Evaluation of RC28-E Injection in Diabetic Macular Edema

Study Overview
=================
Brief Summary
-----------------
This is a non-randomized, open-label, multicenter, 48-week study to investigate the efficacy, safety and pharmacokinetics of RC28-E injection in the treatment of patients with diabetic macular edema.

Official Title
-----------------
Protein by Dual Blockage of VEGF and FGF-2) in Subjects With Diabetic Macular Edema.

Conditions
-----------------
Diabetic Macular Edema

Intervention / Treatment
-----------------
* Biological: intravitreal injection of RC28-E
* Biological: Conbercept


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Sign the consent form, willing and able to comply with clinic visits and study-related procedures; Aged 18 years to 80 years, male or female; Diabetes mellitus(type 1 or 2); The study eye must followed: Retinal thickening secondary to diabetes mellitus (DME) involving the center of the fovea; Decrease in vision determined to be primarily the result of DME and not to other causes. BCVA score in the study eye of 73 to 24 using the ETDRS protocol at an initial testing distance of 4 meters. The central subfield thickness ≥300μm in the center subfield as assessed on OCT by the reading center; If both eyes meet the inclusion criterion, one eye with poor BCVA is selected as the study eye; the researchers judged that the fellow eye should not be treated with other anti-VEGF drugs recently. Exclusion Criteria: The macular edema caused by others instead of diabetes mellitus; Structural damage to the center of the macula in the study eye that is likely to preclude improvement in BCVA following the resolution of macular edema including atrophy of the retinal pigment epithelium, subretinal fibrosis or scar, significant macular ischemia or organized hard exudates; Current iris neovascularization, vitreous hemorrhage, tractional retinal detachment or epiretinal membrane involving the macula in the study eye; Only one functional eye even if that eye is otherwise eligible for the study; Evidence of periocular or intraocular inflammation or infection including infectious blepharitis, keratitis, scleritis, conjunctivitis, endophthalmitis or uveitis at screening assessment in either eye; Previous treatment with anti-angiogenic drugs in either eye or system (ranibizumab, aflibercept, conbercept, etc) within 3 months of the Day 0; History of cardiovascular and cerebrovascular events within 6 months of screening visit: myocardial infarction, unstable angina pectoris, ventricular arrhythmias, New York heart association grade II + heart failure, stroke, etc.; Uncontrolled clinical disease (such as severe psychiatric, neurological, cardiovascular, respiratory disease or other systemic diseases) and tumors; Those who participated in clinical trials for 3 months or 5 half-lives of the investigational product (the longer the time) before the baseline period; Those who considered unsuitable for enrollment by investigator.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1.0mg RC28-E injection Q8<br>In the loading phase (from week 0 to week 8), the study eye will receive intravitreal injection of 1.0 mg RC28-E every 4 weeks, for 3 consecutive times; From then on to the 48th week, the patients were visited every 4 weeks and given medicine every 8 weeks. | Biological: intravitreal injection of RC28-E<br>* a chimric decoy receptor trap fusion protein by dual blockage of VEGF and FGF<br>|
| Experimental: 1.0mg RC28-E injection as needed<br>In the loading phase (from week 0 to week 16), the study eye will receive intravitreal injection of 1.0mg RC28-E every 4 weeks, for 5 consecutive times;In the as needed (pro re nata,PRN)phase (from then on to week 48), the study eye will receive the same dose on an PRN schedule based upon the physician assessment in accordance with pre-specified criteria. | Biological: intravitreal injection of RC28-E<br>* a chimric decoy receptor trap fusion protein by dual blockage of VEGF and FGF<br>|
| Experimental: 2.0mg RC28-E injection Q8<br>In the loading phase (from week 0 to week 8), the study eye will receive intravitreal injection of 2.0mg RC28-E every 4 weeks, for 3 consecutive times; From then on to the 48th week, the patients were visited every 4 weeks and given medicine every 8 weeks. | Biological: intravitreal injection of RC28-E<br>* a chimric decoy receptor trap fusion protein by dual blockage of VEGF and FGF<br>|
| Experimental: 2.0mg RC28-E injection as needed<br>In the loading phase (from week 0 to week 16), the study eye will receive intravitreal injection of 2.0mg RC28-E every 4 weeks, for 5 consecutive times;In the as needed (pro re nata,PRN)phase (from then on to week 48), the study eye will receive the same dose on an PRN schedule based upon the physician assessment in accordance with pre-specified criteria. | Biological: intravitreal injection of RC28-E<br>* a chimric decoy receptor trap fusion protein by dual blockage of VEGF and FGF<br>|
| Experimental: control group<br>In the loading phase (from week 0 to week 8), the study eye will receive intravitreal injection of Conbercept every 4 weeks, for 3 consecutive times;In the as needed (pro re nata,PRN)phase (from then on to week 48), the study eye will receive the same dose on an PRN schedule based upon the physician assessment in accordance with pre-specified criteria. | Biological: Conbercept<br>* KH902(Conbercept）<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change from baseline in BCVA at 24 week; | BCVA=Best-corrected visual acuity;Measurement of visual acuity with Early Treatment Diabetic Retinopathy Study (ETDRS) charts. | Baseline,week 24 | 
| Mean change from baseline in BCVA at 52 week; | Measurement of visual acuity with Early Treatment Diabetic Retinopathy Study (ETDRS) charts. | Baseline, Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change from baseline in BCVA at every visit during treatment period; | Measurement of visual acuity with Early Treatment Diabetic Retinopathy Study (ETDRS) charts. | Baseline up to Week 52 | 
| Mean change from baseline in central subfield thickness at 12, 24, 36, 52 week. | Measurement of central subfield thickness by OCT. | 12, 24, 36, 52 week. | 
| Percentage of subjects with VA improvement (who gained >0 letters, ≥5 letters, ≥10 letters, ≥ 15 letters in their BCVA) from baseline at 52 week; | Measurement of visual acuity with Early Treatment Diabetic Retinopathy Study (ETDRS) charts. | Baseline up to Week 52 | 
| Percentage of subjects with VA worsen (who lost ≥5 letters, ≥10 letters, ≥15 letters in their BCVA) from baseline at 52 week; | Measurement of visual acuity with Early Treatment Diabetic Retinopathy Study (ETDRS) charts. | Baseline, Week 52 | 
| Percentage of subjects with BCVA ≥ 68 letters(a visual acuity Snellen equivalent of 20/40 or better) at 52 week; | Measurement of visual acuity with Early Treatment Diabetic Retinopathy Study (ETDRS) charts. | Baseline, Week 52 | 
| Frequency of administration RC28-E; | Number of intravitreal injections | Baseline, Week 52 | 
| Safety of RC28-E injection | Incidence of AE in ocular and non-ocular | Baseline up to Week 52 |