Efficacy and Safety Trial of Conbercept Intravitreal Injection for Neovascular AMD (PANDA-2)

A Multicenter, Double-Masked, Randomized, Dose-Ranging Trial to Evaluate the Efficacy and Safety of Conbercept Intravitreal Injection in Subjects With Neovascular Age-Related Macular Degeneration (AMD) (PANDA-2)

The purpose of this clinical study is to evaluate the efficacy and safety of two different levels of conbercept intravitreal (IVT) injection as compared to the approved vascular endothelial growth factor (VEGF) antagonist active control, aflibercept intravitreal injection (2.0 mg/eye, Eylea®), in subjects with neovascular AMD.

Study Overview

• Status: Terminated
• Conditions: Neovascular Age-related Macular Degeneration
• Intervention / Treatment: Biological: 0.5 mg Conbercept Intravitreal Injection; Biological: 1.0 mg Conbercept Intravitreal Injection; Biological: 2.0 mg Aflibercept Intravitreal Injection

Detailed Description

A multicenter, multinational, double-masked, parallel-group, dose-ranging, active-controlled, randomized trial, which will randomize approximately 1140 subjects in a ratio of 1:1:1 to receive IVT injections of 0.5 mg conbercept, 1.0 mg conbercept, or 2.0 mg aflibercept. The trial includes a screening period of less than or equal to 14 days, followed by a treatment period of 92 weeks (last assessment at 96 weeks) with primary efficacy analysis at 36 weeks.

• Study Type: Interventional
• Enrollment (Actual): 1157
• Phase: Phase 3

Contacts and Locations

Study Locations

• Bulgaria
  • Plovdiv, Bulgaria, 4003
    • Kanghong Investigative Site
  • Sofia, Bulgaria, 1408
    • Kanghong Investigative Site
  • Sofia, Bulgaria, 1517
    • Kanghong Investigative Site
  • Varna, Bulgaria, 9010
    • Kanghong Investigative Site
• China
  • Beijing
    • Beijing, Beijing, China, 100044
      • Kanghong Investigative Site
  • Shanghai
    • Shanghai, Shanghai, China, 200031
      • Kanghong Investigative Site
    • Shanghai, Shanghai, China, 200080
      • Kanghong Investigative Site
  • Tianjin
    • Tianjin, Tianjin, China, 300384
      • Kanghong Investigative Site
• Czechia
  • Brno, Czechia, 625 00
    • Kanghong Investigative Site
  • Praha 10, Czechia, 100 34
    • Kanghong Investigative Site
  • Praha 10, Czechia, 10034
    • Kanghong Investigative Site
  • Praha 2, Czechia, 128 00
    • Kanghong Investigative Site
  • Praha 5, Czechia, 15000
    • Kanghong Investigative Site
• Denmark
  • Aalborg, Denmark, 9100
    • Kanghong Investigative Site
  • Aarhus N, Denmark, 8200
    • Kanghong Investigative Site
  • Glostrup, Denmark, 2600
    • Kanghong Investigative Site
  • Roskilde, Denmark, 4000
    • Kanghong Investigative Site
  • Sonderborg, Denmark, 6400
    • Kanghong Investigative Site
• France
  • Bordeaux, France, 33000
    • Kanghong Investigative Site
  • Créteil, France, 94010
    • Kanghong Investigative Site
  • Dijon, France, 21079
    • Kanghong Investigative Site
  • Marseille, France, 13008
    • Kanghong Investigative Site
  • Paris, France, 75010
    • Kanghong Investigative Site
  • Paris, France, 75012
    • Kanghong Investigative Site
  • Paris, France, 75015
    • Kanghong Investigative Site
  • Paris, France, 75019
    • Kanghong Investigative Site
  • Poitiers Cedex, France, 86021
    • Kanghong Investigative Site
  • Saint-Cyr sur Loire, France, 37540
    • Kanghong Investigative Site
  • Strasbourg, France, 67000
    • Kanghong Investigative Site
• Hungary
  • Baranya
    • Pécs, Baranya, Hungary, 7621
      • Kanghong Investigative Site
  • Csongrád
    • Szeged, Csongrád, Hungary, 6720
      • Kanghong Investigative Site
  • Hajdu Bihar
    • Debrecen, Hajdu Bihar, Hungary, 4032
      • Kanghong Investigative Site
  • Pest
    • Budapest, Pest, Hungary, 1062
      • Kanghong Investigative Site
    • Budapest, Pest, Hungary, 1076
      • Kanghong Investigative Site
    • Budapest, Pest, Hungary, 1085
      • Kanghong Investigative Site
    • Budapest, Pest, Hungary, 1106
      • Kanghong Investigative Site
    • Budapest, Pest, Hungary, 1133
      • Kanghong Investigative Site
    • Budapest, Pest, Hungary, 1204
      • Kanghong Investigative Site
  • Zala
    • Zalaegerszeg, Zala, Hungary, 8900
      • Kanghong Investigative Site
• Israel
  • Beer Sheva, Israel, 8457108
    • Kanghong Investigative Site
  • Haifa, Israel, 31048
    • Kanghong Investigative Site
  • Haifa, Israel, 31096
    • Kanghong Investigative Site
  • Haifa, Israel, 3436212
    • Kanghong Investigative Site
  • Jerusalem, Israel, 9103102
    • Kanghong Investigative Site
  • Jerusalem, Israel, 9112001
    • Kanghong Investigative Site
  • Kfar Saba, Israel, 4428164
    • Kanghong Investigative Site
  • Petach Tikva, Israel, 4941492
    • Kanghong Investigative Site
  • Poriyya, Israel, 1520800
    • Kanghong Investigative Site
  • Rehovot, Israel, 76100
    • Kanghong Investigative Site
  • Tel Aviv, Israel, 64239
    • Kanghong Investigative Site
  • Zrifin, Israel, 7030000
    • Kanghong Investigative Site
  • Ha'Darom
    • Ashkelon, Ha'Darom, Israel, 7830604
      • Kanghong Investigative Site
• Italy
  • Chieti, Italy, 66100
    • Kanghong Investigative Site
  • Firenze, Italy, 50134
    • Kanghong Investigative Site
  • Genova, Italy, 16132
    • Kanghong Investigative Site
  • Milano, Italy, 20122
    • Kanghong Investigative Site
  • Milano, Italy, 20132
    • Kanghong Investigative Site
  • Milano, Italy, 20157
    • Kanghong Investigative Site
  • Negrar, Italy, 37024
    • Kanghong Investigative Site
  • Roma, Italy, 00133
    • Kanghong Investigative Site
  • Roma, Italy, 00198
    • Kanghong Investigative Site
  • Udine, Italy, 33100
    • Kanghong Investigative Site
• Latvia
  • Riga, Latvia, LV-1002
    • Kanghong Investigative Site
  • Riga, Latvia, LV-1006
    • Kanghong Investigative Site
  • Riga, Latvia, LV-1009
    • Kanghong Investigative Site
• Slovakia
  • Bratislava, Slovakia, 82606
    • Kanghong Investigative Site
  • Trenčín, Slovakia, 91171
    • Kanghong Investigative Site
  • Zilina, Slovakia, 010 08
    • Kanghong Investigative Site
  • Žilina, Slovakia, 01207
    • Kanghong Investigative Site
• United Kingdom
  • Belfast, United Kingdom, BT12 6BA
    • Kanghong Investigative Site
  • Bradford, United Kingdom, BD9 6RJ
    • Kanghong Investigative Site
  • Bristol, United Kingdom, BS1 2LX
    • Kanghong Investigative Site
  • Canterbury, United Kingdom, CT1 3NG
    • Kanghong Investigative Site
  • Derby, United Kingdom, DE22 3NE
    • Kanghong Investigative Site
  • Gorleston-On-Sea, United Kingdom, NR31 6LA
    • Kanghong Investigative Site
  • Leeds, United Kingdom, LS9 7TF
    • Kanghong Investigative Site
  • London, United Kingdom, EC1V 2PD
    • Kanghong Investigative Site
  • London, United Kingdom, NW1 5QH
    • Kanghong Investigative Site
  • London, United Kingdom, NW10 7NS
    • Kanghong Investigative Site
  • Sheffield, United Kingdom, S10 2JF
    • Kanghong Investigative Site
  • Sunderland, United Kingdom, SR2 9HP
    • Kanghong Investigative Site
  • Essex
    • Westcliff on Sea, Essex, United Kingdom, SS0 0RY
      • Kanghong Investigative Site
  • Hampshire
    • Southampton, Hampshire, United Kingdom, SO16 6YD
      • Kanghong Investigative Site
  • Norfolk
    • Gorleston-on-Sea, Norfolk, United Kingdom, NR31 6LA
      • Kanghong Investigative Site
  • Surrey
    • Frimley, Surrey, United Kingdom, GU16 7UJ
      • Kanghong Investigative Site
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85020
      • Kanghong Investigative Site
    • Phoenix, Arizona, United States, 85021
      • Kanghong Investigative Site
  • Arkansas
    • Springdale, Arkansas, United States, 72762
      • Kanghong Investigative Site
  • California
    • Arcadia, California, United States, 91006
      • Kanghong Investigative Site
    • Arcadia, California, United States, 91007
      • Kanghong Investigative Site
    • Bakersfield, California, United States, 93309
      • Kanghong Investigative Site
    • Encino, California, United States, 91436
      • Kanghong Investigative Site
    • Glendale, California, United States, 91203
      • Kanghong Investigative Site
    • Glendora, California, United States, 91741
      • Kanghong Investigative Site
    • Huntington Beach, California, United States, 92647
      • Kanghong Investigative Site
    • Pasadena, California, United States, 91107
      • Kanghong Investigative Site
    • Poway, California, United States, 92064
      • Kanghong Investigative Site
    • Redlands, California, United States, 92373
      • Kanghong Investigative Site
    • Redlands, California, United States, 92374
      • Kanghong Investigative Site
    • Riverside, California, United States, 92505
      • Kanghong Investigative Site
    • San Francisco, California, United States, 94109
      • Kanghong Investigative Site
    • Santa Barbara, California, United States, 93013
      • Kanghong Investigative Site
  • Colorado
    • Colorado Springs, Colorado, United States, 80909
      • Kanghong Investigative Site
  • Connecticut
    • Waterford, Connecticut, United States, 06385
      • Kanghong Investigative Site
  • Florida
    • Boynton Beach, Florida, United States, 33426
      • Kanghong Investigative Site
    • Bradenton, Florida, United States, 34209
      • Kanghong Investigative Site
    • Miami, Florida, United States, 33126
      • Kanghong Investigative Site
    • Miami, Florida, United States, 33143
      • Kanghong Investigative Site
    • Stuart, Florida, United States, 34994
      • Kanghong Investigative Site
    • Winter Haven, Florida, United States, 33880
      • Kanghong Investigative Site
  • Georgia
    • Atlanta, Georgia, United States, 30328
      • Kanghong Investigative Site
    • Augusta, Georgia, United States, 30909
      • Kanghong Investigative Site
    • Marietta, Georgia, United States, 30060
      • Kanghong Investigative Site
  • Illinois
    • Elmhurst, Illinois, United States, 60126
      • Kanghong Investigative Site
  • Indiana
    • Indianapolis, Indiana, United States, 46290
      • Kanghong Investigative Site
    • New Albany, Indiana, United States, 47150
      • Kanghong Investigative Site
  • Kansas
    • Leawood, Kansas, United States, 66211
      • Kanghong Investigative Site
  • Massachusetts
    • Springfield, Massachusetts, United States, 01107
      • Kanghong Investigative Site
  • Michigan
    • Grand Rapids, Michigan, United States, 49546
      • Kanghong Investigative Site
    • Traverse City, Michigan, United States, 49686
      • Kanghong Investigative Site
  • Missouri
    • Saint Louis, Missouri, United States, 63128
      • Kanghong Investigative Site
  • Nevada
    • Reno, Nevada, United States, 89502
      • Kanghong Investigative Site
  • New Jersey
    • Northfield, New Jersey, United States, 08205
      • Kanghong Investigative Site
    • Teaneck, New Jersey, United States, 07666
      • Kanghong Investigative Site
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • Kanghong Investigative Site
  • New York
    • Brooklyn, New York, United States, 11201
      • Kanghong Investigative Site
    • Great Neck, New York, United States, 11021
      • Kanghong Investigative Site
    • Liverpool, New York, United States, 13088
      • Kanghong Investigative Site
    • Shirley, New York, United States, 11967
      • Kanghong Investigative Site
  • North Carolina
    • Asheville, North Carolina, United States, 28803
      • Kanghong Investigative Site
    • Winston-Salem, North Carolina, United States, 27157
      • Kanghong Investigative Site
  • Ohio
    • Youngstown, Ohio, United States, 44505
      • Kanghong Investigative Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Kanghong Investigative Site
  • Oregon
    • Medford, Oregon, United States, 97504
      • Kanghong Investigative Site
    • Portland, Oregon, United States, 97225
      • Kanghong Investigative Site
    • Springfield, Oregon, United States, 97477
      • Kanghong Investigative Site
  • Pennsylvania
    • Camp Hill, Pennsylvania, United States, 17011
      • Kanghong Investigative Site
    • Kingston, Pennsylvania, United States, 18704
      • Kanghong Investigative Site
  • South Carolina
    • Ladson, South Carolina, United States, 29456
      • Kanghong Investigative Site
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Kanghong Investigative Site
  • Texas
    • Arlington, Texas, United States, 76012
      • Kanghong Investigative Site
    • Austin, Texas, United States, 78705
      • Kanghong Investigative Site
    • Austin, Texas, United States, 78731
      • Kanghong Investigative Site
    • Bellaire, Texas, United States, 77401
      • Kanghong Investigative Site
    • Dallas, Texas, United States, 75231
      • Kanghong Investigative Site
    • Fort Worth, Texas, United States, 76102
      • Kanghong Investigative Site
    • Kingwood, Texas, United States, 77339
      • Kanghong Investigative Site
    • McAllen, Texas, United States, 78503
      • Kanghong Investigative Site
    • Midland, Texas, United States, 79706
      • Kanghong Investigative Site
    • Temple, Texas, United States, 76502
      • Kanghong Investigative Site
  • Utah
    • Salt Lake City, Utah, United States, 84107
      • Kanghong Investigative Site
  • Vermont
    • Burlington, Vermont, United States, 05401
      • Kanghong Investigative Site
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • Kanghong Investigative Site
  • Washington
    • Bellevue, Washington, United States, 98004
      • Kanghong Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Men and women ≥ 50 years of age at the Screening visit;

2. Females must be at least 1 year postmenopausal, or surgically sterilized, or, if of childbearing potential, must have a negative pregnancy test at the Screening visit;

   o Women of childbearing potential must agree to use a highly effective method of contraception throughout the study.

3. Have received no previous treatment for neovascular AMD, including laser photocoagulation and/or photodynamic therapy (PDT) and/or IVT VEGF antagonists (treatment naïve) and;
4. Have active subfoveal choroidal neovascularization (CNV) lesions secondary to AMD (including polypoidal choroidal vasculopathy (PCV)) evidenced by subfoveal fluorescein angiography (FA) leakage, or definite subfoveal fluid by SD-OCT in the study eye at Screening;
5. Have a ETDRS BCVA letter score of 78 to 25 in the study eye at Screening;
6. Are willing and able to sign the study written informed consent form (ICF).

Exclusion Criteria:

1. Have had any prior ocular or systemic treatment (investigational or approved) or surgery for the treatment of neovascular AMD in the study eye except dietary supplements or vitamins;
2. Have participated as a subject in any interventional clinical trial within one month (30 days) prior to Baseline visit;
3. Have a subretinal hemorrhage that is either 50% or more of the total lesion area, or blood is under the fovea and is one or more disc areas in size (greater than 2.5 mm2) in the study eye at Screening;
4. Have any retinal pigment epithelial tears or rips in the study eye at Screening or upon examination at Baseline;
5. Have any vitreous hemorrhage in the study eye upon examination at Baseline or history of vitreous hemorrhage within eight weeks prior to Screening;
6. Have any other cause of CNV;
7. Have had prior pars plana vitrectomy in the study eye;
8. Have presence of a full thickness macular hole at Screening or upon examination at Baseline or a history of a full thickness macular hole in the study eye;
9. Have prior trabeculectomy or other filtration surgery in the study eye;
10. Have uncontrolled glaucoma;
11. Have active intraocular inflammation in either eye at Screening or upon examination at Baseline or a history of uveitis in either eye;
12. Have aphakia or pseudophakia with absence of posterior capsule (unless it occurred as a result of yttrium aluminum garnet (YAG) posterior capsulotomy) in the study eye.
13. Significant media opacities, including cataract, in the study eye that, in the opinion of the Investigator, could require either medical or surgical intervention during the study period;
14. Have any use of long acting intraocular steroids, including implants, within six months prior to Day 1, Baseline;
15. Have any known allergy to povidone iodine or known serious allergy to the fluorescein sodium for injection in angiography;
16. Any history of known contraindications indicated in the Food and Drug Administration (FDA)-approved label for the active control;
17. If female, be pregnant (positive urine pregnancy test at Screening) or breastfeeding.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 0.5 mg Conbercept; Subjects received 0.5 mg conbercept intravitreal injection at Day 1, Week 4 and Week 8 (three injection loading dose), and treated every eight weeks thereafter (0.5 mg, q8w) through Week 36. At the Week 40 visit, the criteria-based pro re nata (PRN) approach will begin through the end of the treatment period at Week 92, for a total of 92 weeks treatment in the study eye.	Biological: 0.5 mg Conbercept Intravitreal Injection; Subjects received 0.5 mg conbercept intravitreal injection at Day 1, Week 4 and Week 8 (three injection loading dose), and treated every eight weeks thereafter (0.5 mg, q8w) through Week 36. At the Week 40 visit, the criteria-based pro re nata (PRN) approach will begin through the end of the treatment period at Week 92, for a total of 92 weeks treatment in the study eye.
Experimental: 1.0 mg Conbercept; Subjects received 1.0 mg conbercept intravitreal injection at Day 1, Week 4 and Week 8 (three injection loading dose), and treated every twelve weeks thereafter (1.0 mg, q12w) through Week 36. At the Week 40 visit, the criteria-based PRN approach will begin through the end of the treatment period at Week 92, for a total of 92 weeks treatment in the study eye.	Biological: 1.0 mg Conbercept Intravitreal Injection; Subjects received 1.0 mg conbercept intravitreal injection at Day 1, Week 4 and Week 8 (three injection loading dose), and treated every twelve weeks thereafter (1.0 mg, q12w) through Week 36. At the Week 40 visit, the criteria-based PRN approach will begin through the end of the treatment period at Week 92, for a total of 92 weeks treatment in the study eye.
Active Comparator: Aflibercept; Subjects received 2.0 mg aflibercept intravitreal injection at Day 1, Week 4 and Week 8 (three injection loading dose), and treated every eight weeks thereafter (2.0 mg, q8w) through Week 36. At the Week 40 visit, the criteria-based PRN approach will begin through the end of the treatment period at Week 92, for a total of 92 weeks treatment in the study eye.	Biological: 2.0 mg Aflibercept Intravitreal Injection; Subjects received 2.0 mg aflibercept intravitreal injection at Day 1, Week 4 and Week 8 (three injection loading dose), and treated every eight weeks thereafter (2.0 mg, q8w) through Week 36. At the Week 40 visit, the criteria-based PRN approach will begin through the end of the treatment period at Week 92, for a total of 92 weeks treatment in the study eye.; Other Names: Eylea®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean change from baseline in best corrected visual acuity (BCVA) at Week 36 in the study eye	BCVA was assessed by Early Treatment of Diabetic Retinopathy Study (ETDRS) method	Baseline to Week 36

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of subjects maintaining vision (i.e., losing <15 ETDRS BCVA letters) from baseline to Week 36	To Assess Proportion of subjects maintaining vision (i.e., losing <15 ETDRS BCVA letters) from baseline to Week 36	Baseline to Week 36
Proportion of subjects gaining ≥15 ETDRS BCVA letters from baseline to Week 36	To Assess Proportion of subjects gaining ≥15 ETDRS BCVA letters from baseline to Week 36	Baseline to Week 36
Mean change from baseline in central retinal thickness (µm) by spectral domain optical coherence tomography (SD-OCT) at Week	To Assess Mean change from baseline in central retinal thickness (µm) by spectral domain optical coherence tomography (SD-OCT) at Week	Baseline and Week 36
Proportion of subjects maintaining vision (i.e. losing <15 ETDRS BCVA letters) from baseline to Week 48	To Assess Proportion of subjects maintaining vision (i.e. losing <15 ETDRS BCVA letters) from baseline to Week 48	Baseline to Week 48
Mean change from baseline in ETDRS BCVA letter score at Week 96	To Assess Mean change from baseline in ETDRS BCVA letter score at Week 96	Baseline and Week 96
Number of participants with adverse events as measure of safety and tolerability	To Assess Number of participants with adverse events as measure of safety and tolerability	Baseline to Week 96
Blood concentration of conbercept doses conducted in a subgroup of subjects, when feasible	To Assess Blood concentration of conbercept doses conducted in a subgroup of subjects, when feasible	Baseline to Week 96
Half-life (t1/2) of conbercept doses conducted in a subgroup of subjects, when feasible	To Assess Half-life (t1/2) of conbercept doses conducted in a subgroup of subjects, when feasible	Baseline to Week 96
Presence of anti-drug antibody of conbercept doses conducted in a subgroup of subjects, when feasible	To Assess Presence of anti-drug antibody of conbercept doses conducted in a subgroup of subjects, when feasible	Baseline to Week 96

Collaborators and Investigators

• Sponsor: Chengdu Kanghong Biotech Co., Ltd.
• Investigators: Study Director: Yan Cheng, MD, PhD, Chengdu Kanghong Biotechnology Co.,Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): December 21, 2018
• Primary Completion (Actual): September 10, 2020
• Study Completion (Actual): May 19, 2021

Study Registration Dates

• First Submitted: August 11, 2018
• First Submitted That Met QC Criteria: August 11, 2018
• First Posted (Actual): August 15, 2018

Study Record Updates

• Last Update Posted (Actual): June 23, 2021
• Last Update Submitted That Met QC Criteria: June 22, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration; Wet Macular Degeneration; Physiological Effects of Drugs; Antineoplastic Agents; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Aflibercept
• Other Study ID Numbers: KHB-1802

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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