None listed
Conditions
Brief summary
This is a prospective, open-labelled study in patients with pigment epithelial detachment (PED) secondary to neovascular macular degeneration. All subjects will receive 6.0mg of intravitreal brolucizumab every 4 weeks between baseline and week 8 (3 loading doses), and subsequently receive 6.0mg of intravitreal brolucizumab every 8 or 12 weeks for the remainder of the study period (weeks 52). Fifty five subjects who meet the inclusion/exclusion criteria will be recruited from Sydney Retina Clinic and followed up for 52 weeks. All assessments and treatments will be performed at Sydney Retina Clinic. All eligible subjects will initially receive 3 monthly loading doses of 6.0mg of intravitreal brolucizumab injection. Following these loading doses, a disease activity assessment will be performed at week 16. Disease Activity Criteria at Week 16: • Decrease in BCVA of greater than or equal to 5 letters compared with Baseline • Decrease in BCVA of greater than or equal to 3 letters and CSFT increase greater than 75µm compared with Week 12 • Decrease in BCVA of greater than or equal 5 letters due to neovascular AMD disease activity compared with Week 12 • New or worse intraretinal cysts (IRC) /intraretinal fluid (IRF) compared with Week 12 If a subject meet any of the above disease criteria at week 16, the subject will be assigned to receive injections every 8 weeks (q8w) thereafter, up to study exit (Week 16, 24, 32, 40 and 48). If a subject does not meet any of the above disease activity criteria, the subject will be injected every 12 weeks (q12w) up to study exit (week 20, 32 and 44).
Interventions
Intravitreal injection of brolucizumab 6.0mg will be administered by an ophthalmologist.
All eligible subjects will initially receive 3 monthly loading doses of 6.0mg of intravitreal brolucizumab injection. Following these loading doses, a disease activity assessment will be performed at week 16.
Disease Activity Criteria at Week 16:
• Decrease in BCVA of greater than or equal to 5 letters compared with Baseline
• Decrease in BCVA of greater than or equal to 3 letters and CSFT increase greater t
Intravitreal injection of brolucizumab 6.0mg will be administered by an ophthalmologist. All eligible subjects will initially receive 3 monthly loading doses of 6.0mg of intravitreal brolucizumab injection. Following these loading doses, a disease activity assessment will be performed at week 16. Disease Activity Criteria at Week 16: • Decrease in BCVA of greater than or equal to 5 letters compared with Baseline • Decrease in BCVA of greater than or equal to 3 letters and CSFT increase greater than 75µm compared with Week 12 • Decrease in BCVA of greater than or equal 5 letters due to neovascular AMD disease activity compared with Week 12 • New or worse intraretinal cysts (IRC) /intraretinal fluid (IRF) compared with Week 12 If a subject meet any of the above disease criteria at week 16, the subject will be assigned to receive injections every 8 weeks (q8w) thereafter, up to study exit (Week 16, 24, 32, 40 and 48). If a subject does not meet any of the above disease activity criteria, the subject will be injected every 12 weeks (q12w) up to study exit (week 20, 32 and 44). Patients will be given individual timetable for their scheduled appointments.
Sponsors
Sydney Retina Clinic & Day Surgery
Study design
Allocation
Non-randomised trial
Primary purpose
Treatment
Eligibility
Sex/Gender
All
Age
50 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Subjects must give written informed consent before any study related procedures are performed Subjects must be 50 years of age or older at baseline Pigment epithelial detachment (PED) secondary to neovascular macular degeneration (AMD). PED is defined as a discrete or localised dome-shaped or irregular elevation of the retinal pigment epithelium (RPE) on SD-OCT that was optically empty (i.e. serous) with a focus of neovascularisation at the edge or that was comprised of heterogeneous tissue of mixed reflectivity or layering within the sub-PED compartment. Previously treated neovascular age-related macular degeneration, “treatment resistance” is defined as eyes with persistent active/exudation despite at least 4 previous ranibizumab and/or aflibercept treatments in the 6 months prior to baseline, not including loading dose, with a minimal interval of 8 weeks between the last anti-vascular endothelial growth factor (anti-VEGF) injection and the baseline injection Best corrected baseline visual acuity between 20-78 letters on ETDRS chart (Snellen equivalent 6/12 to 6/120) in the study eye. Active choroidal neovascularisation (CNV) lesions secondary to AMD that affect the central subfield (excluding retinal angiomatous proliferation [RAP] and polypoidal vasculopathy [PCV]) in the study eye, confirmed by the angiography and Principal Investigator. Total area of CNV must comprise >50% of the total lesion area in the study eye. Intra and or subretinal fluid affecting the central subfield of the study eye.
Exclusion criteria
Any active intraocular or periocular infection or active intraocular inflammation (eg, infectious conjunctivitis, keratitis, scleritis, endophthalmitis, infectious blepharitis) in either eye at Baseline Central subfield of the study eye affected by fibrosis or geographic atrophy assessed by colour fundus photography autofluorescence. Total area of fibrosis greater than or equal to 50% of the total lesion in the study eye Subretinal blood affecting the central subfield and/or greater than or equal to 50% of the lesion of the study eye Subject has received any investigational treatment for neovascular AMD (other than vitamin supplements) in the study eye at any time Eyes diagnosed with Retinal Angiomatous Proliferation or Polypoidal Choroidal Vasculopathy lesion Any history or evidence of a concurrent intraocular condition in the study eye, including retinal diseases other than neovascular AMD, that, in the judgment of the Investigator, could either require medical or surgical intervention during the course of the study to prevent or treat visual loss that might result from that condition or that limits the potential to gain visual acuity upon treatment with the investigational product Retinal pigment epithelium (RPE) rip/tear in the study eye at Baseline Current vitreous haemorrhage or history of vitreous haemorrhage in the study eye within 4 weeks prior to Baseline History or evidence of the following in the study eye: Previous photodynamic therapy (PDT) Intraocular or refractive surgery within the 90-day period prior to Baseline Previous penetrating keratoplasty or vitrectomy Previous panretinal photocoagulation Previous submacular surgery, other surgical intervention or laser treatment for AMD Uncontrolled glaucoma in the study eye defined as intraocular pressure (IOP) > 25 mmHg on medication or according to Investigator’s judgment at Baseline Aphakia and/or absence of the posterior capsule in the study eye at Screening or Baseline Intra- or periocular use of corticosteroids in the study eye during the 6-month period prior to Baseline Use of topical ocular corticosteroids in the study eye for 60 or more consecutive days within the 90-day period prior to Baseline Use of systemic corticosteroids for 30 or more consecutive days within the 90 days prior to Baseline, with the exception of low stable doses of corticosteroids (defined as less than or equal to 10 mg prednisolone or equivalent dose used for 90 days or more). Inhaled, nasal or dermal steroids are also permitted Previous therapeutic radiation near the region of the study eye History of a medical condition (disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding) that, in the judgment of the Investigator, would preclude scheduled study visits, completion of the study, or a safe administration of investigational product History of hypersensitivity to any component of the test article, control article, or clinically relevant sensitivity to fluorescein dye (or indocyanine green), as assessed by the Investigator Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until termination of gestation, confirmed by a positive hCG pregnancy test and women of child-bearing potential, defined as all women less than 1 year postmenopausal or less than 6 weeks since sterilization at Baseline, unless they are using effective methods of contraception during dosing of study treatment. Effective contraception methods include: Total abstinence (when this is in line with the preferred and usual lifestyle of the subject). Periodic abstinence (eg, calendar, ovulation, symptothermal, postovulation methods) and withdrawal are not acceptable methods of contraception Female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least 6 weeks before Baseline. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment Male sterilization (at least 6 months prior to Baseline). For female subjects in the study, the vasectomized male partner should be the sole partner for that subject Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example hormone vaginal ring or transdermal hormone contraception Placement of an intrauterine device (IUD) or intrauterine system (IUS) Participation in an investigational drug, biologic, or device study within 30 days or the duration of 5 half-lives of the investigational product (whichever is longer) prior to Baseline Note: observational clinical studies solely involving over-the-counter vitamins, supplements, or diets are not exclusionary Systemic anti-vascular endothelial growth factor (VEGF) therapy within the 90-day period prior to Baseline Stroke or myocardial infarction in the 90-day period prior to Baseline Uncontrolled blood pressure defined as a systolic value greater than or equal to 160 mmHg or diastolic value greater than or equal to 100 mmHg at Screening
Outcome results
None listed