An early-stage study to see if U8:ranibizumab eye drops are safe, well-tolerated, and effective for patients with a specific eye condition called choroidal neovascularisation

ISRCTN	ISRCTN16566739
DOI	https://doi.org/10.1186/ISRCTN16566739
Integrated Research Application System (IRAS)	1011235
Sponsor's protocol code number	118988
Sponsor	University College London
Funder	Wellcome Trust

Submission date: 30/01/2026
Registration date: 12/02/2026
Last edited: 07/05/2026

Recruitment status: Recruiting
Overall study status: Ongoing
Condition category: Eye Diseases

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Background and study aims
U8:ranibizumab eye drops are being developed as a potential treatment for wet age-related macular degeneration (AMD), which is where abnormal blood vessels grow in the macula (part of the eye), leading to fluid or blood leakage, rapid damage to central vision, and eventual scarring. Symptoms include distorted vision, blind spots, and difficulty seeing colours. The current medicine used to treat wet AMD is given by injection to the eye, which is an uncomfortable and potentially risky procedure for patients. A medicine given as an eye drop would be minimally invasive and would eliminate any side effects caused by the injection procedure. In this trial, we will investigate whether the study drug causes any important side effects and compare its effectiveness with medicines currently used to treat wet AMD.

Who can participate?
Patients aged 60+ years who have been diagnosed with wet AMD

What does the study involve?
Participants will initially receive three doses of the current medicine used to treat wet AMD and then they will be provided the study drug to self-administer once daily for 12 weeks. Participants will be monitored throughout the trial for any side effects and they will return to the unit every 2 weeks for safety assessments to be performed. Once participants have completed dosing, they will be monitored for a further 4 weeks for any side effects. Participants will return to the unit for one final visit at the end of the follow-up period to be discharged from the trial and returned to standard of care treatment. Participants will be involved in the trial for 28 weeks (7 months) in total, from the first injection of the current medicine until the discharge visit.

What are the possible benefits and risks of participating?
Although ranibizumab has been used for many years in eye treatments, it has previously been administered as an injection rather than as an eye drop. The eye drop being tested in this study is therefore new and has not been available before, meaning that only limited information is currently available about its effects. So far, no side effects have been observed when ranibizumab eye drops have been used in living eyes. Because this particular ranibizumab formulation has not previously been used in humans to treat wet AMD, the data we have are limited. It is unlikely that you will experience all, or even many, of the side effects listed below, but it is not possible to predict which ones you may experience or how severe they might be. Given the limited data, there is also a possibility that other side effects could occur.
Possible side effects associated with ranibizumab eye drops include: eye discomfort or pain, very mild irritation (including slight redness or swelling of the eye), and occasional minor eye discharge.
Side effects that have been linked to chitosan include constipation, flatulence, and abdominal symptoms. Lutrol-127 has been associated with mild eye or skin irritation.
Other potential risks include:
Eye examination (as part of standard care): This may be uncomfortable, as you will need to remain still for 3–4 minutes, and bright or flashing lights may be used, which can cause temporary discomfort.
Routine eye drops used during eye examinations (as part of standard care):
Dilating drops (phenylephrine 2.5%, proxymetacaine hydrochloride 0.5%, and tropicamide 1%) may occasionally cause allergic reactions, breathing difficulties, low blood pressure, palpitations, abnormal heart rhythm (arrhythmia), heart attack, redness or irritation of the eyes, headache, blurred vision, nausea, or dizziness.
Fluorescein sodium 1% eye drops can, in very rare cases, cause allergic reactions, irritation, or swelling of the eye.
Any potential side effects or reactions will be minimised through more frequent follow-up visits every 2 weeks during the trial while participants are using the study eye drops. This regular monitoring will help identify any problems early. These visits are more frequent than those in standard care, which normally occur every 2 months.
Participants will be closely monitored and if there is any concern, then they will be returned to standard care (eye injections).

Where is the study run from?
Imperial College Ophthalmology Research Group Unit (UK), Western Eye Hospital

When is the study starting and how long is it expected to run for?
April 2026 to July 2026

Who is funding the study?
Wellcome Trust (UK)

Who is the main contact?
Prof. Francesca Cordeiro, m.cordeiro@ucl.ac.uk

Contact information

Prof Francesca Cordeiro
Scientific, Public

Joint Research Office, 4th Floor West, 250 Euston Road
London
NW1 2PG
United Kingdom

Email	m.cordeiro@ucl.ac.uk

Dr Saad Younis
Principal investigator

Western Eye Hospital, 153- 173 Marylebone Road
London
NW1 5QH
United Kingdom

Email	saad.younis@nhs.net

Study information

Primary study design	Interventional
Allocation	N/A: single arm study
Masking	Open (masking not used)
Control	Uncontrolled
Assignment	Single
Purpose	Treatment
Scientific title	A Phase I/IIa open-label proof of concept study to assess the safety, tolerability and efficacy of U8:Ranibizumab Eye drops in patients with choroidal neovascularisation
Study acronym	AVID
Study objectives	Primary objective: To assess the safety and tolerability of topical U8:ranibizumab 8.5 mg/ml eye drops Secondary objective: To assess the efficacy of U8:ranibizumab 8.5 mg/ml eye drops
Ethics approval(s)	Approved 26/03/2026, London - Surrey Borders Research Ethics Committee (2 Redman Place, Stratford, London, E20 1JQ, United Kingdom; -; surreyborders.rec@hra.nhs.uk), ref: 26/LO/0164
Health condition(s) or problem(s) studied	Wet age-related macular degeneration
Intervention	U8:ranibizumab 8.5 mg/ml eye drops – a single daily dose for 12 weeks
Intervention type	Drug
Phase	Phase I
Drug / device / biological / vaccine name(s)	Ranibizumab
Primary outcome measure(s)	Observations relating to local ocular tolerability, including: visual analogue scale (VAS) scores for comfort, slit lamp biomicroscopy findings (e.g., conjunctival hyperaemia, corneal changes), visual acuity and fundus ophthalmoscopy 1. A global ocular discomfort score will be determined using a 100 mm visual analogue scale (VAS) on which 0 means no symptoms and 100 means the worst possible discomfort. This evaluation is to be performed before any ophthalmic assessment at a given study visit 2. Specific ocular symptoms assessed at the time of the VAS including foreign body sensation, burning/stinging, itching, pain, sticky feeling, blurred vision, photophobia 3. Slit-lamp examination to assess the eyelid margin, conjunctiva, cornea, anterior chamber, iris and lens with the instillation of fluorescein to evaluate corneal fluorescein staining (modified Oxford scale) and tear film break-up time Measured 2 weekly whilst taking the trial eye drop, starting from 1 month (30 days) following the third standard anti-VEGF injection 3 until the patient completes 4 months of the trial eye drop.
Key secondary outcome measure(s)	Secondary efficacy endpoint and outcome measures: Patterns of disease activity that may need for retreatment where the re-treatment with intravitreal ranibizumab is indicated by any new or increase in disease activity as determined by: 1. >5-letter decrease in VA compared to previous vision 2. Any evidence of disease activity on SD-OCT (e.g. intraretinal fluid, subretinal fluid, or subretinal pigment epithelial fluid) using Spectralis-OCT Safety endpoints: 1. Observations on the safety and tolerability of U8:ranibizumab 8.5 mg/ml eye drops, including ocular and non-ocular events noted during treatment and 30 days following trial discontinuation. 2. Non-ocular adverse events will be assessed for the safety set; ocular adverse events will be assessed for the primary treated eye set. 3. Safety will be assessed through AEs, and change in local ocular tolerability - assessed using a visual analogue scale (VAS), slit-lamp biomicroscopy to assess conjunctival hyperaemia and corneal toxicity, visual acuity and fundus ophthalmoscopy 4. A global ocular discomfort score will be determined using a 100 mm visual analogue scale (VAS) on which 0 means no symptoms and 100 means the worst possible discomfort. This evaluation is to be performed before any ophthalmic assessment at a given study visit. 5. Specific ocular symptoms to be assessed with the VAS include: foreign body sensation, burning/stinging, itching, pain, sticky feeling, blurred vision, photophobia 6. Slit-lamp examination to assess the eyelid margin, conjunctiva, cornea, anterior chamber, iris and lens with the instillation of fluorescein to evaluate corneal fluorescein staining (modified Oxford scale) and tear film break-up time. 7. Concomitant medication use will also be documented. 8. All SAEs reported to or noted by the clinician from the time the patient signs the informed consent until 30 days after study discontinuation will be recorded in the AE CRF and reported to Sponsor (please see section 9: Pharmacovigilance). All AEs will be captured on the AE CRF throughout the entire study period. AEs detected through ophthalmic examinations will be collected if available. Measured 2 weekly whilst taking the trial eye drop, starting from 1 month (30 days) following the third standard anti-VEGF injection 3 until the patient completes 4 months of the trial eye drop
Completion date	31/07/2026

Eligibility

Participant type(s)
Age group	Mixed
Lower age limit	60 Years
Upper age limit	100 Years
Sex	All
Target sample size at registration	3
Key inclusion criteria	1. Aged ≥60 years at the time of signing informed consent. 2. Males and females (WONCBP) 3. Clear optical media in the studied eye. 4. Refractive error not higher than spherical equivalent of 10 D and best corrected visual acuity equal to 6/24 or better at qualification. 5. Subjects who have capacity to consent, have personally signed and dated the informed consent form 6. Subjects who are having treatment with ranibizumab for wet AMD initiated. 7. Subjects should have shown a good response to loading doses of anti-VEGF (3 injections of anti-VEGF over 3 months) before ranibizumab eye drops are started. The good response will be as determined by the clinician. 8. Ability to administer eye drops independently or with assistance WONCBP: not considered to be a women of childbearing potential, i.e., postmenopausal or permanently sterilised (e.g. tubal occlusion, hysterectomy, bilateral salpingectomy). A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle-stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient. ** Participant will be provided with necessary training tools to facilitate eye drop use, this will be through the means of visual graphics and booklets demonstrating use.
Key exclusion criteria	1. Subjects with “only eye” (one functional eye) 2. Presence of severe, unstable or uncontrolled systemic disease, for example, recent myocardial infarction, recent stroke 3. Body weight <40 kg or >150 kg 4. If patients are unable to self-administer, comply with the study or follow-up procedures, we will explore whether there is a carer or friend/relative who can. If there is no such person who can help instil drops, then this patient will be excluded. 5. Subjects who have had ocular surgery within the past 3 months, or planned surgery in the study eye during the course of the trial 6. Currently being treated for cancer or any other disease likely to adversely affect participation in this study 7. Positive Hepatitis B surface antigen (HBsAg), Hepatitis C virus antibody (HCV Ab) or Human Immunodeficiency Virus (HIV) 1 and 2 antibody results, as per patients’ electronic medical records 8. History of alcoholism or drug addiction within the last 2 years, as per patients’ electronic medical records 9. History or active uveitis 10. History of systemic vasculitis or collagenosis 11. Evidence of previous retinal vascular disease, for example, retinal vein occlusion, retinal artery occlusion 12. Individuals with terminal illness, or clinically significant mental illness as judged by the investigator 13. Simultaneous participation in a study that includes administration of any investigational drug or procedure 14. Systemic or ocular treatment with any VEGF inhibitor other than ranibizumab in the 90 days prior to enrolment 15. The non-study eye has a best corrected visual acuity (BCVA) worse than 20 letters (ETDRS) at the screening visit 16. Women of childbearing potential (WOCBP) 17. If participant is unable to read and understand English language
Date of first enrolment	20/05/2026
Date of final enrolment	31/07/2026

Locations

Countries of recruitment

United Kingdom
England

Study participating centre

Western Eye Hospital

153-173 Marylebone Road
London
NW1 5QH
England

Results and Publications

Individual participant data (IPD) Intention to share	No

Editorial Notes

07/05/2026: The date of first enrolment was changed from 01/05/2026 to 20/05/2026.
02/04/2026: The date of first enrolment was changed from 01/04/2026 to 01/05/2026.
31/03/2026: ISRCTN received notification of combined HRA/MHRA approval for this trial on 31/03/2026
30/03/2026: Ethics approval was added.
30/01/2026: Study's existence confirmed by the HRA.