Overview
Sponsor-declared trial summary
Phase
Therapeutic use (Phase IV)
Status
Ended
Participants planned
45
Countries
3
Sites
8
Neovascular age-related macular degeneration (nAMD)
To evaluate the systemic pharmacokinetics after bilateral 8 mg aflibercept treatment.
Key facts
- Sponsor
- Bayer AG
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Eye Diseases [C11]
- Trial duration
- 29 Aug 2024 → 14 Oct 2025
- Decision date (initial)
- 2024-08-20
- Transition trial
- No
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
- Funding sources
- Bayer AG
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Pharmacokinetic
To evaluate the systemic pharmacokinetics after bilateral 8 mg aflibercept treatment.
Conditions and MedDRA coding
Neovascular age-related macular degeneration (nAMD)
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.1 | LLT | 10057934 | Diabetic macular edema | 10015919 |
| 20.0 | PT | 10071129 | Neovascular age-related macular degeneration | 100000004853 |
Study design 1 period
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Overall study The study consists of an up to 21-day screening period, an up to 48-week treatment period, and an end of study (EOS) Visit 4 weeks after the last treatment administration. Two populations of patients with DME or nAMD requiring treatment with bilateral antiVEGF treatment will be assigned based upon their clinical presentation to one of 3 treatment regimens. In each treatment regimen all participants will receive 8 mg aflibercept as scheduled.
|
2 | None | Regimen 1: 15 participants will be assigned to Regimen 1. Regimen 1 participants will be administered 8 mg aflibercept injections according to the Regimen 1 dosing schedule. Regimen 2: Up to 15 participants will be assigned to Regimen 2. Regimen 2 participants will be administered 8 mg aflibercept injections according to the Regimen 2 dosing schedule. Regimen 3: Up to 15 participants will be assigned to Regimen 3. Regimen 3 participants will be administered 8 mg aflibercept injections according to the Regimen 3 dosing schedule. |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 5
- Men or women ≥18 years of age (or country’s legal age of adulthood if the legal age is >18 years).
- Participants (treatment naïve or previously treated) requiring intravitreal anti-Vascular endothelial growth factor (VEGF) treatment in both eyes in the opinion of the investigator.
- Participants with type 1 or type 2 diabetes mellitus and DME in both eyes with active central involvement (CI-DME) in at least one eye with Central retinal thickness (CRT) ≥300 µm (or ≥320 µm on Spectralis) as determined by the investigator at the screening visit, OR diagnosis of nAMD in both eyes with active subfoveal Choroidal neovascularization (CNV) in at least one eye with intraretinal fluid (IRF) and/or subretinal fluid (SRF) on OCT as determined by the investigator at the screening visit.
- Best corrected visual acuity (BCVA) Early Treatment Diabetic Retinopathy Study (ETDRS) letter score of 78 to 24 (approximate Snellen equivalent of 20/32 to 20/320) in eyes with active disease and decreased vision determined to be primarily the result of DME or nAMD.
- A female participant is eligible to participate if she is not pregnant or breastfeeding. Women of childbearing potential (WOCBP) or men who are sexually active with partners of childbearing potential must agree to use highly effective contraception prior to the initial dose/start of the first treatment, during the study, and for at least 4 months after the last administration of study intervention.
Exclusion criteria 7
- Evidence of macular edema due to any cause other than diabetes mellitus in patients with DME or neovascular age-related macular degeneration in patients with nAMD in either eye.
- Active proliferative diabetic retinopathy (DR) in either eye.
- Panretinal laser photocoagulation (PRP) or macular laser photocoagulation in either eye with CI-DME or active nAMD within 12 weeks (84 days) of the screening visit.
- Prior treatment with intravitreal (IVT) 2 mg aflibercept (EYLEA) in either eye within 12 weeks (84 days) of the screening visit or with IVT 8 mg or HD aflibercept in either eye within 24 weeks (168 days) of the screening visit.
- Prior treatment with any other approved IVT agent with anti-VEGF effect (e.g. ranibizumab, bevacizumab, brolucizumab, faricimab, pegaptanib sodium or biosimilars) in either eye within 4 weeks (28 days) of the screening visit.
- Prior treatment with any ocular gene or cell therapy treatment in either eye.
- Previous use of intraocular or periocular corticosteroids in either eye within 16 weeks (112 days) of the screening visit, or OZURDEX® implant within 180 days of the screening visit or ILUVIEN® or RETISERT® implant at any time
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Maximum observed concentration (Cmax) of free aflibercept
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
Eylea 114.3 mg/ml solution for injection
PRD11034383 · Product
- Active substance
- Aflibercept
- Substance synonyms
- BAY 86-5321, ABP 938, AVE0005, BAY86-5321, VEGF TRAP, BAY 86-5319
- Pharmaceutical form
- SOLUTION FOR INJECTION
- Route of administration
- INTRAVITREAL USE
- Max daily dose
- 16 mg milligram(s)
- Max total dose
- 96 mg milligram(s)
- Max treatment duration
- 48 Week(s)
- Authorisation status
- Authorised
- ATC code
- S01LA05 — -
- Marketing authorisation
- EU/1/12/797/003
- MA holder
- BAYER AG
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- Yes
- Modification description
- IMP is modified compared to its MA with regards to labeling/secondary packaging
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Bayer AG
- Sponsor organisation
- Bayer AG
- Address
- -
- City
- Leverkusen
- Postcode
- 51368
- Country
- Germany
Scientific contact point
- Organisation
- Bayer AG
- Contact name
- Therapeutic Area Head
Public contact point
- Organisation
- Bayer AG
- Contact name
- Therapeutic Area Head
Third parties 7
| Organisation | City, country | Duties |
|---|---|---|
| Optymedge LLC ORG-100045359
|
Rockville, United States | Other |
| Medidata Solutions Inc. ORG-100016256
|
New York, United States | E-data capture |
| Parexel International (IRL) Limited ORG-100022780
|
Dublin 8, Ireland | Code 12, Code 2, Code 5, Data management, Code 8 |
| Suvoda LLC ORG-100043523
|
Conshohocken, United States | Interactive response technologies (IRT) |
| PPD Global Central Labs ORG-100046496
|
Zaventem, Belgium | Laboratory analysis |
| Eresearchtechnology Inc. ORG-100013039
|
Philadelphia, United States | Other |
| Greenphire LLC ORG-100041621
|
King Of Prussia, United States | Other |
Locations
3 EU/EEA countries · 8 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Czechia | Ended | 15 | 2 |
| Hungary | Ended | 15 | 4 |
| Slovakia | Ended | 15 | 2 |
| Rest of world | — | 0 | — |
Investigational sites
Axon Clinical s.r.o.
Oční ambulance, Ostrovskeho 253/3, Smichov, Prague 5
Fakultni Nemocnice Kralovske Vinohrady
Oftalmologická klinika, Srobarova 1150/50, Vinohrady, Prague
Budapest Retina Associates Kft.
NA, Vaci Ut 76, Kerulet, Budapest XIII
University Of Debrecen
Szemklinika, Nagyerdei Korut 98, 4032, Debrecen
Budapesti Bajcsy-Zsilinszky Korhaz Es Rendelointezet
Szemészeti Osztály, Maglodi Ut 89-91, Kerulet, Budapest
Semmelweis University
Szemészeti Klinika, Rokk Szilard Utca 13, 1085, Budapest VIII
University Hospital Bratislava
Ocna klinika, Antolska 11, Petrzalka, Bratislava
Fakultna Nemocnica S Poliklinikou Zilina
Oftalmologicka ambulancia, Vojtecha Spanyola 43, 010 01, Zilina
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 |
|---|---|---|---|---|---|
| Czechia | 2024-08-29 | 2025-10-14 | 2024-09-02 | 2024-09-30 | |
| Hungary | 2024-08-30 | 2025-09-15 | 2024-09-02 | 2024-09-16 | |
| Slovakia | 2024-09-04 | 2025-10-14 | 2024-09-09 | 2024-11-13 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 9 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Recruitment arrangements (for publication) | K2_Recruitment materials_HU_HU_Flip Chart_public | 1 |
| Recruitment arrangements (for publication) | K2_Recruitment materials_HU_HU_Study Information Brochure_public | 1 |
| Subject information and informed consent form (for publication) | L1_ICF_EN_HU_NtF_Genomic Research Statement_public | 1 |
| Subject information and informed consent form (for publication) | L1_ICF_HU_HU_Hungary Model Main ICF Public | 1.2 |
| Subject information and informed consent form (for publication) | L1_ICF_HU_HU_Hungary Model Pregnant Participant ICF_public | 1.2 |
| Subject information and informed consent form (for publication) | L1_ICF_HU_HU_Hungary Model Pregnant Partner ICF_public | 1.2 |
| Subject information and informed consent form (for publication) | L1_ICF_HU_HU_Submitted document list_public | 1 |
| Subject information and informed consent form (for publication) | L2_Other subject info material_EN_HU_Subject ID Card Justification Letter_public | 1 |
| Subject information and informed consent form (for publication) | L2_Other subject info material_HU_HU_Subject ID Card_public | 1 |
Application history
4 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-04-24 | Slovakia | Acceptable 2024-08-19
|
2024-08-19 |
| 2 | NON SUBSTANTIAL MODIFICATION | NSM-1 | 2024-08-27 | Acceptable 2024-08-19
|
2024-08-27 | |
| 3 | SUBSTANTIAL MODIFICATION | SM-1 | 2024-08-28 | Acceptable | 2024-10-09 | |
| 4 | NON SUBSTANTIAL MODIFICATION | NSM-2 | 2025-02-25 | Slovakia | Acceptable | 2025-02-25 |