Safety and Efficacy of Repeated Intravitreal Administration of Vascular Endothelial Growth Factor (VEGF) Trap in Patients With Wet Age-Related Macular Degeneration (AMD)

A Randomized, Controlled Study of the Safety, Tolerability and Biological Effect of Repeated Intravitreal Administration of VEGF Trap in Patients With Neovascular Age-Related Macular Degeneration

Status

Completed

Phases

Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00320788

Enrollment

159

Registered

2006-05-03

Start date

2006-04-30

Completion date

2008-08-31

Last updated

2012-03-01

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Macular Degeneration

Keywords

Neovascular Age-Related Macular Degeneration

Brief summary

This study examines the effect of intravitreally administered VEGF Trap in patients with wet AMD. The purpose of this trial is to assess the ocular and systemic safety and tolerability of repeated intravitreal doses of VEGF Trap in patients with subfoveal choroidal neovascularization (CNV) due to AMD.

Detailed description

This is a double masked, prospective, randomized study in which five groups of approximately 30 patients meeting the eligibility criteria will be randomly assigned in a balanced ratio to receive a series of intravitreal (IVT) injections of VEGF Trap into the study eye at 4- or 12 -week intervals over a 12-week period. After Week 12, patients will be evaluated every 4 weeks. Patients will remain on study or may be eligible to enter a long-term extension study, in which they will continue to receive VEGF Trap.

Interventions

BIOLOGICALaflibercept injection (VEGF Trap-Eye, BAY86-5321)

Participants received 0.5 mg of aflibercept injection (VEGF Trap-Eye, BAY86-5321) at 4 week intervals through Week 12

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Caregiver, Investigator)

Eligibility

Sex/Gender

ALL

Age

50 Years to No maximum

Healthy volunteers

Inclusion criteria

* Subfoveal CNV secondary to AMD. * Central retinal (including lesion) thickness ≥ 300 µm as measured by Optical Coherence Tomography (OCT). * Early Treatment of Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity of 73 letters to 34 letters.

Exclusion criteria

* History of any vitreous hemorrhage within 4 weeks prior to Day 1. * Aphakia. * Significant subfoveal atrophy or scarring. * Prior treatment with the following in the study eye: * Subfoveal thermal laser therapy. * Submacular surgery or other surgical intervention for the treatment of AMD. * Extrafoveal laser coagulation treatment within 12 weeks prior to Day 1. * Photodynamic therapy (PDT) within 12 weeks prior to Visit 2 (Day 1). * Pegaptanib sodium (Macugen) within 8 weeks of Visit 2 (Day 1). * Juxtascleral steroids or anecortave acetate within 24 weeks (6 months) prior to Visit 2 (Day 1). * Intravitreal administration of triamcinolone acetonide or other steroids within 24 weeks prior to Visit 2 (Day 1), unless no visible residue of drug substance can be seen in the vitreous cavity using indirect ophthalmoscopy. * Prior systemic or intravitreal treatment with VEGF Trap, ranibizumab (Lucentis) or bevacizumab (Avastin). * Presence of any other condition or laboratory abnormality, which, in the opinion of the Investigator, would interfere with the assessment of disease status/progression or jeopardize the patient's appropriate participation in this Phase II study.

Design outcomes

Primary

Measure	Time frame	Description
Mean Change of CR/LT From Baseline at Week 12	Baseline and at Week 12	CR/LT measured in micrometers (µm); lower individual values represent better outcomes.

Secondary

Measure	Time frame	Description
Mean Percent Change of CR/LT From Baseline at Week 12	Baseline and at Week 12	CR/LT measured in micrometers (µm); a more negative percentage represents a better outcome
Mean Change in Best Corrected Visual Acuity (BCVA) as Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) From Baseline at Week 12	Baseline and at week 12	Defined study baseline range of ETDRS Best Corrected Visual Acuity of: letter score of 73 to 25 (20/40 to 20/320) in the study eye; a higher score represents better functioning
Percentage of Participants Who Gained at Least 15 Letters of Vision in the ETDRS Letter Score From Baseline at Week 12	At Week 12	Defined study baseline range of ETDRS Best Corrected Visual Acuity of: letter score of 73 to 25 (20/40 to 20/320) in the study eye; a higher score represents better functioning

Countries

United States

Participant flow

Recruitment details

The study was conducted at 29 study sites in the United States. Recruitment period: May 2006 to April 2007.

Pre-assignment details

A total of 301 participants were screened; 159 participants were randomized; 157 participants were included in both the Safety Analysis Set (SAF) and the Full Analysis Set (FAS) as all received study treatment, had baseline assessments and at least 1 post-baseline assessment.

Participants by arm

Arm	Count
Aflibercept Injection 0.5mg q4 Participants received 0.5 mg of aflibercept injection at 4 week intervals through Week 12.	32
Aflibercept Injection 0.5mg q12 Participants received 0.5 mg of aflibercept injection at 12 week intervals through Week 12.	32
Aflibercept Injection 2.0mg q4 Participants received 2.0 mg of aflibercept injection at 4 week intervals through Week 12.	31
Aflibercept Injection 2.0mg q12 Participants received 2.0 mg of aflibercept injection at 12 week intervals through Week 12.	31
Aflibercept Injection 4.0mg q12 Participants received 4.0 mg of aflibercept injection at 12 week intervals through Week 12.	31
Total	157

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002	FG003	FG004
Overall Study	Adverse Event	0	0	0	1	0
Overall Study	Death	0	0	1	0	1
Overall Study	Decision by the Sponsor	1	1	0	0	1
Overall Study	Lost to Follow-up	0	2	1	0	0
Overall Study	Other	1	2	1	1	1
Overall Study	Physician Decision	1	1	0	0	0
Overall Study	Protocol Violation	0	0	0	0	1
Overall Study	Withdrawal by Subject	3	0	0	3	1

Baseline characteristics

Characteristic	Aflibercept Injection 0.5mg q12	Aflibercept Injection 2.0mg q4	Aflibercept Injection 2.0mg q12	Aflibercept Injection 4.0mg q12	Aflibercept Injection 0.5mg q4	Total
Age Continuous	78.5 years STANDARD_DEVIATION 10.12	74.9 years STANDARD_DEVIATION 7.63	79.6 years STANDARD_DEVIATION 8.91	78.3 years STANDARD_DEVIATION 5.97	79.6 years STANDARD_DEVIATION 7.56	78.2 years STANDARD_DEVIATION 8.25
Best Corrected Visual Acuity (BCVA)	55.6 letters read STANDARD_DEVIATION 11.75	57.9 letters read STANDARD_DEVIATION 12.02	57.2 letters read STANDARD_DEVIATION 10.47	53.0 letters read STANDARD_DEVIATION 14.52	54.1 letters read STANDARD_DEVIATION 13.77	55.5 letters read STANDARD_DEVIATION 12.57
Central Retinal/Lesion Thickness (CR/LT)	442.6 µm STANDARD_DEVIATION 136.6	453.3 µm STANDARD_DEVIATION 143.93	447.0 µm STANDARD_DEVIATION 119.11	497.5 µm STANDARD_DEVIATION 191.17	442.2 µm STANDARD_DEVIATION 109.81	456.4 µm STANDARD_DEVIATION 142.41
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants 0	2 Participants 0	1 Participants 0	0 Participants 0	0 Participants 0	4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	31 Participants 0	29 Participants 0	30 Participants 0	31 Participants 0	32 Participants 0	153 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants 0	0 Participants 0	0 Participants 0	0 Participants 0	0 Participants 0	0 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants 0	1 Participants 0	0 Participants 0	0 Participants 0	0 Participants 0	1 Participants
Race (NIH/OMB) Asian	0 Participants 0	0 Participants 0	0 Participants 0	0 Participants 0	0 Participants 0	0 Participants
Race (NIH/OMB) Black or African American	0 Participants 0	0 Participants 0	0 Participants 0	0 Participants 0	0 Participants 0	0 Participants
Race (NIH/OMB) More than one race	0 Participants 0	0 Participants 0	0 Participants 0	0 Participants 0	0 Participants 0	0 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants 0	0 Participants 0	0 Participants 0	0 Participants 0	0 Participants 0	0 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants 0	0 Participants 0	0 Participants 0	0 Participants 0	0 Participants 0	0 Participants
Race (NIH/OMB) White	32 Participants 0	30 Participants 0	31 Participants 0	31 Participants 0	32 Participants 0	156 Participants
Sex: Female, Male Female	25 Participants 0	20 Participants 0	16 Participants 0	20 Participants 0	17 Participants 0	98 Participants
Sex: Female, Male Male	7 Participants 0	11 Participants 0	15 Participants 0	11 Participants 0	15 Participants 0	59 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk	EG004 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —	— / —	— / —
other Total, other adverse events	26 / —	25 / —	27 / —	22 / —	22 / —
serious Total, serious adverse events	11 / —	5 / —	10 / —	7 / —	2 / —

Outcome results

Primary

Mean Change of CR/LT From Baseline at Week 12

CR/LT measured in micrometers (µm); lower individual values represent better outcomes.

Time frame: Baseline and at Week 12

Population: Full Analysis Set (FAS) used for analysis, Last Observation Carried Forward (LOCF)

Arm	Measure	Value (MEAN)	Dispersion
Aflibercept Injection 0.5mg q4	Mean Change of CR/LT From Baseline at Week 12	-153.5 μm	Standard Deviation 113.3
Aflibercept Injection 0.5mg q12	Mean Change of CR/LT From Baseline at Week 12	-75.6 μm	Standard Deviation 110.64
Aflibercept Injection 2.0mg q4	Mean Change of CR/LT From Baseline at Week 12	-169.2 μm	Standard Deviation 138.46
Aflibercept Injection 2.0mg q12	Mean Change of CR/LT From Baseline at Week 12	-56.3 μm	Standard Deviation 133.05
Aflibercept Injection 4.0mg q12	Mean Change of CR/LT From Baseline at Week 12	-139.8 μm	Standard Deviation 228.59
Total	Mean Change of CR/LT From Baseline at Week 12	-118.8 μm	Standard Deviation 155.31

Secondary

Mean Change in Best Corrected Visual Acuity (BCVA) as Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) From Baseline at Week 12

Defined study baseline range of ETDRS Best Corrected Visual Acuity of: letter score of 73 to 25 (20/40 to 20/320) in the study eye; a higher score represents better functioning

Time frame: Baseline and at week 12