A Randomized, Double-Masked, Multicenter Trial of Topical Acrizanib (LHA510), a Tyrosine Kinase VEGF-Receptor Inhibitor, in Treatment-Experienced Subjects With Neovascular Age-Related Macular Degeneration
To evaluate whether topical acrizanib (LHA510), a small-molecule vascular endothelial growth factor receptor inhibitor, could suppress the need for anti–vascular endothelial growth factor therapy over a 12-week period in patients with neovascular age-related macular degeneration. A phase 2 multicent...
Saved in:
| Published in: | American journal of ophthalmology Vol. 239; pp. 180 - 189 |
|---|---|
| Main Authors: | , , , , , , , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
United States
Elsevier Inc
01.07.2022
Elsevier Limited |
| Subjects: | |
| ISSN: | 0002-9394, 1879-1891, 1879-1891 |
| Online Access: | Get full text |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Abstract | To evaluate whether topical acrizanib (LHA510), a small-molecule vascular endothelial growth factor receptor inhibitor, could suppress the need for anti–vascular endothelial growth factor therapy over a 12-week period in patients with neovascular age-related macular degeneration.
A phase 2 multicenter randomized double-masked, vehicle-controlled proof-of-concept study.
Trial includes n = 90 patients with active choroidal neovascularization due to neovascular age-related macular degeneration and under anti–vascular endothelial growth factor treatment. All patients received an intravitreal injection of ranibizumab at baseline and were retreated when there was evidence of disease recurrence (rescue). Patients were randomized 1:1 to receive topical LHA510 or vehicle for 12 weeks. Drops were administered twice a day for 8 weeks and then 3 times a day for the last 4 weeks.
The primary outcome was the number of patients requiring rescue over 84 days of topical dosing. Key secondary outcome measures were time to first rescue, total number of ranibizumab injections, changes in central subfield thickness, and changes of visual acuity from baseline to day 84.
The extended per protocol set included 70 patients of whom 25 of 33 patients in the LHA510 group (75.8%) and 25 of 37 patients in the placebo group (67.6%) required rescue by day 84 (P = .8466). Secondary and subgroup analysis did not support evidence of efficacy. Twenty-one of 46 patients administered LHA510 developed a reversible corneal haze that resolved with cessation of treatment and did not recur in patients restarted at once daily frequency.
In spite of extensive optimization for topical efficacy, LHA510 failed to demonstrate clinical efficacy. |
|---|---|
| AbstractList | To evaluate whether topical acrizanib (LHA510), a small-molecule vascular endothelial growth factor receptor inhibitor, could suppress the need for anti–vascular endothelial growth factor therapy over a 12-week period in patients with neovascular age-related macular degeneration.
A phase 2 multicenter randomized double-masked, vehicle-controlled proof-of-concept study.
Trial includes n = 90 patients with active choroidal neovascularization due to neovascular age-related macular degeneration and under anti–vascular endothelial growth factor treatment. All patients received an intravitreal injection of ranibizumab at baseline and were retreated when there was evidence of disease recurrence (rescue). Patients were randomized 1:1 to receive topical LHA510 or vehicle for 12 weeks. Drops were administered twice a day for 8 weeks and then 3 times a day for the last 4 weeks.
The primary outcome was the number of patients requiring rescue over 84 days of topical dosing. Key secondary outcome measures were time to first rescue, total number of ranibizumab injections, changes in central subfield thickness, and changes of visual acuity from baseline to day 84.
The extended per protocol set included 70 patients of whom 25 of 33 patients in the LHA510 group (75.8%) and 25 of 37 patients in the placebo group (67.6%) required rescue by day 84 (P = .8466). Secondary and subgroup analysis did not support evidence of efficacy. Twenty-one of 46 patients administered LHA510 developed a reversible corneal haze that resolved with cessation of treatment and did not recur in patients restarted at once daily frequency.
In spite of extensive optimization for topical efficacy, LHA510 failed to demonstrate clinical efficacy. PurposeTo evaluate whether topical acrizanib (LHA510), a small-molecule vascular endothelial growth factor receptor inhibitor, could suppress the need for anti–vascular endothelial growth factor therapy over a 12-week period in patients with neovascular age-related macular degeneration.DesignA phase 2 multicenter randomized double-masked, vehicle-controlled proof-of-concept study.MethodsTrial includes n = 90 patients with active choroidal neovascularization due to neovascular age-related macular degeneration and under anti–vascular endothelial growth factor treatment. All patients received an intravitreal injection of ranibizumab at baseline and were retreated when there was evidence of disease recurrence (rescue). Patients were randomized 1:1 to receive topical LHA510 or vehicle for 12 weeks. Drops were administered twice a day for 8 weeks and then 3 times a day for the last 4 weeks.Main outcome measureThe primary outcome was the number of patients requiring rescue over 84 days of topical dosing. Key secondary outcome measures were time to first rescue, total number of ranibizumab injections, changes in central subfield thickness, and changes of visual acuity from baseline to day 84.ResultsThe extended per protocol set included 70 patients of whom 25 of 33 patients in the LHA510 group (75.8%) and 25 of 37 patients in the placebo group (67.6%) required rescue by day 84 (P = .8466). Secondary and subgroup analysis did not support evidence of efficacy. Twenty-one of 46 patients administered LHA510 developed a reversible corneal haze that resolved with cessation of treatment and did not recur in patients restarted at once daily frequency.ConclusionIn spite of extensive optimization for topical efficacy, LHA510 failed to demonstrate clinical efficacy. To evaluate whether topical acrizanib (LHA510), a small-molecule vascular endothelial growth factor receptor inhibitor, could suppress the need for anti-vascular endothelial growth factor therapy over a 12-week period in patients with neovascular age-related macular degeneration.PURPOSETo evaluate whether topical acrizanib (LHA510), a small-molecule vascular endothelial growth factor receptor inhibitor, could suppress the need for anti-vascular endothelial growth factor therapy over a 12-week period in patients with neovascular age-related macular degeneration.A phase 2 multicenter randomized double-masked, vehicle-controlled proof-of-concept study.DESIGNA phase 2 multicenter randomized double-masked, vehicle-controlled proof-of-concept study.Trial includes n = 90 patients with active choroidal neovascularization due to neovascular age-related macular degeneration and under anti-vascular endothelial growth factor treatment. All patients received an intravitreal injection of ranibizumab at baseline and were retreated when there was evidence of disease recurrence (rescue). Patients were randomized 1:1 to receive topical LHA510 or vehicle for 12 weeks. Drops were administered twice a day for 8 weeks and then 3 times a day for the last 4 weeks.METHODSTrial includes n = 90 patients with active choroidal neovascularization due to neovascular age-related macular degeneration and under anti-vascular endothelial growth factor treatment. All patients received an intravitreal injection of ranibizumab at baseline and were retreated when there was evidence of disease recurrence (rescue). Patients were randomized 1:1 to receive topical LHA510 or vehicle for 12 weeks. Drops were administered twice a day for 8 weeks and then 3 times a day for the last 4 weeks.The primary outcome was the number of patients requiring rescue over 84 days of topical dosing. Key secondary outcome measures were time to first rescue, total number of ranibizumab injections, changes in central subfield thickness, and changes of visual acuity from baseline to day 84.MAIN OUTCOME MEASUREThe primary outcome was the number of patients requiring rescue over 84 days of topical dosing. Key secondary outcome measures were time to first rescue, total number of ranibizumab injections, changes in central subfield thickness, and changes of visual acuity from baseline to day 84.The extended per protocol set included 70 patients of whom 25 of 33 patients in the LHA510 group (75.8%) and 25 of 37 patients in the placebo group (67.6%) required rescue by day 84 (P = .8466). Secondary and subgroup analysis did not support evidence of efficacy. Twenty-one of 46 patients administered LHA510 developed a reversible corneal haze that resolved with cessation of treatment and did not recur in patients restarted at once daily frequency.RESULTSThe extended per protocol set included 70 patients of whom 25 of 33 patients in the LHA510 group (75.8%) and 25 of 37 patients in the placebo group (67.6%) required rescue by day 84 (P = .8466). Secondary and subgroup analysis did not support evidence of efficacy. Twenty-one of 46 patients administered LHA510 developed a reversible corneal haze that resolved with cessation of treatment and did not recur in patients restarted at once daily frequency.In spite of extensive optimization for topical efficacy, LHA510 failed to demonstrate clinical efficacy.CONCLUSIONIn spite of extensive optimization for topical efficacy, LHA510 failed to demonstrate clinical efficacy. |
| Author | Ciulla, Thomas A. Poor, Stephen H. Grosskreutz, Cynthia L. Glazer, Louis C. Normand, Guillaume Weissgerber, Georges Chastain, James Gedif, Kinfemichael Bhatt, Harit Joondeph, Brian C. Sheth, Veeral Adams, Christopher M. Ferriere, Michael Watters, Christie Browning, David J. |
| Author_xml | – sequence: 1 givenname: Stephen H. orcidid: 0000-0003-4374-1178 surname: Poor fullname: Poor, Stephen H. email: stephen.poor@novartis.com organization: From the Translational Medicine/Research (S.H.P., C.L.G.) – sequence: 2 givenname: Georges surname: Weissgerber fullname: Weissgerber, Georges organization: Clinical Development (G.W., G.N.) – sequence: 3 givenname: Christopher M. orcidid: 0000-0002-5246-884X surname: Adams fullname: Adams, Christopher M. organization: Global Discovery Chemistry (C.M.A.) – sequence: 4 givenname: Harit surname: Bhatt fullname: Bhatt, Harit organization: Retina and Macula Associates, Oak Forest (H.B.) – sequence: 5 givenname: David J. surname: Browning fullname: Browning, David J. organization: Charlotte Eye, Ear, Nose, and Throat Associates, Charlotte, North Carolina – sequence: 6 givenname: James orcidid: 0000-0001-6864-6236 surname: Chastain fullname: Chastain, James organization: PK Sciences (J.C.) – sequence: 7 givenname: Thomas A. orcidid: 0000-0001-5557-6777 surname: Ciulla fullname: Ciulla, Thomas A. organization: Clearside Biomedical Inc, Alpharetta, Georgia – sequence: 8 givenname: Michael orcidid: 0000-0003-3112-9328 surname: Ferriere fullname: Ferriere, Michael organization: Clinical Data Operations (M.F.) – sequence: 9 givenname: Kinfemichael surname: Gedif fullname: Gedif, Kinfemichael organization: Biostatistician, Novartis Pharma Inc (K.G.), Basel, Switzerland – sequence: 10 givenname: Louis C. surname: Glazer fullname: Glazer, Louis C. organization: Vitreo-Retinal Associates, Grand Rapids, Michigan – sequence: 11 givenname: Brian C. orcidid: 0000-0001-8781-4370 surname: Joondeph fullname: Joondeph, Brian C. organization: Colorado Retina Associates, Denver, Colorado, USA – sequence: 12 givenname: Guillaume orcidid: 0000-0003-1228-3813 surname: Normand fullname: Normand, Guillaume organization: Clinical Development (G.W., G.N.) – sequence: 13 givenname: Veeral orcidid: 0000-0002-7467-9947 surname: Sheth fullname: Sheth, Veeral organization: Retina and Macula Associates, Oak Forest (H.B.) – sequence: 14 givenname: Christie surname: Watters fullname: Watters, Christie organization: and Biostatistician (C.W., C.L.G.), Novartis Institutes for Biomedical Research, Cambridge, Massachusetts, USA (C.W., C.L.G.) – sequence: 15 givenname: Cynthia L. surname: Grosskreutz fullname: Grosskreutz, Cynthia L. organization: From the Translational Medicine/Research (S.H.P., C.L.G.) |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/35247334$$D View this record in MEDLINE/PubMed |
| BookMark | eNqFkk1vEzEQhleoiKaFH8AFWeJSpGywvd4Pi1PUph8iAakEOFpe72zr7cYOtrci_Y38KBzSXnIo8kiesZ73le2Zo-TAWANJ8pbgCcGk-NhNZGcnFFM6wTEIf5GMSFXylFScHCQjjDFNecbZYXLkfRfLomTlq-Qwyykrs4yNkj9TdC1NY1f6AZoxOrND3UO6kP5uWy6GPmgFJoBDS6dlj2yLlnatVUynyukHaXSNTuaX05zgD2Mk0XLjrNcG0GdtpAf0Y3Zxnl6DgnWwDl2ZW13rmI2RNtESZFhF-3T2ew1Og1HQoG9D3YEKHv3U4RZ9AXsvvRp66dD0BqJVL0OkFnJ3dgY3YMDJoK15nbxsZe_hzeN-nHw_ny1PL9P514ur0-k8VQyzkDZ5W1U4h6wlJdQceFXTXDZ1XIUkStG6aQgjsuSStiyrOGYZYbTKc8l5AXV2nJzsfNfO_hrAB7HSXkHfSwN28IIWWUEYLqo8ou_30M4OzsTbRarMc15hWkXq3SM11CtoxNrplXQb8dSnCJQ7QMXf9Q5aoXT49-bgpO4FwWI7EaITcSLEdiIEjkF4VJI95ZP5c5pPOw3ET7zX4IRXu-ZoFzsjGqufVfM9teq12Y7MHWz-o_0LDdPhqg |
| CitedBy_id | crossref_primary_10_3390_ijms231911769 crossref_primary_10_3390_ijms24098045 crossref_primary_10_3390_ph18050655 crossref_primary_10_3389_fbioe_2023_1199922 crossref_primary_10_1080_10837450_2025_2562196 crossref_primary_10_3390_jcto3030016 crossref_primary_10_1080_17425247_2025_2516668 crossref_primary_10_3390_ph17070959 crossref_primary_10_1016_j_ijpharm_2024_124018 crossref_primary_10_1080_14728214_2023_2259790 crossref_primary_10_1016_j_ajo_2025_03_016 crossref_primary_10_1016_j_arr_2024_102322 crossref_primary_10_3390_ijms252313053 crossref_primary_10_3390_medicina60101647 crossref_primary_10_3389_fphar_2023_1307860 |
| Cites_doi | 10.1016/j.ophtha.2013.08.011 10.1016/j.oret.2019.05.017 10.1111/bcp.13794 10.1167/iovs.16-19952 10.1016/j.ophtha.2017.11.036 10.1016/S2214-109X(13)70145-1 10.1021/jm7011276 10.1016/j.ophtha.2016.07.012 10.1001/archopht.1984.01040031330019 10.1016/j.ophtha.2008.10.018 10.1016/j.ophtha.2014.09.036 10.1001/jamaophthalmol.2013.5002 10.1136/bjophthalmol-2013-303117 10.1016/j.ajo.2011.01.053 10.1016/j.ophtha.2015.02.009 10.1021/acs.jmedchem.7b01731 |
| ContentType | Journal Article |
| Copyright | 2022 The Authors Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved. 2022. The Authors |
| Copyright_xml | – notice: 2022 The Authors – notice: Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved. – notice: 2022. The Authors |
| DBID | 6I. AAFTH AAYXX CITATION NPM K9. NAPCQ 7X8 |
| DOI | 10.1016/j.ajo.2022.02.019 |
| DatabaseName | ScienceDirect Open Access Titles Elsevier:ScienceDirect:Open Access CrossRef PubMed ProQuest Health & Medical Complete (Alumni) Nursing & Allied Health Premium MEDLINE - Academic |
| DatabaseTitle | CrossRef PubMed ProQuest Health & Medical Complete (Alumni) Nursing & Allied Health Premium MEDLINE - Academic |
| DatabaseTitleList | ProQuest Health & Medical Complete (Alumni) MEDLINE - Academic PubMed |
| Database_xml | – sequence: 1 dbid: NPM name: PubMed url: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: 7X8 name: MEDLINE - Academic url: https://search.proquest.com/medline sourceTypes: Aggregation Database |
| DeliveryMethod | fulltext_linktorsrc |
| Discipline | Medicine |
| EISSN | 1879-1891 |
| EndPage | 189 |
| ExternalDocumentID | 35247334 10_1016_j_ajo_2022_02_019 S0002939422000848 |
| Genre | Journal Article |
| GeographicLocations | United States--US |
| GeographicLocations_xml | – name: United States--US |
| GroupedDBID | --- --K --M -~X .1- .55 .FO .GJ .~1 0R~ 1B1 1CY 1P~ 1~. 1~5 23M 4.4 457 4G. 53G 5GY 5RE 5VS 6J9 7-5 71M 8P~ AABNK AAEDT AAEDW AAHTB AAIKJ AAKOC AALRI AAOAW AAQFI AAQQT AAQXK AATTM AAWTL AAXKI AAXUO AAYWO ABBQC ABCQX ABDPE ABFNM ABFRF ABJNI ABLJU ABMAC ABMZM ABOCM ABPEJ ABWVN ABXDB ACDAQ ACGFO ACGFS ACIEU ACIUM ACLOT ACNCT ACRLP ACRPL ACVFH ADBBV ADCNI ADEZE ADFRT ADMUD ADNMO AEBSH AEFWE AEIPS AEKER AENEX AEUPX AEVXI AFFNX AFJKZ AFPUW AFRHN AFTJW AFXIZ AGHFR AGQPQ AGUBO AGYEJ AHMBA AI. AIEXJ AIGII AIIUN AIKHN AITUG AJRQY AJUYK AKBMS AKRWK AKYEP ALMA_UNASSIGNED_HOLDINGS AMRAJ ANKPU ANZVX APXCP ASPBG AVWKF AXJTR AZFZN BKEYQ BKOJK BLXMC BNPGV BPHCQ BVXVI CS3 EBS EFJIC EFKBS EFLBG EJD EMOBN EO8 EO9 EP2 EP3 EX3 F5P FDB FEDTE FGOYB FIRID FNPLU FYGXN G-Q GBLVA HVGLF HZ~ IHE J1W J5H K-O KOM L7B M41 MO0 N4W N9A O-L O9- OAUVE OF- OPF OQ~ OZT P-8 P-9 P2P PC. PQQKQ PROAC Q38 R2- ROL RPZ SCC SDF SDG SDP SEL SES SPCBC SSH SSZ SV3 T5K UNMZH UV1 VH1 WH7 WOW X7M XPP Z5R ZGI ZXP ~G- ~HD 3V. 6I. 7RV 7X7 8FI AACTN AAFTH AAIAV ABLVK ABYKQ AFCTW AFKRA AFKWA AHPSJ AJBFU AJOXV AMFUW AZQEC BENPR FYUFA G8K GUQSH LCYCR M1P M2O RIG ZA5 9DU AAYXX CITATION NPM K9. NAPCQ 7X8 |
| ID | FETCH-LOGICAL-c404t-d5f8805e3f17eb9e98b25adbdbd6a1cc2bdd141a79a2f4389043142855a996eb3 |
| ISICitedReferencesCount | 16 |
| ISICitedReferencesURI | http://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=Summon&SrcAuth=ProQuest&DestLinkType=CitingArticles&DestApp=WOS_CPL&KeyUT=000806243000019&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| ISSN | 0002-9394 1879-1891 |
| IngestDate | Sun Sep 28 03:50:57 EDT 2025 Mon Oct 06 18:27:58 EDT 2025 Thu Apr 03 07:06:52 EDT 2025 Tue Nov 18 22:01:43 EST 2025 Sat Nov 29 07:32:06 EST 2025 Fri Feb 23 02:40:56 EST 2024 Tue Oct 14 19:35:27 EDT 2025 |
| IsDoiOpenAccess | true |
| IsOpenAccess | true |
| IsPeerReviewed | true |
| IsScholarly | true |
| Language | English |
| License | This is an open access article under the CC BY license. Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved. |
| LinkModel | OpenURL |
| MergedId | FETCHMERGED-LOGICAL-c404t-d5f8805e3f17eb9e98b25adbdbd6a1cc2bdd141a79a2f4389043142855a996eb3 |
| Notes | ObjectType-Article-2 SourceType-Scholarly Journals-1 content type line 14 ObjectType-Feature-3 ObjectType-Evidence Based Healthcare-1 ObjectType-Feature-1 content type line 23 ObjectType-Undefined-3 |
| ORCID | 0000-0003-1228-3813 0000-0001-6864-6236 0000-0002-5246-884X 0000-0002-7467-9947 0000-0001-8781-4370 0000-0001-5557-6777 0000-0003-3112-9328 0000-0003-4374-1178 |
| OpenAccessLink | https://dx.doi.org/10.1016/j.ajo.2022.02.019 |
| PMID | 35247334 |
| PQID | 2675598028 |
| PQPubID | 41749 |
| PageCount | 10 |
| ParticipantIDs | proquest_miscellaneous_2636140685 proquest_journals_2675598028 pubmed_primary_35247334 crossref_citationtrail_10_1016_j_ajo_2022_02_019 crossref_primary_10_1016_j_ajo_2022_02_019 elsevier_sciencedirect_doi_10_1016_j_ajo_2022_02_019 elsevier_clinicalkey_doi_10_1016_j_ajo_2022_02_019 |
| PublicationCentury | 2000 |
| PublicationDate | 2022-07-01 |
| PublicationDateYYYYMMDD | 2022-07-01 |
| PublicationDate_xml | – month: 07 year: 2022 text: 2022-07-01 day: 01 |
| PublicationDecade | 2020 |
| PublicationPlace | United States |
| PublicationPlace_xml | – name: United States – name: Chicago |
| PublicationTitle | American journal of ophthalmology |
| PublicationTitleAlternate | Am J Ophthalmol |
| PublicationYear | 2022 |
| Publisher | Elsevier Inc Elsevier Limited |
| Publisher_xml | – name: Elsevier Inc – name: Elsevier Limited |
| References | McLaughlin, Paglione, Slakter (bib0008) 2013; 131 Gadek (bib0014) 2011 Arnold, Campain, Barthelmes (bib0019) 2015; 122 Accessed January 2022. Ciulla, Hussain, Pollack, Williams (bib0006) 2020; 4 Csaky, Dugel, Pierce (bib0009) 2015; 122 Joussen, Wolf, Kaiser (bib0010) 2019; 85 Schmidt-Erfurth, Kaiser, Korobelnik (bib0004) 2014; 121 Modern Retina. Topical treatment for neovascular AMD within sight; 2016. Available at Ferris, Fine, Hyman (bib0003) 1984; 102 Wong, Su, Li (bib0001) 2014; 2 Day, Acquah, Mruthyunjaya (bib0007) 2011; 152 Ohr Pharmaceutical Inc. Efficacy and safety study of squalamine ophthalmic solution in subjects with neovascular AMD (MAKO); 2017. Available at PanOptica. Study of PAN-90806 eye drops, suspension for neovascular AMD. Available at Essex, Nguyen, Walton (bib0020) 2016; 123 Accessed October 2019. Accessed July 2019. Brown, Michels, Kaiser (bib0005) 2009; 116 Chakravarthy, Bailey, Johnston (bib0002) 2018; 125 Danis, McLaughlin, Tolentino (bib0021) 2014; 98 Connolly, Desai, Garcia, Thomas, Gast (bib0012) 2006; 19 Palanki, Akiyama, Campochiaro (bib0011) 2008; 51 Adams, Anderson, Artman (bib0015) 2018; 61 Rush, Bingaman, Chaney, Wax, Ceresa (bib0013) 2016; 57 Day (10.1016/j.ajo.2022.02.019_bib0007) 2011; 152 Gadek (10.1016/j.ajo.2022.02.019_bib0014) 2011 Palanki (10.1016/j.ajo.2022.02.019_bib0011) 2008; 51 Chakravarthy (10.1016/j.ajo.2022.02.019_bib0002) 2018; 125 Connolly (10.1016/j.ajo.2022.02.019_bib0012) 2006; 19 Joussen (10.1016/j.ajo.2022.02.019_bib0010) 2019; 85 Arnold (10.1016/j.ajo.2022.02.019_bib0019) 2015; 122 Wong (10.1016/j.ajo.2022.02.019_bib0001) 2014; 2 Brown (10.1016/j.ajo.2022.02.019_bib0005) 2009; 116 Danis (10.1016/j.ajo.2022.02.019_bib0021) 2014; 98 10.1016/j.ajo.2022.02.019_bib0017 10.1016/j.ajo.2022.02.019_bib0016 Rush (10.1016/j.ajo.2022.02.019_bib0013) 2016; 57 Ferris (10.1016/j.ajo.2022.02.019_bib0003) 1984; 102 10.1016/j.ajo.2022.02.019_bib0022 McLaughlin (10.1016/j.ajo.2022.02.019_bib0008) 2013; 131 Csaky (10.1016/j.ajo.2022.02.019_bib0009) 2015; 122 Adams (10.1016/j.ajo.2022.02.019_bib0015) 2018; 61 Essex (10.1016/j.ajo.2022.02.019_bib0020) 2016; 123 Schmidt-Erfurth (10.1016/j.ajo.2022.02.019_bib0004) 2014; 121 Ciulla (10.1016/j.ajo.2022.02.019_bib0006) 2020; 4 |
| References_xml | – volume: 102 start-page: 1640 year: 1984 end-page: 1642 ident: bib0003 article-title: Age-related macular degeneration and blindness due to neovascular maculopathy publication-title: Arch Ophthalmol – volume: 98 start-page: 172 year: 2014 end-page: 178 ident: bib0021 article-title: Pazopanib eye drops: a randomised trial in neovascular age-related macular degeneration publication-title: Br J Ophthalmol – volume: 19 start-page: 381 year: 2006 end-page: 391 ident: bib0012 article-title: Squalamine lactate for exudative age-related macular degeneration publication-title: Ophthalmol Clin North Am – reference: . Accessed October 2019. – volume: 4 start-page: 19 year: 2020 end-page: 30 ident: bib0006 article-title: Visual acuity outcomes and anti-vascular endothelial growth factor therapy intensity in neovascular age-related macular degeneration patients: a real-world analysis of 49 485 eyes publication-title: Ophthalmol Retina – volume: 51 start-page: 1546 year: 2008 end-page: 1559 ident: bib0011 article-title: Development of prodrug 4-chloro-3-(5-methyl-3-{[4-(2-pyrrolidin-1-ylethoxy)phenyl]amino}-1,2,4-benzotria zin-7-yl)phenyl benzoate (TG100801): a topically administered therapeutic candidate in clinical trials for the treatment of age-related macular degeneration publication-title: J Med Chem – volume: 61 start-page: 1622 year: 2018 end-page: 1635 ident: bib0015 article-title: The discovery of N-(1-methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl)-5-((6-((methylamino)methyl)pyrimidin-4-yl)oxy)-1H-indole-1-carboxamide (acrizanib), a VEGFR-2 inhibitor specifically designed for topical ocular delivery, as a therapy for neovascular age-related macular degeneration publication-title: J Med Chem – volume: 122 start-page: 579 year: 2015 end-page: 588 ident: bib0009 article-title: Clinical evaluation of pazopanib eye drops versus ranibizumab intravitreal injections in subjects with neovascular age-related macular degeneration publication-title: Ophthalmology – volume: 57 start-page: 5864 year: 2016 end-page: 5871 ident: bib0013 article-title: Administration of menadione, vitamin K3, ameliorates off-target effects on corneal epithelial wound healing due to receptor tyrosine kinase inhibition publication-title: Invest Ophthalmol Vis Sci – volume: 121 start-page: 193 year: 2014 end-page: 201 ident: bib0004 article-title: Intravitreal aflibercept injection for neovascular age-related macular degeneration: ninety-six–week results of the VIEW studies publication-title: Ophthalmology – volume: 152 start-page: 266 year: 2011 end-page: 272 ident: bib0007 article-title: Ocular complications after anti-vascular endothelial growth factor therapy in Medicare patients with age-related macular degeneration publication-title: Am J Ophthalmol – volume: 123 start-page: 2393 year: 2016 end-page: 2400 ident: bib0020 article-title: Treatment patterns and visual outcomes during the maintenance phase of treat-and-extend therapy for age-related macular degeneration publication-title: Ophthalmology – volume: 2 start-page: e106 year: 2014 end-page: e116 ident: bib0001 article-title: Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis publication-title: Lancet Glob Health – reference: Ohr Pharmaceutical Inc. Efficacy and safety study of squalamine ophthalmic solution in subjects with neovascular AMD (MAKO); 2017. Available at – volume: 122 start-page: 1212 year: 2015 end-page: 1219 ident: bib0019 article-title: Two-year outcomes of “treat and extend” intravitreal therapy for neovascular age-related macular degeneration publication-title: Ophthalmology – volume: 125 start-page: 842 year: 2018 end-page: 849 ident: bib0002 article-title: Characterizing disease burden and progression of geographic atrophy secondary to age-related macular degeneration publication-title: Ophthalmology – volume: 131 start-page: 1595 year: 2013 end-page: 1601 ident: bib0008 article-title: Initial exploration of oral pazopanib in healthy participants and patients with age-related macular degeneration publication-title: JAMA Ophthalmol – volume: 85 start-page: 347 year: 2019 end-page: 355 ident: bib0010 article-title: The Developing Regorafenib Eye drops for neovascular Age-related Macular degeneration (DREAM) study: an open-label phase II trial publication-title: Br J Clin Pharmacol – year: 2011 ident: bib0014 article-title: Topical Drug Delivery to the Back of the Eye – reference: PanOptica. Study of PAN-90806 eye drops, suspension for neovascular AMD. Available at – reference: . Accessed January 2022. – reference: Modern Retina. Topical treatment for neovascular AMD within sight; 2016. Available at – reference: . Accessed July 2019. – volume: 116 start-page: 57 year: 2009 end-page: 65 ident: bib0005 article-title: Ranibizumab versus verteporfin photodynamic therapy for neovascular age-related macular degeneration: two-year results of the ANCHOR study publication-title: Ophthalmology – volume: 121 start-page: 193 year: 2014 ident: 10.1016/j.ajo.2022.02.019_bib0004 article-title: Intravitreal aflibercept injection for neovascular age-related macular degeneration: ninety-six–week results of the VIEW studies publication-title: Ophthalmology doi: 10.1016/j.ophtha.2013.08.011 – ident: 10.1016/j.ajo.2022.02.019_bib0016 – volume: 4 start-page: 19 year: 2020 ident: 10.1016/j.ajo.2022.02.019_bib0006 article-title: Visual acuity outcomes and anti-vascular endothelial growth factor therapy intensity in neovascular age-related macular degeneration patients: a real-world analysis of 49 485 eyes publication-title: Ophthalmol Retina doi: 10.1016/j.oret.2019.05.017 – volume: 85 start-page: 347 year: 2019 ident: 10.1016/j.ajo.2022.02.019_bib0010 article-title: The Developing Regorafenib Eye drops for neovascular Age-related Macular degeneration (DREAM) study: an open-label phase II trial publication-title: Br J Clin Pharmacol doi: 10.1111/bcp.13794 – volume: 57 start-page: 5864 year: 2016 ident: 10.1016/j.ajo.2022.02.019_bib0013 article-title: Administration of menadione, vitamin K3, ameliorates off-target effects on corneal epithelial wound healing due to receptor tyrosine kinase inhibition publication-title: Invest Ophthalmol Vis Sci doi: 10.1167/iovs.16-19952 – volume: 125 start-page: 842 year: 2018 ident: 10.1016/j.ajo.2022.02.019_bib0002 article-title: Characterizing disease burden and progression of geographic atrophy secondary to age-related macular degeneration publication-title: Ophthalmology doi: 10.1016/j.ophtha.2017.11.036 – volume: 2 start-page: e106 year: 2014 ident: 10.1016/j.ajo.2022.02.019_bib0001 article-title: Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis publication-title: Lancet Glob Health doi: 10.1016/S2214-109X(13)70145-1 – volume: 51 start-page: 1546 year: 2008 ident: 10.1016/j.ajo.2022.02.019_bib0011 publication-title: J Med Chem doi: 10.1021/jm7011276 – volume: 123 start-page: 2393 year: 2016 ident: 10.1016/j.ajo.2022.02.019_bib0020 article-title: Treatment patterns and visual outcomes during the maintenance phase of treat-and-extend therapy for age-related macular degeneration publication-title: Ophthalmology doi: 10.1016/j.ophtha.2016.07.012 – volume: 102 start-page: 1640 year: 1984 ident: 10.1016/j.ajo.2022.02.019_bib0003 article-title: Age-related macular degeneration and blindness due to neovascular maculopathy publication-title: Arch Ophthalmol doi: 10.1001/archopht.1984.01040031330019 – volume: 116 start-page: 57 year: 2009 ident: 10.1016/j.ajo.2022.02.019_bib0005 article-title: Ranibizumab versus verteporfin photodynamic therapy for neovascular age-related macular degeneration: two-year results of the ANCHOR study publication-title: Ophthalmology doi: 10.1016/j.ophtha.2008.10.018 – volume: 122 start-page: 579 year: 2015 ident: 10.1016/j.ajo.2022.02.019_bib0009 article-title: Clinical evaluation of pazopanib eye drops versus ranibizumab intravitreal injections in subjects with neovascular age-related macular degeneration publication-title: Ophthalmology doi: 10.1016/j.ophtha.2014.09.036 – year: 2011 ident: 10.1016/j.ajo.2022.02.019_bib0014 – ident: 10.1016/j.ajo.2022.02.019_bib0022 – volume: 131 start-page: 1595 year: 2013 ident: 10.1016/j.ajo.2022.02.019_bib0008 article-title: Initial exploration of oral pazopanib in healthy participants and patients with age-related macular degeneration publication-title: JAMA Ophthalmol doi: 10.1001/jamaophthalmol.2013.5002 – volume: 19 start-page: 381 year: 2006 ident: 10.1016/j.ajo.2022.02.019_bib0012 article-title: Squalamine lactate for exudative age-related macular degeneration publication-title: Ophthalmol Clin North Am – volume: 98 start-page: 172 year: 2014 ident: 10.1016/j.ajo.2022.02.019_bib0021 article-title: Pazopanib eye drops: a randomised trial in neovascular age-related macular degeneration publication-title: Br J Ophthalmol doi: 10.1136/bjophthalmol-2013-303117 – ident: 10.1016/j.ajo.2022.02.019_bib0017 – volume: 152 start-page: 266 year: 2011 ident: 10.1016/j.ajo.2022.02.019_bib0007 article-title: Ocular complications after anti-vascular endothelial growth factor therapy in Medicare patients with age-related macular degeneration publication-title: Am J Ophthalmol doi: 10.1016/j.ajo.2011.01.053 – volume: 122 start-page: 1212 year: 2015 ident: 10.1016/j.ajo.2022.02.019_bib0019 article-title: Two-year outcomes of “treat and extend” intravitreal therapy for neovascular age-related macular degeneration publication-title: Ophthalmology doi: 10.1016/j.ophtha.2015.02.009 – volume: 61 start-page: 1622 year: 2018 ident: 10.1016/j.ajo.2022.02.019_bib0015 publication-title: J Med Chem doi: 10.1021/acs.jmedchem.7b01731 |
| SSID | ssj0006747 |
| Score | 2.4675963 |
| Snippet | To evaluate whether topical acrizanib (LHA510), a small-molecule vascular endothelial growth factor receptor inhibitor, could suppress the need for... PurposeTo evaluate whether topical acrizanib (LHA510), a small-molecule vascular endothelial growth factor receptor inhibitor, could suppress the need for... |
| SourceID | proquest pubmed crossref elsevier |
| SourceType | Aggregation Database Index Database Enrichment Source Publisher |
| StartPage | 180 |
| SubjectTerms | Antibodies Clinical trials Diabetic retinopathy Drug dosages Immunoglobulins Kinases Laboratories Macular degeneration Monoclonal antibodies Patients Vascular endothelial growth factor |
| Title | A Randomized, Double-Masked, Multicenter Trial of Topical Acrizanib (LHA510), a Tyrosine Kinase VEGF-Receptor Inhibitor, in Treatment-Experienced Subjects With Neovascular Age-Related Macular Degeneration |
| URI | https://www.clinicalkey.com/#!/content/1-s2.0-S0002939422000848 https://dx.doi.org/10.1016/j.ajo.2022.02.019 https://www.ncbi.nlm.nih.gov/pubmed/35247334 https://www.proquest.com/docview/2675598028 https://www.proquest.com/docview/2636140685 |
| Volume | 239 |
| WOSCitedRecordID | wos000806243000019&url=https%3A%2F%2Fcvtisr.summon.serialssolutions.com%2F%23%21%2Fsearch%3Fho%3Df%26include.ft.matches%3Dt%26l%3Dnull%26q%3D |
| hasFullText | 1 |
| inHoldings | 1 |
| isFullTextHit | |
| isPrint | |
| journalDatabaseRights | – providerCode: PRVESC databaseName: ScienceDirect Freedom Collection - Elsevier customDbUrl: eissn: 1879-1891 dateEnd: 99991231 omitProxy: false ssIdentifier: ssj0006747 issn: 0002-9394 databaseCode: AIEXJ dateStart: 19950101 isFulltext: true titleUrlDefault: https://www.sciencedirect.com providerName: Elsevier |
| link | http://cvtisr.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwtV1bb9MwFLZ2QYgXxJ3CmIwECGgzNY7TxI8VtAzoCkLZ6FvkxO6W0qWl7aaxP8af4EdxHNtpy1iBB9TIitzYbXQ-n4t9Lgg9cUGKhYJIh_lh6lBfCCfsS9X0Q8GY8GgR4X3QCbrdsNdjH9fWvttYmNNhkOfh2Rkb_1dSQx8QW4XO_gO5y0mhA-6B6NAC2aH9K8I3q594LkbH2bnexwQVORlKZ49Pv-iOIuZWOWXKSTUqinaAwhiNxppcwEXOeZ4lRa2P3SYspqeEFT6e1egbiFSllb7PchB-1YPWm7YDeqccg-EOnOYoS7KZNv-zHKY2LuzOPJ2yUIxqUDiQfFYbwF05d4VtHkqncM2TyvND972Wh0Va7BI9Nl-uPWdaSHwxGh_NjvjweH5OYDYzyNzx1eyw2Sibi9FdinMzTxdE3pGaWYcBc9xQV_uy3Jzo3EiGH7u6TNQFOaG3LAY7fKACQAkp8rYa3r2Uk7v7IW7vdzpx1OpFz8ZfHVWuTB3rm9ot62iTBD4DdrrZfNvqvSuVgEZAA2t5qb9tD9QL18JffvUylegyk6dQfaIb6LqxWXBTY-0mWpP5LXR1z3hl3EY_mngOuRpeAlwNL8ANF3DDoz42cMMl3PBzDbYXNcyxBRrWQMNLQMMl0Go4y_FvYYYtzLCCGV6AGV6AGTYww4swu4P2263o1a5jqoQ4Ka3TmSP8PsggX3p9N5AJkyxMiM9FAp8Gd9OUJEK41OUB46RPQT9X6aTA6PZ9Dra-TLy7aCMf5fI-wq4rBaOJ55JUUioajMqAew0uiZBeIr0KqltCxalJoa8quQxj6ys5iIG2saJtXIfLZRX0shwy1vljVj1MLPVjGxgNojwG1K4aRMtBRmvW2vCfhm1ZeMVmrU5j0ghUwQawOSrocfk1CBx1ishzOTpRz3ig0tcboV9B9zQsyzcDa44GnkcfrJ78Ibo2X_xbaGM2OZGP0JX0dJZNJ9toPeiF22ZB_QT9gwHo |
| linkProvider | Elsevier |
| openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=A+Randomized%2C+Double-Masked%2C+Multicenter+Trial+of+Topical+Acrizanib+%28LHA510%29%2C+a+Tyrosine+Kinase+VEGF-Receptor+Inhibitor%2C+in+Treatment-Experienced+Subjects+With+Neovascular+Age-Related+Macular+Degeneration&rft.jtitle=American+journal+of+ophthalmology&rft.date=2022-07-01&rft.pub=Elsevier+Limited&rft.issn=0002-9394&rft.eissn=1879-1891&rft.volume=239&rft.spage=180&rft_id=info:doi/10.1016%2Fj.ajo.2022.02.019&rft.externalDBID=NO_FULL_TEXT |
| thumbnail_l | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=0002-9394&client=summon |
| thumbnail_m | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=0002-9394&client=summon |
| thumbnail_s | http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=0002-9394&client=summon |