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

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-2)

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03630952
• Other study ID #: KHB-1802
• Status: Terminated
• Phase: Phase 3
• Start date: December 21, 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 10, 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) 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.
• 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.
• 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.

Locations

Country	Name	City	State
Bulgaria	Kanghong Investigative Site	Plovdiv
Bulgaria	Kanghong Investigative Site	Sofia
Bulgaria	Kanghong Investigative Site	Sofia
Bulgaria	Kanghong Investigative Site	Varna
China	Kanghong Investigative Site	Beijing	Beijing
China	Kanghong Investigative Site	Shanghai	Shanghai
China	Kanghong Investigative Site	Shanghai	Shanghai
China	Kanghong Investigative Site	Tianjin	Tianjin
Czechia	Kanghong Investigative Site	Brno
Czechia	Kanghong Investigative Site	Praha 10
Czechia	Kanghong Investigative Site	Praha 10
Czechia	Kanghong Investigative Site	Praha 2
Czechia	Kanghong Investigative Site	Praha 5
Denmark	Kanghong Investigative Site	Aalborg
Denmark	Kanghong Investigative Site	Aarhus N
Denmark	Kanghong Investigative Site	Glostrup
Denmark	Kanghong Investigative Site	Roskilde
Denmark	Kanghong Investigative Site	Sonderborg
France	Kanghong Investigative Site	Bordeaux
France	Kanghong Investigative Site	Créteil
France	Kanghong Investigative Site	Dijon
France	Kanghong Investigative Site	Marseille
France	Kanghong Investigative Site	Paris
France	Kanghong Investigative Site	Paris
France	Kanghong Investigative Site	Paris
France	Kanghong Investigative Site	Paris
France	Kanghong Investigative Site	Poitiers Cedex
France	Kanghong Investigative Site	Saint-Cyr sur Loire
France	Kanghong Investigative Site	Strasbourg
Hungary	Kanghong Investigative Site	Budapest	Pest
Hungary	Kanghong Investigative Site	Budapest	Pest
Hungary	Kanghong Investigative Site	Budapest	Pest
Hungary	Kanghong Investigative Site	Budapest	Pest
Hungary	Kanghong Investigative Site	Budapest	Pest
Hungary	Kanghong Investigative Site	Budapest	Pest
Hungary	Kanghong Investigative Site	Debrecen	Hajdu Bihar
Hungary	Kanghong Investigative Site	Pécs	Baranya
Hungary	Kanghong Investigative Site	Szeged	Csongrád
Hungary	Kanghong Investigative Site	Zalaegerszeg	Zala
Israel	Kanghong Investigative Site	Ashkelon	Ha'Darom
Israel	Kanghong Investigative Site	Beer Sheva
Israel	Kanghong Investigative Site	Haifa
Israel	Kanghong Investigative Site	Haifa
Israel	Kanghong Investigative Site	Haifa
Israel	Kanghong Investigative Site	Jerusalem
Israel	Kanghong Investigative Site	Jerusalem
Israel	Kanghong Investigative Site	Kfar Saba
Israel	Kanghong Investigative Site	Petach Tikva
Israel	Kanghong Investigative Site	Poriyya
Israel	Kanghong Investigative Site	Rehovot
Israel	Kanghong Investigative Site	Tel Aviv
Israel	Kanghong Investigative Site	Zrifin
Italy	Kanghong Investigative Site	Chieti
Italy	Kanghong Investigative Site	Firenze
Italy	Kanghong Investigative Site	Genova
Italy	Kanghong Investigative Site	Milano
Italy	Kanghong Investigative Site	Milano
Italy	Kanghong Investigative Site	Milano
Italy	Kanghong Investigative Site	Negrar
Italy	Kanghong Investigative Site	Roma
Italy	Kanghong Investigative Site	Roma
Italy	Kanghong Investigative Site	Udine
Latvia	Kanghong Investigative Site	Riga
Latvia	Kanghong Investigative Site	Riga
Latvia	Kanghong Investigative Site	Riga
Slovakia	Kanghong Investigative Site	Žilina
Slovakia	Kanghong Investigative Site	Bratislava
Slovakia	Kanghong Investigative Site	Trencín
Slovakia	Kanghong Investigative Site	Zilina
United Kingdom	Kanghong Investigative Site	Belfast
United Kingdom	Kanghong Investigative Site	Bradford
United Kingdom	Kanghong Investigative Site	Bristol
United Kingdom	Kanghong Investigative Site	Canterbury
United Kingdom	Kanghong Investigative Site	Derby
United Kingdom	Kanghong Investigative Site	Frimley	Surrey
United Kingdom	Kanghong Investigative Site	Gorleston-on-Sea	Norfolk
United Kingdom	Kanghong Investigative Site	Gorleston-On-Sea
United Kingdom	Kanghong Investigative Site	Leeds
United Kingdom	Kanghong Investigative Site	London
United Kingdom	Kanghong Investigative Site	London
United Kingdom	Kanghong Investigative Site	London
United Kingdom	Kanghong Investigative Site	Sheffield
United Kingdom	Kanghong Investigative Site	Southampton	Hampshire
United Kingdom	Kanghong Investigative Site	Sunderland
United Kingdom	Kanghong Investigative Site	Westcliff on Sea	Essex
United States	Kanghong Investigative Site	Albuquerque	New Mexico
United States	Kanghong Investigative Site	Arcadia	California
United States	Kanghong Investigative Site	Arcadia	California
United States	Kanghong Investigative Site	Arlington	Texas
United States	Kanghong Investigative Site	Asheville	North Carolina
United States	Kanghong Investigative Site	Atlanta	Georgia
United States	Kanghong Investigative Site	Augusta	Georgia
United States	Kanghong Investigative Site	Austin	Texas
United States	Kanghong Investigative Site	Austin	Texas
United States	Kanghong Investigative Site	Bakersfield	California
United States	Kanghong Investigative Site	Bellaire	Texas
United States	Kanghong Investigative Site	Bellevue	Washington
United States	Kanghong Investigative Site	Boynton Beach	Florida
United States	Kanghong Investigative Site	Bradenton	Florida
United States	Kanghong Investigative Site	Brooklyn	New York
United States	Kanghong Investigative Site	Burlington	Vermont
United States	Kanghong Investigative Site	Camp Hill	Pennsylvania
United States	Kanghong Investigative Site	Charlottesville	Virginia
United States	Kanghong Investigative Site	Colorado Springs	Colorado
United States	Kanghong Investigative Site	Dallas	Texas
United States	Kanghong Investigative Site	Elmhurst	Illinois
United States	Kanghong Investigative Site	Encino	California
United States	Kanghong Investigative Site	Fort Worth	Texas
United States	Kanghong Investigative Site	Glendale	California
United States	Kanghong Investigative Site	Glendora	California
United States	Kanghong Investigative Site	Grand Rapids	Michigan
United States	Kanghong Investigative Site	Great Neck	New York
United States	Kanghong Investigative Site	Huntington Beach	California
United States	Kanghong Investigative Site	Indianapolis	Indiana
United States	Kanghong Investigative Site	Kingston	Pennsylvania
United States	Kanghong Investigative Site	Kingwood	Texas
United States	Kanghong Investigative Site	Ladson	South Carolina
United States	Kanghong Investigative Site	Leawood	Kansas
United States	Kanghong Investigative Site	Liverpool	New York
United States	Kanghong Investigative Site	Marietta	Georgia
United States	Kanghong Investigative Site	McAllen	Texas
United States	Kanghong Investigative Site	Medford	Oregon
United States	Kanghong Investigative Site	Miami	Florida
United States	Kanghong Investigative Site	Miami	Florida
United States	Kanghong Investigative Site	Midland	Texas
United States	Kanghong Investigative Site	New Albany	Indiana
United States	Kanghong Investigative Site	Northfield	New Jersey
United States	Kanghong Investigative Site	Oklahoma City	Oklahoma
United States	Kanghong Investigative Site	Pasadena	California
United States	Kanghong Investigative Site	Phoenix	Arizona
United States	Kanghong Investigative Site	Phoenix	Arizona
United States	Kanghong Investigative Site	Portland	Oregon
United States	Kanghong Investigative Site	Poway	California
United States	Kanghong Investigative Site	Rapid City	South Dakota
United States	Kanghong Investigative Site	Redlands	California
United States	Kanghong Investigative Site	Redlands	California
United States	Kanghong Investigative Site	Reno	Nevada
United States	Kanghong Investigative Site	Riverside	California
United States	Kanghong Investigative Site	Saint Louis	Missouri
United States	Kanghong Investigative Site	Salt Lake City	Utah
United States	Kanghong Investigative Site	San Francisco	California
United States	Kanghong Investigative Site	Santa Barbara	California
United States	Kanghong Investigative Site	Shirley	New York
United States	Kanghong Investigative Site	Springdale	Arkansas
United States	Kanghong Investigative Site	Springfield	Massachusetts
United States	Kanghong Investigative Site	Springfield	Oregon
United States	Kanghong Investigative Site	Stuart	Florida
United States	Kanghong Investigative Site	Teaneck	New Jersey
United States	Kanghong Investigative Site	Temple	Texas
United States	Kanghong Investigative Site	Traverse City	Michigan
United States	Kanghong Investigative Site	Waterford	Connecticut
United States	Kanghong Investigative Site	Winston-Salem	North Carolina
United States	Kanghong Investigative Site	Winter Haven	Florida
United States	Kanghong Investigative Site	Youngstown	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
Chengdu Kanghong Biotech Co., Ltd.

Countries where clinical trial is conducted

United States,  Bulgaria,  China,  Czechia,  Denmark,  France,  Hungary,  Israel,  Italy,  Latvia,  Slovakia,  United Kingdom, 

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	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
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 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 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 Presence of anti-drug antibody of conbercept doses conducted in a subgroup of subjects, when feasible	Baseline to Week 96