recent progress of conbercept in clinical studies
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9
Phase I Center Point Thickness Change
Graph showing the mean change from baseline in center point thickness for all patients given escalating doses of KH902 (p<0.05).
resulting from exudative AMD. • Indicating that further study is warranted.
11
HOPE Study
open label, multicentre, randomized N=36
Patients randomized 1：1
• Published in WHO Drug Information and finally identified by International Pharmacopoeia.
• Commercial Name: 朗沐 (in Chinese) • Used Name: KH902, FP3
3
Recent Progress of Conbercept in CliWneictaAlMSDtudies
High affinity and binds VEGF more tightly than native receptors or monclonal antibody
Blocks all VEGF-A isoforms and Placental Growth Factor (PlGF)
Penetrates all layers of the retina
17
Mean Change of BCVA of Phase II AURORA
15.43 14.31 12.42 9.31
BCVA after 12 months, n=120, p<0.05)
19
Mean Change of CRT in AURORA Study
CRT after 12 months，n=120, p<0.05)
-203.94 -214.6
16
Study Design of Phase II AURORA
Randomized 1: 1
Fixed dose until Wk 12 Randomized again 1: 1
Randomized, double-masked， multicentre, parallel-group
• Other Ocular Adverse Events: Cataract formation; Vitreous floater; Conjunctivitis; Uveitis; Retinal hemorrhage; etc.
• Ocular AEs were similar to those reported for Lucentis and Eylea after intravitreal injection
5
Clinical Trials in Age- related Macular Degeneration
• Study design, Paticipants, Setting and Results • Summary and Assessment
6
Primary Outcome in Phase I Safety and Adverse Events
• Randomized、Open label • AMD（n=12）+ PM（n=12）
Recent Progress of Conbercept in Clinical Studies
1
Conbercept: A New VEGF Blocker
Schematic Diagram of Conbersept
Produced from industry standard Chinese hamster Overy Cell Line
Fusion protein of domain 2 from human VEGFR1 and domain 3 and 4 from human VEGFR2 with human IgG Fc (MW~142.7,000)
Contains all human amino acid sequence
Received Sham Injection
BCVA changes after 12 months ，n=124, Conbercept group: n=65; control group: n=35 Until 1st Sept, 2013, all subjects finished 12 month day
10
Conclusion from Phase I Study
• Improvement in Visual Acuity. • Reduction in central retinal thickness. • A decrease in CVN area in patients with CNV
• Injection of 0.5 mg Conbercept has been recommended to be the most effective regimen for the treatment of wet AMD
23
Study Arrangement of Phase III PHOENIX
26
Comparison of PHOENIX &PIER (Lucentis)
27
Study Design of BRIDGE study
• A comparison between old vial (Cryopreservation) and new vial (cold storage ) about the characteristics in safety , efficacy and pharmacokinetic after a single intravitreal injection
randomized ，double masked ， multicentre，sham control
N=120
Participants randomized 2：1
0.5 mg q3mo
n=80
Sham
n=40
Primary Endpoint： Best-Corrected visual
Acuity (BCVA)
IgG=immunoglobulin G; MW=molecular weight
2
Nomencloture of Conbercept Ophthalmic Injection
• Conbercept (INN) has been proposed and adopted by the World Health Organization on the advice of experts from the Fifty-first WHO Expert Advisory Panel
• No safety concerns after a maximum single dose (3.0mg)
• No dose-limiting toxicity. • No drug-related intraocular inflammation, no cases of
Endophthalmitis. • No drug-related serious systemic adverse events.
• Ocular adverse events were mild, including transient IOP elevation and injection-site subconjunctival hemorrhage after injections.
8
Phase I Visual Acuity Change
14
Best-Corrected Visual Acuit Changes of HOPE Study
16.44 15.11
( n=36, p<0.05)
Week
15
Centre Retinal Thickness Changes of HOPE Study
Week
( n=36, p<0.05)
• Transient or mild ocular Adverse Events occurring after intravitreal injection procedule ,such as subconjunctival hemorrhage from the injection site
Graph showing mean visual acuity (VA) changes for each dose group after a single intravitreal injection of KH902 through day 42. The vertical bars at each visit represent the standard errors of the mean. (P<0.05).
0.5 mg q44 wks
n=18
Primary endpoint: Safety ,Tolerability
Fixed dosing to Week 12
Secondary endpoint:
Best-Corrected visual Acuity（BCVA）
Assessment on Week 52
22
Regimen Recommended
• Intravitreal administration of 0.5mg and 2.0mg Conbercept has the same effects for the participants in wet AMD clinical trials; no significant difference between Group PRN and Q1month; no significant difference in adverse events between 0.5mg and 2.0mg Conbercept
12
Safety Profile of HOPE Study
• No drug or treatment regiments related systemic and ocular Adverse Events reported in the study
• No severe ocular Adverse Events reported , such as Endophthalmitis, Retinal Detachment
20
Safety Evaluation of Phase II AURORA
• Most Common Ocular Adverse Events: injection-site subconjunctival hemorrhage after intravitreal injection procedure; transient IOP elevation
loading dose ended on Month 3
Secondary Endpoint： Central Ratinal Thickness (CRT)
Evaluation on Month 12
24
Efficacy of Phase III PHOENIX
9.2
2.0
Received Conbercept 0.5mg
N=120
0.5 mg q1mo
n=60
2 mg q1mo
n=60
0.5 mg PRN
n=30
0.5 mg q1mo
n=30
2.0 mg PRN
n=30
2.0 mg q1mo
n=30
Primary Endpoint： Best-Corrected Visual
Acuity (BCVA)
Secondary Endpoint： Central Ratinal Thickness (CRT)
Phase I Center Point Thickness Change
Graph showing the mean change from baseline in center point thickness for all patients given escalating doses of KH902 (p<0.05).
resulting from exudative AMD. • Indicating that further study is warranted.
11
HOPE Study
open label, multicentre, randomized N=36
Patients randomized 1：1
• Published in WHO Drug Information and finally identified by International Pharmacopoeia.
• Commercial Name: 朗沐 (in Chinese) • Used Name: KH902, FP3
3
Recent Progress of Conbercept in CliWneictaAlMSDtudies
High affinity and binds VEGF more tightly than native receptors or monclonal antibody
Blocks all VEGF-A isoforms and Placental Growth Factor (PlGF)
Penetrates all layers of the retina
17
Mean Change of BCVA of Phase II AURORA
15.43 14.31 12.42 9.31
BCVA after 12 months, n=120, p<0.05)
19
Mean Change of CRT in AURORA Study
CRT after 12 months，n=120, p<0.05)
-203.94 -214.6
16
Study Design of Phase II AURORA
Randomized 1: 1
Fixed dose until Wk 12 Randomized again 1: 1
Randomized, double-masked， multicentre, parallel-group
• Other Ocular Adverse Events: Cataract formation; Vitreous floater; Conjunctivitis; Uveitis; Retinal hemorrhage; etc.
• Ocular AEs were similar to those reported for Lucentis and Eylea after intravitreal injection
5
Clinical Trials in Age- related Macular Degeneration
• Study design, Paticipants, Setting and Results • Summary and Assessment
6
Primary Outcome in Phase I Safety and Adverse Events
• Randomized、Open label • AMD（n=12）+ PM（n=12）
Recent Progress of Conbercept in Clinical Studies
1
Conbercept: A New VEGF Blocker
Schematic Diagram of Conbersept
Produced from industry standard Chinese hamster Overy Cell Line
Fusion protein of domain 2 from human VEGFR1 and domain 3 and 4 from human VEGFR2 with human IgG Fc (MW~142.7,000)
Contains all human amino acid sequence
Received Sham Injection
BCVA changes after 12 months ，n=124, Conbercept group: n=65; control group: n=35 Until 1st Sept, 2013, all subjects finished 12 month day
10
Conclusion from Phase I Study
• Improvement in Visual Acuity. • Reduction in central retinal thickness. • A decrease in CVN area in patients with CNV
• Injection of 0.5 mg Conbercept has been recommended to be the most effective regimen for the treatment of wet AMD
23
Study Arrangement of Phase III PHOENIX
26
Comparison of PHOENIX &PIER (Lucentis)
27
Study Design of BRIDGE study
• A comparison between old vial (Cryopreservation) and new vial (cold storage ) about the characteristics in safety , efficacy and pharmacokinetic after a single intravitreal injection
randomized ，double masked ， multicentre，sham control
N=120
Participants randomized 2：1
0.5 mg q3mo
n=80
Sham
n=40
Primary Endpoint： Best-Corrected visual
Acuity (BCVA)
IgG=immunoglobulin G; MW=molecular weight
2
Nomencloture of Conbercept Ophthalmic Injection
• Conbercept (INN) has been proposed and adopted by the World Health Organization on the advice of experts from the Fifty-first WHO Expert Advisory Panel
• No safety concerns after a maximum single dose (3.0mg)
• No dose-limiting toxicity. • No drug-related intraocular inflammation, no cases of
Endophthalmitis. • No drug-related serious systemic adverse events.
• Ocular adverse events were mild, including transient IOP elevation and injection-site subconjunctival hemorrhage after injections.
8
Phase I Visual Acuity Change
14
Best-Corrected Visual Acuit Changes of HOPE Study
16.44 15.11
( n=36, p<0.05)
Week
15
Centre Retinal Thickness Changes of HOPE Study
Week
( n=36, p<0.05)
• Transient or mild ocular Adverse Events occurring after intravitreal injection procedule ,such as subconjunctival hemorrhage from the injection site
Graph showing mean visual acuity (VA) changes for each dose group after a single intravitreal injection of KH902 through day 42. The vertical bars at each visit represent the standard errors of the mean. (P<0.05).
0.5 mg q44 wks
n=18
Primary endpoint: Safety ,Tolerability
Fixed dosing to Week 12
Secondary endpoint:
Best-Corrected visual Acuity（BCVA）
Assessment on Week 52
22
Regimen Recommended
• Intravitreal administration of 0.5mg and 2.0mg Conbercept has the same effects for the participants in wet AMD clinical trials; no significant difference between Group PRN and Q1month; no significant difference in adverse events between 0.5mg and 2.0mg Conbercept
12
Safety Profile of HOPE Study
• No drug or treatment regiments related systemic and ocular Adverse Events reported in the study
• No severe ocular Adverse Events reported , such as Endophthalmitis, Retinal Detachment
20
Safety Evaluation of Phase II AURORA
• Most Common Ocular Adverse Events: injection-site subconjunctival hemorrhage after intravitreal injection procedure; transient IOP elevation
loading dose ended on Month 3
Secondary Endpoint： Central Ratinal Thickness (CRT)
Evaluation on Month 12
24
Efficacy of Phase III PHOENIX
9.2
2.0
Received Conbercept 0.5mg
N=120
0.5 mg q1mo
n=60
2 mg q1mo
n=60
0.5 mg PRN
n=30
0.5 mg q1mo
n=30
2.0 mg PRN
n=30
2.0 mg q1mo
n=30
Primary Endpoint： Best-Corrected Visual
Acuity (BCVA)
Secondary Endpoint： Central Ratinal Thickness (CRT)