Vitrectomy and subretinal TPA for submacular haemorrhage secondary to wet AMD (TIGER).

Overview

Sponsor-declared trial summary

Key facts

Sponsor

King's College London, King's College Hospital NHS Foundation Trust

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Eye Diseases [C11]

Trial duration

24 Sep 2024 → ongoing

Decision date (initial)

2023-11-20

Transition trial

Yes

Low-intervention

Yes

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Fight for Sight · King's College Hospital Charity

External identifiers

EU CT number

2023-504751-28-00

EudraCT number

2020-004917-10

ClinicalTrials.gov

NCT04663750

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To assess the safety and efficacy of vitrectomy, subretinal TPA, intravitreal SF6 gas and intravitreal anti-VEGF as a treatment for SMH secondary to exudative AMD, versus standard of care with anti-VEGF
monotherapy.

Secondary objectives 6

1. Gain of at least 10 ETDRS letters of vision (month 6)
2. Mean ETDRS BCVA
3. Radner reading speed
4. National Eye Institute (NEI) Visual Function Questionnaire composite score
5. Scotoma size (Humphrey Field Analyser 10-2)
6. Presence/absence of subfoveal fibrosis and/or atrophy and area of fibrosis/atrophy using multimodal reading centre image analysis (month 12)

Conditions and MedDRA coding

Exudative age-related macular degeneration

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Males or females aged at least 50 years
2. Study eye 2.SMH, comprising sub-neuroretinal haemorrhage with or without sub- RPE haemorrhage, that occurs secondary to treatment naïve, or previously treated exudative AMD, including choroidal neovascularisation (CNV), idiopathic polypoidal choroidal vasculopathy (IPCV) and retinal angiomatous proliferation (RAP).
3. SMH involving the foveal centre that measures at least 1 disc diameter in greatest linear dimension.
4. Sub-neuroretinal haemorrhage at least 125 microns thick, measured at the foveal centre using spectral-domain optical coherence tomography (SD-OCT).
5. BCVA between counting fingers and an Early Treatment of Diabetic Retinopathy Study (ETDRS) letter score of 70, inclusive.

Exclusion criteria 18

1. Serious allergy to fluorescein or indocyanine green (ICG).
2. Hypersensitivity to alteplase (Actilyse), gentamicin, arginine, phosphoric acid, polysorbate 80 or aflibercept (Eylea).
3. Stroke, transient ischaemic attack or myocardial infarction within 6 months, unless both the investigator and prospective participant consider that the ocular risks of withholding intravitreal anti-VEGF therapy exceed the potential systemic risks of arteriothrombotic events that have been variably reported in association with intravitreal anti- VEGF therapy. Given the very low dose of TPA (50 micrograms versus 15 to 90 milligrams), its delivery inside the blood ocular barrier, and very short half-life, many of the systemic risks of TPA are thought unlikely to apply.
4. Participation in another interventional study within 12 weeks of enrolment or planned to occur during this study.
5. Women who are breast feeding, pregnant, or planning to become pregnant during the clinical trial. Any sexually active women of childbearing potential must agree continued abstinence from heterosexual intercourse or to use highly effective methods of birth control for the duration up to 12 weeks post IMP administration. Men must also agree to use a condom if their partner is of child bearing potential, even if they have had a successful vasectomy. Females of childbearing potential are females who have experienced menarche and are not surgically sterilised (e.g. hysterectomy or bilateral salpingectomy) or post-menopausal (defined as at least 1 year since last regular menstrual period). Highly effective methods of birth control are those with a failure rate of < 1% per year when employed consistently and correctly, eg. combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation via oral, intravaginal, and transdermal routes; progestogen-only hormonal contraception associated with inhibition of ovulation via oral, injectable, implantable, intrauterine device (IUD), or intrauterine hormonereleasing system ( IUS); or vasectomised partner.
6. International Normalised Ratio (INR) greater than 3.5, unless it is anticipated that the INR can be brought below this level prior to vitrectomy, balancing the systemic risks with those of intraocular haemorrhage
7. Unwilling, unable, or unlikely to return for scheduled follow-up for the duration of the trial.
8. Any other condition which, in the opinion of the investigator, would prevent the participant from granting informed consent or complying with the protocol, such as dementia, mental illness, or serious systemic medical disease.
9. SMH that is known or estimated to have been present for longer than 15 days, as evidenced by history, pre-trial clinical documentation, or fundus appearance.
10. SMH due to eye disease other than exudative AMD.
11. Current active proliferative diabetic retinopathy.
12. Current intraocular inflammation.
13. Current ocular or periocular infection other than blepharitis.
14. Current or known former high myopia (>6 dioptres).
15. Aphakia.
16. Other current or pre-existing ocular conditions that, in the opinion of the Investigator, will preclude any improvement in BCVA following resolution of SMH, such as severe central macular atrophy or fibrosis, dense amblyopia, macular hole involving the fovea, or very poor BCVA prior to presentation with SMH (counting fingers or worse).
17. Inadequate pupillary dilation or significant media opacities, which will prevent adequate clinical evaluation of the posterior segment or fundus imaging.
18. Intraocular surgery within 12 weeks of enrolment except for uncomplicated cataract surgery, which is permitted within 8 weeks of enrolment.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Gain of at least 10 ETDRS letters in BCVA in the study eye at the month 12 visit.

Secondary endpoints 6

1. Gain of at least 10 ETDRS letters (month 6)
2. Mean ETDRS BCVA.
3. Radner reading vision.
4. National Eye Institute 25 item Visual Function Questionnaire composite score.
5. Scotoma size (Humphrey Field Analyser 10-2)
6. Presence/absence of subfoveal fibrosis and/or atrophy and area of fibrosis/atrophy using multimodal reading centre image analysis (month 12).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

King's College London

Sponsor organisation

King's College London

Address

Strand

City

London

Postcode

WC2R 2LS

Country

United Kingdom

Scientific contact point

Organisation

King's College London

Contact name

Prof Tim Jackson

Public contact point

Organisation

King's College London

Contact name

Prof Tim Jackson

King's College Hospital NHS Foundation Trust

Sponsor organisation

King's College Hospital NHS Foundation Trust

Address

Denmark Hill

City

London

Postcode

SE5 9RS

Country

United Kingdom

Public contact point

Organisation

King's College Hospital NHS Foundation Trust

Contact name

Chief Investigator

Sponsor responsibilities

Article 77 compliance

King's College London

Article 77 implementation

King's College London

Locations

5 EU/EEA countries · 19 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 64 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

10 submissions — initial application plus substantial / non-substantial modifications