Effectiveness of Brolucizumab in Pre-treated Patients With nAMD in the Real-world Setting

Effectiveness of Brolucizumab in Pretreated Patients With nAMD in the Real-world Setting in Gulf Countries United Arab of Emirates, Kuwait , Bahrain , Oman and Qatar

The study is a prospective and retrospective, observational, single-arm, non-randomized cohort study of ocular treatment with intravitreal injections of brolucizumab in nAMD patients. This study will be conducted prospectively and retrospectively (for patients who had their first brolucizumab injection before study start) using data collected in a standardized manner.

Study Overview

• Status: Recruiting
• Conditions: Neovascular Age-related Macular Degeneration
• Intervention / Treatment: Other: Brolucizumab

Detailed Description

Retrospective data will be collected for all patients starting treatment with brolucizumab for up to 12 months before baseline.

Patients who received brolucizumab before the study start will be recruited into the study and presented an informed consent form (ICF) at their first visit. Their index date will be the date of their first brolucizumab injection, which must have occurred during the recruitment period or in 6 months prior to the first visit in the recruitment period. Patient history and characteristics will be recorded in the 12 months prior to the index date.

Index date (Baseline): defined as the date of the first anti-VEGF injection (brolucizumab) in the patient study eye.

Index period: The patients fulfilling the inclusion criteria will be identified during the period 01-Nov-2021 and onwards.

Study period: The period is between May-2020 and Nov-2023 to allow 6-month pre-index period and at least a 12-month follow-up period for each recruited patient.

• Study Type: Observational
• Enrollment (Estimated): 99

Contacts and Locations

• Study Contact: Name: Novartis Pharmaceuticals; Phone Number: +41613241111; Email: novartis.email@novartis.com
• Study Contact Backup: Name: Novartis Pharmaceuticals

Study Locations

• United Arab Emirates
  • Abu Dhabi, United Arab Emirates
    • Recruiting
    • Novartis Investigative Site
  • Abu Dhabi, United Arab Emirates, 112412
    • Recruiting
    • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients that started brolucizumab treatment during the study recruitment period or patients that started brolucizumab treatment during the 6 months preceding the start of study recruitment

Description

Inclusion Criteria:

• Diagnosis of nAMD
• Patients with ≥18 years of age at index
• Receipt of at least one injection of brolucizumab (not necessarily the first one) during the index period
• Signed informed consent

Exclusion Criteria:

• Patients treated for retinal vein occlusion (RVO), diabetic macular edema (DME), myopic choroidal neovascularization (mCNV), and have diagnoses of diabetes-related macular degeneration within 6 months prior to the index date
• Receipt of any anti-VEGF treatment other than brolucizumab in the study eye during the index period
• Receipt of brolucizumab in the study eye more than 6 months before the index period, i.e., brolucizumab treatment started more than 6 months before the start of the study
• Any active intraocular or periocular infection or active intraocular inflammation in the study eye at index date
• Patients who have any contraindication and are not eligible for treatment with brolucizumab as according to the label
• Patients who were treated with more than 2 types of anti-VEGF before index date (4th line brolucizumab patients or more)
• Any medical or psychological condition in the treating physician's opinion which may prevent the patient from the 12-month study participation
• Patients participating in parallel in an interventional clinical trial Note: if a patient experiences an adverse event (AE), they may still be recruited in another study following this AE if they fulfill their inclusion criteria. Their data will still be collected as planned by the current protocol
• Patients participating in parallel in any other NIS generating primary data for an anti-VEGF drug

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Other

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Brolucizumab; patients who received their first injection of Brolucizumab either during the active recruitment period (1 year prospective) or during the 6 months pre-start of the recruitment (6 months retrospective)	Other: Brolucizumab; There is no treatment allocation. Patients administered brolucizumab by prescription will be enrolled.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients with absence of SRF and IRF	percentage of treated patients with absence of SRF and IRF. Patients who have discontinued brolucizumab before Month 12 will be counted as not having achieved the endpoint of fluid resolution (absence of SRF and IRF), unless they reached it at the last visit while still on brolucizumab treatment before the discontinuation.	Month 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of patients ≥ 80 years old	Percentage of patients ≥ 80 years old will be collected	Baseline
Duration of diagnosis	Time since first diagnosis (years) will be collected	Baseline
Percentage of patients with baseline visit	Percentage of patients with baseline visit will be collected	Baseline
Percentage of patients with bilateral disease	Percentage of patients with bilateral disease will be collected	Baseline
Percentage of patients with lesion type	Percentage of patients by lesion type will be collected: occult, minimally classic, predominantly classic, other	Baseline
Percentage of patients with presence of SRF, IRF and sub-RPE	It will be collected the percentage of patients with presence of: Subretinal Fluid (SRF); Intra-Retinal Fluid (IRF); Subretinal Fluid (SRF) and/or Intra-Retinal Fluid (IRF); Sub-Retinal Pigment Epithelium	Baseline
Baseline CST	Central Subfield Thickness (CST) in μm will be collected	Baseline, Month 3, Month 6, Month 9 and Month 12
Baseline VA	Visual Acuity (VA) will be measured with Early Treatment Diabetic Retinopathy Study (ETDRS) letters. Conversion of VA readings to approximate ETDRS Letters: For Snellen fraction decimal >0.025 (< logMAR1.60) the following formula is used: approximate ETDRS letters = 85+50*log10(Snellen fraction) For Snellen fractions decimal ≤ 0.025 four bins are defined: > 0.020 to 0.025 (logMAR 1.70 to 1.60) is 5 letters; > 0.015 to 0.020 (logMAR 1.82 to 1.70) is 3 letters; > 0.005 to 0.015 (logMAR 2.30 to 1.82) is 1 letter; ≤ 0.005 (logMAR ≥ 2.30) is 0 letter	Baseline
Percentage of patients with the study eye that has VA equal or less than the VA in fellow eye	Percentage of patients with the study eye that has Visual Acuity (VA) equal or less than the VA in fellow eye will be collected	Baseline
Percentage of patients with baseline VA in the following categories (≤35, 36-69, ≥ 70 ETDRS letters)	Percentage of patients with baseline Visual Acuity (VA) in the following categories (≤35, 36-69, ≥ 70 ETDRS letters) will be collected	Baseline
Percentage of patients with VA between 34 and 72 ETDRS letters	Percentage of patients with Visual Acuity (VA) within these values will be collected: 33 < VA < 73	Baseline
Percentage of patients with baseline VA < 73 ETDRS letters and active (SRF only)	Percentage of patients with baseline VA < 73 ETDRS letters and active (SRF only) Active SRF is described as patients with new presence of SRF or increased SRF	Baseline
Percentage of patients with different ethnic groups	Percentage of patients by ethnicity will be presented	Baseline
Switch Patients: Previous anti-VEGF treatments of nAMD pre-treated patients	Previous anti-VEGF treatments of nAMD pre-treated patients will be collected	Baseline
Switch Patients: Duration of previous anti-VEGF treatments	Duration of previous anti-VEGF treatments will be collected	Baseline
Switch Patients: Number of injections in the last year before switching to brolucizumab	Number of injections in the last year before switching to brolucizumab will be collected	Baseline
Switch Patients: Last interval of anti-VEGF treatment before switching	Last interval of anti-VEGF treatment before switching will be collected	Baseline
Percentage of patients with absence of SRF	The total percentage of patients with absence of Subretinal Fluid (SRF) and percentage of patients with absence of SRF from those with presence of SRF at baseline will be collected	Month 3, Month 6, Month 9 and Month 12
Percentage of patients with stable SRF	Percentage of patients with stable Subretinal Fluid (SRF), from those with absence of SRF at baseline	Month 3, Month 6, Month 9 and Month 12
Time to absence of SRF during the 12-month treatment with brolucizumab	Time to absence of Subretinal Fluid (SRF) will be collected	12 months
Percentage of patients with absence of IRF	Percentage of patients with absence of Intra-Retinal Fluid (IRF), and percentage of patients with absence of IRF from those with presence of IRF at baseline will be collected	Month 3, Month 6, Month 9 and Month 12
Percentage of patients with stable IRF	Percentage of patients with stable Intra-Retinal Fluid (IRF), from those with absence of IRF at baseline	Month 3, Month 6, Month 9 and Month 12
Time to absence of IRF during the 12-month treatment with brolucizumab	Time to absence of Intra-Retinal Fluid (IRF) during the 12-month treatment with brolucizumab will be collected	12 months
Percentage of patients with absence of sub-RPE	Percentage of patients with absence of sub-Retinal Pigment Epithelium (RPE) and percentage of patients with absence of sub-RPE, from those with presence of sub-RPE at baseline will be collected	Month 3, Month 6, Month 9 and Month 12
Percentage of patients with stable sub-RPE	Percentage of patients with stable sub-Retinal Pigment Epithelium (RPE), from those with absence of sub-RPE at baseline	Month 3, Month 6, Month 9 and Month 12
Time to absence of sub-RPE during the 12-month treatment with brolucizumab	Time to absence of sub-Retinal Pigment Epithelium (RPE) during the 12-month treatment with brolucizumab will be collected	12 months
Percentage of patients with absence of SRF, IRF and sub-RPE	Percentage of patients with absence of Subretinal Fluid (SRF), Intra-Retinal Fluid (IRF) and sub-Retinal Pigment Epithelium (RPE) and percentage of patients with absence of SRF and IRF and sub-RPE, from those with presence of SRF or IRF or sub-RPE at baseline will be collected	Month 3, Month 6, Month 9 and Month 12
Time to absence of IRF and SRF and sub-RPE during the 12-month treatment with brolucizumab	Time to absence of IRF and SRF and sub-RPE during the 12-month treatment with brolucizumab	12 months
Estimate CST change from baseline	Estimate Central Subfield Thickness (CST) change from baseline (in μm) will be collected	Month 3, Month 6, Month 9 and Month 12
Percentage of patients with reduced CST vs baseline	Percentage of patients with reduced CST vs baseline will be collected	Baseline, Month 3, Month 6, Month 9 and Month 12
Association between CST variability at Months 1-12 and VA change from baseline	Correlation statistical tests between CST variability at Months 1-12 (quartiles) and VA change from baseline to Months 3, 6, 9 and 12	Month 3, Month 6, Month 9 and Month 12
Association between CST variability at Months 1-12 and number of injections	Correlation statistical tests between CST variability at Months 1-12 (quartiles) and number of injections during the 12-month treatment with brolucizumab	Month 12
Percentage of patients with clinician-graded subretinal fibrosis and/or macular atrophy	Percentage of patients with clinician-graded subretinal fibrosis and/or macular atrophy	Month 12
VA change from baseline	Visual Acuity (VA) change from baseline (in ETDRS letters)	Baseline, Month 3, Month 6, Month 9 and Month 12
Percentage of patients with VA change from baseline	Percentage of patients with Visual Acuity (VA) change from baseline categorized as: ≤ -20, ≤ -15, (-15, -10], (-10, -5], (-5, 5), [5, 10), [10, 15), ≥ 15, ≥ 20 (in ETDRS letters)	Baseline, Month 3, Month 6, Month 9 and Month 12
Percentage of patients with ≥ 70 ETDRS letters	Percentage of patients with ≥ 70 ETDRS letters will be collected	Month 3, Month 6, Month 9 and Month 12
Number of brolucizumab visits	Number of brolucizumab injections, non-injection visits and total number of visits will be collected	Over Months 1-3, 3-6, 6-12 and 1-12
Distribution of injection intervals	Distribution of injection intervals < 4; [4, 6); [6, 8); [8, 10); [10, 12); ≥12 weeks will be collected	During Months 1-6 and 1-12
Percentage of patients with at least one duration of interval between injections	Percentage of patients with at least one duration of interval between injections < 4; [4, 6); [6, 8); [8, 10); [10, 12); ≥ 12 weeks (the maximum injection interval will be kept) One duration of interval is defined as the time between one injection and the following one	12 months
Percentage of patients with at least two consecutive duration of intervals between injections	Percentage of patients with at least two consecutive duration of intervals between injections < 4; [4, 6); [6, 8); [8, 10); [10, 12); ≥12 weeks (the maximum duration will be kept) Two consecutive duration of intervals is the time between one injection and the second consecutive one.	12 months
Percentage of switch patients from other anti-VEGF that prolonged injection intervals with brolucizumab	Percentage of switch patients from other anti-VEGF that prolonged injection intervals with brolucizumab will be collected	Month 6, Month 9 and Month 12
Percentage of patients with ≥ 3 brolucizumab injections	Percentage of patients with ≥ 3 brolucizumab injections will be collected	Month 3
Number of participants by last recorded injection interval	Number of participants by last recorded injection interval (in weeks)	Month 6 and Month 12
Time between two consecutive brolucizumab injections	Time (in days) between two consecutive brolucizumab injections will be collected	Over Months 1-3
Number of visits with/without OCT	Number of visits with/without Optical Coherence Tomography (OCT) will be collected	Over Months 1-6 and 1-12
Association between number of OCT and CNV activity	Correlation statistical tests between number of Optical Coherence Tomography (OCT) (0-1, 2-3, ≥ 4) and Choroidal Neovascularization (CNV) activity [active, active (SRF only), inactive]	Month 6, Month 9 and Month 12
Association between number of OCT and VA change from baseline	Correlation statistical tests between number of Optical Coherence Tomography (OCT) (0-1, 2-3, ≥ 4) and Visual Acuity (VA) change from baseline (in ETDRS letters)	Month 6, Month 9 and Month 12
Association between number of OCT and number of injections	Correlation statistical tests between number of Optical Coherence Tomography (OCT) (0-1, 2-3, ≥ 4) at Months 6, 9 and 12 and number of injections during the Months 1-6, 1-9 and 1-12 of treatment with brolucizumab	12 months
proportion of participants by baseline CNV activity	Baseline Choroidal Neovascularization (CNV) activity (active, active (SRF only), inactive) will be collected	Baseline
Proportion of participants with and without Loading phase	Proportion of participants with and without Loading phase will be collected. Loading phase (yes/no) defined as ≥ 3-injections within 90 days post-index	12 months
VA at the end of the loading phase	Visual Acuity (VA) at the end of the loading phase will be collected. Loading phase is defined as ≥ 3-injections within 90 days post-index	Month 3
CNV activity at the end of the loading phase	Choroidal Neovascularization (CNV) activity at the end of the loading phase (active, active (SRF only), inactive) will be measured. Loading phase is defined as ≥ 3-injections within 90 days post-index	Month 3
Number of injections during the maintenance phase	Number of injections during the maintenance phase will me measured	Over months 3-12
Percentage of patients with geographic atrophy	Percentage of patients with geographic atrophy will be measured	12 Months
Percentage of patients with subretinal fibrosis	Percentage of patients with subretinal fibrosis will be measured	12 Months
Assessment of criteria for no retreatment	Percentage of patients by criteria for no retreatment will be measured. ( i.e., disease activity assessed by: VA, anatomic parameters, predetermined by regimen, other (e.g., organizational, patient choice, etc.)	12 months
Percentage of patients who switch to another anti-VEGF	Percentage of patients who switch to another anti-VEGF during the first 6, 9 and 12 months of treatment with brolucizumab will be measured	6 Months, 9 Months and 12 Months
VA at time of switch	Visual Acuity (VA) at time of switch will be measured with Early Treatment Diabetic Retinopathy Study (ETDRS) letters.	Up to 12 months
Percentage of patients with activity at time of switch	Percentage of patients with activity at time of switch: Intra-Retinal Fluid (IRF) activity; Subretinal Fluid (SRF) activity; sub-Retinal Pigment Epithelium (RPE) activity; Central Subfield Thickness (CST) activity; Choroidal Neovascularization (CNV) activity	Up to 12 months
Percentage of switchers with full loading phase	Percentage of switchers with full loading phase will be collected Loading phase (yes/no) defined as ≥ 3-injections within 90 days post-index	12 months
Percentage of patients by injection rate at pre-switch period	Percentage of patients by injection rate at pre-switch period will be collected	Up to 12 months
Reason for switching to another anti-VEGF	Percentage of patients by reason for switching to another anti-VEGF will be collected	12 months
Last recorded injection interval before switching	Last recorded injection interval (in weeks) before switching will be collected	Month 6 and Month 12
Duration of brolucizumab treatment before switching	Duration of brolucizumab treatment before switching will be collected	Up to month 12
Percentage of patients who discontinue therapy	Percentage of patients who discontinue therapy and reasons for discontinuation. Discontinuation is defined as if anti-VEGF brolucizumab was stopped (including treatment switch to another anti-VEGF) at some point and never re-introduced for at least 180 days, while the patient has at least one clinical or anatomical assessment during that period	Up to 12 months
Days of persistence	Persistence is defined as the time (in days) on drug from from the initiation of anti-VEGF therapy with brolucizumab to its discontinuation (defined as injection gap of >180 days)	Up to 12 Months
Percentage of patients with AEs	Percentage of patients with AEs will be collected	12 Months
AE rate	AE rate (per 10,000 injections) will be collected	Month 3, Month 6, Month 9 and Month 12

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Publications and helpful links

Helpful Links

• Results for CRTH258AAE01 that is getting linked from the Novartis Clinical Trials Website

Study record dates

Study Major Dates

• Study Start (Actual): April 13, 2022
• Primary Completion (Estimated): September 30, 2024
• Study Completion (Estimated): September 30, 2024

Study Registration Dates

• First Submitted: February 23, 2022
• First Submitted That Met QC Criteria: February 23, 2022
• First Posted (Actual): March 4, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2024
• Last Update Submitted That Met QC Criteria: March 22, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: NIS; brolucizumab; nAMD
• Additional Relevant MeSH Terms: Eye Diseases; Retinal Degeneration; Retinal Diseases; Macular Degeneration
• Other Study ID Numbers: CRTH258AAE01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO