Efficacy and Safety of RTH258 Versus Aflibercept - Study 1

NCT ID: NCT02307682

Last Updated: 2025-01-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1775 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-12-08
• Study Completion Date: 2018-03-28

Brief Summary

The purpose of this study is to compare brolucizumab (RTH258) ophthalmic solution for intravitreal (IVT) injection at two dosage levels (3 mg and 6 mg) to aflibercept ophthalmic solution for IVT injection (2 mg) in subjects with untreated active choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) in the study eye.

Detailed Description

Subjects were randomized to brolucizumab 3 mg, brolucizumab 6 mg,and aflibercept 2 mg in a 1:1:1 ratio. Subjects in all treatment arms received 3 monthly loading doses (Day 0, Week 4 and Week 8), followed by a maintenance regimen, until the end of the study (Week 96/Exit). All subjects attended pre-specified visits every 4 weeks.

Subjects in the brolucizumab 3 mg and brolucizumab 6 mg arms followed a q12w/q8w maintenance regimen. Within the q12w/q8w regimen, the initial treatment after the loading phase was q12w (1 injection every 12 weeks). If disease activity was identified by the masked investigator at any of the disease activity assessments, dosing was adjusted to q8w (1 injection every 8 weeks) ("q12w/q8w regimen"). Once subjects were adjusted to the q8w interval, they stayed on that interval until the end of the study.

Subjects in the aflibercept 2 mg arm followed a q8w maintenance regimen until the end of the study.

Results reported up to Week 48 are based on the database locked for the primary analysis at Week 48. Results reported after Week 48 are based on the database locked at the end of study (final analysis).

Conditions

Neovascular Age-Related Macular Degeneration; Choroidal Neovascularization

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Brolucizumab 3 mg

Single intravitreal (IVT) injection of brolucizumab ophthalmic solution administered as a 3 mg/50 microliter (μL) dose at Day 0, Week 4, and Week 8, followed by 1 injection every 8 weeks/1 injection every 12 weeks (q8w/q12w) maintenance regimen until study exit

Group Type: EXPERIMENTAL

Brolucizumab ophthalmic solution

Intervention Type: DRUG

Ophthalmic solution for IVT injection

Brolucizumab 6 mg

Single IVT injection of brolucizumab ophthalmic solution administered as a 6 mg/50 μL dose at Day 0, Week 4, and Week 8, followed by q8w/q12w maintenance regimen until study exit

Group Type: EXPERIMENTAL

Brolucizumab ophthalmic solution

Intervention Type: DRUG

Ophthalmic solution for IVT injection

Aflibercept 2 mg

Single IVT injection of aflibercept ophthalmic solution administered as a 2 mg/50 μL dose at Day 0, Week 4, and Week 8, followed by q8w maintenance regimen until study exit

Group Type: ACTIVE_COMPARATOR

Aflibercept ophthalmic solution

Intervention Type: DRUG

Ophthalmic solution for IVT injection

Interventions

Brolucizumab ophthalmic solution

Ophthalmic solution for IVT injection

Intervention Type: DRUG

Aflibercept ophthalmic solution

Ophthalmic solution for IVT injection

Intervention Type: DRUG

Other Intervention Names

RTH258; EYLEA®

Eligibility Criteria

Inclusion Criteria

• Provide written informed consent
• Active choroidal neovascularization (CNV) lesions secondary to age-related macular degeneration (AMD) that affected the central subfield in the study eye at Screening;
• Total area of CNV comprising >50% of the total lesion area in the study eye at Screening;
• Intraretinal and/or subretinal fluid affecting the central subfield of the study eye at Screening;
• Best Corrected Visual Acuity (BCVA) between 78 and 23 letters, inclusive, in the study eye at Screening and Baseline using Early Treatment Diabetic Retinopathy Study (ETDRS) testing.

Exclusion Criteria

• Any active intraocular or periocular infection or active intraocular inflammation in either eye at Baseline;
• Central subfield of the study eye affected by fibrosis or geographic atrophy or total area of fibrosis >50% of the total lesion in the study eye at Screening;
• Subretinal blood affecting the foveal center point and/or >50% of the lesion of the study eye at Screening;
• Any approved or investigational treatment for neovascular age-related macular degeneration (nAMD) in the study eye at any time;
• Retinal pigment epithelial rip/tear in the study eye at Screening or Baseline or current vitreous hemorrhage or history of vitreous hemorrhage in the study eye within 4 weeks prior to Baseline;
• Pregnant or nursing women; women of child-bearing potential;
• Stroke or myocardial infarction in the 90-day period prior to Baseline.

• Minimum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Alcon Research

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Group Trial Lead

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Contact Alcon Call Center for Trial Locations

Fort Worth, Texas, United States

Countries

United States

References

Khanani AM, Sadda SR, Sarraf D, Tadayoni R, Wong DT, Kempf AS, Saffar I, Gedif K, Chang A. Effect of Brolucizumab and Aflibercept on the Maximum Thickness of Pigment Epithelial Detachments and Sub-Retinal Pigment Epithelium Fluid in HAWK and HARRIER. Ophthalmol Retina. 2025 Jan;9(1):13-21. doi: 10.1016/j.oret.2024.07.012. Epub 2024 Jul 19.

Reference Type: DERIVED

PMID: 39033924 (View on PubMed)

Yordi S, Cakir Y, Cetin H, Talcott KE, Srivastava SK, Hu J, Ehlers JP. Bacillary Layer Detachment in Neovascular Age-Related Macular Degeneration from a Phase III Clinical Trial. Ophthalmol Retina. 2024 Aug;8(8):754-764. doi: 10.1016/j.oret.2024.02.007. Epub 2024 Feb 13.

Reference Type: DERIVED

PMID: 38360182 (View on PubMed)

Singh RP, Jhaveri C, Wykoff CC, Gale RP, Staurenghi G, Iida T, Koh A, B G, Gedif K, Singer M. Efficacy Outcomes of Brolucizumab Versus Aflibercept in Neovascular Age-Related Macular Degeneration Patients with Early Residual Fluid. Ophthalmol Retina. 2022 May;6(5):377-386. doi: 10.1016/j.oret.2021.12.014. Epub 2021 Dec 27.

Reference Type: DERIVED

PMID: 34968756 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33207259 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 30986442 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

CRTH258A2301

Identifier Type: OTHER

Identifier Source: secondary_id

RTH258-C001

Identifier Type: -

Identifier Source: org_study_id