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

Recruiting

• Conditions: Neovascular Age-related Macular Degeneration
• Interventions: Other: Brolucizumab

• Registration Number: NCT05266495
• Lead Sponsor: Novartis Pharmaceuticals

Brief Summary

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.

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2022-02-23
• Study First Submitted QC: 2022-02-23
• Study First Posted: 2022-03-04
• Study Start: 2022-04-13
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-22
• Last Update Posted: 2024-03-25
• Primary Completion: 2024-09-30
• Study Completion: 2024-09-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 99

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

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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

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Brolucizumab	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)

Primary Outcome Measures

Name	Time	Method
Percentage of patients with absence of SRF and IRF	Month 12	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.

Secondary Outcome Measures

Name	Time	Method
Switch Patients: Number of injections in the last year before switching to brolucizumab	Baseline	Number of injections in the last year before switching to brolucizumab will be collected
Percentage of patients with the study eye that has VA equal or less than the VA in fellow eye	Baseline	Percentage of patients with the study eye that has Visual Acuity (VA) equal or less than the VA in fellow eye will be collected
Switch Patients: Last interval of anti-VEGF treatment before switching	Baseline	Last interval of anti-VEGF treatment before switching will be collected
Percentage of patients with absence of SRF, IRF and sub-RPE	Month 3, Month 6, Month 9 and Month 12	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
Association between CST variability at Months 1-12 and VA change from baseline	Month 3, Month 6, Month 9 and Month 12	Correlation statistical tests between CST variability at Months 1-12 (quartiles) and VA change from baseline to Months 3, 6, 9 and 12
Association between CST variability at Months 1-12 and number of injections	Month 12	Correlation statistical tests between CST variability at Months 1-12 (quartiles) and number of injections during the 12-month treatment with brolucizumab
Percentage of patients with clinician-graded subretinal fibrosis and/or macular atrophy	Month 12	Percentage of patients with clinician-graded subretinal fibrosis and/or macular atrophy
Percentage of patients with baseline visit	Baseline	Percentage of patients with baseline visit will be collected
Percentage of patients with baseline VA in the following categories (≤35, 36-69, ≥ 70 ETDRS letters)	Baseline	Percentage of patients with baseline Visual Acuity (VA) in the following categories (≤35, 36-69, ≥ 70 ETDRS letters) will be collected
Percentage of patients with stable IRF	Month 3, Month 6, Month 9 and Month 12	Percentage of patients with stable Intra-Retinal Fluid (IRF), from those with absence of IRF at baseline
Percentage of patients with VA between 34 and 72 ETDRS letters	Baseline	Percentage of patients with Visual Acuity (VA) within these values will be collected: 33 \< VA \< 73
Time to absence of IRF during the 12-month treatment with brolucizumab	12 months	Time to absence of Intra-Retinal Fluid (IRF) during the 12-month treatment with brolucizumab will be collected
Percentage of patients with absence of sub-RPE	Month 3, Month 6, Month 9 and Month 12	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
Time to absence of IRF and SRF and sub-RPE during the 12-month treatment with brolucizumab	12 months	Time to absence of IRF and SRF and sub-RPE during the 12-month treatment with brolucizumab
Estimate CST change from baseline	Month 3, Month 6, Month 9 and Month 12	Estimate Central Subfield Thickness (CST) change from baseline (in μm) will be collected
Percentage of patients ≥ 80 years old	Baseline	Percentage of patients ≥ 80 years old will be collected
Duration of diagnosis	Baseline	Time since first diagnosis (years) will be collected
Percentage of patients with baseline VA < 73 ETDRS letters and active (SRF only)	Baseline	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
Percentage of patients with different ethnic groups	Baseline	Percentage of patients by ethnicity will be presented
Percentage of patients with stable SRF	Month 3, Month 6, Month 9 and Month 12	Percentage of patients with stable Subretinal Fluid (SRF), from those with absence of SRF at baseline
Time to absence of SRF during the 12-month treatment with brolucizumab	12 months	Time to absence of Subretinal Fluid (SRF) will be collected
Baseline CST	Baseline, Month 3, Month 6, Month 9 and Month 12	Central Subfield Thickness (CST) in μm will be collected
Percentage of patients with absence of IRF	Month 3, Month 6, Month 9 and Month 12	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
Percentage of patients with bilateral disease	Baseline	Percentage of patients with bilateral disease will be collected
Percentage of patients with lesion type	Baseline	Percentage of patients by lesion type will be collected: occult, minimally classic, predominantly classic, other
Baseline VA	Baseline	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
Switch Patients: Previous anti-VEGF treatments of nAMD pre-treated patients	Baseline	Previous anti-VEGF treatments of nAMD pre-treated patients will be collected
Percentage of patients with reduced CST vs baseline	Baseline, Month 3, Month 6, Month 9 and Month 12	Percentage of patients with reduced CST vs baseline will be collected
Switch Patients: Duration of previous anti-VEGF treatments	Baseline	Duration of previous anti-VEGF treatments will be collected
Percentage of patients with absence of SRF	Month 3, Month 6, Month 9 and Month 12	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
Percentage of patients with stable sub-RPE	Month 3, Month 6, Month 9 and Month 12	Percentage of patients with stable sub-Retinal Pigment Epithelium (RPE), from those with absence of sub-RPE at baseline
Percentage of patients with presence of SRF, IRF and sub-RPE	Baseline	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
Time to absence of sub-RPE during the 12-month treatment with brolucizumab	12 months	Time to absence of sub-Retinal Pigment Epithelium (RPE) during the 12-month treatment with brolucizumab will be collected
VA change from baseline	Baseline, Month 3, Month 6, Month 9 and Month 12	Visual Acuity (VA) change from baseline (in ETDRS letters)
Percentage of patients with VA change from baseline	Baseline, Month 3, Month 6, Month 9 and Month 12	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)
Distribution of injection intervals	During Months 1-6 and 1-12	Distribution of injection intervals \< 4; \[4, 6); \[6, 8); \[8, 10); \[10, 12); ≥12 weeks will be collected
Percentage of patients with at least one duration of interval between injections	12 months	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
Number of participants by last recorded injection interval	Month 6 and Month 12	Number of participants by last recorded injection interval (in weeks)
Percentage of patients with geographic atrophy	12 Months	Percentage of patients with geographic atrophy will be measured
Percentage of switchers with full loading phase	12 months	Percentage of switchers with full loading phase will be collected Loading phase (yes/no) defined as ≥ 3-injections within 90 days post-index
Percentage of patients with ≥ 70 ETDRS letters	Month 3, Month 6, Month 9 and Month 12	Percentage of patients with ≥ 70 ETDRS letters will be collected
Number of brolucizumab visits	Over Months 1-3, 3-6, 6-12 and 1-12	Number of brolucizumab injections, non-injection visits and total number of visits will be collected
Percentage of patients with at least two consecutive duration of intervals between injections	12 months	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.
Percentage of switch patients from other anti-VEGF that prolonged injection intervals with brolucizumab	Month 6, Month 9 and Month 12	Percentage of switch patients from other anti-VEGF that prolonged injection intervals with brolucizumab will be collected
Number of visits with/without OCT	Over Months 1-6 and 1-12	Number of visits with/without Optical Coherence Tomography (OCT) will be collected
Percentage of patients with ≥ 3 brolucizumab injections	Month 3	Percentage of patients with ≥ 3 brolucizumab injections will be collected
Time between two consecutive brolucizumab injections	Over Months 1-3	Time (in days) between two consecutive brolucizumab injections will be collected
Association between number of OCT and VA change from baseline	Month 6, Month 9 and Month 12	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)
Association between number of OCT and number of injections	12 months	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
Duration of brolucizumab treatment before switching	Up to month 12	Duration of brolucizumab treatment before switching will be collected
VA at the end of the loading phase	Month 3	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
Association between number of OCT and CNV activity	Month 6, Month 9 and Month 12	Correlation statistical tests between number of Optical Coherence Tomography (OCT) (0-1, 2-3, ≥ 4) and Choroidal Neovascularization (CNV) activity \[active, active (SRF only), inactive\]
proportion of participants by baseline CNV activity	Baseline	Baseline Choroidal Neovascularization (CNV) activity (active, active (SRF only), inactive) will be collected
Proportion of participants with and without Loading phase	12 months	Proportion of participants with and without Loading phase will be collected. Loading phase (yes/no) defined as ≥ 3-injections within 90 days post-index
CNV activity at the end of the loading phase	Month 3	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
Number of injections during the maintenance phase	Over months 3-12	Number of injections during the maintenance phase will me measured
Percentage of patients with subretinal fibrosis	12 Months	Percentage of patients with subretinal fibrosis will be measured
Percentage of patients who switch to another anti-VEGF	6 Months, 9 Months and 12 Months	Percentage of patients who switch to another anti-VEGF during the first 6, 9 and 12 months of treatment with brolucizumab will be measured
Reason for switching to another anti-VEGF	12 months	Percentage of patients by reason for switching to another anti-VEGF will be collected
Last recorded injection interval before switching	Month 6 and Month 12	Last recorded injection interval (in weeks) before switching will be collected
Days of persistence	Up to 12 Months	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)
Assessment of criteria for no retreatment	12 months	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.)
VA at time of switch	Up to 12 months	Visual Acuity (VA) at time of switch will be measured with Early Treatment Diabetic Retinopathy Study (ETDRS) letters.
Percentage of patients with activity at time of switch	Up to 12 months	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
Percentage of patients by injection rate at pre-switch period	Up to 12 months	Percentage of patients by injection rate at pre-switch period will be collected
Percentage of patients who discontinue therapy	Up to 12 months	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
Percentage of patients with AEs	12 Months	Percentage of patients with AEs will be collected
AE rate	Month 3, Month 6, Month 9 and Month 12	AE rate (per 10,000 injections) will be collected

Trial Locations

Locations (1)

Novartis Investigative Site; 🇦🇪 Abu Dhabi, United Arab Emirates