Evaluation of RC28-E Injection in Diabetic Macular Edema

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

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.

Study Overview

• Status: Completed
• Conditions: Diabetic Macular Edema
• Intervention / Treatment: Biological: intravitreal injection of RC28-E; Biological: Conbercept

• Study Type: Interventional
• Enrollment (Actual): 156
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China
      • The Second Hospital of Anhui Medical University
  • Beijing
    • Beijing, Beijing, China
      • Peking University Third Hospital
    • Beijing, Beijing, China
      • Chinese PLA General Hospital
    • Beijing, Beijing, China
      • Beijing Aier Intech Eye Hospital
    • Beijing, Beijing, China
      • Beijing Hospital
    • Beijing, Beijing, China, 100010
      • Peking Union Medical College Hospital
  • Chongqing
    • Chongqing, Chongqing, China
      • The First Affiliated Hospital of Chongqing Medical University
    • Chongqing, Chongqing, China
      • The Second Affiliated Hospital of Chongqing Medical University
  • Guangdong
    • Guangzhou, Guangdong, China
      • the Second Affiliated Hospital of Guangzhou Medical University
    • Guangzhou, Guangdong, China
      • Zhongshan Ophthalmic Center of Sun Yat-sen University
    • Huizhou, Guangdong, China
      • Huizhou Central People's Hospital
  • Guizhou
    • Guiyang, Guizhou, China
      • The Affiliated Hospital Of GuiZhou Medical University
    • Zunyi, Guizhou, China
      • The First People's Hospital of Zunyi
  • Hebei
    • Langfang, Hebei, China
      • CNPC Central Hospital
    • Xingtai, Hebei, China
      • Hebei Eye Hospital
  • Heilongjiang
    • Harbin, Heilongjiang, China
      • The First Affiliated Hospital Of Harbin Medical University
  • Henan
    • Zhengzhou, Henan, China
      • The First Affiliated Hospital of Zhengzhou University
    • Zhengzhou, Henan, China
      • Henan Provincial Eye Hospital
    • Zhengzhou, Henan, China
      • Zhengzhou Second Hospital
  • Hubei
    • Wuhan, Hubei, China
      • Zhongnan Hospital of Wuhan University
    • Wuhan, Hubei, China
      • Renmin Hospital of Wuhan University
  • Hunan
    • Changsha, Hunan, China
      • The Second Xiangya Hospital of Central South University
    • Changsha, Hunan, China
      • Xiangya Hospital Central South University
  • Inner Mongolia
    • Hohhot, Inner Mongolia, China
      • The affiliated hospital of Inner Mongolia Medical University
  • Jiangsu
    • Nanjing, Jiangsu, China
      • The Affiliated Eye Hospital of Nanjing Medical University
  • Jiangxi
    • Nanchang, Jiangxi, China
      • JiangXi Provincial People's Hospital
    • Nanchang, Jiangxi, China
      • The Affiliated Eye Hospital of Nanchang University
  • Jilin
    • Changchun, Jilin, China
      • The Second Hospital of Jilin University
  • Liaoning
    • Shenyang, Liaoning, China
      • Shenyang He Eye Specialist Hospital
    • Shenyang, Liaoning, China
      • The Fourth People's Hospital of Shenyang
  • Ningxia
    • Yinchuan, Ningxia, China
      • People's Hospital of Ningxia Hui Autonomous Region
  • Shandong
    • Weifang, Shandong, China
      • Weifang Eye Hospital
    • Yantai, Shandong, China
      • Yantai Yuhuangding Hospital
  • Shanxi
    • Taiyuan, Shanxi, China
      • The First Hospital of Shanxi Medical University
    • Taiyuan, Shanxi, China
      • Shanxi Eye Hospital
  • Sichuan
    • Chengdu, Sichuan, China
      • West China Hospital of Sichuan University
  • Zhejiang
    • Rui'an, Zhejiang, China
      • Ruian People's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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:

  1. 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.
  2. BCVA score in the study eye of 73 to 24 using the ETDRS protocol at an initial testing distance of 4 meters.
  3. 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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1.0mg RC28-E injection Q8; 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; a chimric decoy receptor trap fusion protein by dual blockage of VEGF and FGF
Experimental: 1.0mg RC28-E injection as needed; 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; a chimric decoy receptor trap fusion protein by dual blockage of VEGF and FGF
Experimental: 2.0mg RC28-E injection Q8; 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; a chimric decoy receptor trap fusion protein by dual blockage of VEGF and FGF
Experimental: 2.0mg RC28-E injection as needed; 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; a chimric decoy receptor trap fusion protein by dual blockage of VEGF and FGF
Experimental: control group; 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; KH902(Conbercept）

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

Collaborators and Investigators

• Sponsor: RemeGen Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): March 17, 2021
• Primary Completion (Actual): July 31, 2023
• Study Completion (Actual): July 31, 2023

Study Registration Dates

• First Submitted: March 1, 2021
• First Submitted That Met QC Criteria: March 1, 2021
• First Posted (Actual): March 4, 2021

Study Record Updates

• Last Update Posted (Actual): December 18, 2023
• Last Update Submitted That Met QC Criteria: December 15, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Macular Edema; Edema; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; RC28-E protein
• Other Study ID Numbers: 28C002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No