PMID- 32882310
OWN - NLM
STAT- MEDLINE
DCOM- 20210730
LR  - 20211218
IS  - 1549-4713 (Electronic)
IS  - 0161-6420 (Linking)
VI  - 128
IP  - 4
DP  - 2021 Apr
TI  - C5 Inhibitor Avacincaptad Pegol for Geographic Atrophy Due to Age-Related Macular 
      Degeneration: A Randomized Pivotal Phase 2/3 Trial.
PG  - 576-586
LID - S0161-6420(20)30845-9 [pii]
LID - 10.1016/j.ophtha.2020.08.027 [doi]
AB  - PURPOSE: The complement pathway may play a key role in the pathogenesis of 
      age-related macular degeneration (AMD). The safety and efficacy of avacincaptad 
      pegol (Zimura, IVERIC bio Inc, New York, NY), a C5 inhibitor, were assessed in 
      participants with geographic atrophy (GA) secondary to AMD (GATHER1 Study). 
      DESIGN: International, prospective, randomized, double-masked, sham-controlled, 
      pivotal phase 2/3 clinical trial. PARTICIPANTS: A total of 286 participants with 
      GA secondary to AMD. MAIN OUTCOME MEASURES: The primary efficacy endpoint was the 
      mean rate of change in GA over 12 months measured by fundus autofluorescence 
      (FAF) at 3 timepoints: baseline, month 6, and month 12. RESULTS: The reduction in 
      the mean rate of GA growth (square root transformation) over 12 months was 27.4% 
      (P = 0.0072) for the avacincaptad pegol 2 mg cohort and 27.8% (P = 0.0051) for 
      the avacincaptad pegol 4 mg cohort compared with their corresponding sham 
      cohorts. The results for both dose groups were statistically significant. 
      Avacincaptad pegol was generally well tolerated after monthly administration over 
      12 months. There were no avacincaptad pegol-related adverse events (AEs) or 
      inflammation. Further, there were no ocular serious AEs (SAEs) and no cases of 
      endophthalmitis. The most frequent ocular AEs were related to the injection 
      procedure. CONCLUSIONS: Intravitreal administration of avacincaptad pegol 2 mg 
      and 4 mg led to a significant reduction of GA growth in eyes with AMD over a 
      12-month period. Because C5 inhibition theoretically preserves C3 activity, it 
      may offer additional safety advantages. A second confirmatory pivotal clinical 
      trial is underway to confirm the efficacy and safety of avacincaptad pegol in 
      slowing the GA growth (GATHER2 Study).
CI  - Copyright (c) 2020 American Academy of Ophthalmology. Published by Elsevier Inc. 
      All rights reserved.
FAU - Jaffe, Glenn J
AU  - Jaffe GJ
AD  - Department of Ophthalmology, Duke University, Durham, North Carolina.
FAU - Westby, Keith
AU  - Westby K
AD  - IVERIC bio, Inc., New York, New York.
FAU - Csaky, Karl G
AU  - Csaky KG
AD  - Retina Foundation of Southwest, Dallas, Texas.
FAU - Mones, Jordi
AU  - Mones J
AD  - Institut de la Macula and Barcelona Macula Foundation, Barcelona, Spain.
FAU - Pearlman, Joel A
AU  - Pearlman JA
AD  - Vitreoretinal Medical Group, Inc., Sacramento, California.
FAU - Patel, Sunil S
AU  - Patel SS
AD  - West Texas Retina Consultants, Abilene, Texas.
FAU - Joondeph, Brian C
AU  - Joondeph BC
AD  - Colorado Retina, Denver, Colorado.
FAU - Randolph, John
AU  - Randolph J
AD  - Center for Retina and Macular Disease, Winter Haven, Florida.
FAU - Masonson, Harvey
AU  - Masonson H
AD  - IVERIC bio, Inc., New York, New York.
FAU - Rezaei, Kourous A
AU  - Rezaei KA
AD  - IVERIC bio, Inc., New York, New York. Electronic address: karezaei@yahoo.com.
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Clinical Trial, Phase III
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20200901
PL  - United States
TA  - Ophthalmology
JT  - Ophthalmology
JID - 7802443
RN  - 0 (Aptamers, Nucleotide)
RN  - 0 (Complement C5)
RN  - 0 (Complement Inactivating Agents)
SB  - IM
CIN - Ophthalmology. 2021 May;128(5):e26-e27. PMID: 33551285
CIN - Ophthalmology. 2021 May;128(5):e25-e26. PMID: 33551286
CIN - Ophthalmology. 2021 Dec;128(12):e219. PMID: 34600774
CIN - Ophthalmology. 2021 Dec;128(12):e219-e220. PMID: 34600775
MH  - Aged
MH  - Aged, 80 and over
MH  - Aptamers, Nucleotide/*therapeutic use
MH  - Complement C5/*antagonists & inhibitors
MH  - Complement Inactivating Agents/*therapeutic use
MH  - Double-Blind Method
MH  - Female
MH  - Fluorescein Angiography
MH  - Follow-Up Studies
MH  - Geographic Atrophy/diagnosis/*drug therapy/physiopathology
MH  - Humans
MH  - Intravitreal Injections
MH  - Macular Degeneration/diagnosis/drug therapy/physiopathology
MH  - Male
MH  - Prospective Studies
MH  - Visual Acuity/physiology
OTO - NOTNLM
OT  - C5 inhibitor
OT  - Complement
OT  - GATHER1
OT  - GATHER2
OT  - Zimura
OT  - age-related macular degeneration
OT  - avacincaptad pegol
OT  - dry
OT  - geographic atrophy
EDAT- 2020/09/04 06:00
MHDA- 2021/07/31 06:00
CRDT- 2020/09/04 06:00
PHST- 2020/05/11 00:00 [received]
PHST- 2020/08/05 00:00 [revised]
PHST- 2020/08/26 00:00 [accepted]
PHST- 2020/09/04 06:00 [pubmed]
PHST- 2021/07/31 06:00 [medline]
PHST- 2020/09/04 06:00 [entrez]
AID - S0161-6420(20)30845-9 [pii]
AID - 10.1016/j.ophtha.2020.08.027 [doi]
PST - ppublish
SO  - Ophthalmology. 2021 Apr;128(4):576-586. doi: 10.1016/j.ophtha.2020.08.027. Epub 
      2020 Sep 1.