Overview
Sponsor-declared trial summary
Phase
Therapeutic use (Phase IV)
Status
Ongoing, recruiting
Participants planned
442
Countries
2
Sites
7
Corneal transplantation, Descemet's Membrane Endothelial Keratoplasty (DMEK)
To evaluate an evidence-based short- and long-term immunosuppressive protocol for DMEK that minimizes IOP elevation and endothelial cell loss.
Key facts
- Sponsor
- University Hospital Maastricht
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Eye Diseases [C11]
- Trial duration
- 29 Jul 2024 → ongoing
- Decision date (initial)
- 2023-10-30
- Transition trial
- No
- Low-intervention
- Yes
- Rare-disease indication
- No
- Vulnerable population
- No
- Funding sources
- ZonMW
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Efficacy, Pharmacoeconomic, Therapy
To evaluate an evidence-based short- and long-term immunosuppressive protocol for DMEK that minimizes IOP elevation and endothelial cell loss.
Secondary objectives 3
- Evaluate the cost-effectiveness of the immunosuppressive protocols with a time horizon of two years (trial-based cost-effectiveness evaluation, TBEE)
- Model the lifelong cost-effectiveness of the immunosuppressive protocols (model-based cost effectiveness evaluation, MBEE).
- Evaluate patient experiences and satisfaction with the immunosuppressive protocols
Conditions and MedDRA coding
Corneal transplantation, Descemet's Membrane Endothelial Keratoplasty (DMEK)
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 22.0 | PT | 10081851 | Corneal graft failure | 100000004863 |
| 20.1 | PT | 10011017 | Corneal graft rejection | 100000004870 |
| 21.1 | LLT | 10011016 | Corneal graft | 10042613 |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 1
- Patients aged 21 years or older registered on the NOTR as candidates for DMEK corneal transplantation
Exclusion criteria 7
- Inability to complete follow up or comply with study procedures
- Previous corneal graft in the study eye
- Known sensitivity or contraindication to the ingredients in the study medications
- History of uveitis or herpetic keratitis
- Human Leukocyte Antigen (HLA) typed allograft
- Pregnancy (current and planned) or lactation
- Use of other local or systemic immunosuppressive drugs
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 2
- Step I (Year 1): The primary outcome of Step I, IOP elevation, is the development of IOP elevation, defined as an IOP ≥24 mmHg or an increase of ≥10 mmHg compared to preoperative baseline at any postoperative examination.
- Step II (Year 2): The primary outcome of Step II is the Endothelial Cell Loss (ECL) in the second year. This will be calculated based on specular microscopy images of the central cornea taken at 12 months and 24 months post-operatively
Secondary endpoints 6
- Rejection-free graft survival
- Short-term trial-based economic evaluation (TBEE, cost-effectiveness analyses)
- Life-long model-based economic evaluation (MBEE, cost-effectiveness analyses)
- Patient-reported outcome measures (PROMs): vision-specific and generic health-related quality of life, patient experiences and satisfaction, and compliance
- Best-corrected distance visual acuity (BCDVA)
- Structural outcomes: corneal, central macular, and retinal nerve fiber layer thickness
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
FML Liquifilm 0.1% w/v Sterile Eye Drops Suspension
PRD526247 · Product
- Active substance
- Fluorometholone
- Pharmaceutical form
- EYE DROPS, SUSPENSION
- Route of administration
- TOPICAL APPLICATION ON CORNEAL AND LIMBAL AREA OF THE EYE
- Max daily dose
- 4 Gtt drop(s)
- Max total dose
- 4 Gtt drop(s)
- Max treatment duration
- 104 Week(s)
- Authorisation status
- Authorised
- ATC code
- S01BA07 — FLUOROMETHOLONE
- Marketing authorisation
- PA 148/7/1
- MA holder
- ALLERGAN PHARMACEUTICALS IRELAND
- MA country
- Ireland
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Comparator 1
Dexamethason 1 mg/ml Teva, oogdruppels
PRD606031 · Product
- Active substance
- Dexamethasone
- Pharmaceutical form
- EYE DROPS, SOLUTION
- Route of administration
- TOPICAL APPLICATION ON CORNEAL AND LIMBAL AREA OF THE EYE
- Max daily dose
- 6 Gtt drop(s)
- Max total dose
- 6 Gtt drop(s)
- Max treatment duration
- 52 Week(s)
- Authorisation status
- Authorised
- ATC code
- S01BA01 — DEXAMETHASONE
- Marketing authorisation
- RVG 56003
- MA holder
- TEVA NEDERLAND B.V.
- MA country
- Netherlands
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
University Hospital Maastricht
- Sponsor organisation
- University Hospital Maastricht
- Address
- Po Box 616
- City
- Maastricht
- Postcode
- 6200 MD
- Country
- Netherlands
Scientific contact point
- Organisation
- University Hospital Maastricht
- Contact name
- Dr Mor Dickman
Public contact point
- Organisation
- University Hospital Maastricht
- Contact name
- Dr Mor Dickman
Locations
2 EU/EEA countries · 7 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Germany | Ongoing, recruiting | 100 | 1 |
| Netherlands | Ongoing, recruiting | 342 | 6 |
| Rest of world | — | 0 | — |
Investigational sites
Stichting Radboud University Medical Center
Radboud UMC Oogheelkunde Centrum, Geert Grooteplein Noord 9, 6525 EZ, Nijmegen
Universitair Medisch Centrum Utrecht
Ophthalmology, Heidelberglaan 100, 3584 CX, Utrecht
University Medical Center Groningen
Department of Ophthalmology, Postbus 30.001, 9700 RB, Groningen
Leiden University Medical Center
Ophthalmology, Albinusdreef 2, 2333 ZA, Leiden
Gelre Hospitals
Ophthalmology, Albert Schweitzerlaan 31, 7334 DZ, Apeldoorn
University Hospital Maastricht
MUMC Ophthalmology, Po Box 5800, 6202 AZ, Maastricht
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Germany | 2024-07-29 | 2024-07-29 | |||
| Netherlands | 2024-07-29 | 2024-07-29 |
Oversight and notifications
Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77
Corrective measures 1 · Art. 77 CTR
Corrective measure CM-DE-0001
- Member state
- Germany
- Publication date
- 2024-03-18
- Type
- 3
- Reason
- 7
- Reverted date
- 2024-03-18
- Immediate action required
- No
- Notes
- Reverted (2024-03-18)
- Justification
- Several Part I and Part II DE issues have been identified during assessment which has been taken
place from 24/10/2023 to 27/10/2023 (refer to the document enclosed).
The missing proof of insurance, several issues related to the protocol, the IB, the supply chain and
the German labels as well as issues related to other Part II documents such as e.g. the patient
information/ICF makes it necessary to ensure that patient recruitment is started only after
resolution of these issues.
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 16 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1. Protocol 2022-500109-41-00 Clean | 7.2 |
| Protocol (for publication) | D1. Protocol 2022-500109-41-00 METC Primary Submission unsigned | 2.0 |
| Protocol (for publication) | D1. Protocol 2022-500109-41-00 TC | 7.2 |
| Protocol (for publication) | D4. Patient facing documents - Questionnaires German translations | 1 |
| Recruitment arrangements (for publication) | K1. Recruitment arrangements | 1 |
| Recruitment arrangements (for publication) | K1. Recruitment arrangements | 2.0 |
| Subject information and informed consent form (for publication) | L1. SIS and ICF Dutch Appendix A Contact Details Clean | 2 |
| Subject information and informed consent form (for publication) | L1. SIS and ICF Dutch Clean | 4 |
| Subject information and informed consent form (for publication) | L1. SIS and ICF German Clean | 4 |
| Subject information and informed consent form (for publication) | L1. SIS andd ICF German TC | 4 |
| Summary of Product Characteristics (SmPC) (for publication) | E2. SmPC Dexamethasone EN | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2. SmPC Dexamethasone NL | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2. SmPC Fluormetholone EN | 2 |
| Summary of Product Characteristics (SmPC) (for publication) | E2. SmPC Fluorometholone NL | 1 |
| Synopsis of the protocol (for publication) | D1. Protocol synopsis EN 2022-500109-41-00 Clean | 3 |
| Synopsis of the protocol (for publication) | D1. Protocol synopsis NL 2022-500109-41-00 Clean | 3 |
Application history
9 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2022-03-24 | Netherlands | Acceptable 2022-06-30
|
2022-06-30 |
| 2 | SUBSTANTIAL MODIFICATION | SM-1 | 2023-01-31 | Netherlands | Acceptable 2023-03-29
|
2023-03-29 |
| 3 | SUBSTANTIAL MODIFICATION | SM-2 | 2023-05-24 | Netherlands | Acceptable 2023-07-17
|
2023-07-17 |
| 4 | SUBSEQUENT ADDITION OF MSC | APP-4 | 2023-09-05 | Acceptable 2022-06-30
|
2023-10-30 | |
| 5 | SUBSTANTIAL MODIFICATION | SM-3 | 2023-11-29 | Netherlands | Acceptable 2024-03-15
|
2024-03-18 |
| 6 | SUBSTANTIAL MODIFICATION | SM-10 | 2024-06-10 | Netherlands | Acceptable 2024-07-02
|
2024-07-02 |
| 7 | SUBSTANTIAL MODIFICATION | SM-14 | 2025-02-18 | Netherlands | Acceptable 2025-05-20
|
2025-05-22 |
| 8 | SUBSTANTIAL MODIFICATION | SM-15 | 2025-10-06 | Netherlands | Acceptable 2026-01-14
|
2026-01-14 |
| 9 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2026-02-02 | Netherlands | Acceptable 2026-01-14
|
2026-02-02 |