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

NCT05710471 | Completed Phase 4 DMC FDA Drug

• 1 other identifier: Switch Study
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Age-Related Macular Degeneration

Outcome Measures

Primary Outcomes (1)

• Central Macular thickness

  Measurement of the change in macular thickness (um)

  1 year

Secondary Outcomes (4)

• Visual acuity

  1 year

• Treatment interval

  1 year

• Complications

  1 year

• Optical Coherence Tomography features

  1 year

Study Arms (2)

Brolucizumab

EXPERIMENTAL

new drug (brolocizumab) and novel treatment protocol

Drug: Brolucizumab

Aflibercept

ACTIVE COMPARATOR

aflibercept and continuing on the traditional T\&E protocol. There will also be a rescue option for those in the aflibercept arm who are not responding well to also switch to brolocizumab

Drug: Aflibercept

Interventions

Brolucizumab DRUG

Intravitreal injection

Also known as: Beovu

Brolucizumab

Aflibercept DRUG

Intravitreal injection

Also known as: Eylea

Aflibercept

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• The University of Hong Kong: lead

Study Sites (1)

Grantham Hospital

Hong Kong, Hong Kong

Location

Related Publications (17)

• 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.

  PMID: 15078675 BACKGROUND

• 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.

  PMID: 15108691 BACKGROUND

• 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.

  PMID: 25104651 BACKGROUND

• 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.

  PMID: 24661862 BACKGROUND

• 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.

  PMID: 17021319 BACKGROUND

• 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.

  PMID: 17021318 BACKGROUND

• 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.

  PMID: 25193672 BACKGROUND

• 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.

  PMID: 31047517 BACKGROUND

• 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.

  PMID: 25136079 BACKGROUND

• 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.

  PMID: 25913443 BACKGROUND

• 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.

  PMID: 30986442 BACKGROUND

• 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.

  PMID: 28535756 BACKGROUND

• 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.

  PMID: 33846161 BACKGROUND

• 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.

  PMID: 34201729 BACKGROUND

• 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.

  PMID: 33207259 BACKGROUND

• 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.

  PMID: 32344075 BACKGROUND

• 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.

  PMID: 33007521 BACKGROUND

MeSH Terms

Conditions

Macular Degeneration

Interventions

brolucizumab; aflibercept

Condition Hierarchy (Ancestors)

Retinal Degeneration; Retinal Diseases; Eye Diseases

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Patients are randomised and masked from the treatment
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Clinical Assistant Professor

Model Details: Parallel interventional arms with option of rescue treatment

Study Record Dates

• First Submitted: January 25, 2023
• First Posted: February 2, 2023
• Study Start: July 25, 2022
• Primary Completion: July 25, 2023
• Study Completion: August 30, 2023
• Last Updated: May 8, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, CSR
• Time Frame: 5 years after study ends
• Access Criteria: Case by case

Locations

HK (1)