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Open-label Extension Study of Intravitreal Aflibercept Injection (IAI; EYLEA®; BAY86-5321) in Neovascular ("Wet") Age-related Macular Degeneration (AMD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00964795
Recruitment Status : Completed
First Posted : August 25, 2009
Results First Posted : March 23, 2015
Last Update Posted : March 23, 2015
Sponsor:
Collaborator:
Bayer
Information provided by (Responsible Party):
Regeneron Pharmaceuticals

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Neovascular Age-related Macular Degeneration
Intervention Drug: Intravitreal Aflibercept Injection 2mg
Enrollment 323
Recruitment Details After informed consent was obtained, the 323 participants who completed the parent study, VGFT-OD-0605 (NCT00509795), and met the protocol eligibility criteria, were enrolled at 71 clinical sites in the US & Canada. The first visit occurred concurrently with the last visit in the parent study. The last participant entered this study on 18-May-2011.
Pre-assignment Details Intravitreal Aflibercept Injection [commercially known EYLEA® (aflibercept) Injection] was approved in the US for treatment of neovascular ("wet") age-related macular degeneration (AMD) as the study was ongoing. For collection of long-term safety and best corrected visual acuity data on EYLEA®, the study was extended in the US from 30 to 45 months.
Arm/Group Title Open-label Intravitreal Aflibercept Injection
Hide Arm/Group Description Open-label Intravitreal Aflibercept Injection (IAI; EYLEA®; BAY86-5321) 2mg (40 mg/mL) was administered no more frequently than every 4 weeks, but no less frequently than every 12 weeks until amendment 4. Starting with amendment 4, Intravitreal Aflibercept Injection was administered no less frequently than every 8 weeks. Within these limits, the investigator would determine the interval of Intravitreal Aflibercept Injection administration on an as-needed basis according to the protocol-suggested re-treatment criteria, however the injections must have occurred at least every 12 weeks prior to amendment 4, and at least every 8 weeks starting from amendment 4 as noted above.
Period Title: Overall Study
Started 323 [1]
Number of Participants Treated 320
Completed 16 [2]
Not Completed 307
Reason Not Completed
Withdrawal by Subject             79
Adverse Event             12
Death             14
Lost to Follow-up             7
Termination of Study by Sponsor             169
Unwilling to sign ICF for amendment 4             3
Other             23
[1]
randomized
[2]
Prior to amendment 4, 16 participants completed up to Week 120. No participants completed Week 180.
Arm/Group Title Open-label Intravitreal Aflibercept Injection
Hide Arm/Group Description Open-label Intravitreal Aflibercept Injection (IAI; EYLEA®; BAY86-5321) 2mg (40 mg/mL) was administered no more frequently than every 4 weeks, but no less frequently than every 12 weeks until amendment 4. Starting with amendment 4, Intravitreal Aflibercept Injection was administered no less frequently than every 8 weeks. Within these limits, the investigator would determine the interval of Intravitreal Aflibercept Injection administration on an as-needed basis according to the protocol-suggested re-treatment criteria, however the injections must have occurred at least every 12 weeks prior to amendment 4, and at least every 8 weeks starting from amendment 4 as noted above.
Overall Number of Baseline Participants 323
Hide Baseline Analysis Population Description
Randomized participants included all participants who were enrolled in the study. The data were used to analyze the safety and efficacy parameters to characterize the long-term effect of Intravitreal Aflibercept Injection treatment. The average study duration for all enrolled participants was 116.9 weeks.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 323 participants
79  (7.83)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 323 participants
Female
196
  60.7%
Male
127
  39.3%
1.Primary Outcome
Title Safety and Tolerability of Intravitreal Aflibercept Injection in Participants With Neovascular AMD
Hide Description

The primary endpoint in the study is the safety and tolerability of Intravitreal Aflibercept Injection in patients with neovascular AMD (Age-related Macular Degeneration) from day 1 through the end of treatment visit (week 180) based on the number of participants who experienced any treatment-emergent adverse event (TEAE).

Treatment-emergent adverse events were categorized according to Ocular TEAEs in the study eye, Ocular TEAEs in the fellow eye, and Non-Ocular TEAEs

Time Frame Baseline (day 1) through end of treatment (Week 180)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Open-label Intravitreal Aflibercept Injection
Hide Arm/Group Description:
Open-label Intravitreal Aflibercept Injection (IAI; EYLEA®; BAY86-5321) 2 mg (40 mg/mL) was administered no more frequently than every 4 weeks, but no less frequently than every 12 weeks until amendment 4. Starting with amendment 4, Intravitreal Aflibercept Injection was administered no less frequently than every 8 weeks. Within these limits, the investigator would determine the interval of Intravitreal Aflibercept Injection administration on an as-needed basis according to the protocol-suggested re-treatment criteria, however the injections must have occurred at least every 12 weeks prior to amendment 4, and at least every 8 weeks starting from amendment 4 as noted above.
Overall Number of Participants Analyzed 323
Measure Type: Number
Unit of Measure: participants
Number of participants with any TEAE 290
Any ocular TEAE 239
Any ocular TEAE: Study eye 204
Any ocular TEAE: Fellow eye 169
Any non-ocular TEAE 232
Any serious TEAE 105
Discontinuation of study due to AE 12
Any Death due to TEAE 17
2.Secondary Outcome
Title Change in BCVA Letter Score (mLOCF)
Hide Description

The secondary endpoint in the study is the change in BCVA letter score from baseline through Week 116.

(mLOCF: The last non-missing observation prior to the missing visit was carried forward to impute the missing data; no imputation after last visit; no baseline value carried forward).

Time Frame Baseline through Week 116
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Open-label Intravitreal Aflibercept Injection
Hide Arm/Group Description:
Open-label Intravitreal Aflibercept Injection (IAI; EYLEA®; BAY86-5321) 2mg (40 mg/mL) was administered no more frequently than every 4 weeks, but no less frequently than every 12 weeks until amendment 4. Starting with amendment 4, Intravitreal Aflibercept Injection was administered no less frequently than every 8 weeks. Within these limits, the investigator would determine the interval of Intravitreal Aflibercept Injection administration on an as-needed basis according to the protocol-suggested re-treatment criteria, however the injections must have occurred at least every 12 weeks prior to amendment 4, and at least every 8 weeks starting from amendment 4 as noted above.
Overall Number of Participants Analyzed 323
Mean (Standard Deviation)
Unit of Measure: letters correctly read
-2.7  (12.50)
3.Other Pre-specified Outcome
Title Summary of Treatment Duration (Weeks)
Hide Description Treatment Duration = (last dose date - first dose date + 28)/7
Time Frame Baseline through end of treatment (Week 180)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Open-label Intravitreal Aflibercept Injection
Hide Arm/Group Description:
Open-label Intravitreal Aflibercept Injection (IAI; EYLEA®; BAY86-5321) 2mg (40 mg/mL) was administered no more frequently than every 4 weeks, but no less frequently than every 12 weeks until amendment 4. Starting with amendment 4, Intravitreal Aflibercept Injection was administered no less frequently than every 8 weeks. Within these limits, the investigator would determine the interval of Intravitreal Aflibercept Injection administration on an as-needed basis according to the protocol-suggested re-treatment criteria, however the injections must have occurred at least every 12 weeks prior to amendment 4, and at least every 8 weeks starting from amendment 4 as noted above.
Overall Number of Participants Analyzed 323
Mean (Standard Deviation)
Unit of Measure: weeks
110.4  (42.16)
4.Other Pre-specified Outcome
Title Summary of Study Duration (Weeks)
Hide Description Study Duration = (last visit/ discontinuation date - first dose date + 28)/7
Time Frame Baseline through end of treatment (Week 180)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Open-label Intravitreal Aflibercept Injection
Hide Arm/Group Description:
Open-label Intravitreal Aflibercept Injection (IAI; EYLEA®; BAY86-5321) 2mg (40 mg/mL) was administered no more frequently than every 4 weeks, but no less frequently than every 12 weeks until amendment 4. Starting with amendment 4, Intravitreal Aflibercept Injection was administered no less frequently than every 8 weeks. Within these limits, the investigator would determine the interval of Intravitreal Aflibercept Injection administration on an as-needed basis according to the protocol-suggested re-treatment criteria, however the injections must have occurred at least every 12 weeks prior to amendment 4, and at least every 8 weeks starting from amendment 4 as noted above.
Overall Number of Participants Analyzed 323
Mean (Standard Deviation)
Unit of Measure: weeks
116.9  (44.3)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Open-label Intravitreal Aflibercept Injection
Hide Arm/Group Description Open-label Intravitreal Aflibercept Injection (IAI; EYLEA®; BAY86-5321) 2 mg (40 mg/mL) was administered no more frequently than every 4 weeks, but no less frequently than every 12 weeks until amendment 4. Starting from amendment 4, Intravitreal Aflibercept Injection was administered no less frequently than every 8 weeks. Within these limits, the investigator would determine the interval of Intravitreal Aflibercept Injection administration on an as-needed basis according to the protocol-suggested re-treatment criteria, however the injections must have occurred at least every 12 weeks prior to amendment 4, and at least every 8 weeks starting from amendment 4 as noted above.
All-Cause Mortality
Open-label Intravitreal Aflibercept Injection
Affected / at Risk (%)
Total   --/-- 
Hide Serious Adverse Events
Open-label Intravitreal Aflibercept Injection
Affected / at Risk (%)
Total   105/323 (32.51%) 
Blood and lymphatic system disorders   
Anaemia  2/323 (0.62%) 
Coagulopathy  1/323 (0.31%) 
Haemorrhagic Anaemia  1/323 (0.31%) 
Iron Deficiency Anaemia  1/323 (0.31%) 
Cardiac disorders   
Acute Myocardial Infarction  5/323 (1.55%) 
Angina Pectoris  3/323 (0.93%) 
Arrhythmia  2/323 (0.62%) 
Atrial Fibrillation  12/323 (3.72%) 
Bundle Branch Block Right  1/323 (0.31%) 
Cardiac Arrest  4/323 (1.24%) 
Cardiac Failure Acute  3/323 (0.93%) 
Cardiac Failure Congestive  3/323 (0.93%) 
Cardiogenic Shock  1/323 (0.31%) 
Cardiomyopathy  1/323 (0.31%) 
Coronary Artery Disease  4/323 (1.24%) 
Myocardial Infarction  4/323 (1.24%) 
Myocardial Rupture  1/323 (0.31%) 
Pericarditis  1/323 (0.31%) 
Tachycardia  1/323 (0.31%) 
Ventricular Tachycardia  1/323 (0.31%) 
Eye disorders   
Retinal Haemorrhage  1/323 (0.31%) 
Angle Closure Glaucoma 1 [1]  1/323 (0.31%) 
Cataract 1 [1]  1/323 (0.31%) 
Glaucoma 1 [1]  1/323 (0.31%) 
Retinal Haemorrhage 1 [1]  2/323 (0.62%) 
Retinal Oedema 1 [1]  1/323 (0.31%) 
Visual Acuity Reduced 1 [1]  1/323 (0.31%) 
Gastrointestinal disorders   
Appendix Disorder  1/323 (0.31%) 
Colitis  1/323 (0.31%) 
Colitis Ischaemic  1/323 (0.31%) 
Diarrhoea  3/323 (0.93%) 
Dysphagia  1/323 (0.31%) 
Gastrointestinal Angiodysplasia Haemorrhagic  1/323 (0.31%) 
Hiatus Hernia  1/323 (0.31%) 
Ileus  1/323 (0.31%) 
Impaired Gastric Emptying  1/323 (0.31%) 
Intestinal Obstruction  1/323 (0.31%) 
Large Intestine Perforation  1/323 (0.31%) 
Lower Gastrointestinal Haemorrhage  1/323 (0.31%) 
Nausea  1/323 (0.31%) 
Pancreatitis  2/323 (0.62%) 
Vomiting  3/323 (0.93%) 
General disorders   
Asthenia  1/323 (0.31%) 
Chest Pain  1/323 (0.31%) 
Device Dislocation  1/323 (0.31%) 
Multi-Organ Failure  1/323 (0.31%) 
Non-Cardiac Chest Pain  1/323 (0.31%) 
Device Dislocation 1 [1]  1/323 (0.31%) 
Hepatobiliary disorders   
Biliary Dyskinesia  1/323 (0.31%) 
Cholecystitis Acute  1/323 (0.31%) 
Hepatic Haemorrhage  1/323 (0.31%) 
Immune system disorders   
Anaphylactic Reaction  1/323 (0.31%) 
Infections and infestations   
Abdominal Abscess  1/323 (0.31%) 
Abscess  1/323 (0.31%) 
Appendicitis  1/323 (0.31%) 
Bronchitis  1/323 (0.31%) 
Bronchitis Viral  1/323 (0.31%) 
Cellulitis  3/323 (0.93%) 
Clostridium Difficile Colitis  1/323 (0.31%) 
Escherichia Urinary Tract Infection  1/323 (0.31%) 
Gastroenteritis  1/323 (0.31%) 
Gastroenteritis Norovirus  1/323 (0.31%) 
Gastroenteritis Viral  1/323 (0.31%) 
Pericolic Abscess  1/323 (0.31%) 
Peritonitis  1/323 (0.31%) 
Pneumonia  5/323 (1.55%) 
Pneumonia Bacterial  1/323 (0.31%) 
Pneumonia Respiratory Syncytial Viral  1/323 (0.31%) 
Pneumonia Viral  1/323 (0.31%) 
Pyelonephritis Acute  1/323 (0.31%) 
Sepsis  3/323 (0.93%) 
Septic Shock  1/323 (0.31%) 
Urinary Tract Infection  5/323 (1.55%) 
Urosepsis  1/323 (0.31%) 
Endophthalmitis 1 [1]  3/323 (0.93%) 
Injury, poisoning and procedural complications   
Accident  2/323 (0.62%) 
Coronary Artery Restenosis  1/323 (0.31%) 
Facial Bones Fracture  3/323 (0.93%) 
Fall  16/323 (4.95%) 
Femoral Neck Fracture  2/323 (0.62%) 
Gastrointestinal Anastomotic Leak  1/323 (0.31%) 
Hip Fracture  2/323 (0.62%) 
Humerus Fracture  3/323 (0.93%) 
Pancreatic Leak  1/323 (0.31%) 
Radius Fracture  1/323 (0.31%) 
Road Traffic Accident  1/323 (0.31%) 
Splenic Rupture  2/323 (0.62%) 
Upper Limb Fracture  1/323 (0.31%) 
Wrist Fracture  1/323 (0.31%) 
Corneal Abrasion 1 [1]  1/323 (0.31%) 
Femur Fracture  2/323 (0.62%) 
Investigations   
Blood Pressure Increased  1/323 (0.31%) 
Intraocular Pressure Increased 1 [1]  1/323 (0.31%) 
Metabolism and nutrition disorders   
Dehydration  4/323 (1.24%) 
Diabetes Mellitus Inadequate Control  1/323 (0.31%) 
Hyperglycaemia  1/323 (0.31%) 
Hypokalaemia  1/323 (0.31%) 
Hyponatraemia  1/323 (0.31%) 
Malnutrition  1/323 (0.31%) 
Musculoskeletal and connective tissue disorders   
Arthritis  1/323 (0.31%) 
Back Pain  1/323 (0.31%) 
Haemarthrosis  1/323 (0.31%) 
Osteoarthritis  4/323 (1.24%) 
Osteoporotic Fracture  1/323 (0.31%) 
Spinal Osteoarthritis  2/323 (0.62%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Bone Cancer  1/323 (0.31%) 
Breast Cancer  2/323 (0.62%) 
Breast Cancer Recurrent  1/323 (0.31%) 
Chronic Leukaemia  1/323 (0.31%) 
Chronic Myelomonocytic Leukaemia  1/323 (0.31%) 
Intraductal Proliferative Breast Lesion  1/323 (0.31%) 
Invasive Ductal Breast Carcinoma  1/323 (0.31%) 
Laryngeal Squamous Cell Carcinoma  1/323 (0.31%) 
Lung Adenocarcinoma  2/323 (0.62%) 
Oesophageal Carcinoma  1/323 (0.31%) 
Rectal Adenocarcinoma  2/323 (0.62%) 
Renal Cancer  1/323 (0.31%) 
Squamous Cell Carcinoma  1/323 (0.31%) 
Squamous Cell Carcinoma Of Lung  1/323 (0.31%) 
Nervous system disorders   
Carotid Artery Stenosis  1/323 (0.31%) 
Cerebral Haemorrhage  1/323 (0.31%) 
Cerebral Infarction  1/323 (0.31%) 
Cerebrovascular Accident  5/323 (1.55%) 
Convulsion  1/323 (0.31%) 
Embolic Stroke  1/323 (0.31%) 
Facial Neuralgia  1/323 (0.31%) 
Hemiplegia  1/323 (0.31%) 
Hypertensive Encephalopathy  1/323 (0.31%) 
Intracranial Haematoma  1/323 (0.31%) 
Ischaemic Stroke  1/323 (0.31%) 
Subarachnoid Haemorrhage  1/323 (0.31%) 
Syncope  8/323 (2.48%) 
Transient Ischaemic Attack  4/323 (1.24%) 
Psychiatric disorders   
Major Depression  1/323 (0.31%) 
Mental Status Changes  3/323 (0.93%) 
Psychotic Disorder  1/323 (0.31%) 
Renal and urinary disorders   
Calculus Ureteric  1/323 (0.31%) 
Nephrolithiasis  1/323 (0.31%) 
Obstructive Uropathy  1/323 (0.31%) 
Renal Failure Acute  4/323 (1.24%) 
Renal Failure Chronic  1/323 (0.31%) 
Ureteric Obstruction  1/323 (0.31%) 
Reproductive system and breast disorders   
Uterine Polyp  1/323 (0.31%) 
Respiratory, thoracic and mediastinal disorders   
Acute Respiratory Failure  1/323 (0.31%) 
Aspiration  1/323 (0.31%) 
Chronic Obstructive Pulmonary Disease  4/323 (1.24%) 
Dyspnoea  1/323 (0.31%) 
Laryngospasm  1/323 (0.31%) 
Pleural Effusion  1/323 (0.31%) 
Pulmonary Embolism  2/323 (0.62%) 
Respiratory Arrest  1/323 (0.31%) 
Skin and subcutaneous tissue disorders   
Perivascular Dermatitis  1/323 (0.31%) 
Surgical and medical procedures   
Colectomy  1/323 (0.31%) 
Medical Device Removal  1/323 (0.31%) 
Vascular disorders   
Hypertension  1/323 (0.31%) 
1
Term from vocabulary, MedDRA 14.0
[1]
Study eye
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Open-label Intravitreal Aflibercept Injection
Affected / at Risk (%)
Total   102/323 (31.58%) 
Eye disorders   
Age-Related Macular Degeneration  30/323 (9.29%) 
Retinal Haemorrhage  39/323 (12.07%) 
Cataract 1 [1]  17/323 (5.26%) 
Conjunctival Haemorrhage 1 [1]  30/323 (9.29%) 
Posterior Capsule Opacification 1 [1]  18/323 (5.57%) 
Retinal Detachment 1 [1]  17/323 (5.26%) 
Retinal Haemorrhage 1 [1]  34/323 (10.53%) 
Gastrointestinal disorders   
Nausea  22/323 (6.81%) 
Infections and infestations   
Bronchitis  19/323 (5.88%) 
Nasopharyngitis  22/323 (6.81%) 
Upper Respiratory Tract Infection  20/323 (6.19%) 
Injury, poisoning and procedural complications   
Fall  23/323 (7.12%) 
Musculoskeletal and connective tissue disorders   
Arthralgia  17/323 (5.26%) 
Vascular disorders   
Hypertension  29/323 (8.98%) 
1
Term from vocabulary, MedDRA 14.0
[1]
Study eye
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
The investigator (PI) may publish results provided a copy of oral/ written publication is received by sponsor at least 45 days in advance for review & comment. If the parties disagree, PI agrees to meet with sponsor prior to submission to resolve any disagreement. Sponsor reserves the right to remove confidential information from such submission. It is also agreed that publication of results shall be made only as part of a publication of the results obtained by all sites performing the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Clinical Trials Administrator
Organization: Regeneron
Phone: 9148475385
EMail: clinicaltrials@regeneron.com
Layout table for additonal information
Responsible Party: Regeneron Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00964795    
Other Study ID Numbers: VGFT-OD-0910
First Submitted: August 20, 2009
First Posted: August 25, 2009
Results First Submitted: August 28, 2014
Results First Posted: March 23, 2015
Last Update Posted: March 23, 2015