Antisense Oligonucleotide Eye Drops against IRS-1 to Optimize Pretransplant Lymphangio-regression Prior to High-Risk Keratoplasty (Olisens-Precon)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

University Of Cologne

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Eye Diseases [C11]

Decision date (initial)

2026-01-28

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

European Health and Digital Executive Agency (HADEA; Project 101080611 – RESTORE VISION)

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

Evaluate the efficacy of antisense oligonucleotide eye drops against IRS-1 (Olisens) in the treatment of pathological neovascularization due to herpetic keratopathy in combination with physical angioregressive treatment using corneal crosslinking.

Secondary objectives 13

1. Visual acuity
2. Glare visual acuity
3. Vision-related quality of life
4. Intraocular pressure
5. Ocular surface staining according to Oxford Grading Scale
6. Corneal sensation via corneal esthesiometry
7. Central Corneal Thickness acquired through Pentacam Tomography (or Casia 2 if Pentacam is technically not possible)
8. Vessel Morphometry, Vessel Thickness, Vessel length, Vessel Regression, Vessel Recurrence
9. Ocular pain perception via Ocular Pain Assessment Survey (OPAS)
10. Safety and tolerability of antisense oligonucleotide eye drops against IRS-1
11. Change in need for subsequent transplantation (as assessed by PI)
12. Compliance of CXL postoperative medication
13. Active infectious keratitis or corneal ulceration

Conditions and MedDRA coding

Pathologically prevascularized corneas due to herpetic keratopathy prior to “high-risk” corneal transplantation (keratoplasty)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Pathologically prevascularized cornea due to herpetic keratopathy (diagnosis either through virology or clinical findings) with need for corneal transplantation
2. Written informed consent by participant and/or witness prior to any study-related procedures
3. Adult male and female participants ≥ 18 years old
4. ≥ 2 corneal quadrants covered by pathological corneal neovascularization due to herpetic keratitis
5. Absence of other clinical contraindications to any part or product of the treatment plan
6. A cooperative attitude to follow up the study procedures
7. In case of bilateral disease only one eye will be included (the responsible investigator will decide based on which eye is more affected)
8. High-risk eye on the waitlist for a corneal transplantation

Exclusion criteria 19

1. < 2 corneal quadrants covered by pathological neovascularization
2. Rheumatic diseases that require systemic treatment
3. Participants unlikely to comply with the study protocol or unable to understand the nature and scope of the study or the possible benefits or unwanted effects of the study procedures and treatments
4. Participation in another clinical trial where an investigational drug was received less than 4 weeks prior to screening visit
5. Known abuse of alcohol, drugs, or medicinal products
6. Evidence of any other medical conditions (such as psychiatric illness, physical ex-amination, or laboratory findings) that may interfere with the planned treatment, affect the participant’s compliance, or place the participant at high risk of complications related to the treatment
7. Employees of the sponsor, or employees or relatives of the investigator
8. Pregnant women and nursing mothers as the effects of study medication is unknown in these conditions
9. Persons held in an institution by legal or official order
10. Use of autologous or allogenous serum eye drops during study period (have to be stopped 14 days prior to trial start)
11. Corneal stromal thickness below 400 μm (unless not affecting more than 50% of the corneal surface area)
12. Active or suspected intraocular inflammation
13. Active corneal ulceration
14. Dysregulated glaucoma with IOP values > 25 mmHg despite local therapy
15. Compromised eyelid mobility and/or symblepharon
16. Allergy, sensitivity or intolerance to riboflavin or UV
17. Contraindications to the local or systemic antibiotics and/or corticosteroids foreseen by the protocol
18. Contraindications to the surgical protocol
19. Failure to use highly-effective contraceptive methods (for women of childbearing potential and males who have a partner of childbearing potential) during the study period. The following contraceptive methods with a Pearl Index lower than 1% are regarded as highly-effective: o Oral hormonal contraception (‘pill’) o Dermal hormonal contraception o Vaginal hormonal contraception (NuvaRing® ) o Contraceptive plaster o Long-acting injectable contraceptives o Implants that release progesterone (Implanon® ) o Tubal ligation (female sterilisation) o Intrauterine devices that release hormones (hormone spiral) o Avoiding sexual activities that could lead to pregnancy

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Relative change in the corneal area covered by CoNV measured by digital standardized slit-lamp images.

Secondary endpoints 12

1. Best corrected visual acuity measured by ETDRS charts (transformed to LogMAR (Logarithm of the Minimum Angle of Resolution))
2. Best corrected glare visual acuity measured by ETDRS charts (transformed to LogMAR (Loga-rithm of the Minimum Angle of Resolution))
3. Vision related Quality of Life assessed by overall score of NEI-VFQ25
4. Intraocular Pressure measured by Goldmann applanation tonometry, reported as mmHg
5. Ocular Surface Staining according to Oxford Grading Scale (Grades 0-5)
6. Corneal Sensation measured by length of the nylon monofilament of Cochet-Bonnet esthesiometer when the applied pressure is noticed by the participants
7. Central Corneal Thickness measured by Scheimpflug Corneal Tomography (Pentacam) or Anterior Segment Optical Coherence Tomography (Casia-2)
8. Vessel Morphometry (vessel thickness, vessel length, vessel regression, vessel recurrence)
9. Quality of Life (Ocular Pain) assessed by overall score of Ocular Pain Assessment Survey (OPAS)
10. Safety: Retinal adverse events (Optical Coherence Tomography)
11. Change in need for subsequent transplantation (as assessed by PI)
12. Compliance of CXL postoperative medication recorded via daily patient self-documentation

Investigational products

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

Test 1

Placebo 1

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

University Of Cologne

Sponsor organisation

University Of Cologne

Address

Albertus-Magnus-Platz 1

City

Cologne

Postcode

50923

Country

Germany

Scientific contact point

Organisation

University Of Cologne

Contact name

Claus Cursiefen

Public contact point

Organisation

University Of Cologne

Contact name

Claus Cursiefen

Third parties 7

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Results and documents

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

Documents 8 files

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

Application history

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