Clinical Studies:
GATHER1
Citation: Jaffe, G.J., Westby, K., Csaky, K.G., et al., C5 inhibitor avacincaptad pegol for geographic atrophy due to age-related macular degeneration. Ophthalmology 2021; 128:576-586.
Key Points
- GATHER1 was an international, prospective, randomized, double-masked, sham-controlled phase 2/3 pivotal clinical trial that evaluated avacincaptad pegol 2 mg or avacincaptad pegol 4 mg for treatment of geographic atrophy (GA) vs sham
- There was a decrease in GA lesion growth in both avacincaptad pegol groups vs sham
- Both avacincaptad pegol groups were well-tolerated in the elderly patient population, with no reported ocular adverse events (AEs) or serious adverse events (SAEs)
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Objective
To evaluate the safety and efficacy of avacincaptad pegol, a complement C5 inhibitor, for treatment of GA
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STUDY DESIGN
International, prospective, randomized, double-masked, sham-controlled phase 2/3 pivotal clinical trial
STUDY SUBJECTS
- At least 50 years of age
- Best corrected visual acuity (BCVA) between 20/25 and 20/320 in the study eye
- GA secondary to age-related macular degeneration (AMD)
- Total GA area ≥2.5 and ≤17.5 mm2
- For multifocal GA lesions, at least 1 focal lesion had to be ≥1.25 mm2
Major Inclusion criteria:
- GA secondary to any condition other than AMD in either eye
- Prior treatment for AMD (dry or wet)
- Prior intravitreal treatment for any indication in either eye
- Evidence of choroidal neovascularization (CNV) in either eye
Major exclusion criteria:
RANDOMIZATION SCHEME AND INTERVENTIONS
- 1 mg avacincaptad pegol monthly
- 2 mg avacincaptad pegol monthly
- Sham
Part 1 randomized 1:1:1 to
- 2 mg avacincaptad pegol monthly
- 4 mg avacincaptad pegol monthly
- Sham
Part 2 randomized 1:2:2 to
Because avacincaptad pegol 2 mg and corresponding sham arm were present in both parts 1 and 2 of the trial, eyes randomized in part 1 were combined with the eyes randomized in part 2, analyzed including a regression factor by part
Primary Endpoint
- Mean rate of change in GA area with square root transformation over 12 months at baseline, month 6, and month 12
Secondary Endpoint
- Mean change in BCVA from baseline to month 12
- Mean change in low luminance BCVA from baseline to month 12
- Safety
Results
Study Population
- 286 participants
- 77 participants in part 1
- 209 participants in part 2
- Baseline characteristics balanced between various study groups
- Study completion 88.6%
Primary Outcome: Square root transformation of the GA lesion area from baseline to month 12
- 2 mg avacincaptad pegol: +.292 mm (27.4% smaller increase compared to sham)
- 2 mg sham: +.402 mm
- 4 mg avacincaptad pegol: +.321 mm (27.8% smaller increase compared to sham)
- 4 mg sham: +.444 mm
Secondary Outcomes:
- No difference in BCVA or low-luminance BCVA between either avacincaptad pegol group and their corresponding sham group
Safety Analyses:
- No reported avacincaptad pegol-related AEs, SAEs, or endophthalmitis cases
- Similar nonocular AEs across all groups
- Choroidal neovascular membrane (CNVM) reported in fellow eyes of 3.5% of participants, in the study eye of 2.7% of participants in the sham cohort, 4% of participants in the avacincaptad pegol 1 mg cohort, 9.0% of participants in the avacincaptad pegol 2 mg cohort, and 9.6% of participants in the avacincaptad pegol 4 mg cohort
Conclusions:
- Monthly treatment of GA secondary to AMD through C5 inhibition with 2 mg and 4 mg avacincaptad pegol reduced GA lesion growth rate by 27.4% and 27.8%, respectively, compared with sham treatment
- There were increased rates of CNVM/exudation in avacincaptad-treated eyes, especially at higher dosages.