A Phase 3 Safety and Efficacy Study of Intravitreal Administration of Zimura (Complement C5 Inhibitor)

Phase 3

Completed

• Conditions: Geographic Atrophy; Macular Degeneration
• Interventions: Drug: Avacincaptad Pegol; 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

Study Timeline

• Study First Submitted: 2020-05-12
• Study First Submitted QC: 2020-06-15
• Study First Posted: 2020-06-17
• Study Start: 2020-06-22
• Primary Completion: 2022-07-25
• Disposition First Submitted: 2023-07-21
• Study Completion: 2023-08-22
• Results First Submitted: 2023-11-01
• Results First Submitted QC: 2023-12-07
• Results First Posted: 2023-12-28
• Disposition First Posted: 2023-12-28
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-23
• Last Update Posted: 2024-12-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 448

Inclusion Criteria

• Subjects of either gender aged ≥ 50 years
• Diagnosis of Non-foveal GA secondary to dry AMD

Exclusion Criteria

• 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.

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

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