Long-term need of Ranibizumab injections with or without early targeted peripheral laser photocoagulation for treatment of macular edema due to central retinal vein occlusion (CoRaLa II trial)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Justus-Liebig-Universitaet Giessen

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Eye Diseases [C11]

Trial duration

17 Aug 2020 → ongoing

Decision date (initial)

2023-10-30

Transition trial

Yes

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Funding sources

Federal Ministry of Education and Research / Bundesamt für Bildung und Forschung (BMBF)

External identifiers

EU CT number

2023-507816-11-00

EudraCT number

2020-000681-42

ClinicalTrials.gov

NCT04444492

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

The primary objective is to evaluate whether or not the duration of guideline-conform periodic ranibizumab injections may be shortened or even be successfully terminated in patients with macular edema due to central retinal vein occlusion if early targeted peripheral laser photocoagulation is applied in parallel.

Secondary objectives 3

1. Secondary objectives are to evaluate the visual acuity during and after the course of intervention, quality of life associated aspects and possible problems which might possibly be associated with the trial’s intervention. Secondary endpoints (sEP) are: the best corrected visual acuity (BCVA), central subfield thickness (CST), the number of ranibizumab injections required until treatment success and up to the end of observation.
2. Complementary outcomes of interest are: the proportion of subjects developing neovascularization(s) over total observation period, health-related quality of life (HrQoL), the area of non-perfusion, vessel density & areal of fovelar avascular zone, potential visual field loss, development of collaterals, the number of laser treatments and the laser spots given in the experimental group (RL-arm)
3. Furthermore, the safety profile of the combined intervention will be compared to that of the guideline-based standard intervention in terms of (S)AEs/(S)ARs occurrence until 4 weeks after the last trial-related intervention. Critical ocular events will be evaluated until the end of study.

Conditions and MedDRA coding

Macular edema due to central retinal vein occlusion

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Diagnosis of macular edema due to central retinal vein occlusion foveal thickness > 250 μm (measured by OCT)
2. Age ≥ 18 years
3. Written informed consent of the patient
4. BCVA score in the study eye between 24 letters (20/320) and 78 letters (20/25) measured in ETDRS chart
5. History of CRVO no longer than 6 months
6. Presence of capillary non-perfusion in peripheral retina larger than 5 disc areas documented in ultra wide-field fluorescein angiography
7. Ability and willingness to attend all scheduled visits and assessments

Exclusion criteria 18

1. CRVO with ischemic maculopathy defined as diameter of the foveolar avascular zone larger than 2 optic disc diameters
2. Macular edema due to another etiology than retinal vein occlusion (e.g. diabetic maculopathy, uveitis, age related macular degeneration, Irvine-Gass syndrome)
3. History of idiopathic central serous chorioretinopathy
4. Presence of vitreoretinal interface disease (e.g. vitreomacular traction, epiretinal membrane), either on clinical examination or in OCT
5. An eye that, in the investigator's opinion, would not benefit from resolution of macular edema, such as eyes with foveal atrophy, dense pigmentary changes, or dense subfoveal hard exudates
6. Aphakia in the study eye
7. Scatter laser photocoagulation or macular photocoagulation in the study eye prior to study entry
8. Intraocular or periocular injection of steroids in the study eye prior to study entry
9. Previous use of an anti-VEGF drug in the study eye
10. Cataract surgery or any other intraocular surgery in the study eye within 3 months prior to study entry
11. Uncontrolled glaucoma (defined as intraocular pressure ≥ 30 mm Hg despite treatment with maximal anti-glaucoma medications)
12. History of stroke, myocardial infarction, transient ischemic attacks within 3 months prior to the study
13. Pregnancy (positive urine pregnancy test) or lactation
14. The presence of active malignancy, including lymphoproliferative disorders.
15. History of allergy to fluorescein or any component of the ranibizumab formulation
16. Active intraocular infection
17. Participation in another simultaneous interventional medical investigation or trial
18. Women with child bearing potency without effective contraception (i. e. implants, injectables, combined oral contraceptives, some IUDs or vasectomised partner) during the conduct of the trial.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Primary efficacy endpoint is the time to treatment success, defined as time from randomisation until the date of last criteria-based intravitreal injection in case that thereafter a treatment-free period for (at least) 6 months was observed. Objective criteria for further treatment indication (according to details in section 6.3) have to be fulfilled for decisions regarding further re-treatment. Drop-outs/deaths without earlier success will be censored at the end of their observation time and al

Secondary endpoints 3

1. the best corrected visual acuity (BCVA) in BCVA letter scores (EDTRS charts) per visit
2. central subfield thickness (CST) measured by OCT per visit
3. the number of Ranibizumab injections required (after three initial monthly injections) according to re-treatment criteria (see 6.3) until “success” is reached as well as up to month 29 after randomisation (the entire period of observation, in case of late recurrence of ME)

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Justus-Liebig-Universitaet Giessen

Sponsor organisation

Justus-Liebig-Universitaet Giessen

Address

Friedrichstrasse 18

City

Giessen

Postcode

35392

Country

Germany

Scientific contact point

Organisation

Justus-Liebig-Universitaet Giessen

Contact name

Coordinating Investigator

Public contact point

Organisation

Justus-Liebig-Universitaet Giessen

Contact name

Coordinating Investigator

Locations

2 EU/EEA countries · 13 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 14 files

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

Application history

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