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

Phase 3
Terminated
Conditions
Neovascular Age-related Macular Degeneration
Interventions
Biological: 2.0 mg Aflibercept Intravitreal Injection
Biological: 0.5 mg Conbercept Intravitreal Injection
Biological: 1.0 mg Conbercept Intravitreal Injection
Registration Number
NCT03577899
Lead Sponsor
Chengdu Kanghong Biotech Co., Ltd.
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.

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
1157
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Aflibercept2.0 mg Aflibercept Intravitreal InjectionSubjects 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.
0.5 mg Conbercept0.5 mg Conbercept Intravitreal InjectionSubjects 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 Conbercept1.0 mg Conbercept Intravitreal InjectionSubjects 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.
Primary Outcome Measures
NameTimeMethod
Mean change from baseline in best corrected visual acuity (BCVA) at Week 36 in the study eyeBaseline to Week 36

BCVA was assessed by Early Treatment of Diabetic Retinopathy Study (ETDRS) method

Secondary Outcome Measures
NameTimeMethod
Proportion of subjects maintaining vision (i.e., losing <15 ETDRS BCVA letters) from baseline to Week 36Baseline to Week 36

To assess proportion of subjects maintaining vision (i.e., losing \<15 ETDRS BCVA letters) from baseline to Week 36

Half-life (t1/2) of conbercept doses conducted in a subgroup of subjects, when feasibleBaseline to Week 96

To assess half-life (t1/2) of conbercept doses conducted in a subgroup of subjects, when feasible

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

To assess the presence of anti-drug antibody of conbercept doses conducted in a subgroup of subjects, when feasible

Proportion of subjects gaining ≥15 ETDRS BCVA letters from baseline to Week 36Baseline to Week 36

To assess proportion of subjects gaining ≥15 ETDRS BCVA letters from baseline to Week 36

Number of participants with adverse events as measure of safety and tolerabilityBaseline to Week 96

To assess the number of participants with adverse events as measure of safety and tolerability

Mean change from baseline in central retinal thickness (µm) by spectral domain optical coherence tomography (SD-OCT) at Week 36Baseline and Week 36

To assess mean change from baseline in central retinal thickness (µm) by spectral

Proportion of subjects maintaining vision (i.e. losing <15 ETDRS BCVA letters) from baseline to Week 48Baseline to Week 48

To assess proportion of subjects maintaining vision (i.e. losing \<15 ETDRS BCVA letters) from baseline to Week 48

Blood concentration of conbercept doses conducted in a subgroup of subjects, when feasibleBaseline to Week 96

To assess the blood concentration of conbercept doses conducted in a subgroup of subjects, when feasible

Mean change from baseline in ETDRS BCVA letter score at Week 96Baseline and Week 96

To assess mean change from baseline in ETDRS BCVA letter score at Week 96

Trial Locations

Locations (9)

Kanghong Investigative Site in MD

🇺🇸

Hagerstown, Maryland, United States

Kanghong Investigative Site

🇨🇳

Taoyuan, Taiwan

Kanghong Investigative Site in TX

🇺🇸

San Antonio, Texas, United States

Kanghong Investigator Site

🇵🇪

Lima, Peru

Kanghong Investigative Site in Zaragoza

🇪🇸

Zaragoza, Spain

Kanghong Investigatvie Site

🇪🇸

Barcelona, Spain

Kanghong Ivestigative Site

🇨🇦

Vancouver, British Columbia, Canada

Kanghong Investigative Site in Linz

🇦🇹

Linz, Austria

Kanghong Investigative Site in Hong Kong

🇭🇰

Hong Kong, Hong Kong

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