VEGA: Japanese Phase 3 Study of Aflibercept in Neovascular Glaucoma Patients

• Sponsor: Bayer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02396316
• Collaborator: Regeneron Pharmaceuticals (Industry)
• Enrollment: 54
• Locations: 19
• Arms: 2
• Actual Duration (Months): 17.2
• Patients Per Site: 2.8
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

To assess the efficacy and safety of the administration of aflibercept by intravitreal injection in comparison to sham to control intraocular pressure in patients with neovascular glaucoma.

Condition or Disease	Intervention/Treatment	Phase
Glaucoma, Neovascular	Drug: Aflibercept (Eylea, BAY 86-5321); Drug: Sham Injection	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 54 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-masked, and Controlled Phase 3 Study to Evaluate the Efficacy, Safety, and Tolerability of Intravitreal Administration of Aflibercept in Japanese Patients With Neovascular Glaucoma
• Actual Study Start Date: Apr 2, 2015
• Actual Primary Completion Date: Jun 16, 2016
• Actual Study Completion Date: Sep 6, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Aflibercept Aflibercept 2 mg Intravitreal (IVT) injection group	Drug: Aflibercept (Eylea, BAY 86-5321); After the first aflibercept IVT injection on Day 1, subjects may receive sham injection at Week 1, and aflibercept injection at Week 5 and/or Week 9 if the re-treatment criteria are met.
Sham Comparator: Sham Injection Sham injection group	Drug: Sham Injection; After the first sham injection on Day 1, subjects may receive aflibercept IVT injection at Week 1, Week 5 and/or Week 9 if re-treatment criteria are met.

Outcome Measures

Primary Outcome Measures

1. Change in Intraocular Pressure (IOP) From Baseline to Pre-dose at Week 1 [From baseline to pre-dose at Week 1]

   It compared the change in IOP from baseline to pre-dose at Week 1 between the aflibercept group vs the sham group.

Secondary Outcome Measures

1. Percentage of Subjects Who Had Improved Neovascularization of the Iris (NVI) Grade From Baseline to Pre-dose at Week 1 [From baseline to pre-dose at Week 1]

   NVI were assessed in the study eye using the NVI grading systems (grade 0 to grade 4). A subject who shows the improvement by at least one grade is considered to be improved. Percentage of subjects who had improved NVI grade was reported.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Japanese men and women aged 20 years or older,

• Patients diagnosed as having Neovascular glaucoma (NVG) with neovascularization in the anterior segment (both iris and anterior chamber angle),

• Patients with Intraocular pressure (IOP) higher than 25 mmHg in the study eye due to anterior segment (both iris and anterior chamber angle) neovascularization.

Exclusion Criteria:

• Patients with angle-closure due to conditions other than Neovascular glaucoma

• Patients with a known or suspected ocular or peri-ocular infection,

• Patients with severe intraocular inflammation in the study eye,

• Women who are pregnant, suspected of being pregnant or lactating,

• Patients with known allergy to aflibercept.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Yoshida	Fukui	Japan	910-1193
2		Amagasaki	Hyogo	Japan	660-8550
3		Himeji	Hyogo	Japan	671-1227
4		Kobe	Hyogo	Japan	650-0017
5		Kanazawa	Ishikawa	Japan	920-8641
6		Kawasaki	Kanagawa	Japan	216-8511
7		Sendai	Miyagi	Japan	980-8574
8		Yufu	Oita	Japan	879-5593
9		Hirakata	Osaka	Japan	573-1191
10		Suita	Osaka	Japan	565-0871
11		Takatsuki	Osaka	Japan	569-8686
12		Izumo	Shimane	Japan	693-8501
13		Bunkyo-ku	Tokyo	Japan	113-8655
14		Mitaka	Tokyo	Japan	181-8611
15		Ube	Yamaguchi	Japan	755-8505
16		Chuo	Yamanashi	Japan	409-3898
17		Gifu		Japan	501-1194
18		Kyoto		Japan	602-0841
19		Osaka		Japan	545-8586

Sponsors and Collaborators

• Bayer
• Regeneron Pharmaceuticals

Investigators

• Study Director: Bayer Study Director, Bayer

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Bayer
• ClinicalTrials.gov Identifier: NCT02396316
• Other Study ID Numbers: 17584
• First Posted: Mar 24, 2015
• Last Update Posted: Sep 15, 2017
• Last Verified: Aug 1, 2017

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Additional relevant MeSH terms: Glaucoma; Glaucoma, Neovascular; Aflibercept

Study Results

Participant Flow

Recruitment Details	Study was conducted at nineteen study centers in Japan, between 02 April 2015 (first subject first visit) and 06 Sep 2016 (last subject last visit).
Pre-assignment Detail	A total of 63 subjects were screened and 54 subjects were randomized into the aflibercept group (N=27) and the sham group (N =27).

Arm/Group Title	Aflibercept 2 mg Intravitreal (IVT) Injection Group	Sham Injection Group
Arm/Group Description	Subjects received intravitreal (IVT) injection of 2 mg (0.05 milliliter [ml] * 40 milligram per milliliter [mg/ml]) aflibercept on Day 1. Then, subjects may receive sham injection at Week 1, and aflibercept injection at Week 5 and/or Week 9 if the re-treatment criteria are met. Re-treatment criteria (subjects could receive aflibercept IVT injection when all the following retreatment criteria were met) : IOP higher than 21mmHg; Incomplete regression of iris neovascularization and; Aflibercept IVT deemed necessary by the investigator.	Subjects received a sham injection on Day 1. Then, subjects may receive aflibercept injection at Week 1, Week 5 and/or Week 9 if the re-treatment criteria specified in the protocol are met. Re-treatment criteria (subjects could receive aflibercept IVT injection when all the following retreatment criteria were met) : IOP higher than 21mmHg; Incomplete regression of iris neovascularization and; Aflibercept IVT deemed necessary by the investigator.
Period Title: Overall Study
STARTED	27	27
Treated	27	27
Received Sham Injection at Week 1	10	0
Received AFL Injection at Week 1	0	22
Received Active Injection at Week 5	4	4
Received Active Injection at Week 9	2	1
COMPLETED	20	22
NOT COMPLETED	7	5

Baseline Characteristics

Arm/Group Title	Aflibercept 2 mg Intravitreal (IVT) Injection Group	Sham Injection Group	Total
Arm/Group Description	Subjects received intravitreal (IVT) injection of 2 mg (0.05 milliliter [ml] * 40 milligram per milliliter [mg/ml]) aflibercept on Day 1. Then, subjects may receive sham injection at Week 1, and aflibercept injection at Week 5 and/or Week 9 if the re-treatment criteria are met. Re-treatment criteria (subjects could receive aflibercept IVT injection when all the following retreatment criteria were met) : IOP higher than 21mmHg; Incomplete regression of iris neovascularization and; Aflibercept IVT deemed necessary by the investigator.	Subjects received a sham injection on Day 1. Then, subjects may receive aflibercept injection at Week 1, Week 5 and/or Week 9 if the re-treatment criteria specified in the protocol are met. Re-treatment criteria (subjects could receive aflibercept IVT injection when all the following retreatment criteria were met) : IOP higher than 21mmHg; Incomplete regression of iris neovascularization and; Aflibercept IVT deemed necessary by the investigator.	Total of all reporting groups
Overall Participants	27	27	54
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	68.1 (12.7)	66.2 (13.7)	67.1 (13.1)
Sex: Female, Male (Count of Participants)
Female	5 18.5%	4 14.8%	9 16.7%
Male	22 81.5%	23 85.2%	45 83.3%

Outcome Measures

1. Primary Outcome

Title	Change in Intraocular Pressure (IOP) From Baseline to Pre-dose at Week 1
Description	It compared the change in IOP from baseline to pre-dose at Week 1 between the aflibercept group vs the sham group.
Time Frame	From baseline to pre-dose at Week 1

Outcome Measure Data

Analysis Population Description

FAS: The Full Analysis Set (FAS) included all randomized subjects who have received any study drug (including sham injection) and had had a baseline and at least one post-baseline IOP measurement on a posterior date. The FAS was analyzed as randomized.

Arm/Group Title	Aflibercept 2 mg Intravitreal (IVT) Injection Group	Sham Injection Group
Arm/Group Description	Subjects received intravitreal (IVT) injection of 2 mg (0.05 ml * 40 mg/ml) aflibercept on Day 1. Then, subjects may receive sham injection at Week 1, and aflibercept injection at Week 5 and/or Week 9 if the re-treatment criteria are met. Re-treatment criteria (subjects could receive aflibercept IVT injection when all the following retreatment criteria were met) : IOP higher than 21mmHg; Incomplete regression of iris neovascularization and; Aflibercept IVT deemed necessary by the investigator.	Subjects received a sham injection on Day 1. Then, subjects may receive aflibercept injection at Week 1, Week 5 and/or Week 9 if the re-treatment criteria specified in the protocol are met. Re-treatment criteria (subjects could receive aflibercept IVT injection when all the following retreatment criteria were met) : IOP higher than 21mmHg; Incomplete regression of iris neovascularization and; Aflibercept IVT deemed necessary by the investigator.
Measure Participants	27	27
Mean (Standard Deviation) [mmHg]	-8.5 (8.7)	-4.9 (10.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Aflibercept 2 mg Intravitreal (IVT) Injection Group, Sham Injection Group
	Comments	Point estimate, 95% CI and P-value were based on treatment difference of the LS mean changes using an ANCOVA model with treatment group and stage of NVG for randomization as fixed effects, baseline value as covariate. The superiority of aflibercept injection to sham injection was to be established if the upper limit of the two-sided 95% confidence interval for the difference (the aflibercept group minus the sham group) is less than 0.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0644
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference of LS mean change
	Estimated Value	-4.9
	Confidence Interval	(2-Sided) 95%; -10.2 to 0.3
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Percentage of Subjects Who Had Improved Neovascularization of the Iris (NVI) Grade From Baseline to Pre-dose at Week 1
Description	NVI were assessed in the study eye using the NVI grading systems (grade 0 to grade 4). A subject who shows the improvement by at least one grade is considered to be improved. Percentage of subjects who had improved NVI grade was reported.
Time Frame	From baseline to pre-dose at Week 1

Outcome Measure Data

Analysis Population Description

FAS

Arm/Group Title	Aflibercept 2 mg Intravitreal (IVT) Injection Group	Sham Injection Group
Arm/Group Description	Subjects received intravitreal (IVT) injection of 2 mg (0.05 ml * 40 mg/ml) aflibercept on Day 1. Then, subjects may receive sham injection at Week 1, and aflibercept injection at Week 5 and/or Week 9 if the re-treatment criteria are met. Re-treatment criteria (subjects could receive aflibercept IVT injection when all the following retreatment criteria were met) : IOP higher than 21mmHg; Incomplete regression of iris neovascularization and; Aflibercept IVT deemed necessary by the investigator.	Subjects received a sham injection on Day 1. Then, subjects may receive aflibercept injection at Week 1, Week 5 and/or Week 9 if the re-treatment criteria specified in the protocol are met. Re-treatment criteria (subjects could receive aflibercept IVT injection when all the following retreatment criteria were met) : IOP higher than 21mmHg; Incomplete regression of iris neovascularization and; Aflibercept IVT deemed necessary by the investigator.
Measure Participants	27	27
Number [Percentage of participants]	70.4 260.7%	11.5 42.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Aflibercept 2 mg Intravitreal (IVT) Injection Group, Sham Injection Group
	Comments	The point estimate of the treatment difference (the aflibercept group minus the sham group) at Week 1 and its two-sided 95% confidence interval stratified by stage of NVG (as randomized) using Mantel-Haenszel weights.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	MH adjusted difference
	Estimated Value	59.1
	Confidence Interval	(2-Sided) 95%; 37.0 to 81.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Adverse event data were collected after the first dose of study drug and no later than 30 days after the last dose of study drug. AEs from the first dose of study drug until pre-dose at Week 1 were also reported.
Arm/Group Title	Aflibercept 2 mg Intravitreal (IVT) Injection Group		Sham Injection Group		Aflibercept 2 mg IVT Injection Group (Till Pre-dose at Week 1)		Sham Injection Group (Till Pre-dose at Week 1)
Arm/Group Description	Subjects received intravitreal (IVT) injection of 2 mg (0.05 ml * 40 mg/ml) aflibercept on Day 1. Then, subjects may receive sham injection at Week 1, and aflibercept injection at Week 5 and/or Week 9 if the re-treatment criteria are met. Re-treatment criteria (subjects could receive aflibercept IVT injection when all the following retreatment criteria were met) : IOP higher than 21mmHg; Incomplete regression of iris neovascularization and; Aflibercept IVT deemed necessary by the investigator. (AE time frame: from first dose of study drug until 30 days after the last dose of study drug)		Subjects received a sham injection on Day 1. Then, subjects may receive aflibercept injection at Week 1, Week 5 and/or Week 9 if the re-treatment criteria specified in the protocol are met. Re-treatment criteria (subjects could receive aflibercept IVT injection when all the following retreatment criteria were met) : IOP higher than 21mmHg; Incomplete regression of iris neovascularization and; Aflibercept IVT deemed necessary by the investigator. (AE time frame: from first dose of study drug until 30 days after the last dose of study drug)		Subjects received IVT injection of 2 mg (0.05 ml * 40 mg/ml) aflibercept on Day 1. Then, subjects may receive sham injection at Week 1, and aflibercept injection at Week 5 and/or Week 9 if the re-treatment criteria are met. Re-treatment criteria (subjects could receive aflibercept IVT injection when all the following retreatment criteria were met) : IOP higher than 21mmHg; Incomplete regression of iris neovascularization and; Aflibercept IVT deemed necessary by the investigator. (AE time frame: from the first dose of study drug until pre-dose at Week 1)		Subjects received a sham injection on Day 1. Then, subjects may receive aflibercept injection at Week 1, Week 5 and/or Week 9 if the re-treatment criteria specified in the protocol are met. Re-treatment criteria (subjects could receive aflibercept IVT injection when all the following retreatment criteria were met) : IOP higher than 21mmHg; Incomplete regression of iris neovascularization and; Aflibercept IVT deemed necessary by the investigator. (AE time frame: from the first dose of study drug until pre-dose at Week 1)
All Cause Mortality
	Aflibercept 2 mg Intravitreal (IVT) Injection Group		Sham Injection Group		Aflibercept 2 mg IVT Injection Group (Till Pre-dose at Week 1)		Sham Injection Group (Till Pre-dose at Week 1)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Aflibercept 2 mg Intravitreal (IVT) Injection Group		Sham Injection Group		Aflibercept 2 mg IVT Injection Group (Till Pre-dose at Week 1)		Sham Injection Group (Till Pre-dose at Week 1)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/27 (11.1%)		3/27 (11.1%)		0/27 (0%)		0/27 (0%)
Cardiac disorders
Myocardial ischaemia	0/27 (0%)	0	1/27 (3.7%)	2	0/27 (0%)	0	0/27 (0%)	0
Eye disorders
Diabetic retinopathy	0/27 (0%)	0	1/27 (3.7%)	1	0/27 (0%)	0	0/27 (0%)	0
Retinal artery occlusion	1/27 (3.7%)	1	0/27 (0%)	0	0/27 (0%)	0	0/27 (0%)	0
Retinal vein occlusion	1/27 (3.7%)	1	0/27 (0%)	0	0/27 (0%)	0	0/27 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pancreatic carcinoma	1/27 (3.7%)	1	0/27 (0%)	0	0/27 (0%)	0	0/27 (0%)	0
Psychiatric disorders
Eating disorder	0/27 (0%)	0	1/27 (3.7%)	1	0/27 (0%)	0	0/27 (0%)	0
Other (Not Including Serious) Adverse Events
	Aflibercept 2 mg Intravitreal (IVT) Injection Group		Sham Injection Group		Aflibercept 2 mg IVT Injection Group (Till Pre-dose at Week 1)		Sham Injection Group (Till Pre-dose at Week 1)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	10/27 (37%)		12/27 (44.4%)		6/27 (22.2%)		7/27 (25.9%)
Eye disorders
Conjunctival haemorrhage	2/27 (7.4%)	2	1/27 (3.7%)	1	2/27 (7.4%)	2	0/27 (0%)	0
Eye pain	0/27 (0%)	0	4/27 (14.8%)	5	0/27 (0%)	0	1/27 (3.7%)	1
Hyphaema	0/27 (0%)	0	2/27 (7.4%)	2	0/27 (0%)	0	2/27 (7.4%)	2
Punctate keratitis	2/27 (7.4%)	4	3/27 (11.1%)	4	2/27 (7.4%)	2	1/27 (3.7%)	1
Gastrointestinal disorders
Constipation	1/27 (3.7%)	1	2/27 (7.4%)	2	0/27 (0%)	0	0/27 (0%)	0
Diarrhoea	2/27 (7.4%)	2	0/27 (0%)	0	1/27 (3.7%)	1	0/27 (0%)	0
General disorders
Injection site pain	2/27 (7.4%)	3	1/27 (3.7%)	1	2/27 (7.4%)	3	1/27 (3.7%)	1
Injury, poisoning and procedural complications
Procedural pain	3/27 (11.1%)	4	0/27 (0%)	0	0/27 (0%)	0	0/27 (0%)	0
Investigations
Intraocular pressure increased	0/27 (0%)	0	2/27 (7.4%)	2	0/27 (0%)	0	1/27 (3.7%)	1
Nervous system disorders
Headache	1/27 (3.7%)	1	2/27 (7.4%)	2	0/27 (0%)	0	2/27 (7.4%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.