Study to Evaluate the Safety and Effectiveness of Intravitreal Injections (IVI) of Brolucizumab in Patients With Neovascular Age-related Macular Degeneration (nAMD)

NCT05269966 | Completed Phase 4 Results

• 1 other identifier: CRTH258AIN01
• Study Type: interventional
• Target: 105
• Locations: 1 country
• Sites: 10

Brief Summary

The purpose of this study was to generate additional safety and effectiveness data in Indian neovascular age-related macular degeneration (nAMD) patients that more closely resemble the real-world population intended to be treated with brolucizumab. This study was conducted as part of the post-marketing regulatory commitment to the Indian Health authority.

Conditions

Neovascular Age-related Macular Degeneration (nAMD)

Keywords

Macular degeneration; age-related macular degeneration (ARMD); vision loss; macula damage; retina damage; dry macular degeneration; wet macular degeneration; Subfoveal choroidal neovascularization (CNV) secondary to age-related macular degeneration; AMD; neovascular age-related macular degeneration; nAMD; retinal vein occlusion; RVO

Outcome Measures

Primary Outcomes (4)

• Incidence and Characteristics of Treatment-emergent Adverse Events During the 56 Weeks of Treatment With Brolucizumab.

  An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a clinical investigation participant after providing written informed consent for participation in the study. Treatment-emergent Adverse Events (TEAEs) in this study are defined as AEs suspected to be related to the study drug.

  Adverse events were reported from first dose of study treatment until Week 48, plus 8 weeks follow up, to a maximum timeframe of 56 weeks.

• Incidence of Treatment-emergent Adverse Events During the 56 Weeks of Treatment With Brolucizumab - Ocular AEs - Preferred Term

  An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a clinical investigation participant after providing written informed consent for participation in the study. Treatment-emergent Adverse Events (TEAEs) in this study are defined as AEs suspected to be related to the study drug.

  Adverse events were reported from first dose of study treatment until Week 48, plus 8 weeks follow up, to a maximum timeframe of 56 weeks.

• Characteristics of Treatment-emergent Adverse Events During the 56 Weeks of Treatment With Brolucizumab

  An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a clinical investigation participant after providing written informed consent for participation in the study. Treatment-emergent Adverse Events (TEAEs) in this study are defined as AEs suspected to be related to the study drug.

  Adverse events were reported from first dose of study treatment until Week 48, plus 8 weeks follow up, to a maximum timeframe of 56 weeks.

• Incidence of Ocular Adverse Event (AEs) by System Organ Class (SOC) and Preferred Term (PT) During the 56 Weeks of Treatment With Brolucizumab

  An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and unintended sign \[including abnormal laboratory findings\], symptom or disease) in a clinical investigation participant after providing written informed consent for participation in the study.

  Adverse events were reported from first dose of study treatment until Week 48, plus 8 weeks follow up, to a maximum timeframe of 56 weeks.

Secondary Outcomes (15)

• Mean Change in Best-Corrected Visual Acuity (BCVA) From Baseline at Week 16 and Week 56 as Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Letters - Study Eye

  Baseline, Week 16, Week 56

• Change in Best-Corrected Visual Acuity (BCVA) From Baseline at Week 16 and Week 56 as Measured by Early Treatment Diabetic Retinopathy Study (ETDRS) Letters - Median - Study Eye

  Baseline, Week 16, Week 56

• Number and Percentage (%) of Participants With Gain in Best-Corrected Visual Acuity (BCVA) of 15/10/5 ETDRS Letters or More From Baseline at Week 16 and Week 56 - Study Eye

  Baseline, Week 16 and Week 56

• Number and Percentage (%) of Participants With Loss in Best-Corrected Visual Acuity (BCVA) of 15/10/5 ETDRS Letters or More From Baseline at Week 16 and Week 56 - Study Eye

  Baseline, Week 16 and Week 56

• Number of Anti-VEGF Injections, During the 56 Weeks of Treatment With Brolucizumab - Study Eye

  Week 56

Study Arms (1)

Brolucizumab

EXPERIMENTAL

Brolucizumab, formerly known as ESBA1008, is a humanized single-chain Fv (scFv) antibody fragment. Brolucizumab 6 mg was administered by Intravitreal (IVT) injections as per the Prescribing information (PI) and in line with the treating physician's clinical judgement. Patients received loading doses of brolucizumab at Day 0/Visit 1, Week 4/Visit 2 and Week 8/Visit 3. After the loading doses, at Week 16, disease activity assessment (DAA) was performed based on Best Corrected Visual Acuity (BCVA) and Optical Coherence Tomography (OCT) to assess whether the patient required q8w or q12w dosing.

Biological: Injection Brolucizumab

Interventions

Injection Brolucizumab BIOLOGICAL

Single-chain antibody fragment (scFv) Brolucizumab 6 mg was administered by Intravitreal (IVT) injection as per the Prescribing information (PI) and in line with the treating physician's clinical judgement. Patients received loading doses of brolucizumab at Day 0/Visit 1, Week 4/Visit 2 and Week 8/Visit 3. After the loading doses, at Week 16, disease activity assessment (DAA) were performed based on Best Corrected Visual Acuity (BCVA) and Optical Coherence Tomography (OCT) to assess whether the patient required q8w or q12w dosing.

Also known as: Trade Names: Pagenax, Beovu, Vsiqq

Brolucizumab

Eligibility Criteria

• Age: 50 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female or male, treatment naïve patient with ≥50 years of age, with neovascular age-related macular degeneration (nAMD).
• Patient or legally acceptable representative (LAR) willing to voluntarily provide signed informed consent for participation in the study.
• Note: In case where both eyes are affected, data of only one eye \['study eye'\] will be recorded. Selection of the eye to be considered for the purpose of the study \[referred to as 'study eye'\] will be as per the Investigator's discretion.

You may not qualify if:

• Patients fulfilling any of the following criteria are not eligible for this study:
• Patient having other eye diseases that could compromise the VA.
• Patient with existing or suspected ocular or periocular infection in the study eye.
• Patient with an existing intraocular inflammation (IOI).
• Patient with uncontrolled glaucoma defined as intraocular pressure \> 25 mmHg despite treatment with anti-glaucoma medication, or according to Investigator's judgment.
• Patient who has undergone intraocular surgery within 3 months prior to enrollment in this study.
• Patient having scar, fibrosis and atrophy involving the center of the fovea in the study eye.

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (10)

Novartis Investigative Site

Asarwa, Ahmedabad, 380016, India

Location

Novartis Investigative Site

Ahmedabad, Gujarat, 380052, India

Location

Novartis Investigative Site

Bangalore, Karnataka, 560 010, India

Location

Novartis Investigative Site

Chennai, Tamil Nadu, 600018, India

Location

Novartis Investigative Site

Hyderabad, Telangana, 500 034, India

Location

Novartis Investigative Site

Varanasi, Uttar Pradesh, 221010, India

Location

Novartis Investigative Site

Kolkata, West Bengal, 700 073, India

Location

Novartis Investigative Site

Chandigarh, 160012, India

Location

Novartis Investigative Site

Hugli, 712223, India

Location

Novartis Investigative Site

New Delhi, 110029, India

Location

Related Publications (16)

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  PMID: 19365036 RESULT

• Kawasaki R, Yasuda M, Song SJ, Chen SJ, Jonas JB, Wang JJ, Mitchell P, Wong TY. The prevalence of age-related macular degeneration in Asians: a systematic review and meta-analysis. Ophthalmology. 2010 May;117(5):921-7. doi: 10.1016/j.ophtha.2009.10.007. Epub 2010 Jan 27.

  PMID: 20110127 RESULT

• Smith W, Assink J, Klein R, Mitchell P, Klaver CC, Klein BE, Hofman A, Jensen S, Wang JJ, de Jong PT. Risk factors for age-related macular degeneration: Pooled findings from three continents. Ophthalmology. 2001 Apr;108(4):697-704. doi: 10.1016/s0161-6420(00)00580-7.

  PMID: 11297486 RESULT

• Miller JW. Age-related macular degeneration revisited--piecing the puzzle: the LXIX Edward Jackson memorial lecture. Am J Ophthalmol. 2013 Jan;155(1):1-35.e13. doi: 10.1016/j.ajo.2012.10.018.

  PMID: 23245386 RESULT

• Ferris FL 3rd, Fine SL, Hyman L. Age-related macular degeneration and blindness due to neovascular maculopathy. Arch Ophthalmol. 1984 Nov;102(11):1640-2. doi: 10.1001/archopht.1984.01040031330019.

  PMID: 6208888 RESULT

• Lim LS, Mitchell P, Seddon JM, Holz FG, Wong TY. Age-related macular degeneration. Lancet. 2012 May 5;379(9827):1728-38. doi: 10.1016/S0140-6736(12)60282-7.

  PMID: 22559899 RESULT

• Shah AR, Del Priore LV. Progressive visual loss in subfoveal exudation in age-related macular degeneration: a meta-analysis using Lineweaver-Burke plots. Am J Ophthalmol. 2007 Jan;143(1):83-89. doi: 10.1016/j.ajo.2006.09.043. Epub 2006 Oct 20.

  PMID: 17188044 RESULT

• Shah AR, Del Priore LV. Natural history of predominantly classic, minimally classic, and occult subgroups in exudative age-related macular degeneration. Ophthalmology. 2009 Oct;116(10):1901-7. doi: 10.1016/j.ophtha.2009.03.055. Epub 2009 Jul 9.

  PMID: 19592101 RESULT

• Blinder KJ, Bradley S, Bressler NM, Bressler SB, Donati G, Hao Y, Ma C, Menchini U, Miller J, Potter MJ, Pournaras C, Reaves A, Rosenfeld PJ, Strong HA, Stur M, Su XY, Virgili G; Treatment of Age-related Macular Degeneration with Photodynamic Therapy study group; Verteporfin in Photodynamic Therapy study group. Effect of lesion size, visual acuity, and lesion composition on visual acuity change with and without verteporfin therapy for choroidal neovascularization secondary to age-related macular degeneration: TAP and VIP report no. 1. Am J Ophthalmol. 2003 Sep;136(3):407-18. doi: 10.1016/s0002-9394(03)00223-x.

  PMID: 12967792 RESULT

• Sommer A, Tielsch JM, Katz J, Quigley HA, Gottsch JD, Javitt JC, Martone JF, Royall RM, Witt KA, Ezrine S. Racial differences in the cause-specific prevalence of blindness in east Baltimore. N Engl J Med. 1991 Nov 14;325(20):1412-7. doi: 10.1056/NEJM199111143252004.

  PMID: 1922252 RESULT

• Wong TY, Chakravarthy U, Klein R, Mitchell P, Zlateva G, Buggage R, Fahrbach K, Probst C, Sledge I. The natural history and prognosis of neovascular age-related macular degeneration: a systematic review of the literature and meta-analysis. Ophthalmology. 2008 Jan;115(1):116-26. doi: 10.1016/j.ophtha.2007.03.008. Epub 2007 Aug 6.

  PMID: 17675159 RESULT

• Menrad A, Anderer FA. Expression of LDL receptor on tumor cells induced by growth factors. Anticancer Res. 1991 Jan-Feb;11(1):385-90.

  PMID: 1850220 RESULT

• Campbell JP, Bressler SB, Bressler NM. Impact of availability of anti-vascular endothelial growth factor therapy on visual impairment and blindness due to neovascular age-related macular degeneration. Arch Ophthalmol. 2012 Jun;130(6):794-5. doi: 10.1001/archophthalmol.2011.2480. No abstract available.

  PMID: 22801846 RESULT

• Bloch SB, Larsen M, Munch IC. Incidence of legal blindness from age-related macular degeneration in denmark: year 2000 to 2010. Am J Ophthalmol. 2012 Feb;153(2):209-213.e2. doi: 10.1016/j.ajo.2011.10.016.

  PMID: 22264944 RESULT

• Nguyen QD, Das A, Do DV, Dugel PU, Gomes A, Holz FG, Koh A, Pan CK, Sepah YJ, Patel N, MacLeod H, Maurer P. Brolucizumab: Evolution through Preclinical and Clinical Studies and the Implications for the Management of Neovascular Age-Related Macular Degeneration. Ophthalmology. 2020 Jul;127(7):963-976. doi: 10.1016/j.ophtha.2019.12.031. Epub 2020 Jan 17.

  PMID: 32107066 RESULT

• 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 RESULT

Related Links

• A Plain Language Trial Summary is available on www.novctrd.com

MeSH Terms

Conditions

Macular Degeneration; Vision Disorders; Geographic Atrophy; Wet Macular Degeneration; Choroidal Neovascularization; Retinal Vein Occlusion

Condition Hierarchy (Ancestors)

Retinal Degeneration; Retinal Diseases; Eye Diseases; Sensation Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Choroid Diseases; Uveal Diseases; Neovascularization, Pathologic; Metaplasia; Pathologic Processes; Venous Thrombosis; Thrombosis; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@Novartis.com

+ 1 862 778 8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 16, 2022
• First Posted: March 8, 2022
• Study Start: March 9, 2022
• Primary Completion: August 29, 2023
• Study Completion: August 29, 2023
• Last Updated: March 20, 2025
• Results First Posted: December 10, 2024

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will share

Locations

IN (10)