Neovascular Age-related Macular Degeneration
Conditions
Keywords
nAMD, brolucizumab, NIS
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.
Interventions
OTHERBrolucizumab
There is no treatment allocation. Patients administered brolucizumab by prescription will be enrolled.
Sponsors
Novartis Pharmaceuticals
Study design
Observational model
COHORT
Time perspective
OTHER
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Percentage of patients with lesion type | Baseline | Percentage of patients by lesion type will be collected: occult, minimally classic, predominantly classic, other |
| 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 ≥ 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 visit | Baseline | Percentage of patients with baseline visit will be collected |
| 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 |
| Percentage of patients with bilateral disease | Baseline | Percentage of patients with bilateral disease will be collected |
| 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 |
| 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 |
| 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 VA between 34 and 72 ETDRS letters | Baseline | Percentage of patients with Visual Acuity (VA) within these values will be collected: 33 \< VA \< 73 |
| 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 |
| Switch Patients: Previous anti-VEGF treatments of nAMD pre-treated patients | Baseline | Previous anti-VEGF treatments of nAMD pre-treated patients will be collected |
| Switch Patients: Duration of previous anti-VEGF treatments | Baseline | Duration of previous anti-VEGF treatments will be collected |
| 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 |
| 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 | 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 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 |
| 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 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 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 |
| 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 |
| 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) |
| 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 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 |
| 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 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 |
| Percentage of patients with ≥ 3 brolucizumab injections | Month 3 | Percentage of patients with ≥ 3 brolucizumab injections will be collected |
| Number of participants by last recorded injection interval | Month 6 and Month 12 | Number of participants by last recorded injection interval (in weeks) |
| 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 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 \[active, active (SRF only), inactive\] |
| 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) |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 geographic atrophy | 12 Months | Percentage of patients with geographic atrophy will be measured |
| Percentage of patients with subretinal fibrosis | 12 Months | Percentage of patients with subretinal fibrosis will be measured |
| 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.) |
| 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 |
| 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 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 |
| Baseline CST | Baseline, Month 3, Month 6, Month 9 and Month 12 | Central Subfield Thickness (CST) in μm will be collected |
| 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 |
| Duration of brolucizumab treatment before switching | Up to month 12 | Duration of brolucizumab treatment before switching 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 |
| 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) |
| 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 |
| 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 |
Countries
United Arab Emirates
Outcome results
None listed