A Phase 3 Safety and Efficacy Study of Intravitreal Administration of Zimura (Complement C5 Inhibitor)
- Conditions
- Geographic AtrophyMacular Degeneration
- Interventions
- Drug: Sham
- Registration Number
- NCT04435366
- Lead Sponsor
- IVERIC bio, Inc.
- Brief Summary
The objectives of this study was to evaluate the safety and efficacy of avacincaptad pegol intravitreal administration in participants with geographic atrophy secondary to age-related macular degeneration (AMD)
- Detailed Description
Participants were randomized in a 1:1 ratio to the following monthly treatment groups:
* Avacincaptad pegol 2 mg
* Sham
At Month 12, the participants in the avacincaptad pegol 2mg treatment group were re-randomized to receive the study drug either on a monthly basis or on an every other month basis
The participants initially randomized to sham treatment continued with monthly sham administration through Month 23
All participants had a final follow up visit at Month 24
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 448
- Subjects of either gender aged ≥ 50 years
- Diagnosis of Non-foveal GA secondary to dry AMD
- Any prior treatment for AMD (dry or wet) or any prior intravitreal treatment for any indication in either eye, except oral supplements of vitamins and minerals
- Any intraocular surgery or thermal laser within 3 months of trial entry.
- Any prior thermal laser in the macular region, regardless of indication
- Any ocular or periocular infection (including blepharitis), or ocular surface inflammation in the past 12 weeks.
- Previous therapeutic radiation in the region of the study eye
- Any sign of diabetic retinopathy in either eye
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Avacincaptad Pegol Avacincaptad Pegol Participants received avacincaptad pegol (ACP) 2 milligram (mg)/eye via intravitreal (IVT) injections monthly through Month 11 (Year 1). At month 12, participants were re-randomized to receive ACP 2 mg/eye via IVT injections monthly from month12 through month 23 (Year 2). Sham Sham Participants received sham injections; through Month 11 (Year 1). At month 12, participants continued to receive monthly sham administration from month 12 through month 23 (Year 2). Avacincaptad pegol and Sham Avacincaptad Pegol Participants who received ACP 2mg monthly through Month 11 (Year 1) were re-randomized at month 12, to receive ACP 2 mg/eye via IVT injections every other month at months 13, 15, 17, 19, 21, and 23 and sham injections at months 12, 14, 16,18, 20, and 22.
- Primary Outcome Measures
Name Time Method The Mean Rate of Growth (Slope) Estimated Based on GA Area Measured by Autofluorescence (FAF) at 3 Time Points: Baseline, Month 6, and Month 12 Baseline to month 12 GA was associated with age-related macular degeneration (AMD) and caused bilateral, progressive, and irreversible loss of retinal tissue (photoreceptors, retinal pigment epithelium, and choriocapillaris) leading to a permanent loss of visual function and blindness. The least squares mean used to determine mean rate of change in GA growth (slope) was measured by FAF. LS mean \& SE were based on square-root transformation.
The Mean Rate of Growth (Slope) Estimated Based on GA Area Measured by FAF at 5 Timepoints: Baseline, Month 6, Month 12, Month 18, and Month 24 Baseline to month 24 GA was associated with AMD and caused bilateral, progressive, and irreversible loss of retinal tissue (photoreceptors, retinal pigment epithelium, and choriocapillaris) leading to a permanent loss of visual function and blindness. The least square mean rate of GA growth (slope) was measured by FAF. LS mean \& SE were based on untransformed data.
- Secondary Outcome Measures
Name Time Method Change From Baseline in Best Corrected Visual Acuity (BCVA) Using Early Treatment Diabetic Retinopathy Study (ETDRS) Letters at 24 Months Baseline and month 24 BCVA was assessed using ETDRS visual acuity testing charts. The ETDRS Visual Acuity Score (VAS) is defined as the number of letters read on the ETDRS chart. Minimum and maximum possible scores are 0-100. A higher score represented better visual functioning. A positive change from baseline indicates an improvement and a negative change from baseline indicates a worsening.
Change From Baseline in Low Luminance (LL) BCVA Using ETDRS Letters at 24 Months Baseline and month 24 BCVA was assessed using ETDRS visual acuity testing charts. The ETDRS VAS is defined as the number of letters read on the ETDRS chart. Minimum and maximum possible scores are 0-100. A higher score represented better visual functioning. A positive change from baseline indicates an improvement and a negative change from baseline indicates a worsening. LL BCVA was measured by placing a 2.0 log unit neutral density filter over the best correction for that eye and having the participant read the normally illuminated ETDRS chart.
Change From Baseline in Visual Function Questionnaire (VFQ-25) Composite Scores at 6, 12 and 18 Months Baseline, months 6, 12, and 18 The National Eye Institute Visual Function Questionnaire-25 (VFQ-25) measured the influence of visual disability and visual symptoms on general health domains. The VFQ-25 consisted of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. A higher score represented better visual functioning. Each item was then converted to a 0 to 100 scale so that the lowest and highest possible scores were set at 0 and 100 points, respectively. Each subscale score had a range of 0 to 100 inclusive and were calculated from the re-scaled raw data. A composite score was derived based on the average of the 11 vision-related subscales.
Change From Baseline in Visual Function Questionnaire (VFQ-25) Composite Scores at 24 Months Baseline and month 24 The National Eye Institute Visual Function Questionnaire-25 (VFQ-25) measured the influence of visual disability and visual symptoms on general health domains. The VFQ-25 consisted of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. A higher score represented better visual functioning. Each item was then converted to a 0 to 100 scale so that the lowest and highest possible scores were set at 0 and 100 points, respectively. Each subscale score had a range of 0 to 100 inclusive and were calculated from the re-scaled raw data. A composite score was derived based on the average of the 11 vision-related subscales.
Number of Participants With Categorical One-level Loss in VFQ-25 Subscale Baseline up to month 24 The National Eye Institute VFQ-25 measured the influence of visual disability and visual symptoms on general health domains. The VFQ-25 consisted of a base set of 25 vision-targeted questions representing 11 vision-related constructs, plus an additional single-item general health rating question. A higher score represented better visual functioning. Each item was then converted to a 0 to 100 scale so that the lowest and highest possible scores were set at 0 and 100 points, respectively.Categorical one-level loss in each item was defined as decline of one or more levels at Month 24 on the original scale from Baseline (equivalently 20 points for general vision and 25 points for other vision items in a 0 to 100 scale).
Time to Persistent Vision Loss Baseline up to month 24 Vision loss event was defined as a loss of ≥ 15 letters (equivalent to a loss of 3 lines on the ETDRS chart) in BCVA from Baseline measured at any two or more consecutive visits up to Month 24. These parameters were chosen as a 3-line BCVA loss (equivalent to doubling of visual angle) is widely recognized as a significant deterioration in vision and a minimum of two consecutive visits was representative of persistent disease progression. BCVA was assessed using ETDRS visual acuity testing charts. The ETDRS VAS was defined as the number of letters read on the ETDRS chart. Min and max possible scores are 0-100. A higher score represents better visual functioning. Kaplan-Meier method was used for analysis. Participants with an event were reported and not the median time to event.
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Trial Locations
- Locations (204)
Retina-Vitreous Associates Medical Group
🇺🇸Beverly Hills, California, United States
Retinal Diagnostic Center
🇺🇸Campbell, California, United States
Eye Medical Center of Fresno
🇺🇸Fresno, California, United States
Retina Consultants of Orange County
🇺🇸Fullerton, California, United States
University of California, San Diego
🇺🇸La Jolla, California, United States
Jules Stein Eye Institute/David Geffen School of Medicine
🇺🇸Los Angeles, California, United States
Northern California Retina Vitreous Associates
🇺🇸Mountain View, California, United States
California Retina Consultants
🇺🇸Oxnard, California, United States
Southern California Desert Retina Consultants
🇺🇸Palm Desert, California, United States
Doheny Eye Center, UCLA
🇺🇸Pasadena, California, United States
Scroll for more (194 remaining)Retina-Vitreous Associates Medical Group🇺🇸Beverly Hills, California, United States