Page Nct des essais cliniques

Summary
EudraCT Number:2020-004917-10
Sponsor's Protocol Code Number:TIGER
National Competent Authority:Germany - BfArM
Clinical Trial Type:EEA CTA
Trial Status:Trial now transitioned
Date on which this record was first entered in the EudraCT database:2022-11-28
Trial results
A. Protocol Information
A.1Member State ConcernedGermany - BfArM
A.2EudraCT number2020-004917-10
A.3Full title of the trial
Vitrectomy, subretinal Tissue plasminogen activator and Intravitreal Gas for submacular haemorrhage secondary to Exudative age-Related macular degeneration (TIGER): a phase 3, pan-European, two-group, active-control, observer-masked, superiority, randomised controlled surgical trial.
A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
A study of surgery to clear bleeding due to age-related macular degeneration.
A.3.2Name or abbreviated title of the trial where available
TIGER
A.4.1Sponsor's protocol code numberTIGER
A.7Trial is part of a Paediatric Investigation Plan No
A.8EMA Decision number of Paediatric Investigation Plan
B. Sponsor Information
B.Sponsor: 1
B.1.1Name of SponsorKing's College London
B.1.3.4CountryUnited Kingdom
B.3.1 and B.3.2Status of the sponsorNon-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1Name of organisation providing supportFight for Sight
B.4.2CountryUnited Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1Name of organisationKing's College London
B.5.2Functional name of contact pointTim Jackson
B.5.3 Address:
B.5.3.1Street AddressDepartment of Ophthalmology, King's College Hospital, Denmark Hill
B.5.3.2Town/ cityLondon
B.5.3.3Post codeSE5 9RS
B.5.3.4CountryUnited Kingdom
B.5.4Telephone number+44 020 3299 1297
B.5.6E-mailt.jackson1@nhs.net
B.Sponsor: 2
B.1.1Name of SponsorKing's College Hospital NHS Foundation Trust
B.1.3.4CountryUnited Kingdom
B.3.1 and B.3.2Status of the sponsorNon-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1Name of organisation providing supportFight for Sight
B.4.2CountryUnited Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1Name of organisationKing's College Hospital NHS Foundation Trust
B.5.2Functional name of contact pointTim Jackson
B.5.3 Address:
B.5.3.1Street AddressDepartment of Ophthalmology, King's College Hospital, Denmark Hill
B.5.3.2Town/ cityLondon
B.5.3.3Post codeSE5 9RS
B.5.3.4CountryUnited Kingdom
B.5.4Telephone number+44 020 3299 1297
B.5.6E-mailt.jackson1@nhs.net
D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3IMP RoleTest
D.2 Status of the IMP to be used in the clinical trial
D.2.1IMP to be used in the trial has a marketing authorisation Yes
D.2.1.1.1Trade name Actilyse
D.2.1.1.2Name of the Marketing Authorisation holderBoehringer Ingelheim Limited
D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
D.2.5.1Orphan drug designation number
D.3 Description of the IMP
D.3.1Product nameActilyse
D.3.4Pharmaceutical form Powder and solvent for solution for injection/infusion
D.3.4.1Specific paediatric formulation No
D.3.7Routes of administration for this IMPSubretinal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8INN - Proposed INNAlteplase
D.3.9.3Other descriptive nameALTEPLASE FOR INJECTION
D.3.9.4EV Substance CodeAS1
D.3.10 Strength
D.3.10.1Concentration unit µg/ml microgram(s)/millilitre
D.3.10.2Concentration typeequal
D.3.10.3Concentration number100
D.3.11 The IMP contains an:
D.3.11.1Active substance of chemical origin No
D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) Yes
The IMP is a:
D.3.11.3Advanced Therapy IMP (ATIMP) No
D.3.11.3.1Somatic cell therapy medicinal product No
D.3.11.3.2Gene therapy medical product No
D.3.11.3.3Tissue Engineered Product No
D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
D.3.11.5Radiopharmaceutical medicinal product No
D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
D.3.11.7Plasma derived medicinal product No
D.3.11.8Extractive medicinal product No
D.3.11.9Recombinant medicinal product Yes
D.3.11.10Medicinal product containing genetically modified organisms No
D.3.11.11Herbal medicinal product No
D.3.11.12Homeopathic medicinal product No
D.3.11.13Another type of medicinal product No
D.8 Information on Placebo
E. General Information on the Trial
E.1 Medical condition or disease under investigation
E.1.1Medical condition(s) being investigated
Submacular haemorrhage secondary to exudative age-related macular degeneration
E.1.1.1Medical condition in easily understood language
Wet age-related macular degeneration.
E.1.1.2Therapeutic area Diseases [C] - Eye Diseases [C11]
MedDRA Classification
E.1.2 Medical condition or disease under investigation
E.1.2Version 20.0
E.1.2Level LLT
E.1.2Classification code 10075718
E.1.2Term Exudative age-related macular degeneration
E.1.2System Organ Class 100000004853
E.1.3Condition being studied is a rare disease Yes
E.2 Objective of the trial
E.2.1Main objective of the trial
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.

E.2.2Secondary objectives of the trial
Secondary outcome measures will include (at 6 and 12 months unless noted otherwise):
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)
E.2.3Trial contains a sub-study No
E.3Principal inclusion criteria
General
1.Males or females aged at least 50 years

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.
E.4Principal exclusion criteria
General
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 hormone-releasing 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.

Study eye

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.
E.5 End points
E.5.1Primary end point(s)
Gain of at least 10 ETDRS letters in BCVA in the study eye at the month 12 visit.
E.5.1.1Timepoint(s) of evaluation of this end point
Month 12 visit.
E.5.2Secondary end point(s)
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).
E.5.2.1Timepoint(s) of evaluation of this end point
All recorded at month 6 and month 12 unless otherwise stated above.
E.6 and E.7 Scope of the trial
E.6Scope of the trial
E.6.1Diagnosis No
E.6.2Prophylaxis No
E.6.3Therapy Yes
E.6.4Safety Yes
E.6.5Efficacy Yes
E.6.6Pharmacokinetic No
E.6.7Pharmacodynamic No
E.6.8Bioequivalence No
E.6.9Dose response No
E.6.10Pharmacogenetic No
E.6.11Pharmacogenomic No
E.6.12Pharmacoeconomic No
E.6.13Others No
E.7Trial type and phase
E.7.1Human pharmacology (Phase I) No
E.7.1.1First administration to humans No
E.7.1.2Bioequivalence study No
E.7.1.3Other No
E.7.1.3.1Other trial type description
E.7.2Therapeutic exploratory (Phase II) No
E.7.3Therapeutic confirmatory (Phase III) Yes
E.7.4Therapeutic use (Phase IV) No
E.8 Design of the trial
E.8.1Controlled Yes
E.8.1.1Randomised Yes
E.8.1.2Open No
E.8.1.3Single blind Yes
E.8.1.4Double blind No
E.8.1.5Parallel group Yes
E.8.1.6Cross over No
E.8.1.7Other No
E.8.2 Comparator of controlled trial
E.8.2.1Other medicinal product(s) Yes
E.8.2.2Placebo No
E.8.2.3Other No
E.8.2.4Number of treatment arms in the trial2
E.8.3 The trial involves single site in the Member State concerned No
E.8.4 The trial involves multiple sites in the Member State concerned Yes
E.8.4.1Number of sites anticipated in Member State concerned14
E.8.5The trial involves multiple Member States Yes
E.8.5.1Number of sites anticipated in the EEA30
E.8.6 Trial involving sites outside the EEA
E.8.6.1Trial being conducted both within and outside the EEA Yes
E.8.6.2Trial being conducted completely outside of the EEA No
E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
Austria
France
Poland
Bulgaria
Netherlands
Spain
Switzerland
Germany
Italy
Belgium
Denmark
Hungary
Ireland
Portugal
Slovenia
United Kingdom
E.8.7Trial has a data monitoring committee Yes
E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
Trial end is defined as data lock. This is estimated to occur in April 2025.Write-up and submission of the study results to a peer reviewed publication occurs subsequently.
E.8.9 Initial estimate of the duration of the trial
E.8.9.1In the Member State concerned years4
E.8.9.1In the Member State concerned months5
E.8.9.1In the Member State concerned days31
E.8.9.2In all countries concerned by the trial years5
E.8.9.2In all countries concerned by the trial months8
E.8.9.2In all countries concerned by the trial days11
F. Population of Trial Subjects
F.1 Age Range
F.1.1Trial has subjects under 18 No
F.1.1Number of subjects for this age range: 0
F.1.1.1In Utero No
F.1.1.1.1Number of subjects for this age range: 0
F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
F.1.1.2.1Number of subjects for this age range: 0
F.1.1.3Newborns (0-27 days) No
F.1.1.3.1Number of subjects for this age range: 0
F.1.1.4Infants and toddlers (28 days-23 months) No
F.1.1.4.1Number of subjects for this age range: 0
F.1.1.5Children (2-11years) No
F.1.1.5.1Number of subjects for this age range: 0
F.1.1.6Adolescents (12-17 years) No
F.1.1.6.1Number of subjects for this age range: 0
F.1.2Adults (18-64 years) Yes
F.1.2.1Number of subjects for this age range: 210
F.1.3Elderly (>=65 years) Yes
F.1.3.1Number of subjects for this age range: 210
F.2 Gender
F.2.1Female Yes
F.2.2Male Yes
F.3 Group of trial subjects
F.3.1Healthy volunteers No
F.3.2Patients Yes
F.3.3Specific vulnerable populations Yes
F.3.3.1Women of childbearing potential not using contraception No
F.3.3.2Women of child-bearing potential using contraception Yes
F.3.3.3Pregnant women No
F.3.3.4Nursing women No
F.3.3.5Emergency situation No
F.3.3.6Subjects incapable of giving consent personally No
F.3.3.7Others No
F.4 Planned number of subjects to be included
F.4.1In the member state30
F.4.2 For a multinational trial
F.4.2.1In the EEA 128
F.4.2.2In the whole clinical trial 210
F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
After trial completion, patient may or may not need ongoing treatment for exudative AMD and this will continue to take place as per standard of care for the respective trial units
G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1
N. Review by the Competent Authority or Ethics Committee in the country concerned
N.Competent Authority Decision Authorised
N.Date of Competent Authority Decision2023-02-23
N.Ethics Committee Opinion of the trial applicationFavourable
N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
N.Date of Ethics Committee Opinion2023-06-29
P. End of Trial
P.End of Trial StatusTrial now transitioned