A randomised, double-masked phase III study of the efficacy and safety of Avastin® (bevacizumab) intravitreal injections compared to best available therapy in subjects with choroidal neovascularisation secondary to age-related macular degeneration

ISRCTN	ISRCTN83325075
DOI	https://doi.org/10.1186/ISRCTN83325075
Clinical Trials Information System (CTIS)	2006-001544-31
Protocol serial number	REC reference number 06/Q0504/46. EudraCT number 2006-001544-31
Sponsor	Moorfields Eye Hospital NHS Foundation Trust (UK)
Funder	The Special Trustees of Moorfields Eye Hospital NHS Foundation Trust (UK)

Submission date: 27/10/2006
Registration date: 29/11/2006
Last edited: 10/05/2012

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Eye Diseases

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Mr Adnan Tufail
Scientific

Moorfields Eye Hospital NHS Foundation Trust
162 City Road
London
EC1V 2PD
United Kingdom

Study information

Primary study design	Interventional
Study design	Prospective, double masked, randomised, controlled trial
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title
Study acronym	ABC
Study objectives	To determine the efficacy and safety of intravitreal Avastin® (bevacizumab) intravitreal injections compared to usual care (verteporfin photodynamic therapy, Macugen® or sham) in treating choroidal neovascularisation (CNV) due to age-related macular degeneration (AMD). Please note that, as of 24/09/2008, the anticipated end date of this trial has been updated from 01/12/2007 to 05/12/2008.
Ethics approval(s)	Moorfields and Whittington Local Research Ethics Committee, date of approval 14 July 2006 (ref: 06/Q0504/46). Added as of 06/10/2008: An additional approval has been granted from the Guy's Research Ethics Committee on the 5th April 2007 to allow recruitment at additional trial sites within the UK (ref: 07/Q0704/20).
Health condition(s) or problem(s) studied	Choroidal neovascularisation (CNV) secondary to age-related macular degeneration (AMD)
Intervention	1. Intravitreal Avastin® (bevacizumab) with placebo PDT where necessary to maintain masking 2. Verteporfin PDT with sham intravitreal injection 3. Intravitreal Macugen® (pegaptanib sodium) 4. Sham intravitreal injection
Intervention type	Drug
Phase	Phase III
Drug / device / biological / vaccine name(s)	Avastin® (bevacizumab), verteporfin, Macugen® (pegaptanib sodium)
Primary outcome measure(s)	The proportion of subjects who gain 15 letters (3 lines) or more of best corrected visual acuity score at the 12 month timepoint compared with baseline, based on the ETDRS visual acuity chart and assessment at a starting distance of 4 m.
Key secondary outcome measure(s)	Secondary outcome measures amended as of 24/09/2008: 1. The proportion of subjects who lose fewer than 15 letters (approximately 3 lines), the proportion who have gained 5 letters or more (1 line), and the proportion who have gained 10 letters or more (2 lines) in the best corrected visual acuity score at 12 months compared with baseline, based on the ETDRS visual acuity chart and assessment at a starting distance of 4 m 2. The proportion of patients who meet these visual criteria at 6 months 3. To evaluate the safety and tolerability of intravitreal injections of Avastin® given every 6 weeks 4. Mean change in central OCT thickness 5. If the study is continued after the analysis of data at 12 month timepoint, after the second treatment year of the study, the same objectives will be analysed on unmasked data Previous secondary outcome measures: 1. The proportion of subjects who lose fewer than 15 letters (approximately three lines) and the proportion who have gained five letters or more (one line) in the best corrected visual acuity score at 12 months compared with baseline, based on the ETDRS visual acuity chart and assessment at a starting distance of 4 m 2. The proportion of patients who meet these visual criteria at six months 3. To evaluate the safety and tolerability of intravitreal injections of Avastin® given every six weeks 4. Mean change in central OCT thickness 5. If study is continued after the analysis of data at 12 month time point then after the second treatment year of the study, the same objectives will be analysed on unmasked data
Completion date	05/12/2008

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	All
Target sample size at registration	130
Key inclusion criteria	1. Aged over 50 years 2. Primary or subfoveal CNV lesions secondary to AMD in the study eye 3. An occult lesion must have presumed evidence of disease progression, defined as one or more of the following: a. deterioration of best corrected vision by one Snellen line or five letters on Early Treatment Diabetic Retinopathy Study (ETDRS) chart within the past three months due to progression of CNV b. presence of sub- or intra-retinal blood c. growth of lesion size on the angiogram by more than 10% in the past three months AND evidence of increased central macular thickness on Optical Coherence Tomography (OCT) 4. Area of sub-retinal blood less than 50% of total lesion area 5. Best corrected visual acuity, using ETDRS charts, of 20/40 (6/12) to 20/320 (6/96) Snellen equivalent in the study eye 6. Total lesion size less than 12 disc areas including all contiguous lesion components 7. Area of fibrosis less than 25% of the total lesion area
Key exclusion criteria	Ocular: 1. Sub-retinal haemorrhage in the study eye that involves the centre of the fovea, if the size of the haemorrhage is either more than 50% of the total lesion area or more than one disc areas in size 2. Subfoveal fibrosis or atrophy in the study eye 3. CNV in either eye due to causes other than AMD, such as ocular histoplasmosis, trauma, or pathologic myopia 4. Retinal pigment epithelial tear involving the macula in the study eye 5. Prior treatment with external-beam radiation therapy, Transpupillary Thermal Therapy (TTT), thermal laser, or Photo-Dynamic Therapy (PDT) in the study eye or history of submacular surgery or other surgical intervention for AMD in the study eye 6. PDT in the non-study eye less than seven days preceding day zero 7. Previous participation in a clinical trial (for either eye) involving anti-angiogenic drugs (Macugen®, Avastin®, anecortave acetate, protein kinase C inhibitors, etc.) 8. Previous intravitreal drug delivery (e.g., intravitreal corticosteroid injection or device implantation) in the study eye 9. Amblyopia, infective conjunctivitis or scleritis, glaucoma, corneal disease, inflammatory eye disease 10. Diabetic retinopathy more than mild nonproliferative in the fellow eye as defined by the ETDRS or any diabetic maculopathy 11. Intraocular surgery (including cataract surgery) in the study eye within two months preceding day zero 12. Aphakia or absence of the posterior capsule in the study eye 13. Previous violation of the posterior capsule in the study eye is also excluded unless it occurred as a result of Yttrium Aluminum Garnet (YAG) posterior capsulotomy in association with prior, posterior chamber intraocular lens implantation 14. Spherical equivalent of the refractive error in the study eye demonstrating more than -8 diopters of myopia or signs of pathologic myopia with a refraction of 4-8 diopters 15. For subjects who have undergone prior refractive or cataract surgery in the study eye, the preoperative refractive error in the study eye cannot exceed -8 diopters of myopia Systemic: 1. Recent stroke (last six months), or cardiac event (last six months), uncontrolled angina or uncontrolled hypertension 2. Current treatment for active systemic infection 3. Unable to give informed consent 4. Anticoagulant treatment (anti-platelet drugs allowed) 5. Fluorescein or Indo-Cyanine Green (ICG) allergy 6. Pre-menopausal women not using adequate contraception; the following are considered effective means of contraception: surgical sterilisation, use of oral contraceptives, barrier contraception with either a condom or diaphragm in conjunction with spermicidal gel, an Intra-Uterine Device (IUD), or contraceptive hormone implant or patch
Date of first enrolment	11/08/2006
Date of final enrolment	05/12/2008

Locations

Countries of recruitment

United Kingdom
England

Study participating centre

Moorfields Eye Hospital NHS Foundation Trust

London
EC1V 2PD
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	09/06/2010		Yes	No
Results article	results	11/05/2011		Yes	No
Results article	results	09/03/2012		Yes	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes