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

Neovascular Age-related Macular Degeneration (nAMD) Clinical Trial

Official title:

A Real-world, Prospective, Multi-center, Open-label, Phase IV Clinical Study to Evaluate the Safety and Effectiveness of Intravitreal Injections (IVI) of Brolucizumab in Patients With Neovascular Age-related Macular Degeneration (nAMD)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05269966
• Other study ID #: CRTH258AIN01
• Status: Completed
• Phase: Phase 4
• Start date: March 9, 2022
• Est. completion date: August 29, 2023

Study information

• Verified date: April 2024
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

The study was a prospective, multi-center, open-label, interventional phase IV clinical study.

The study treatment, i.e., brolucizumab was prescribed in terms of the marketing authorization; the assignment of the patient to the therapy was decided within the current practice and the medical indication. It was clearly separated from the decision to include the patient in the study.

All patients with Neovascular Age-related Macular Degeneration (nAMD) who were planned to be treated with brolucizumab and had provided informed consent were enrolled in the study. A total of 12 sites in India were evaluated for the study conduct. This is to note that site #03 was not selected, and site #07 was not initiated, and patients were enrolled in the study only from 10 sites.

The treatment period for each patient was 56 weeks after the start of brolucizumab treatment.

Study visits were scheduled at Week 4, Week 8, Week 16, and thereafter at intervals of 8 weeks or 12 weeks after disease activity assessment at Week 16. If the investigators required more frequent follow-up visits, it was done according to their discretion and clinical judgment. Any patient who suffered from IOI during the study period was not re-challenged with brolucizumab.

The study population consisted of adult male and female outpatients aged 50 years and above, diagnosed with nAMD for whom the treating the physician (Investigator) had prescribed treatment with brolucizumab 6 mg injection in adherence with the local Summary of Product Characteristics (SmPC) or Prescribing Information (PI).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 105
• Est. completion date: August 29, 2023
• Est. primary completion date: August 29, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 50 Years to 100 Years

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Macular Degeneration
• Neovascular Age-related Macular Degeneration (nAMD)
• Wet Macular Degeneration

Intervention

Biological:
• Injection Brolucizumab
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.

Locations

Country	Name	City	State
India	Novartis Investigative Site	Ahmedabad	Gujarat
India	Novartis Investigative Site	Asarwa	Ahmedabad
India	Novartis Investigative Site	Bangalore	Karnataka
India	Novartis Investigative Site	Chandigarh
India	Novartis Investigative Site	Chennai	Tamilnadu
India	Novartis Investigative Site	Hooghly	West Bengal
India	Novartis Investigative Site	Hyderabad	Telangana
India	Novartis Investigative Site	Kolkatta	West Bengal
India	Novartis Investigative Site	New Delhi
India	Novartis Investigative Site	Varanasi	Uttar Pradesh

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

India, 

References & Publications (16)

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 stud — View Citation

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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/a — 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 Neovascul — View Citation

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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. E — View Citation

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. — View Citation

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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. Erratum In: Am J Ophthalmol. 2018 Nov;195:249. — View Citation

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 Degener — View Citation

Rein DB, Wittenborn JS, Zhang X, Honeycutt AA, Lesesne SB, Saaddine J; Vision Health Cost-Effectiveness Study Group. Forecasting age-related macular degeneration through the year 2050: the potential impact of new treatments. Arch Ophthalmol. 2009 Apr;127( — View Citation

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. — View Citation

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. — View Citation

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 — View Citation

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/NEJM19911 — View Citation

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. — View Citation

* Note: There are 16 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence and characteristics of treatment-emergent adverse events during the 56 weeks of treatment with brolucizumab.	To evaluate ocular & non-ocular safety of intravitreal brolucizumab in real-world patients with nAMD.	Week 56
Secondary	Mean change in BCVA from baseline to week 16 and week 56 as measured by Early Treatment Diabetic Retinopathy Study (ETDRS) letters.	To evaluate the effectiveness of brolucizumab in the management of nAMD in terms of change in best-corrected visual acuity (BCVA) from baseline to Week 56.	Week 56
Secondary	Percentage (%) of patient eyes with gain in BCVA of 15/10/5 ETDRS letters or more from baseline to week 16 and week 56.	To evaluate the effectiveness of brolucizumab in the management of nAMD in terms of change in best-corrected visual acuity (BCVA) from baseline to Week 56.	Week 56
Secondary	Percentage (%) of patient eyes with loss in BCVA of 15/10/5 ETDRS letters or more from baseline to week 16 and week 56.	To evaluate the effectiveness of brolucizumab in the management of nAMD in terms of change in best-corrected visual acuity (BCVA) from baseline to Week 56.	Week 56
Secondary	Number of anti-VEGF injections, during the 56 weeks of treatment with brolucizumab.	Characterize the number of anti-VEGF injections during the 56 weeks of treatment with brolucizumab.	Week 56
Secondary	Number of Non-injection visits during the 56 weeks of treatment with brolucizumab.	Characterize number of non-injection visits during the 56 weeks of treatment with brolucizumab.	56 Weeks
Secondary	Total number of visits during the 56 weeks of treatment with brolucizumab.	Characterize the total number of visits during the 56 weeks of treatment with brolucizumab.	56 Weeks
Secondary	Percentage (%) of patient eyes with at least one duration of interval between injections = 8 weeks but <12 weeks.	Estimate the percentage (%) of patient eyes with anti-VEGF injection intervals q8w and q12w during the 56 weeks of treatment with brolucizumab.	Week 56
Secondary	Percentage (%) of patient eyes with at least one duration of interval between injections = 12 weeks.	Estimate the percentage (%) of patient eyes with anti-VEGF injection intervals q8w and q12w during the 56 weeks of treatment with brolucizumab.	Week 56
Secondary	Absence of intra-retinal fluid from baseline to week 16 and week 56.	Estimate effect of brolucizumab on fluid (increased/reduced/unchanged) from baseline to week 16 and week 56 based on Optical Coherence Tomography Image Analysis.	Week 56
Secondary	Absence of sub-retinal fluid from baseline to week 16 and week 56.	Estimate effect of brolucizumab on fluid from baseline to week 16 and week 56.	Week 56
Secondary	Estimate CST change from baseline to week 16 and at week 56.	Estimate effect of brolucizumab on central subfield thickness (CST) from baseline to week 16 and week 56 as measured by Optical Coherence Tomography (in µm)	Week 56