Efficacy and Safety Trial of Conbercept Intravitreal Injection for Neovascular AMD (PANDA-1)

Neovascular Age-related Macular Degeneration Clinical Trial

Official title:

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-1)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03577899
• Other study ID #: KHB-1801
• Status: Terminated
• Phase: Phase 3
• Start date: September 25, 2018
• Est. completion date: May 19, 2021

Study information

• Verified date: June 2021
• Source: Chengdu Kanghong Biotech Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1157
• Est. completion date: May 19, 2021
• Est. primary completion date: September 25, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Macular Degeneration
• Neovascular Age-related Macular Degeneration
• Wet Macular Degeneration

Intervention

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) for a total of 92 weeks treatment in the study eye.
• 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) for a total of 92 weeks treatment in the study eye.
• 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) for a total of 92 weeks of treatment in the study eye.

Locations

Country	Name	City	State
Argentina	Kanghong Investigative Site	Caba	Buenos Aires
Argentina	Kanghong Investigative Site	Caba	Buenos Aires
Argentina	Kanghong Investigative Site	Caba	Buenos Aires
Argentina	Kanghong Investigative Site	Cordoba
Argentina	Kanghong Investigative Site	Córdoba	Cordoba
Argentina	Kanghong Investigative Site	Mendoza
Argentina	Kanghong Investigative Site	Rosario	Santa Fe
Australia	Kanghong Investigative Site	Adelaide	South Australia
Australia	Kanghong Investigative Site	Albury	New South Wales
Australia	Kanghong Investigative Site	Crawley
Australia	Kanghong Investigative Site	Glen Waverley	Victoria
Australia	Kanghong Investigative Site	Liverpool	New South Wales
Australia	Kanghong Investigative Site	Melbourne	Victoria
Australia	Kanghong Investigative Site	Parramatta	New South Wales
Australia	Kanghong Investigative Site	Strathfield	New South Wales
Australia	Kanghong Investigative Site	Sydney	New South Wales
Australia	Kanghong Investigative Site	Sydney
Austria	Kanghong Investigative Site	Feldkirch	Hessen
Austria	Kanghong Investigative Site	Klagenfurt am Wörthersee
Austria	Kanghong Investigative Site	Linz
Austria	Kanghong Investigative Site in Linz	Linz
Austria	Kanghong Investigative Site	Vienna
Austria	Kanghong Investigative Site	Vienna
Belgium	Kanghong Investigative Site	Laeken
Belgium	Kanghong Investigative Site	Leuven
Canada	Kanghong Investigative Site	Calgary	Alberta
Canada	Kanghong Investigative Site	London	Ontario
Canada	Kanghong Investigative Site	Mississauga	Ontario
Canada	Kanghong Investigative Site	Montreal	Quebec
Canada	Kanghong Investigative Site	Montréal	Quebec
Canada	Kanghong Investigative Site	Sherbrooke	Quebec
Canada	Kanghong Investigative Site	Toronto	Ontario
Canada	Kanghong Ivestigative Site	Vancouver	British Columbia
Chile	Kanghong Investigative Site	Santiago	Region Metropolitana
Chile	Kanghong Investigative Site	Santiago	Region Metropolitana
Colombia	Kanghong Investigative Site	Barranquilla	Atlantico
Colombia	Kanghong Investigative Site	Bogotá	Bogota
Colombia	Kanghong Investigative Site	Cali
Colombia	Kanghong Investigative Site	Medellin
Germany	Kanghong Investigative Site	Bonn
Germany	Kanghong Investigative Site	Darmstadt
Germany	Kanghong Investigative Site	Düsseldorf
Germany	Kanghong Investigative Site	Frankfurt am Main
Germany	Kanghong Investigative Site	Freiburg
Germany	Kanghong Investigative Site	Göttingen
Germany	Kanghong Investigative Site	Hannover
Germany	Kanghong Investigative Site	Heidelberg
Germany	Kanghong Investigative Site	Homburg
Germany	Kanghong Investigative Site	Köln
Germany	Kanghong Investigative Site	Leipzig
Germany	Kanghong Investigative Site	Ludwigshafen
Germany	Kanghong Investigative Site	Mainz
Germany	Kanghong Investigative Site	Marburg
Germany	Kanghong Investigative Site	Muenster
Germany	Kanghong Investigative Site	München
Germany	Kanghong Investigative Site	Regensburg
Hong Kong	Kanghong Investigative Site	Hong Kong
Hong Kong	Kanghong Investigative Site in Hong Kong	Hong Kong
Lithuania	Kanghong Investigative Site	Kaunas
Lithuania	Kanghong Investigative Site	Vilnius
Mexico	Kanghong Investigative Site	Jalisco	Guadalajara
Mexico	Kanghong Investigative Site	Jalisco	Guadalajara
Netherlands	Kanghong Investigative Site	Amsterdam
Netherlands	Kanghong Investigative Site	Rotterdam	Zuid Holland
Netherlands	Kanghong Investigative Site	Tilburg
New Zealand	Kanghong Investigative Site	Auckland
Peru	Kanghong Investigative Site	Lima
Peru	Kanghong Investigative Site	Lima
Peru	Kanghong Investigative Site	Lima
Peru	Kanghong Investigator Site	Lima
Philippines	Kanghong Investigative Site	Makati	Manila
Philippines	Kanghong Investigative Site	Pasig City	Manila
Philippines	Kanghong Investigative Site	Quezon City	Manila
Poland	Kanghong Investigative Site	Gdansk
Poland	Kanghong Investigative Site	Kraków	Lesser
Poland	Kanghong Investigative Site	Lodz
Poland	Kanghong Investigative Site	Lodz
Poland	Kanghong Investigative Site	Lublin
Poland	Kanghong Investigative Site	Olsztyn
Poland	Kanghong Investigative Site	Wroclaw
Portugal	Kanghong Investigative Site	Coimbra
Portugal	Kanghong Investigative Site	Coimbra
Portugal	Kanghong Investigative Site	Coimbra
Portugal	Kanghong Investigative Site	Lisbon
Portugal	Kanghong Investigative Site	Lisbon
Portugal	Kanghong Investigative Site	Vila Franca de Xira	Lisboa
Singapore	Kanghong Investigative Site	Singapore
Spain	Kanghong Investigative Site	Barcelona	Cataluna
Spain	Kanghong Investigative Site	Barcelona
Spain	Kanghong Investigative Site	Barcelona
Spain	Kanghong Investigative Site	Barcelona
Spain	Kanghong Investigatvie Site	Barcelona
Spain	Kanghong Investigative Site	Bilbao
Spain	Kanghong Investigative Site	Madrid
Spain	Kanghong Investigative Site	Madrid
Spain	Kanghong Investigative Site	Majadahonda
Spain	Kanghong Investigative Site	Oviedo
Spain	Kanghong Investigative Site	Pamplona
Spain	Kanghong Investigative Site	Sant Cugat Del Vallès
Spain	Kanghong Investigative Site	Santiago De Compostela
Spain	Kanghong Investigative Site	Sevilla	Andalucia
Spain	Kanghong Investigative Site	Valencia
Spain	Kanghong Investigative Site	Valencia
Spain	Kanghong Investigative Site	Valladolid
Spain	Kanghong Investigative Site	Zaragoza
Spain	Kanghong Investigative Site in Zaragoza	Zaragoza
Switzerland	Kanghong Investigative Site	Bern
Switzerland	Kanghong Investigative Site	Bern
Switzerland	Kanghong Investigative Site	Lausanne	Canton De Vaud
Switzerland	Kanghong Investigative Site	Zürich
Switzerland	Kanghong Investigative Site	Zürich
Taiwan	Kanghong Investigative Site	Changhua City
Taiwan	Kanghong Investigative Site	Taipei City
Taiwan	Kanghong Investigative Site	Taipei City
Taiwan	Kanghong Investigative Site	Taipei city
Taiwan	Kanghong Investigative Site	Taoyuan
United States	Kanghong Investigative Site	'Aiea	Hawaii
United States	Kanghong Investigative Site	Abilene	Texas
United States	Kanghong Investigative Site	Albany	New York
United States	Kanghong Investigative Site	Beverly Hills	California
United States	Kanghong Investigator Site	Bloomfield	New Jersey
United States	Kanghong Investigative Site	Bloomington	Illinois
United States	Kanghong Investigative Site	Boston	Massachusetts
United States	Kanghong Investigative Site	Campbell	California
United States	Kanghong Investigative Site	Chicago	Illinois
United States	Kanghong Investigative Site	Cincinnati	Ohio
United States	Kanghong Investigative Site	Cleveland	Ohio
United States	Kanghong Investigative Site	Cleveland	Ohio
United States	Kanghong Investigative Site	Detroit	Michigan
United States	Kanghong Investigative Site	Dublin	Ohio
United States	Kanghong Investigative Site	Eugene	Oregon
United States	Kanghong Investigative Site	Fort Myers	Florida
United States	Kanghong Investigative Site	Fort Myers	Florida
United States	Kanghong Investigative Site	Fullerton	California
United States	Kanghong Investigative Site	Glendale	California
United States	Kanghong Investigative Site	Golden	Colorado
United States	Kanghong Investigative Site	Hagerstown	Maryland
United States	Kanghong Investigative Site in MD	Hagerstown	Maryland
United States	Kanghong Investigative Site	Hauppauge	New York
United States	Kanghong Investigative Site	Jacksonville	Florida
United States	Kanghong Investigative Site	Katy	Texas
United States	Kanghong Investigative Site	La Jolla	California
United States	Kanghong Investigative Site	Lakeland	Florida
United States	Kanghong Investigative Site	Lemont	Illinois
United States	Kanghong Investigative Site	Lynchburg	Virginia
United States	Kanghong Investigative Site	Morgantown	West Virginia
United States	Kanghong Investigative Site	Mountain View	California
United States	Kanghong Investigative Site	Nashville	Tennessee
United States	Kanghong Investigative Site	Norfolk	Virginia
United States	Kanghong Investigative Site	Oakland	California
United States	Kanghong Investigative Site	Ocala	Florida
United States	Kanghong Investigative Site	Orlando	Florida
United States	Kanghong Investigative Site	Paducah	Kentucky
United States	Kanghong Investigative Site	Palm Desert	California
United States	Kanghong Investigative Site	Palm Desert	California
United States	Kanghong Investigative Site	Philadelphia	Pennsylvania
United States	Kanghong Investigative Site	Phoenix	Arizona
United States	Kanghong Investigative Site	Plantation	Florida
United States	Kanghong Investigative Site	Rochester	New York
United States	Kanghong Investigative Site	Sacramento	California
United States	Kanghong Investigative Site	Saint Petersburg	Florida
United States	Kanghong Investigative Site	San Antonio	Texas
United States	Kanghong Investigative Site	San Antonio	Texas
United States	Kanghong Investigative Site	San Antonio	Texas
United States	Kanghong Investigative Site	San Antonio	Texas
United States	Kanghong Investigative Site in TX	San Antonio	Texas
United States	Kanghong Investigative Site	Sarasota	Florida
United States	Kanghong Investigative Site	Silverdale	Washington
United States	Kanghong Investigator Site	Southlake	Texas
United States	Kanghong Investigative Site	Spokane	Washington
United States	Kanghong Investigative Site	Tampa	Florida
United States	Kanghong Investigative Site	The Woodlands	Texas
United States	Kanghong Investigative Site	Tucson	Arizona
United States	Kanghong Investigative Site	Tyler	Texas
United States	Kanghong Investigative Site	Walnut Creek	California
United States	Kanghong Investigative Site	Warrenton	Virginia
United States	Kanghong Investigative Site	West Mifflin	Pennsylvania
United States	Kanghong Investigative Site	Wichita	Kansas
United States	Kanghong Investigative Site	Willow Park	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Chengdu Kanghong Biotech Co., Ltd.

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Canada,  Chile,  Colombia,  Germany,  Hong Kong,  Lithuania,  Mexico,  Netherlands,  New Zealand,  Peru,  Philippines,  Poland,  Portugal,  Singapore,  Spain,  Switzerland,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	Mean change from baseline in central retinal thickness (µm) by spectral domain optical coherence tomography (SD-OCT) at Week 36	To assess mean change from baseline in central retinal thickness (µm) by spectral	Baseline and Week 36
Secondary	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
Secondary	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
Secondary	Number of participants with adverse events as measure of safety and tolerability	To assess the number of participants with adverse events as measure of safety and tolerability	Baseline to Week 96
Secondary	Blood concentration of conbercept doses conducted in a subgroup of subjects, when feasible	To assess the blood concentration of conbercept doses conducted in a subgroup of subjects, when feasible	Baseline to Week 96
Secondary	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
Secondary	Presence of anti-drug antibody of conbercept doses conducted in a subgroup of subjects, when feasible	To assess the presence of anti-drug antibody of conbercept doses conducted in a subgroup of subjects, when feasible	Baseline to Week 96