) End time: December of 2018 (LPLV,
the last time Last Patient Last Visit) Clinical study report (CSR): December of 2018;
Publish: June of 2019
This is an observational study, the investigators aim to observe and collect 5000 patients
from forty nationwide ophthalmic centers that receive ocular injections of conbercept to
treat macular neovascular diseases during December 2016- November 2017. And the follow-up
observation last for one year. The investigators do not interfere patients' treatment plan
during the entire research.
Registration time:
V1: baseline (enrollment period), V2: 1month after treatment, V3: 3 months, V4: 6 months,
V5: 12 months.
Data collection and transfer:
In each visit, patients' demographic information, vital sign, history of systematic
diseases, concomitant medication, eye disease history, eye examinations record, safety
information and blood samples are collected. Clinical data and fundus imaging data collected
by forty clinical centers will be uploaded to Shanghai Jiaotong University Ophthalmic
Reading Center database then be analyzed and evaluated together.
Statistics Program: Statistical general principles:
All data will undergo descriptive statistics and statistical tests,analysis will be based on
baseline and follow-up data.
Sample size:
Plan to enroll 5,000 patients by 40 hospitals. The amount will depend on the registration
capacity and follow-up rate.
Safety: observe the number of cases and the percentage of adverse events and severe adverse
events of conbercept in real world.
Possible bias and solutions:
Patients lost to follow (such as patients from other places, can not undergo regular local
follow up): Solution 1, enroll in local patients or patients who plan to have regular and
long-term follow-up in our hospital; 2, Follow up and register by telephone.
Poor patient compliance: offer some compensation for patients' transport costs.
Patients who cannot afford the drugs due to economic conditions: pharmaceutical has policies
on drug donation for this population.
Quality control and Management:
Object Data Management: Ensure that all enrolled patients have signed informed consent. Each
visit information should be timely, accurately and completely recorded and entered into the
electronic case report form (CRF). The electronic CRF should be consistent with the original
medical records. All adverse events, concomitant medications should be documented, serious
adverse events should be reported to the relevant authorities within 24 hours.
Follow-up management: follow-up should be conducted according to required time point and
rules. Researchers should try to find out the reasons of losing visit and avoid them. If
patients failed to come to clinic, then the researchers should make a phone call follow up.
If patients refused to continue participating in the study for some concerns, they should be
interpreted by reasonable encourages to continue cooperation.
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