Faricimab for high-frequent Aflibercept treated Neovascular age-related macular degeneration: a monocenter, randomized, double-masked comparator-controlled study (FAN study)

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

12 Jun 2023 → 26 Feb 2025

Decision date (initial)

2024-11-18

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-515377-10-00

EudraCT number

2023-000037-32

ClinicalTrials.gov

NCT05941715

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Safety, Efficacy

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

Secondary objectives 2

1. To evaluate the durability, the efficacy on BCVA / anatomic outcome and safety of faricimab, in previous high-frequent aflibercept treated neovascular age-related macular degeneration.
2. Further to evaluate if longer durability can impact patients’ contentment (quality of life) and if the systemic VEGF and Ang-2 levels are influenced differently under faricimab compared to aflibercept treatment.

Conditions and MedDRA coding

Neovascular age-related macular degeneration

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. signed written informed consent
2. willingness and ability to comply with clinic visits and study-related procedures
3. ≥50 years of age
4. MNV due to AMD (nAMD)
5. BVCA between and including 19 and 75 letters (Snellen equivalent approximately 20/400 to 20/32)
6. ≥ 7 previous intravitreal injections with anti-VEGF
7. the last ≥ 4 consecutive intravitreal injections with aflibercept
8. the last aflibercept injections within the last 35 days
9. interval between the last 2 aflibercept injections ≤ 35 days

Exclusion criteria 22

1. use of long-term systemic corticosteroids within the last 3 months
2. uncontrolled blood pressure (either/both systolic blood pressure >180mmHg, diastolic blood pressure >100mmHg)
3. pregnancy (pre-menopausal women MUST take a pregnancy test at time of initiation)
4. breast-feeding
5. myocardial infarction or stroke within the last six months
6. concomitant participation in another clinical study with investigational medicinal products
7. a known allergy or hypersensitivity towards eye drops needed for the examinations planned during the study, and/or the intravitreal procedure
8. a known allergy or hypersensitivity against fluorescein / indocyanine green used during angiography
9. a known allergy or hypersensitivity towards any of the components of the study drug
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)
17. cataract surgery of the study eye within the last 3 months
18. previous intraocular surgery of the study eye other than cataract surgery or intravitreal injections with anti-VEGF (e.g. vitrectomy, corneal transplant, glaucoma surgery)
19. any previous laser therapy of the study eye other than Yag (yttrium aluminium garnet) laser capsulotomy (e.g. panretinal photocoagulation, verteporfin photodynamic therapy)
20. refractive error of more than -6 diopters myopia
21. vitreous hemorrhage
22. retinal detachment

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 26

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 with maximum extended interval without retinal (intra-and subretinal) fluid of ≥ 6, ≥ 8, ≥ 10 and ≥12weeks at 56 weeks
5. proportion of eyes remaining on a 4-weekly interval from baseline to last visit (completed interval) at 56 weeks
6. maximum extended treatment interval without retinal (intra- and subretinal) fluid at 56 weeks
7. number of injections received during 1 year
8. mean change in EDTRS letter score from baseline to an averaged EDTRS letter score between 24 and 32 weeks
9. mean averaged EDTRS letter score between 24 and 32 weeks
10. mean change in EDTRS letter score from baseline to an averaged EDTRS letter score between 48 and 56 weeks
11. mean averaged EDTRS letter score between 48 and 56 weeks
12. proportion of eyes gaining ≥ 5 EDTRS letters from baseline to an averaged EDTRS letter score between 24 and 32 weeks
13. proportion of eyes loosing ≥5 EDTRS letters from baseline to an averaged EDTRS letter score between 24 and 32 weeks
14. proportion of eyes gaining ≥ 5 EDTRS letters from baseline to an averaged EDTRS letter score between 48 and 56 weeks
15. proportion of eyes loosing ≥5 EDTRS letters from baseline to an averaged EDTRS letter score between 48 and 56 weeks
16. mean change in low-luminance BCVA from baseline over time
17. mean CST change from baseline (1mm EDTRS grid) to an averaged CST between 24 and 32 weeks
18. mean CST change from baseline (1mm EDTRS grid) to an averaged CST between 48 and 56 weeks
19. proportion of eyes with no intraretinal fluid at baseline, last visit (completed interval) at or before 32 weeks and at or before 56 weeks
20. proportion of eyes with no subretinal fluid at baseline, last visit (completed interval) at or before 32 weeks and at or before 56 weeks
21. proportion of eyes with no retinal (intra- and subretinal) fluid at baseline, last visit (completed interval) at or before 32 weeks and at or before 56 weeks
22. retinal nerve fiber analysis over time
23. incidence and severity of ocular/non-ocular adverse events
24. initial concentration of plasma VEGF-A, Ang-2
25. mean change in concentration of plasma VEGF-A, Ang-2 over time
26. change in NEI VFO-25 total score over time

Investigational products

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

Test 1

Comparator 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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 7 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