Clinical Efficacy and Mechanistic Evaluation of Aflibercept for Proliferative Diabetic Retinopathy

Phase 1

• Conditions: Proliferative Diabetic Retinopathy (PDR); Therapeutic area: Body processes [G] - Ocular Physiological Phenomena [G14]

• Registration Number: EUCTR2013-003272-12-GB
• Lead Sponsor: Moorfields Eye Hospital

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2014-03-31
• Study Completion: 2016-12-21
• Last Update Posted: 30 April 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 232

Inclusion Criteria

1.Subjects of either sex aged 18 years or over.
2.Diagnosis of diabetes mellitus (type 1 or type 2).
3.Best corrected visual acuity in the study eye better than or equal to 54 ETDRS letters (Snellen visual acuity 6/24).
Please see section 6.3 Re-screening of patients
4.Visual acuity in fellow eye = 2/60
5.PDR with no evidence of previous PRP or presence of new or persistent retinal neovascularisation despite prior PRP that (a) requires treatment in the opinion of the investigator and (b) there is sufficient space in the peripheral retina to perform more PRP treatment. In patients with both eye involvement, the eye with no PRP or the least number of PRP burns will be randomised as the study eye. If both eyes have had no PRP before, the eye with the better visual acuity will be randomised as the study eye. However, patients will be offered a choice and can opt for the ‘worse seeing eye’ to be randomised
6.Media clarity, pupillary dilation and subject cooperation sufficient for adequate fundus photographs. Eyes with mild pre-retinal haemorrhage or mild vitreous haemorrhage that does not interfere with clear visualisation of the macula and optic disc are eligible for this study.
7.Ability to give informed consent
8.Women should use effective contraception, be post-menopausal for at least 12 months prior to trial entry, or surgically sterile

Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 110
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 110

Exclusion Criteria

1.Co-existent ocular disease that will affect visual outcome.
2.Moderate or dense vitreous haemorrhage that prevents clear visualisation of the macula and/or optic disc or prevents PRP treatment.
3.Significant fibrovascular proliferation or tractional retinal detachment in the posterior pole.
4.Prior vitrectomy.
5.Presence of macular oedema at baseline confirmed by 3D OCT-1000 (Topcon) SD-OCT as central subfield thickness of more than 300µm due to the presence of morphological evidence of diffuse or cystoid oedema. The equivalent measurement for Spectralis OCT is 320µm and Cirrus HD-OCT is 300µm. Please see rescreening of patients.
6.Other causes of retinal neovascularisation.
7.Iris or angle neovascularisation and neovascular glaucoma.
8.Anticipated need for cataract extraction or vitrectomy within the next 12 months.
9.Known allergy to fluorescein or any components of aflibercept formulation.
10.Previous intravitreal anti-VEGF or steroid treatment for diabetic macular oedema in the last 4 months. (Previous Iluvien therapy is an exclusion).
11.Panretinal photocoagulation within the last 8 weeks.
12.Aphakia.
13.Uncontrolled glaucoma as per investigator’s judgement.
14.Severe external ocular infection.

Exclusion criteria also apply to systemic conditions as follows:

15.The participant should not have an HbA1c level of more than 12%. Please see section 6.3 Re-screening of patients.
16.The participant should not have a blood pressure of more than 170/110mmHg. Please see section 6.3 Re-screening of patients.
17.A medical condition that, in the opinion of the investigator, would preclude participation in the study.
18.Myocardial infarction, stroke, transient ischaemic attack, acute congestive cardiac failure or any acute coronary event within 6 months of randomisation.
19.Dialysis or renal transplant.
20.Pregnant women.
21.Women of child bearing potential who do not agree to use effective contraception during the study and for at least 3 months after the study has finished.
22.Breast feeding women.
23.Males who do not agree to use an effective form of contraception for the duration of the study and for 3 months after the study has finished.
24.Participation in an investigational trial involving an investigational medicinal product within 30 days of randomisation.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified