Aflibercept 8mg for high-frequent Faricimab and prior Aflibercept 2mg treated Neovascular age-related macular degeneration: a monocenter, single-arm, open-label extension study (A-FAN)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Medical University Of Graz

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Eye Diseases [C11]

Trial duration

24 Oct 2024 → 2 Dec 2025

Decision date (initial)

2024-09-22

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Efficacy

To assess the efficacy of aflibercept 8mg in terms of durability at 32 weeks by extending treatment interval in previous high-frequent faricimab and prior aflibercept 2mg treated neovascular age-related macular degeneration.

Secondary objectives 2

1. To evaluate the durability, the efficacy on BCVA / anatomic outcome and safety of aflibercept 8mg in previous high-frequent faricimab and prior aflibercept 2mg treated neovascular age-related macular degeneration.
2. Further to evaluate if the systemic VEGF levels are influenced differently under aflibercept 8mg. (optional participation)

Conditions and MedDRA coding

Neovascular age-related macular degeneration

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. prior participation in the FAN study
2. signed written informed consent
3. willingness and ability to comply with clinic visits and study-related procedures
4. ≥50 years of age
5. MNV due to AMD (nAMD)
6. BVCA between and including 19 and 75 letters (Snellen equivalent approximately 20/400 to 20/32)
7. ≥ 4 previous intravitreal injections with faricimab
8. eyes remaining on a treatment interval of ≤35 days and/or
9. did/do not meet extension success with faricimab, hence had/has retinal (intra- and or subretinal) fluid at 6 weeks

Exclusion criteria 16

1. uncontrolled blood pressure (either/both systolic blood pressure >180mmHg, diastolic blood pressure >100mmHg)
2. pregnancy
3. breast-feeding
4. myocardial infarction or stroke within the last six months
5. concomitant participation in another clinical study with investigational medicinal products
6. a known allergy or hypersensitivity towards eye drops needed for the examinations planned during the study, and/or the intravitreal procedure.
7. a known allergy or hypersensitivity towards any of the components of the study drug
8. Persons unable to give consent or cannot understand the purpose of the study (dementia, etc.), or should be excluded by investigator's decision
9. treatment interval ≥ 6weeks without retinal (intra- and/or subretinal) fluid on OCT
10. MNV due to other causes than nAMD
11. polypoidal choroidal neovascularization
12. retinal pigment epithelial rip/tear
13. subretinal hemorrhage of > 50% of the lesion, involving the fovea
14. any macular pathology other than AMD causing structural changes of the macula and thereby affecting vision
15. any active intra-/periocular infection/inflammation of the study eye
16. uncontrolled glaucoma under medication (IOP >25mmHg)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. proportion of eyes with at least one extension without retinal (intra- and subretinal) fluid within the time period baseline to 32 weeks (extension success rate)

Secondary endpoints 18

1. proportion of eyes with maximum extended interval without retinal (intra- and subretinal) fluid of ≥ 6, ≥ 8 and ≥ 10 weeks at 32 weeks
2. maximum extended treatment interval without retinal (intra- and subretinal) fluid at 32 weeks
3. number of injections received during 32 weeks
4. proportion of eyes remaining on a 4-weekly interval from baseline to last visit (completed interval) at 32 weeks
5. proportion of eyes extended to 6 weeks, without success (intra- and or subretinal fluid present) from baseline to 32 weeks
6. mean change in ETDRS letter score from baseline to an averaged ETDRS letter score between 24 and 32 weeks
7. mean averaged ETDRS letter score between 24 and 32 weeks
8. proportion of eyes gaining ≥ 5 ETDRS letters from baseline to an averaged ETDRS letter score between 24 and 32 weeks
9. proportion of eyes loosing ≥5 ETDRS letters from baseline to an averaged ETDRS letter score between 24 and 32 weeks
10. mean change in low-luminance BCVA from baseline over time
11. mean CST change from baseline (1mm ETDRS grid) to an averaged CST between 24 and 32 weeks
12. mean CST change from baseline to maximum extended interval without retinal (intra- and subretinal) fluid
13. proportion of eyes with no intraretinal fluid at baseline and final visit (completed interval) at or before 32 weeks
14. proportion of eyes with no subretinal fluid at baseline and final visit (completed interval) at or before 32 weeks
15. proportion of eyes with no retinal (intra- and subretinal) fluid at baseline and final visit (completed interval) at or before 32 weeks
16. retinal nerve fiber analysis over time
17. incidence and severity of ocular/non-ocular adverse events
18. mean change in concentration of plasma VEGF-A over time

Investigational products

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

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Medical University Of Graz

Sponsor organisation

Medical University Of Graz

Address

Neue Stiftingtalstrasse 6

City

Graz

Postcode

8010

Country

Austria

Scientific contact point

Organisation

Medical University Of Graz

Contact name

Coordination Center for Clinical Trials

Public contact point

Organisation

Medical University Of Graz

Contact name

Coordination Center for Clinical Trials

Locations

1 EU/EEA country · 1 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 5 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