Switching to Aflibercept 8mg in Patients Showing Limited Response to Previous Treatment

NCT06683950 | Recruiting Phase 4 FDA Drug

• 1 other identifier: 2024-07-002
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The treatment landscape for neovascular AMD has evolved with various anti-VEGF agents since 2006. Ranibizumab initially led the way, but its limited efficacy in reducing retinal edema paved the way for aflibercept in 2011, which became globally popular for its effectiveness and safety. Yet, aflibercept did not fully meet all patients' needs. In 2019, brolucizumab showed promising anatomical results but had higher risks of inflammation, limiting its use. Faricimab, introduced in 2022, aimed for longer-lasting effects by targeting VEGF-A and angiopoietin 2. Though it required fewer injections, questions remain about its long-term efficacy compared to aflibercept. Despite recent advancements, no agent has established itself as the new standard since aflibercept's introduction, leaving significant unmet needs. Aflibercept 8mg, approved in 2023, has shown promise by matching long-term visual outcomes of aflibercept 2mg with fewer injections and comparable safety. This study examines the effects of switching to aflibercept 8mg for patients with a limited response to previous treatments, addressing the potential for aflibercept 8mg to meet current needs more effectively and providing timely data for its global rollout.

Conditions

Age-related Macular Degeneration (ARMD)

Keywords

Age-related macular degeneration; Choroidal neovascularization; Aflibercept; Aflibercept 8mg; Faricimab; Refractory

Outcome Measures

Primary Outcomes (1)

• Presence of retinal fluid

  To access changes in retinal fluid after switching to aflibercept 8mg in patients who showed limited response to faricimab or aflibercept 2mg treatment in neovascular AMD

  Between 8 - 16 weeks (At the same interval as the previous dosing schedule for aflibercept 2mg or faricimab)

Secondary Outcomes (6)

• Change in best-corrected visual acuity (BCVA)

  Between 8 - 16 weeks (At the same interval as the previous dosing schedule for aflibercept 2mg or faricimab)

• Change in central retinal thickness (CRT)

  Between 8 - 16 weeks (At the same interval as the previous dosing schedule for aflibercept 2mg or faricimab)

• Change in subfoveal choroidal thickness (SCT)

  Between 8 - 16 weeks (At the same interval as the previous dosing schedule for aflibercept 2mg or faricimab)

• Change in the size of neovascularization

  Between 8 - 16 weeks (At the same interval as the previous dosing schedule for aflibercept 2mg or faricimab)

• Maximum fluid-free period

  Between 8 - 16 weeks (At the same interval as the previous dosing schedule for aflibercept 2mg or faricimab or 2 weeks longer or 4 weeks longer)

Study Arms (1)

Aflibercept 8mg

EXPERIMENTAL

In cases where patients previously treated with faricimab or aflibercept 2mg were switched to aflibercept 8mg

Drug: Aflibercept 8mg

Interventions

Aflibercept 8mg DRUG

Switching to intravitreal aflibercept 8mg in patients previously treated with faricimab or aflibercept 2mg. The dosing schedule is as follows. 1. A single dose of 8mg aflibercept was administered to all patients 2. After treatment 1, follow-up observations were conducted at the same intervals as previous treatments. If complete fluid resolution (no evidence of SRF or IRF) is observed, an additional dose of 8mg aflibercept is administered, extending the dosing intervals by two weeks each time. 3. Up to three doses of 8mg aflibercept can be administered. 4. If, after the administration of 8mg aflibercept, follow-up observations reveal remaining SRF or IRF, the study concludes without additional dosing.

Aflibercept 8mg

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing, committed, and able to return for ALL clinic visits and complete all study related procedures.
• Able to read, (or, if unable to read due to visual impairment, be read to verbatim by the person administering the informed consent or a family member) understand and willing to sign the informed consent form.
• Signed informed consent
• Patients aged 50 years or older
• Patients diagnosed with neovascular AMD or PCV
• Patients underwent faricimab or aflibercept 2mg injections with an inverval of 4 to 16 weeks
• Patients who continued to show persistent subretinal fluid (SRF) or intraretinal fluid (IRF) despite receiving two consecutive faricimab or aflibercept 2mg injections at the same injection interval.
• ETDRS BCVA letter score ≥25 letters (approximately 20/320 or better) in the study eye

You may not qualify if:

• Any prior ocular (in the study eye) or systemic treatment or surgery for neovascular AMD except dietary supplements or vitamins.
• Significant media opacities, including cataract, in the study eye that might interfere with visual acuity, assessment of safety, or fundus photography.
• Any concurrent ocular condition in the study eye which, in the opinion of the investigator, could either increase the risk to the patient beyond what is to be expected from standard procedures of intraocular injection, or which otherwise may interfere with the injection procedure or with evaluation of efficacy or safety.
• Any ocular or periocular infection within the last 2 weeks prior to Screening in either eye.
• Any history of uveitis in either eye.
• Presence of definite chorioretional anastomosis
• Scar or fibrosis, making up \> 50% of total lesion in the study eye.
• Scar, fibrosis, or atrophy involving the center of the fovea in the study eye.
• Presence of retinal pigment epithelial tears or rips involving the macula in the study eye.
• History or clinical evidence of diabetic retinopathy, diabetic macular edema or any other vascular disease affecting the retina, other than AMD, in either eye.
• Any concurrent intraocular condition in the study eye (e.g. cataract) that, in the opinion of the investigator, could require either medical or surgical intervention during the 76 week study period.
• Prior vitrectomy in the study eye
• Any history of macular hole of stage 2 and above in the study eye.
• Any intraocular or periocular surgery within 3 months of Day 1 on the study eye, except lid surgery, which may not have taken place within 1 month of day 1, as long as its unlikely to interfere with the injection.
• Prior trabeculectomy or other filtration surgery in the study eye.

Sponsors & Collaborators

• Kim's Eye Hospital: lead

Study Sites (1)

Kim's Eye Hospital

Seoul, Seoul, 150-034, South Korea

RECRUITING

Related Publications (5)

• Lanzetta P, Korobelnik JF, Heier JS, Leal S, Holz FG, Clark WL, Eichenbaum D, Iida T, Xiaodong S, Berliner AJ, Schulze A, Schmelter T, Schmidt-Ott U, Zhang X, Vitti R, Chu KW, Reed K, Rao R, Bhore R, Cheng Y, Sun W, Hirshberg B, Yancopoulos GD, Wong TY; PULSAR Investigators. Intravitreal aflibercept 8 mg in neovascular age-related macular degeneration (PULSAR): 48-week results from a randomised, double-masked, non-inferiority, phase 3 trial. Lancet. 2024 Mar 23;403(10432):1141-1152. doi: 10.1016/S0140-6736(24)00063-1. Epub 2024 Mar 7.

  PMID: 38461841 BACKGROUND

• Wykoff CC, Brown DM, Reed K, Berliner AJ, Gerstenblith AT, Breazna A, Abraham P, Fein JG, Chu KW, Clark WL, Leal S, Schmelter T, Hirshberg B, Yancopoulos GD, Vitti R; CANDELA Study Investigators. Effect of High-Dose Intravitreal Aflibercept, 8 mg, in Patients With Neovascular Age-Related Macular Degeneration: The Phase 2 CANDELA Randomized Clinical Trial. JAMA Ophthalmol. 2023 Sep 1;141(9):834-842. doi: 10.1001/jamaophthalmol.2023.2421.

  PMID: 37535382 BACKGROUND

• Raimondi R, Felfeli T, Bogdanova-Bennet A, Varma D, Habib M, Kotagiri A, Steel DH, Grinton M. Outcomes of Treatment-Resistant Neovascular Age-Related Macular Degeneration Switched from Aflibercept to Faricimab. Ophthalmol Retina. 2024 Jun;8(6):537-544. doi: 10.1016/j.oret.2023.11.015. Epub 2023 Nov 29.

  PMID: 38040055 BACKGROUND

• Wijesingha N, Sivaprasad S. Infographic: Efficacy, durability, and safety of intravitreal faricimab up to every 16 weeks for neovascular age-related macular degeneration (TENAYA and LUCERNE). Eye (Lond). 2024 Aug;38(Suppl 2):53-54. doi: 10.1038/s41433-023-02867-4. Epub 2023 Dec 20. No abstract available.

  PMID: 38123670 BACKGROUND

• Heier JS, Brown DM, Chong V, Korobelnik JF, Kaiser PK, Nguyen QD, Kirchhof B, Ho A, Ogura Y, Yancopoulos GD, Stahl N, Vitti R, Berliner AJ, Soo Y, Anderesi M, Groetzbach G, Sommerauer B, Sandbrink R, Simader C, Schmidt-Erfurth U; VIEW 1 and VIEW 2 Study Groups. Intravitreal aflibercept (VEGF trap-eye) in wet age-related macular degeneration. Ophthalmology. 2012 Dec;119(12):2537-48. doi: 10.1016/j.ophtha.2012.09.006. Epub 2012 Oct 17.

  PMID: 23084240 BACKGROUND

MeSH Terms

Conditions

Macular Degeneration; Choroidal Neovascularization

Interventions

aflibercept

Condition Hierarchy (Ancestors)

Retinal Degeneration; Retinal Diseases; Eye Diseases; Choroid Diseases; Uveal Diseases; Neovascularization, Pathologic; Metaplasia; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Jae Hui kIM, M.D.

CONTACT

+82-02-2639-7813; kjh7997@kimeye.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Clinical Research Center

Study Record Dates

• First Submitted: October 27, 2024
• First Posted: November 12, 2024
• Study Start: October 21, 2024
• Primary Completion: December 31, 2025
• Study Completion (Estimated): May 31, 2026
• Last Updated: November 12, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)