Clinical trial NCT03630952: Efficacy and Safety Trial of Conbercept Intravitreal Injection for Neovascular AMD (PANDA-2)
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)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Neovascular Age-related Macular Degeneration
Lead sponsor: Chengdu Kanghong Biotech Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2018-08-15
Enrollment: 1157
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Mean change from baseline in best corrected visual acuity (BCVA) at Week 36 in the study eye
timeFrame: Baseline to Week 36
Secondary outcomes:
measure: Proportion of subjects maintaining vision (i.e., losing <15 ETDRS BCVA letters) from baseline to Week 36
timeFrame: Baseline to Week 36
measure: Proportion of subjects gaining ≥15 ETDRS BCVA letters from baseline to Week 36
timeFrame: Baseline to Week 36
measure: Mean change from baseline in central retinal thickness (µm) by spectral domain optical coherence tomography (SD-OCT) at Week
timeFrame: Baseline and Week 36
measure: Proportion of subjects maintaining vision (i.e. losing <15 ETDRS BCVA letters) from baseline to Week 48
timeFrame: Baseline to Week 48
measure: Mean change from baseline in ETDRS BCVA letter score at Week 96
timeFrame: Baseline and Week 96
measure: Number of participants with adverse events as measure of safety and tolerability
timeFrame: Baseline to Week 96
measure: Blood concentration of conbercept doses conducted in a subgroup of subjects, when feasible
timeFrame: Baseline to Week 96
measure: Half-life (t1/2) of conbercept doses conducted in a subgroup of subjects, when feasible
timeFrame: Baseline to Week 96
measure: Presence of anti-drug antibody of conbercept doses conducted in a subgroup of subjects, when feasible
timeFrame: Baseline to Week 96
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Kanghong Investigative Site
state: Arizona
city: Phoenix
country: United States
facility: Kanghong Investigative Site
state: Arizona
city: Springdale
country: United States
facility: Kanghong Investigative Site
state: Arkansas
city: Arcadia
country: United States
facility: Kanghong Investigative Site
state: California
city: Arcadia
country: United States
facility: Kanghong Investigative Site
state: California
city: Bakersfield
country: United States
facility: Kanghong Investigative Site
state: California
city: Encino
country: United States
facility: Kanghong Investigative Site
state: California
city: Glendale
country: United States
facility: Kanghong Investigative Site
state: California
city: Glendora
country: United States
facility: Kanghong Investigative Site
state: California
city: Huntington Beach
country: United States
facility: Kanghong Investigative Site
state: California
city: Pasadena
country: United States
facility: Kanghong Investigative Site
state: California
city: Poway
country: United States
facility: Kanghong Investigative Site
state: California
city: Redlands
country: United States
facility: Kanghong Investigative Site
state: California
city: Redlands
country: United States
facility: Kanghong Investigative Site
state: California
city: Riverside
country: United States
facility: Kanghong Investigative Site
state: California
city: San Francisco
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facility: Kanghong Investigative Site
state: California
city: Santa Barbara
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facility: Kanghong Investigative Site
state: California
city: Colorado Springs
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facility: Kanghong Investigative Site
state: Colorado
city: Waterford
country: United States
facility: Kanghong Investigative Site
state: Connecticut
city: Boynton Beach
country: United States
facility: Kanghong Investigative Site
state: Florida
city: Bradenton
country: United States
facility: Kanghong Investigative Site
state: Florida
city: Miami
country: United States
facility: Kanghong Investigative Site
state: Florida
city: Miami
country: United States
facility: Kanghong Investigative Site
state: Florida
city: Stuart
country: United States
facility: Kanghong Investigative Site
state: Florida
city: Winter Haven
country: United States
facility: Kanghong Investigative Site
state: Florida
city: Atlanta
country: United States
facility: Kanghong Investigative Site
state: Georgia
city: Augusta
country: United States
facility: Kanghong Investigative Site
state: Georgia
city: Marietta
country: United States
facility: Kanghong Investigative Site
state: Georgia
city: Elmhurst
country: United States
facility: Kanghong Investigative Site
state: Illinois
city: Indianapolis
country: United States
facility: Kanghong Investigative Site
state: Indiana
city: New Albany
country: United States
facility: Kanghong Investigative Site
state: Indiana
city: Leawood
country: United States
facility: Kanghong Investigative Site
state: Kansas
city: Springfield
country: United States
facility: Kanghong Investigative Site
state: Massachusetts
city: Grand Rapids
country: United States
facility: Kanghong Investigative Site
state: Michigan
city: Traverse City
country: United States
facility: Kanghong Investigative Site
state: Michigan
city: Saint Louis
country: United States
facility: Kanghong Investigative Site
state: Missouri
city: Reno
country: United States
facility: Kanghong Investigative Site
state: Nevada
city: Northfield
country: United States
facility: Kanghong Investigative Site
state: New Jersey
city: Teaneck
country: United States
facility: Kanghong Investigative Site
state: New Jersey
city: Albuquerque
country: United States
facility: Kanghong Investigative Site
state: New Mexico
city: Brooklyn
country: United States
facility: Kanghong Investigative Site
state: New York
city: Great Neck
country: United States
facility: Kanghong Investigative Site
state: New York
city: Liverpool
country: United States
facility: Kanghong Investigative Site
state: New York
city: Shirley
country: United States
facility: Kanghong Investigative Site
state: New York
city: Asheville
country: United States
facility: Kanghong Investigative Site
state: North Carolina
city: Winston-Salem
country: United States
facility: Kanghong Investigative Site
state: North Carolina
city: Youngstown
country: United States
facility: Kanghong Investigative Site
state: Ohio
city: Oklahoma City
country: United States
facility: Kanghong Investigative Site
state: Oklahoma
city: Medford
country: United States
facility: Kanghong Investigative Site
state: Oregon
city: Portland
country: United States
facility: Kanghong Investigative Site
state: Oregon
city: Springfield
country: United States
facility: Kanghong Investigative Site
state: Oregon
city: Camp Hill
country: United States
facility: Kanghong Investigative Site
state: Pennsylvania
city: Kingston
country: United States
facility: Kanghong Investigative Site
state: Pennsylvania
city: Ladson
country: United States
facility: Kanghong Investigative Site
state: South Carolina
city: Rapid City
country: United States
facility: Kanghong Investigative Site
state: South Dakota
city: Arlington
country: United States
facility: Kanghong Investigative Site
state: Texas
city: Austin
country: United States
facility: Kanghong Investigative Site
state: Texas
city: Austin
country: United States
facility: Kanghong Investigative Site
state: Texas
city: Bellaire
country: United States
facility: Kanghong Investigative Site
state: Texas
city: Dallas
country: United States
facility: Kanghong Investigative Site
state: Texas
city: Fort Worth
country: United States
facility: Kanghong Investigative Site
state: Texas
city: Kingwood
country: United States
facility: Kanghong Investigative Site
state: Texas
city: McAllen
country: United States
facility: Kanghong Investigative Site
state: Texas
city: Midland
country: United States
facility: Kanghong Investigative Site
state: Texas
city: Temple
country: United States
facility: Kanghong Investigative Site
state: Texas
city: Salt Lake City
country: United States
facility: Kanghong Investigative Site
state: Utah
city: Burlington
country: United States
facility: Kanghong Investigative Site
state: Vermont
city: Charlottesville
country: United States
facility: Kanghong Investigative Site
state: Virginia
city: Bellevue
country: United States
facility: Kanghong Investigative Site
state: Washington
city: Plovdiv
country: Bulgaria
facility: Kanghong Investigative Site
city: Sofia
country: Bulgaria
facility: Kanghong Investigative Site
city: Sofia
country: Bulgaria
facility: Kanghong Investigative Site
city: Varna
country: Bulgaria
facility: Kanghong Investigative Site
city: Beijing
country: China
facility: Kanghong Investigative Site
state: Beijing
city: Shanghai
country: China
facility: Kanghong Investigative Site
state: Shanghai
city: Shanghai
country: China
facility: Kanghong Investigative Site
state: Shanghai
city: Tianjin
country: China
facility: Kanghong Investigative Site
state: Tianjin
city: Brno
country: Czechia
facility: Kanghong Investigative Site
city: Praha 10
country: Czechia
facility: Kanghong Investigative Site
city: Praha 10
country: Czechia
facility: Kanghong Investigative Site
city: Praha 2
country: Czechia
facility: Kanghong Investigative Site
city: Praha 5
country: Czechia
facility: Kanghong Investigative Site
city: Aalborg
country: Denmark
facility: Kanghong Investigative Site
city: Aarhus N
country: Denmark
facility: Kanghong Investigative Site
city: Glostrup
country: Denmark
facility: Kanghong Investigative Site
city: Roskilde
country: Denmark
facility: Kanghong Investigative Site
city: Sonderborg
country: Denmark
facility: Kanghong Investigative Site
city: Bordeaux
country: France
facility: Kanghong Investigative Site
city: Créteil
country: France
facility: Kanghong Investigative Site
city: Dijon
country: France
facility: Kanghong Investigative Site
city: Marseille
country: France
facility: Kanghong Investigative Site
city: Paris
country: France
facility: Kanghong Investigative Site
city: Paris
country: France
facility: Kanghong Investigative Site
city: Paris
country: France
facility: Kanghong Investigative Site
city: Paris
country: France
facility: Kanghong Investigative Site
city: Poitiers Cedex
country: France
facility: Kanghong Investigative Site
city: Saint-Cyr sur Loire
country: France
facility: Kanghong Investigative Site
city: Strasbourg
country: France
facility: Kanghong Investigative Site
city: Pécs
country: Hungary
facility: Kanghong Investigative Site
state: Baranya
city: Szeged
country: Hungary
facility: Kanghong Investigative Site
state: Csongrád
city: Debrecen
country: Hungary
facility: Kanghong Investigative Site
state: Hajdu Bihar
city: Budapest
country: Hungary
facility: Kanghong Investigative Site
state: Pest
city: Budapest
country: Hungary
facility: Kanghong Investigative Site
state: Pest
city: Budapest
country: Hungary
facility: Kanghong Investigative Site
state: Pest
city: Budapest
country: Hungary
facility: Kanghong Investigative Site
state: Pest
city: Budapest
country: Hungary
facility: Kanghong Investigative Site
state: Pest
city: Budapest
country: Hungary
facility: Kanghong Investigative Site
state: Pest
city: Zalaegerszeg
country: Hungary
facility: Kanghong Investigative Site
state: Zala
city: Ashkelon
country: Israel
facility: Kanghong Investigative Site
state: Ha'Darom
city: Beer Sheva
country: Israel
facility: Kanghong Investigative Site
city: Haifa
country: Israel
facility: Kanghong Investigative Site
city: Haifa
country: Israel
facility: Kanghong Investigative Site
city: Haifa
country: Israel
facility: Kanghong Investigative Site
city: Jerusalem
country: Israel
facility: Kanghong Investigative Site
city: Jerusalem
country: Israel
facility: Kanghong Investigative Site
city: Kfar Saba
country: Israel
facility: Kanghong Investigative Site
city: Petach Tikva
country: Israel
facility: Kanghong Investigative Site
city: Poriyya
country: Israel
facility: Kanghong Investigative Site
city: Rehovot
country: Israel
facility: Kanghong Investigative Site
city: Tel Aviv
country: Israel
facility: Kanghong Investigative Site
city: Zrifin
country: Israel
facility: Kanghong Investigative Site
city: Chieti
country: Italy
facility: Kanghong Investigative Site
city: Firenze
country: Italy
facility: Kanghong Investigative Site
city: Genova
country: Italy
facility: Kanghong Investigative Site
city: Milano
country: Italy
facility: Kanghong Investigative Site
city: Milano
country: Italy
facility: Kanghong Investigative Site
city: Milano
country: Italy
facility: Kanghong Investigative Site
city: Negrar
country: Italy
facility: Kanghong Investigative Site
city: Roma
country: Italy
facility: Kanghong Investigative Site
city: Roma
country: Italy
facility: Kanghong Investigative Site
city: Udine
country: Italy
facility: Kanghong Investigative Site
city: Riga
country: Latvia
facility: Kanghong Investigative Site
city: Riga
country: Latvia
facility: Kanghong Investigative Site
city: Riga
country: Latvia
facility: Kanghong Investigative Site
city: Bratislava
country: Slovakia
facility: Kanghong Investigative Site
city: Trenčín
country: Slovakia
facility: Kanghong Investigative Site
city: Zilina
country: Slovakia
facility: Kanghong Investigative Site
city: Žilina
country: Slovakia
facility: Kanghong Investigative Site
city: Westcliff on Sea
country: United Kingdom
facility: Kanghong Investigative Site
state: Essex
city: Southampton
country: United Kingdom
facility: Kanghong Investigative Site
state: Hampshire
city: Gorleston-on-Sea
country: United Kingdom
facility: Kanghong Investigative Site
state: Norfolk
city: Frimley
country: United Kingdom
facility: Kanghong Investigative Site
state: Surrey
city: Belfast
country: United Kingdom
facility: Kanghong Investigative Site
city: Bradford
country: United Kingdom
facility: Kanghong Investigative Site
city: Bristol
country: United Kingdom
facility: Kanghong Investigative Site
city: Canterbury
country: United Kingdom
facility: Kanghong Investigative Site
city: Derby
country: United Kingdom
facility: Kanghong Investigative Site
city: Gorleston-On-Sea
country: United Kingdom
facility: Kanghong Investigative Site
city: Leeds
country: United Kingdom
facility: Kanghong Investigative Site
city: London
country: United Kingdom
facility: Kanghong Investigative Site
city: London
country: United Kingdom
facility: Kanghong Investigative Site
city: London
country: United Kingdom
facility: Kanghong Investigative Site
city: Sheffield
country: United Kingdom
facility: Kanghong Investigative Site
city: Sunderland
country: United Kingdom
facility: Kanghong Investigative Site
Study officials:
affiliation: Chengdu Kanghong Biotechnology Co.,Ltd.
name: Yan Cheng, MD, PhD
role: STUDY_DIRECTOR
References: