Efficacy and Safety of RTH258 Versus Aflibercept - Study 1

NCT02307682 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: RTH258-C001CRTH258A2301
• Study Type: interventional
• Target: 1,775
• Locations: 1 country
• Sites: 1

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.

Conditions

Neovascular Age-Related Macular Degeneration; Choroidal Neovascularization

Keywords

AMD; CNV; IVT

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Best Corrected Visual Acuity (BCVA) (Letters Read) at Week 48 - Study Eye

  BCVA (with spectacles or other visual corrective devices) was assessed using Early Treatment Diabetic Retinopathy Study (ETDRS) testing at 4 meters and reported in letters read correctly. Baseline was defined as the last measurement prior to first treatment. An increase (gain) in letters read from the baseline assessment indicates improvement. One eye (study eye) contributed to the analysis.

  Baseline, Week 48

Secondary Outcomes (32)

• Average Change From Baseline in BCVA (Letters Read) Over the Period Week 36 Through Week 48 - Study Eye

  Baseline, Weeks 36, 40, 44, 48

• Proportion of Subjects With Positive q12 (Every 12 Weeks) Treatment Status at Week 48

  Weeks 16, 20, 28, 32, 40, 44, 48

• Proportion of Subjects With Positive q12 Treatment Status at Week 48 Within the Subjects With no q8 (Every 8 Weeks) Treatment Need During the First q12 Cycle (Week 16, Week 20)

  Weeks 16, 20, 28, 32, 40, 44, 48

• Proportion of Subjects With Positive q12 Treatment Status up to Week 96

  Weeks 16, 20, 28, 32, 40, 44, 52, 56, 64, 68, 76, 80, 88, 92, 96

• Proportion of Subjects With Positive q12 Treatment Status at Week 96 Within the Subjects With no q8 Treatment Need During the Initial q12 Cycle (Week 16, Week 20)

  Weeks 16, 20, 28, 32, 40, 44, 52, 56, 64, 68, 76, 80, 88, 92, 96

Study Arms (3)

Brolucizumab 3 mg

EXPERIMENTAL

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

Drug: Brolucizumab ophthalmic solution

Brolucizumab 6 mg

EXPERIMENTAL

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

Drug: Brolucizumab ophthalmic solution

Aflibercept 2 mg

ACTIVE COMPARATOR

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

Drug: Aflibercept ophthalmic solution

Interventions

Brolucizumab ophthalmic solution DRUG

Ophthalmic solution for IVT injection

Also known as: RTH258

Brolucizumab 3 mg; Brolucizumab 6 mg

Aflibercept ophthalmic solution DRUG

Ophthalmic solution for IVT injection

Also known as: EYLEA®

Aflibercept 2 mg

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Alcon Research: lead

Study Sites (1)

Contact Alcon Call Center for Trial Locations

Fort Worth, Texas, 76134, United States

Location

Related Publications (5)

• 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.

  PMID: 39033924 DERIVED

• 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.

  PMID: 38360182 DERIVED

• 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.

  PMID: 34968756 DERIVED

• 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 DERIVED

• 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 DERIVED

MeSH Terms

Conditions

Choroidal Neovascularization

Interventions

brolucizumab; aflibercept

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

novartis.email@novartis.com

1-862-778-8300

Study Officials

• Group Trial Lead

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 21, 2014
• First Posted: December 4, 2014
• Study Start: December 8, 2014
• Primary Completion: April 22, 2017
• Study Completion: March 28, 2018
• Last Updated: January 16, 2025
• Results First Posted: October 31, 2019

Record last verified: 2025-01

Locations

US (1)