Treatment of Recalcitrant Neovascular AMD Using Brolocizumab With Immediate T&E

Age-Related Macular Degeneration Clinical Trial

Official title:

Treatment of Recalcitrant Neovascular AMD Using Brolocizumab With a Novel Treat and Extend Protocol - a Randomized Controlled Prospective Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05710471
• Other study ID #: Switch Study
• Status: Completed
• Phase: Phase 4
• Start date: July 25, 2022
• Est. completion date: August 30, 2023

Study information

• Verified date: May 2024
• Source: The University of Hong Kong
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The investigator propose to conduct a randomized clinical trial, investigating the safety and efficacy of brolucizumab for treatment of nAMD patients with CNV, and plans to specifically target those who are not responding to standard Treat and Extend (T&E) treatment. A randomised omized study will be conducted with 2 arms, one with the new drug (brolocizumab) and novel treatment protocol versus a second arm using the current gold standard of aflibercept and the T&E protocol

Description:

In addition, there will also be a rescue option for those in the aflibercept arm who are not responding well to also switch to brolucizumab. The primary outcome is the change in central macular thickness, since we expect the new treatment to be effective in reducing intraretinal and subretinal fluids, which in effect are indicators of disease activity. In addition, investigator will look at the improvement of visual acuity, the reduction of treatment intervals, total number of injections over 1 year, recurrence rate and safety profiles of both drugs.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: August 30, 2023
• Est. primary completion date: July 25, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years and older

Eligibility

Inclusion Criteria:

• Age 50 and above

• Diagnosis of exudative age-related macular degeneration (subfoveal CNV) as shown on optical coherence tomography (OCT) - presence of intraretinal fluid, subretinal fluid or subretinal hyperreflective material and/or FFA (leakage classified as subfoveal or as juxtafoveal or extrafoveal)

• Actively treated with aflibercept and given 3 monthly loading doses followed by treat and extend

• Maximal interval period is less than or equal to 8 weekly injections

• Patients must understand and sign the ethics board approved consent form

Exclusion Criteria:

• Ocular criteria:

• Co-existing retinal and/or macular disease (DME, RVO, high myopia of 8 diopters or more, retinal detachment, macular hole stage 2 or above, significant vitreomacular traction or epiretinal membrane, etc.)

• Co-existing ocular disease (glaucoma, uveitis etc.)

• History of uveitis or intraocular inflammation, scleritis, or episcleritis

• History of corneal transplant, pars planar vitrectomy or aphakia

• History of therapeutic radiation to the region of the study eye

• Media opacity obstructing investigation or assessment (cataract, corneal scar, vitreous hemorrhage)

• Treat and extend period beyond 8 weeks

• Any intravitreal injection of steroid within 3 months before randomization

• Systemic criteria:

• Poorly controlled systemic disease including hypertension and diabetes

• Any acute coronary event or stroke within 6 months before randomization

• Malignancy within 5 years

• Systemic anti-VEGF treatment

• Allergy or sensitivity to investigational product, including fluoresceine dye, anesthetics, aflibercept or brolucizumab

Related Conditions & MeSH terms

• Age-Related Macular Degeneration
• Macular Degeneration

Intervention

Drug:
• Brolucizumab
Intravitreal injection
• Aflibercept
Intravitreal injection

Locations

Country	Name	City	State
Hong Kong	Grantham Hospital	Hong Kong

Sponsors (1)

Lead Sponsor	Collaborator
The University of Hong Kong

Country where clinical trial is conducted

Hong Kong, 

References & Publications (17)

Baumal CR, Bodaghi B, Singer M, Tanzer DJ, Seres A, Joshi MR, Feltgen N, Gale R. Expert Opinion on Management of Intraocular Inflammation, Retinal Vasculitis, and Vascular Occlusion after Brolucizumab Treatment. Ophthalmol Retina. 2021 Jun;5(6):519-527. doi: 10.1016/j.oret.2020.09.020. Epub 2020 Sep 29. — View Citation

Baumal CR, Spaide RF, Vajzovic L, Freund KB, Walter SD, John V, Rich R, Chaudhry N, Lakhanpal RR, Oellers PR, Leveque TK, Rutledge BK, Chittum M, Bacci T, Enriquez AB, Sund NJ, Subong ENP, Albini TA. Retinal Vasculitis and Intraocular Inflammation after Intravitreal Injection of Brolucizumab. Ophthalmology. 2020 Oct;127(10):1345-1359. doi: 10.1016/j.ophtha.2020.04.017. Epub 2020 Apr 25. — View Citation

Bilgic A, Kodjikian L, March de Ribot F, Vasavada V, Gonzalez-Cortes JH, Abukashabah A, Sudhalkar A, Mathis T. Real-World Experience with Brolucizumab in Wet Age-Related Macular Degeneration: The REBA Study. J Clin Med. 2021 Jun 23;10(13):2758. doi: 10.3390/jcm10132758. — View Citation

Boulanger-Scemama E, Querques G, About F, Puche N, Srour M, Mane V, Massamba N, Canoui-Poitrine F, Souied EH. Ranibizumab for exudative age-related macular degeneration: A five year study of adherence to follow-up in a real-life setting. J Fr Ophtalmol. 2015 Sep;38(7):620-7. doi: 10.1016/j.jfo.2014.11.015. Epub 2015 Apr 23. — View Citation

Bressler NM. Age-related macular degeneration is the leading cause of blindness.. JAMA. 2004 Apr 21;291(15):1900-1. doi: 10.1001/jama.291.15.1900. No abstract available. — View Citation

Brown DM, Kaiser PK, Michels M, Soubrane G, Heier JS, Kim RY, Sy JP, Schneider S; ANCHOR Study Group. Ranibizumab versus verteporfin for neovascular age-related macular degeneration. N Engl J Med. 2006 Oct 5;355(14):1432-44. doi: 10.1056/NEJMoa062655. — View Citation

Bulirsch LM, Sassmannshausen M, Nadal J, Liegl R, Thiele S, Holz FG. Short-term real-world outcomes following intravitreal brolucizumab for neovascular AMD: SHIFT study. Br J Ophthalmol. 2022 Sep;106(9):1288-1294. doi: 10.1136/bjophthalmol-2020-318672. Epub 2021 Apr 12. — View Citation

Cheung CM, Li X, Cheng CY, Zheng Y, Mitchell P, Wang JJ, Wong TY. Prevalence, racial variations, and risk factors of age-related macular degeneration in Singaporean Chinese, Indians, and Malays. Ophthalmology. 2014 Aug;121(8):1598-603. doi: 10.1016/j.ophtha.2014.02.004. Epub 2014 Mar 22. — View Citation

Dugel PU, Koh A, Ogura Y, Jaffe GJ, Schmidt-Erfurth U, Brown DM, Gomes AV, Warburton J, Weichselberger A, Holz FG; HAWK and HARRIER Study Investigators. HAWK and HARRIER: Phase 3, Multicenter, Randomized, Double-Masked Trials of Brolucizumab for Neovascular Age-Related Macular Degeneration. Ophthalmology. 2020 Jan;127(1):72-84. doi: 10.1016/j.ophtha.2019.04.017. Epub 2019 Apr 12. — View Citation

Friedman DS, O'Colmain BJ, Munoz B, Tomany SC, McCarty C, de Jong PT, Nemesure B, Mitchell P, Kempen J; Eye Diseases Prevalence Research Group. Prevalence of age-related macular degeneration in the United States. Arch Ophthalmol. 2004 Apr;122(4):564-72. doi: 10.1001/archopht.122.4.564. Erratum In: Arch Ophthalmol. 2011 Sep;129(9):1188. — View Citation

Holz FG, Tadayoni R, Beatty S, Berger A, Cereda MG, Cortez R, Hoyng CB, Hykin P, Staurenghi G, Heldner S, Bogumil T, Heah T, Sivaprasad S. Multi-country real-life experience of anti-vascular endothelial growth factor therapy for wet age-related macular degeneration. Br J Ophthalmol. 2015 Feb;99(2):220-6. doi: 10.1136/bjophthalmol-2014-305327. Epub 2014 Sep 5. — View Citation

Mones J, Srivastava SK, Jaffe GJ, Tadayoni R, Albini TA, Kaiser PK, Holz FG, Korobelnik JF, Kim IK, Pruente C, Murray TG, Heier JS. Risk of Inflammation, Retinal Vasculitis, and Retinal Occlusion-Related Events with Brolucizumab: Post Hoc Review of HAWK and HARRIER. Ophthalmology. 2021 Jul;128(7):1050-1059. doi: 10.1016/j.ophtha.2020.11.011. Epub 2020 Nov 15. — View Citation

Rosenfeld PJ, Brown DM, Heier JS, Boyer DS, Kaiser PK, Chung CY, Kim RY; MARINA Study Group. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med. 2006 Oct 5;355(14):1419-31. doi: 10.1056/NEJMoa054481. — View Citation

Schmidt-Erfurth U, Chong V, Loewenstein A, Larsen M, Souied E, Schlingemann R, Eldem B, Mones J, Richard G, Bandello F; European Society of Retina Specialists. Guidelines for the management of neovascular age-related macular degeneration by the European Society of Retina Specialists (EURETINA). Br J Ophthalmol. 2014 Sep;98(9):1144-67. doi: 10.1136/bjophthalmol-2014-305702. — View Citation

Waizel M, Todorova MG, Masyk M, Wolf K, Rickmann A, Helaiwa K, Blanke BR, Szurman P. Switch to aflibercept or ranibizumab after initial treatment with bevacizumab in eyes with neovascular AMD. BMC Ophthalmol. 2017 May 23;17(1):79. doi: 10.1186/s12886-017-0471-x. — View Citation

Wong WL, Su X, Li X, Cheung CM, Klein R, Cheng CY, Wong TY. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet Glob Health. 2014 Feb;2(2):e106-16. doi: 10.1016/S2214-109X(13)70145-1. Epub 2014 Jan 3. — View Citation

Wykoff CC, Ou WC, Brown DM, Croft DE, Wang R, Payne JF, Clark WL, Abdelfattah NS, Sadda SR; TREX-AMD Study Group. Randomized Trial of Treat-and-Extend versus Monthly Dosing for Neovascular Age-Related Macular Degeneration: 2-Year Results of the TREX-AMD Study. Ophthalmol Retina. 2017 Jul-Aug;1(4):314-321. doi: 10.1016/j.oret.2016.12.004. Epub 2017 Feb 2. — View Citation

* Note: There are 17 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Central Macular thickness	Measurement of the change in macular thickness (um)	1 year
Secondary	Visual acuity	Change in best corrected visual acuity (BCVA), LogMAR	1 year
Secondary	Treatment interval	Change in the duration of the treatment interval between each injection (weeks)	1 year
Secondary	Complications	Relating to the drug (eg. Inflammation), relating to the procedure (glaucoma, cataract, retinal detachment, haemorrhage etc)	1 year
Secondary	Optical Coherence Tomography features	Changes and presence of OCT features during every follow-up visit	1 year