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Pegcetacoplan for the treatment of geographic atrophy secondary to age-related macular degeneration (OAKS and DERBY): two multicentre, randomised, double-masked, sham-controlled, phase 3 trials

dc.rights.licenseopenen_US
dc.contributor.authorHEIER, Jeffrey S
dc.contributor.authorLAD, Eleonora M.
dc.contributor.authorHOLZ, Frank G.
dc.contributor.authorROSENFELD, Philip J.
dc.contributor.authorGUYMER, Robyn H.
dc.contributor.authorBOYER, David
dc.contributor.authorGROSSI, Federico
dc.contributor.authorBAUMAL, Caroline R.
hal.structure.identifierBordeaux population health [BPH]
dc.contributor.authorKOROBELNIK, Jean-Francois
dc.contributor.authorSLAKTER, Jason S.
dc.contributor.authorWAHEED, Nadia K.
dc.contributor.authorMETLAPALLY, Ravi
dc.contributor.authorPEARCE, Ian
dc.contributor.authorSTEINLE, Nathan
dc.contributor.authorFRANCONE, Anibal A.
dc.contributor.authorHU, Allen
dc.contributor.authorLALLY, David R.
dc.contributor.authorDESCHATELETS, Pascal
dc.contributor.authorFRANCOIS, Cedric
dc.contributor.authorBLISS, Caleb
dc.contributor.authorSTAURENGHI, Giovanni
dc.contributor.authorMONES, Jordi
dc.contributor.authorSINGH, Rishi P.
dc.contributor.authorRIBEIRO, Ramiro
dc.contributor.authorWYKOFF, Charles C.
dc.contributor.authorCOLE, Abosede O.
dc.contributor.authorGERSTENBLITH, Adam T.
dc.contributor.authorKOTAGIRI, Ajay
dc.contributor.authorEDWARDS, Albert O.
dc.contributor.authorZAMBRANO, Alberto D.
dc.contributor.authorEATON, Alexander M.
dc.contributor.authorRUBOWITZ, Alexander
dc.contributor.authorLYON, Alice T.
dc.contributor.authorCHIANG, Allen
dc.contributor.authorHO, Allen
dc.contributor.authorHU, Allen Y.
dc.contributor.authorGUERAMI, Amir H.
dc.contributor.authorDESSOUKI, Amr L.
dc.contributor.authorDE CARVALHO, André Corrêa Maia
dc.contributor.authorEMANUELLI, Andrés
dc.contributor.authorCHANG, Andrew A.
dc.contributor.authorANTOSZYK, Andrew N.
dc.contributor.authorFRANCONE, Anibal Andrés
dc.contributor.authorPRASAD, Anita
dc.contributor.authorWOLF, Armin
dc.contributor.authorKHANANI, Arshad M.
dc.contributor.authorABBEY, Ashkan Michael
dc.contributor.authorMOULANA, Asma
dc.contributor.authorWIHELM, Barbara
dc.contributor.authorSIKORSKI, Bartosz L.
dc.contributor.authorKUPPERMANN, Baruch D.
dc.contributor.authorWOLFF, Benjamin
dc.contributor.authorJEWART, Brian H.
dc.contributor.authorDO, Brian K.
dc.contributor.authorCHAN-KAI, Brian T.
dc.contributor.authorMEIN, Calvin
dc.contributor.authorHOYNG, Carel B.
dc.contributor.authorAWH, Carl C.
dc.contributor.authorREGILLIO, Carl
dc.contributor.authorZEOLITE, Carlos
dc.contributor.authorBAUMAL, Caroline R.
dc.contributor.authorCREUZOT-GARCHER, Catherine
dc.contributor.authorMAURY, Catherine Français
dc.contributor.authorWYKOFF, Charles C.
dc.contributor.authorNEWELL, Charles K.
dc.contributor.authorJHAVERI, Chirag
dc.contributor.authorLOHMANN, Chris P.
dc.contributor.authorDINAH, Christiana B.
dc.contributor.authorMA, Colin
dc.contributor.authorCRAWFORD, Courtney
dc.contributor.authorPARKE, D. Wilkin
dc.contributor.authorLAVINSKY, Daniel
dc.contributor.authorROTH, Daniel
dc.contributor.authorPIERAMICI, Dante J.
dc.contributor.authorMOSHFEGHI, Darius M.
dc.contributor.authorLEVIN, Darrin
dc.contributor.authorSAPERSTEIN, David A.
dc.contributor.authorBROWN, David
dc.contributor.authorGAUCHER, David
dc.contributor.authorLALLY, David R.
dc.contributor.authorLIAO, David S.
dc.contributor.authorBROWN, David Warren
dc.contributor.authorGOLDSTEIN, Debra
dc.contributor.authorMARCUS, Dennis
dc.contributor.authorCHAN, Derek G.
dc.contributor.authorDHOOT, Dilsher
dc.contributor.authorTACITE, Domingo
dc.contributor.authorZALEWSKI, Dominik
dc.contributor.authorESPANA, Edgar M.
dc.contributor.authorLAD, Eleonora M.
dc.contributor.authorSOUIED, Eric H.
dc.contributor.authorSUAN, Eric P.
dc.contributor.authorETING, Eva
dc.contributor.authorSOLA, Federico Furno
dc.contributor.authorDE BATS, Flore
dc.contributor.authorBANDELLO, Francesco
dc.contributor.authorGÓMEZ-ULLA, Francisco
dc.contributor.authorDEVIN, François
dc.contributor.authorHOLZ, Frank G.
dc.contributor.authorCHEN, Fred K.
dc.contributor.authorMAKKOUK, Fuad
dc.contributor.authorDYER, Gawain
dc.contributor.authorSPITAL, George
dc.contributor.authorSTAURENGHI, Giovanni
dc.contributor.authorSTOLLER, Glenn
dc.contributor.authorCOUSINS, Gwen
dc.contributor.authorSALEHI-HAD, Hani
dc.contributor.authorAGOSTINI, Hansjürgen
dc.contributor.authorELEFTHERIADIS, Haralabos
dc.contributor.authorWEISS, Harold
dc.contributor.authorSULTAN, Harris C.
dc.contributor.authorMASSÉ, Hélène
dc.contributor.authorPEARCE, Ian
dc.contributor.authorDIAS, Indra
dc.contributor.authorBARBAZETTO, Irene
dc.contributor.authorROSENBLATT, Irit
dc.contributor.authorSUÑER, Ivan J.
dc.contributor.authorKOVACH, Jaclyn L.
dc.contributor.authorKALUZNY, Jakub
dc.contributor.authorBORTHWICK, James
dc.contributor.authorHOWARD, James G.
dc.contributor.authorWONG, James
dc.contributor.authorERNEST, Jan
dc.contributor.authorNĚMČANSKÝ, Jan
dc.contributor.authorYSASAGA, Jason Edward
dc.contributor.authorHANDZA, Jason M.
dc.contributor.authorMORENO, Javier Antonio Montero
dc.contributor.authorKOROBELNIK, Jean-Francois
dc.contributor.authorHEIER, Jeffrey S.
dc.contributor.authorARNOLD, Jennifer J.
dc.contributor.authorBROWN, Jeremiah
dc.contributor.authorBAFALLUY, Joaquin
dc.contributor.authorPEARLMAN, Joel
dc.contributor.authorPITCHER, John D.
dc.contributor.authorKITCHENS, John
dc.contributor.authorCARLSON, John P.
dc.contributor.authorGILHOTRA, Jolly
dc.contributor.authorFEIN, Jordana
dc.contributor.authorMONÉS, Jordi M.
dc.contributor.authorLUNA, José Domingo
dc.contributor.authorMORENO, José María Ruiz
dc.contributor.authorCONEY, Joseph M.
dc.contributor.authorSALLUM, Juliana Maria Ferraz
dc.contributor.authorOLSEN, Karl R.
dc.contributor.authorBLOBNER, Katharina
dc.contributor.authorMACOUL, Katherine A.
dc.contributor.authorOH, Kean T.
dc.contributor.authorMALIK, Khurram Javed
dc.contributor.authorHATTENBACH, Lars-Olof
dc.contributor.authorKODJIKIAN, Laurent
dc.contributor.authorNETO, Laurentino Biccas
dc.contributor.authorSINGERMAN, Lawrence J.
dc.contributor.authorALTAY, Lebriz
dc.contributor.authorSHECK, Leo- H.
dc.contributor.authorFEINER, Leonard
dc.contributor.authorHARRIS, Lindsey D.
dc.contributor.authorCHISHOLD, Lionel D.
dc.contributor.authorRAO, Llewelyn J.
dc.contributor.authorNEHEMY, Márcio Bittar
dc.contributor.authorELIZALDE, Maria Jose Capella
dc.contributor.authorGAMULESCU, Maria-Andreea
dc.contributor.authorSARAVIA, Mario J.
dc.contributor.authorJOHNSON, Mark W.
dc.contributor.authorMCKIBBIN, Martin
dc.contributor.authorMACCUMBER, Mathew
dc.contributor.authorVIDOSEVICH, Matko
dc.contributor.authorOHR, Matthew P.
dc.contributor.authorSAMUEL, Michael A.
dc.contributor.authorSINGER, Michael A.
dc.contributor.authorCASSELL, Michael
dc.contributor.authorDOLLIN, Michael
dc.contributor.authorELMAN, Michael J.
dc.contributor.authorIP, Michael S.
dc.contributor.authorGOLDSTEIN, Michaella
dc.contributor.authorBUSQUETS, Miguel
dc.contributor.authorMITITELU, Mihai
dc.contributor.authorSHAH, Milan
dc.contributor.authorVEITH, Miroslav
dc.contributor.authorFINEMAN, Mitchell
dc.contributor.authorVARANO, Monica
dc.contributor.authorCHRISTMAS, Nancy
dc.contributor.authorSTEINLE, Nathan C.
dc.contributor.authorCHAUDHRY, Nauman
dc.contributor.authorCHINSKEY, Nicholas D.
dc.contributor.authorETER, Nicole
dc.contributor.authorLONDON, Nikolas J. S.
dc.contributor.authorMATHALONE, Nurit
dc.contributor.authorSCHLOTTMANN, Patricio G.
dc.contributor.authorCOADY, Patrick
dc.contributor.authorHIGGINS, Patrick M.
dc.contributor.authorRASKAUSKAS, Paul A.
dc.contributor.authorYATES, Paul A.
dc.contributor.authorBERNSTEIN, Paul
dc.contributor.authorMITCHELL, Paul
dc.contributor.authorMONSOUR, Paul
dc.contributor.authorRAPHAELIAN, Paul V.
dc.contributor.authorSTANGA, Paulo E.
dc.contributor.authorSTODULKA, Pavel
dc.contributor.authorISSA, Peter Charbel
dc.contributor.authorPAVAN, Peter
dc.contributor.authorFERRONE, Phil J.
dc.contributor.authorOLEKSY, Piotr
dc.contributor.authorABRAHAM, Prema
dc.contributor.authorMRUTHYUNJAYA, Prithvi
dc.contributor.authorNGUYEN, Quan Dong
dc.contributor.authorREDDY, Rahul K.
dc.contributor.authorKHURANA, Rahul N.
dc.contributor.authorTULI, Raman
dc.contributor.authorTADAYONI, Ramin
dc.contributor.authorKATZ, Randy Steven
dc.contributor.authorARORA, Rashi
dc.contributor.authorSCHLINGEMANN, Reinier O.
dc.contributor.authorROSEN, Richard B.
dc.contributor.authorGALE, Richard
dc.contributor.authorSCARTOZZI, Richard
dc.contributor.authorISERNHARGE, Ricky
dc.contributor.authorSINGH, Rishi P.
dc.contributor.authorSTOLTZ, Robert A.
dc.contributor.authorAVERY, Robert L.
dc.contributor.authorWIRTHLIN, Robert S.
dc.contributor.authorGUYMER, Robyn
dc.contributor.authorGOLDBERG, Roger A.
dc.contributor.authorFRENKEL, Ronald
dc.contributor.authorBELFORT, Rubens, Jr.
dc.contributor.authorMOHAND-SAID, Saddek
dc.contributor.authorGRISANTI, Salvatore
dc.contributor.authorRAZAVI, Sam
dc.contributor.authorFRASER-BELL, Samantha
dc.contributor.authorSHAH, Sandeep N.
dc.contributor.authorWICKREMASINGHE, Sanjeewa
dc.contributor.authorHAUG, Sara Joy
dc.contributor.authorADREAN, Sean D.
dc.contributor.authorPRIGLINGER, Siegfried G.
dc.contributor.authorESPOSTI, Simona Degli
dc.contributor.authorGUEST, Stephen
dc.contributor.authorHUDDLESTON, Stephen
dc.contributor.authorITTY, Sujit
dc.contributor.authorMOON, Suk Jin
dc.contributor.authorBHATIA, Sumit P.
dc.contributor.authorGUPTA, Sunil
dc.contributor.authorPATEL, Sunil S.
dc.contributor.authorGARG, Sunir J.
dc.contributor.authorJOSHI, Sunir
dc.contributor.authorNGHIEM-BUFFET, Sylvia
dc.contributor.authorJOHNSON, T. Mark
dc.contributor.authorJAOUNI, Tareq
dc.contributor.authorACH, Thomas
dc.contributor.authorWILLIAMS, Thomas R.
dc.contributor.authorSHEIDOW, Thomas
dc.contributor.authorCLELAND, Timothy P.
dc.contributor.authorYOU, Timothy T.
dc.contributor.authorPETO, Tunde
dc.contributor.authorKONIDARIS, Vasileios
dc.contributor.authorGONZALEZ, Victor H.
dc.contributor.authorKORDA, Vladimir
dc.contributor.authorFREEMAN, William R.
dc.contributor.authorBRIDGES, William Z.
dc.contributor.authorBARAK, Yoreh
dc.contributor.authorZAGORSKI, Zbigniew
dc.contributor.authorYEHOSHUA, Zohar
dc.contributor.authorDUBSKA, Zora
dc.date.accessioned2023-12-11T09:42:35Z
dc.date.available2023-12-11T09:42:35Z
dc.date.issued2023-10-21
dc.identifier.issn1474-547Xen_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/186542
dc.description.abstractEnBACKGROUND: Geographic atrophy is a leading cause of progressive, irreversible vision loss. The objectives of OAKS and DERBY were to assess the efficacy and safety of pegcetacoplan compared with sham treatment in patients with geographic atrophy. METHODS: OAKS and DERBY were two 24-month, multicentre, randomised, double-masked, sham-controlled, phase 3 studies, in which patients aged 60 years and older with geographic atrophy secondary to age-related macular degeneration were enrolled at 110 clinical sites and 122 clinical sites worldwide, respectively. Patients were randomly assigned (2:2:1:1) by central web-based randomisation system to intravitreal 15 mg per 0·1 mL pegcetacoplan monthly or every other month, or sham monthly or every other month using stratified permuted block randomisation (stratified by geographic atrophy lesion area at screening, history or presence of active choroidal neovascularisation in the eye not under assessment, and block size of six). Study site staff, patients, reading centre personnel, evaluating physicians, and the funder were masked to group assignment. Sham groups were pooled for the analyses. The primary endpoint was the change from baseline to month 12 in the total area of geographic atrophy lesions in the study eye based on fundus autofluorescence imaging, in the modified intention-to-treat population (ie, all patients who received one or more injections of pegcetacoplan or sham and had a baseline and at least one post-baseline value of lesion area). Key secondary endpoints (measured at 24 months) were change in monocular maximum reading speed of the study eye, change from baseline in mean functional reading independence index score, change from baseline in normal luminance best-corrected visual acuity score, and change from baseline in the mean threshold sensitivity of all points in the study eye by mesopic microperimetry (OAKS only). Safety analyses included patients who were randomly assigned and received at least one injection of pegcetacoplan or sham. The now completed studies are registered with ClinicalTrials.gov, NCT03525613 (OAKS) and NCT03525600 (DERBY). FINDINGS: Between Aug 30, 2018, and July 3, 2020, 1258 patients were enrolled in OAKS and DERBY. The modified intention-to-treat populations comprised 614 (96%) of 637 patients in OAKS (202 receiving pegcetacoplan monthly, 205 pegcetacoplan every other month, and 207 sham) and 597 (96%) of 621 patients in DERBY (201 receiving pegcetacoplan monthly, 201 pegcetacoplan every other month, and 195 sham). In OAKS, pegcetacoplan monthly and pegcetacoplan every other month significantly slowed geographic atrophy lesion growth by 21% (absolute difference in least-squares mean -0·41 mm(2), 95% CI -0·64 to -0·18; p=0·0004) and 16% (-0·32 mm(2), -0·54 to -0·09; p=0·0055), respectively, compared with sham at 12 months. In DERBY, pegcetacoplan monthly and pegcetacoplan every other month slowed geographic atrophy lesion growth, although it did not reach significance, by 12% (-0·23 mm(2), -0·47 to 0·01; p=0·062) and 11% (-0·21 mm(2), -0·44 to 0·03; p=0·085), respectively, compared with sham at 12 months. At 24 months, pegcetacoplan monthly and pegcetacoplan every other month slowed geographic atrophy lesion growth by 22% (-0·90 mm(2), -1·30 to -0·50; p<0·0001) and 18% (-0·74 mm(2), -1·13 to -0·36; p=0·0002) in OAKS, and by 19% (-0·75 mm(2), -1·15 to -0·34; p=0·0004) and 16% (-0·63 mm(2), -1·05 to -0·22; p=0·0030) in DERBY, respectively, compared with sham. There were no differences in key secondary visual function endpoints at 24 months. Serious ocular treatment-emergent adverse events were reported in five (2%) of 213, four (2%) of 212, and one (<1%) of 211 patients in OAKS, and in four (2%) of 206, two (1%) of 208, and two (1%) of 206 patients in DERBY receiving pegcetacoplan monthly, pegcetacoplan every other month, and sham, respectively, at 24 months. New-onset exudative age-related macular degeneration was reported in 24 (11%), 16 (8%), and four (2%) patients in OAKS, and in 27 (13%), 12 (6%), and nine (4%) patients in DERBY receiving pegcetacoplan monthly, pegcetacoplan every other month, and sham, respectively, at 24 months. INTERPRETATION: Pegcetacoplan, the first treatment approved by the US Food and Drug Administration for geographic atrophy, slowed geographic atrophy lesion growth with an acceptable safety profile. FUNDING: Apellis Pharmaceuticals.
dc.language.isoENen_US
dc.title.enPegcetacoplan for the treatment of geographic atrophy secondary to age-related macular degeneration (OAKS and DERBY): two multicentre, randomised, double-masked, sham-controlled, phase 3 trials
dc.title.alternativeLancet
dc.typeArticle de revueen_US
dc.identifier.doi10.1016/S0140-6736(23)01520-9en_US
dc.subject.halSciences du Vivant [q-bio]/Santé publique et épidémiologieen_US
dc.identifier.pubmed37865470en_US
bordeaux.journalThe Lanceten_US
bordeaux.page1434-1448en_US
bordeaux.volume402en_US
bordeaux.hal.laboratoriesBordeaux Population Health Research Center (BPH) - UMR 1219en_US
bordeaux.issue10411en_US
bordeaux.institutionUniversité de Bordeauxen_US
bordeaux.institutionINSERMen_US
bordeaux.teamLEHA_BPHen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.identifier.funderIDApellis Pharmaceuticalsen_US
hal.popularnonen_US
hal.audienceInternationaleen_US
dc.rights.ccPas de Licence CCen_US
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