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

Neovascular Age-related Macular Degeneration Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05266495
• Other study ID #: CRTH258AAE01
• Status: Recruiting
• Start date: April 13, 2022
• Est. completion date: September 30, 2024

Study information

• Verified date: March 2024
• Source: Novartis
• Contact: Novartis Pharmaceuticals
• Phone: +41613241111
• Email: novartis.email[@]novartis.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 99
• Est. completion date: September 30, 2024
• Est. primary completion date: September 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 100 Years

Eligibility

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

Related Conditions & MeSH terms

• Macular Degeneration
• Neovascular Age-related Macular Degeneration

Intervention

Other:
• Brolucizumab
There is no treatment allocation. Patients administered brolucizumab by prescription will be enrolled.

Locations

Country	Name	City	State
United Arab Emirates	Novartis Investigative Site	Abu Dhabi
United Arab Emirates	Novartis Investigative Site	Abu Dhabi

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Country where clinical trial is conducted

United Arab Emirates, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Percentage of patients = 80 years old	Percentage of patients = 80 years old will be collected	Baseline
Secondary	Duration of diagnosis	Time since first diagnosis (years) will be collected	Baseline
Secondary	Percentage of patients with baseline visit	Percentage of patients with baseline visit will be collected	Baseline
Secondary	Percentage of patients with bilateral disease	Percentage of patients with bilateral disease will be collected	Baseline
Secondary	Percentage of patients with lesion type	Percentage of patients by lesion type will be collected: occult, minimally classic, predominantly classic, other	Baseline
Secondary	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
Secondary	Baseline CST	Central Subfield Thickness (CST) in µm will be collected	Baseline, Month 3, Month 6, Month 9 and Month 12
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Percentage of patients with different ethnic groups	Percentage of patients by ethnicity will be presented	Baseline
Secondary	Switch Patients: Previous anti-VEGF treatments of nAMD pre-treated patients	Previous anti-VEGF treatments of nAMD pre-treated patients will be collected	Baseline
Secondary	Switch Patients: Duration of previous anti-VEGF treatments	Duration of previous anti-VEGF treatments will be collected	Baseline
Secondary	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
Secondary	Switch Patients: Last interval of anti-VEGF treatment before switching	Last interval of anti-VEGF treatment before switching will be collected	Baseline
Secondary	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
Secondary	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
Secondary	Time to absence of SRF during the 12-month treatment with brolucizumab	Time to absence of Subretinal Fluid (SRF) will be collected	12 months
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	VA change from baseline	Visual Acuity (VA) change from baseline (in ETDRS letters)	Baseline, Month 3, Month 6, Month 9 and Month 12
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Percentage of patients with = 3 brolucizumab injections	Percentage of patients with = 3 brolucizumab injections will be collected	Month 3
Secondary	Number of participants by last recorded injection interval	Number of participants by last recorded injection interval (in weeks)	Month 6 and Month 12
Secondary	Time between two consecutive brolucizumab injections	Time (in days) between two consecutive brolucizumab injections will be collected	Over Months 1-3
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	proportion of participants by baseline CNV activity	Baseline Choroidal Neovascularization (CNV) activity (active, active (SRF only), inactive) will be collected	Baseline
Secondary	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
Secondary	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
Secondary	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
Secondary	Number of injections during the maintenance phase	Number of injections during the maintenance phase will me measured	Over months 3-12
Secondary	Percentage of patients with geographic atrophy	Percentage of patients with geographic atrophy will be measured	12 Months
Secondary	Percentage of patients with subretinal fibrosis	Percentage of patients with subretinal fibrosis will be measured	12 Months
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Reason for switching to another anti-VEGF	Percentage of patients by reason for switching to another anti-VEGF will be collected	12 months
Secondary	Last recorded injection interval before switching	Last recorded injection interval (in weeks) before switching will be collected	Month 6 and Month 12
Secondary	Duration of brolucizumab treatment before switching	Duration of brolucizumab treatment before switching will be collected	Up to month 12
Secondary	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
Secondary	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
Secondary	Percentage of patients with AEs	Percentage of patients with AEs will be collected	12 Months
Secondary	AE rate	AE rate (per 10,000 injections) will be collected	Month 3, Month 6, Month 9 and Month 12

External Links

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