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IRIS
Background: Sparsentan is a novel, non-immunosuppressive, single-molecule, dual endothelin and angiotensin receptor antagonist being examined in an ongoing phase 3 trial in adults with IgA nephropathy. We report the prespecified interim analysis of the primary proteinuria efficacy endpoint, and safety. Methods: PROTECT is an international, randomised, double-blind, active-controlled study, being conducted in 134 clinical practice sites in 18 countries. The study examines sparsentan versus irbesartan in adults (aged ≥18 years) with biopsy-proven IgA nephropathy and proteinuria of 1·0 g/day or higher despite maximised renin-angiotensin system inhibitor treatment for at least 12 weeks. Participants were randomly assigned in a 1:1 ratio to receive sparsentan 400 mg once daily or irbesartan 300 mg once daily, stratified by estimated glomerular filtration rate at screening (30 to <60 mL/min per 1·73 m2 and ≥60 mL/min per 1·73 m2) and urine protein excretion at screening (≤1·75 g/day and >1·75 g/day). The primary efficacy endpoint was change from baseline to week 36 in urine protein-creatinine ratio based on a 24-h urine sample, assessed using mixed model repeated measures. Treatment-emergent adverse events (TEAEs) were safety endpoints. All endpoints were examined in all participants who received at least one dose of randomised treatment. The study is ongoing and is registered with ClinicalTrials.gov, NCT03762850. Findings: Between Dec 20, 2018, and May 26, 2021, 404 participants were randomly assigned to sparsentan (n=202) or irbesartan (n=202) and received treatment. At week 36, the geometric least squares mean percent change from baseline in urine protein-creatinine ratio was statistically significantly greater in the sparsentan group (-49·8%) than the irbesartan group (-15·1%), resulting in a between-group relative reduction of 41% (least squares mean ratio=0·59; 95% CI 0·51-0·69; p<0·0001). TEAEs with sparsentan were similar to irbesartan. There were no cases of severe oedema, heart failure, hepatotoxicity, or oedema-related discontinuations. Bodyweight changes from baseline were not different between the sparsentan and irbesartan groups. Interpretation: Once-daily treatment with sparsentan produced meaningful reduction in proteinuria compared with irbesartan in adults with IgA nephropathy. Safety of sparsentan was similar to irbesartan. Future analyses after completion of the 2-year double-blind period will show whether these beneficial effects translate into a long-term nephroprotective potential of sparsentan. Funding: Travere Therapeutics.
Sparsentan in patients with IgA nephropathy: a prespecified interim analysis from a randomised, double-blind, active-controlled clinical trial
Heerspink H. J. L.;Radhakrishnan J.;Alpers C. E.;Barratt J.;Bieler S.;Diva U.;Inrig J.;Komers R.;Mercer A.;Noronha I. L.;Rheault M. N.;Rote W.;Rovin B.;Trachtman H.;Trimarchi H.;Wong M. G.;Perkovic V.;Alarmartine E.;Chae D. W.;Del Vecchio L.;Floege J.;Hwang S. -J.;Jelakovic B.;Maes B.;Malecki R.;Miglinas M.;Nolasco F. E. B.;Praga M.;Rabindranath K.;Rosenberg M.;Tang S. C. W.;Tesar V.;Bose B.;Gangadharan M.;McDonald S.;Peh C.;Jahan S.;Yeap C.;Clayton P.;Irish G.;Thyagarajan N.;Hollett P.;Krishnasamy R.;Carroll R.;Jesudason S.;Crail S.;Coates T.;Waugh J.;Noble E.;Mahadevan K.;Campbell V.;Salehi T.;Lim W.;Boudville N.;Chakera A.;Chan D.;Krishnan A.;Eqbal Y.;Gillies A.;Vilayur E.;Maung Myint T. M.;Gray N.;Cheetham M.;Pollock C.;Cooper B.;Mather A.;Roxburgh S.;Shen Y.;Stangenberg S.;Siriwardana A.;O'Lone E.;Wan S.;Neuen B.;Tsun Kit Ha J.;Kim D.;Heath L.;Jain A.;Phua E.;Li Y.;Gallagher M.;Jardine M.;Ritchie A.;Razavian M.;Foote C.;Wyndham R.;Sen S.;Endre Z.;Erlich J.;Fernando M.;Yong K.;Luxton G.;Kotwal S.;Roger S.;Wijeratne V.;Packham D.;Fraser I.;Vandewiele B.;Laute M.;Lemahieu W.;Jamar S.;Ombelet S.;Meeus G.;Decupere M.;Schockaert O.;Doubel P.;Viaene L.;Radermacher L.;Masset C.;Moonen M.;Firre E.;Milicevic M.;Warling X.;Vanacker A.;Malfait T.;Durlen I.;Horvatic I.;Savuk A.;Gellineo L.;Karanovic S.;Dika Z.;Plavljanic D.;Mikacic I.;Trajbar Kentric D.;Barisic D.;Stankovic M.;Majstorovic Barac K.;Kruljac I.;Pavlovic D.;Drinkovic M.;Prkacin I.;Barbic J.;Sitas Z.;Vujcic D.;Rychlik I.;Benesova A.;Drinovska K.;Kratka K.;Maixnerova D.;Ilmoja M.;Unt K.;Lilienthal K.;Auerbach A.;Leis L.;Piel J.;Adoberg A.;Kolvald K.;Veermae K.;Telling K.;Seppet E.;Uhlinova J.;Zaoui P.;Carron P. -L.;Masson I.;Dinic M.;Thibaudin D.;Broyet C.;Maillard N.;Mohey H.;Mariat C.;Claisse G.;Alamartine E.;Dussol B.;Burtey S.;Chiche-Jourde N.;Serre J. -E.;Jeantet G.;Chenine L.;Blanchard A.;Roueff S.;Thervet E.;Fouassier D.;Buffet A.;Livrozet M.;Gaisset R.;Karras A.;Heng A. -E.;Garrouste C.;Philipponnet C.;Nicolo C.;Atenza A.;Lanaret C.;Greze C.;Mayet V.;Dumond C.;Delmas Y.;Combe C.;Rigothier C.;Burguet L.;Labat A.;Mucha S.;de Precigout V.;Weinreich T.;Reichel H.;Draganova D.;Wolf L.;Hohenstein B.;Heinrichs S.;Kulka S.;Sat S.;Weiland L.;Krueger T.;Wolf G.;Kettner C.;Schlosser M.;Herfurth J. K.;Koch A.;Busch M.;Werth S. C.;Nitschke M.;Cakiroglu F.;Sarnow F.;Schulz L.;Weiner S.;Wirtz N.;Koester E.;Moeller M.;Stamellou E.;Sanden S.;Schmidt-Guertler H.;Bernhardt W.;Patecki M.;Schlieper G.;Schulte K.;Girardet A.;Kunzendorf U.;Kwan L. P. Y.;Mok M. M. Y.;Chan G. C. W.;Ma M.;Lie D. N. W.;Chan A. T. P.;Szeto C. C.;Ng K. C. J.;Cheung S. F.;Yue T. T. A.;Fung K. S. S.;Tang H.;Yim K. F.;Law W. P.;Wong Y. H.;Lam C. K. D.;Wong S. H. S.;Marcantoni C.;Aliotta R.;Deodato F.;Patella G.;Comi N.;Vita C.;Carullo N.;Bolignano D.;Musolino M.;Trillini M.;Perico N.;Remuzzi G.;Daina E.;Biancone L.;Colla L.;Burdese M.;Cogno C.;Boaglio E.;Abbasciano I.;Zizzi C. F.;Randone P.;Napodano P.;Ricchiuto A.;Cassia M.;Accarino S.;Cozzolino M.;Baccaro R.;Costanzi S.;Di Maio F.;Arena M.;Urciuolo F.;Vigano S.;Cavalli A.;Limardo M.;Bordoli M.;Ponti S.;Longhi S.;Solazzo A.;Giaroni F.;Donati G.;Torreggiani M.;Catucci D.;Colucci M.;Esposito V.;Esposito C.;Gesualdo L.;Capaccio F.;Diletta Stea E.;Sivo C.;Annese F.;Papadia F.;Messa P.;Belingheri M.;Passerini P.;Malvica S.;Vickiene A.;Zakauskiene U.;Asakiene E.;Bumblyte' I. A.;Stankuviene A.;Santockiene L.;Hayat A.;Williams A.;Sizeland P.;Tan E.;Waters G.;Chan L. W.;Henderson A.;Turnbull A.;McNally A.;Reynolds A.;Pilmore H.;Dittmer I.;Manley P.;Stallworthy E.;Goh T.;Semple D.;Collins M.;Curry E.;Ahmed J.;Nguyen T.;Winiarska A.;Zbrzezniak J.;Stompor T.;Krajewska M.;Augustyniak-Bartosik H.;Zielinska D.;Jander A.;Stanczyk M.;Tkaczyk M.;Miarka P.;Aksamit D.;Jaskowski P.;Sulowicz W.;Cieniawski D.;Gontarek-Kacprzak J.;Felicjanczuk E.;Kwella N.;Kwella B.;Satora E.;Fernandes J. C.;Gomes A. M.;Reis M.;Lopes D.;Almeida C.;Sa H.;Figueiredo A. C.;Pardinhas C.;Almeida E.;Raimundo M.;Cortesao Costa A.;Falcao Goncalves L. P.;Fernandes S.;Silva S.;Teixeira C.;Fernandes A.;Nolasco F.;Alves P.;Gois M.;Fonseca N.;Messias A.;Menezes M.;Cardoso F.;Sousa H.;Marques J.;Barata R.;Lopes J. A.;Jorge S.;Gameiro J.;de Almeida Agapito Fonseca J. N.;Goncalves S.;Farinha A.;Valerio Santos P.;Natario A.;de Jesus Barreto J. C.;Abrantes C.;Quadrado Soares E. S.;Soares Felgueiras J. D. S.;Cunha L.;Parreira L.;Furtado T.;Vaz A.;Oh K. -H.;Lee H.;Joong Kim S.;Jeong J. C.;Hoon Kim Y.;Kim Y.;Park H. C.;Choi H. Y.;Wook Kim H.;Lee M. H.;Yoon S.;Lee K. -B.;Hyun Y.;Yoo T. -H.;Han S. H.;Park J. T.;Kim S.;Song Y. R.;Kim J. -K.;Lee H. -S.;Joo N.;Lee J.;Ryoun Jang H.;Jeon J.;Chung W.;Lee H.;Chang J. H.;Chun K. Y.;Jung J. Y.;Ro H.;Kim A.;Jo S. -K.;Yang J.;Kim M. -G.;Oh S.;Martinez Villanueva C.;Gimeno A. V.;Andres Useche Bonilla G.;Tamarit E.;Galan Serrano A.;Verde Moreno E.;Fernandez J. L.;Goicoechea Diezhandino M. A.;Verdalles Guzman U.;de Jose A. P.;Ortiz Arduan A.;Perez Gomez M. V.;Martin Cleary C.;Prado R. F.;Goma E.;Ballarin J.;Encarnacion M. D.;Da Silva Santos I.;Marco Rusinol H.;Furlano M.;Arias C.;Barrios C.;Garcia E. R.;Sierra Ochoa A.;Vizcaino Castillo B.;Pantoja Perez J.;Gonzalez Moya M.;Sargsyan M.;Calatayud Aristoy E.;Bernabeu A. A.;Perez Lluna L.;Malek Marin T.;Antonia Munar Vila M.;Bobadilla Rico I. M.;Allende Burgos N.;Gutierrez Martinez E.;Gutierrez Solis E.;Sevillano A.;Merida Herrero E.;Miquel Blasco Pelicano J.;Rodas Marin L. M.;Quintana L. F.;Antonieta Azancot Rivero M.;Ramos Terrades N.;Garcia Carro C.;Agraz Pamplona I.;Salgueira Lazo M.;de la Prada Alvarez F.;Alonso Garcia F.;Adrian Aguilera Morales W.;Virxinia Pol Heres S.;Forcen A.;Parra Moncasi E.;Medrano Villarroya C.;Soria Villen A.;Gracia Garcia O.;Velo Plaza M.;Sanchez de la Nieta M. D.;Calvo Arevalo M.;Moreno A.;Cigarran Guldris S.;de Vicente M. P.;Munar Vila M. A.;Hsu B. -G.;Wang C. -H.;Chen C. -H.;Yu T. -M.;Wu M. -J.;Tsai S. -F.;Hsu C. -T.;Chiu H. -F.;Chou K. -J.;Fang H. -C.;Lee P. -T.;Chen H. -Y.;Chen C. -L.;Huang C. -W.;Ou S. -H.;Ho T. -Y.;Hsu C. -Y.;Chang M. -S.;Chiu Y. -L.;Peng Y. -S.;Shu K. -H.;Pan S. -Y.;Hsu S. -P.;Yang J. -Y.;Pai M. -F.;Tseng P. -Y.;Wu H. -Y.;Tsai W. -C.;Tung K. -T.;Chen H. -Y.;Chen H. -C.;Kuo M. -C.;Hwang D. -Y.;Chiu Y. -W.;Hung C. -C.;Kuo H. -T.;Tsai J. -C.;McCafferty K.;Forbes S.;Dasgupta I.;Thomas M.;Mahdi A.;Ajayi B.;Chowdhury P.;Kasimatis T.;Moutzouris D.;Dudreuilh C.;Pruthi R.;Mansfield N.;Doctor G.;Shah S.;Kon S.;Smith P.;Hamilton P.;Kanigicherla D.;Ibrahim Ragy O. S.;Alchi B.;Flossmann O.;Ghalli F.;Lawman S.;Sinha S.;Chrysochou C.;Chukwu C.;Maire De Bhailis A.;Al Chalabi S.;Hudson A.;Gopu A.;Wickens O.;Storrar J.;Wahba M.;Lorde N.;Rony M.;Griffin S.;Latif F.;Ali M.;DaSilva L.;Ayling-Smith J.;Mahdi E.;Willcocks L.;Jones R.;Cheung C. K.;Selvaskandan H.;Pugh D.;Sayer M.;Dhaun N.;Chapman F.;Mark P.;Geddes C.;McQuarrie E.;Patel R.;Solomon L.;Ponnusamy A.;Morris A.;Okoh P.;Floyd L.;Dhaygude A.;Leung J.;Goldsmith C.;Pandya B.;Tez D.;Mikhail A.;Brown K.;Bucknall T.;Lambie M.;Comunale R.;Brandon D.;Martinez S.;Hall A.;Henderson A.;Fearday A.;Douthit N.;Snow B.;Silva A.;Sly C.;Keller C.;Davidson R.;Meng J.;Haws R.;Kattamanchi S.;Mojarrab J.;Pillai U.;Lafayette R.;O'Shaughnessy M.;Kamal F.;Mehta K.;Baker B.;Ruiz M.;Jyothinagaram P.;Peri U.;Paxton W.;Tumlin J.;McGreal K.;McCarthy E.;Kimber C.;Gautam A.;Khalil K.;Nguyen V.;Minasian R.;Arfaania D.;Daneshvari S.;Zakari M.;Patrikyan A.;Afsari R.;Ayvazyan C.;Fakih F.;Lagatta M.;Rodriguez A.;Avella J. E. M.;Patak R.;Kadakia J.;Appel G.;Ahn W.;Nelson B.;Medina A.;Ahmad S.;Peleg Y.;Clement N.;Chiu I.;Hendren E.;Bomback A.;Canetta P.;Spinowitz B.;Charytan C.;Parikh N.;Kuo S.;Raichoudhury R.;Dobre M.;Negrea L.;Padiyar A.;Jittirat A.;Pradhan N.;Dhelaria R.;Balamuthusamy S.;Madhrira M.;Powell T.;Lifland H.;Bailey A.;Ford Sightler S. A.;Suthar M. P.;Green H.;Parikh S.;Ayoub I.;Almaani S.;Contreras G.;Fornoni A.;Drexler Y.;Geara A.;Sheridan B.;Coppock G.;Hogan J.;Gonzalez C.;Bhadra S.;Chowdhury P.;Kyaw K.;Tan M.;Raakesh L.;Mendoza E.;Viramontes V.;Chaudhry A.;Carbonell J.;Gadh R.;Fernandez V.;Kassem M.;Jacob R.;Wilder K.;Newsome B.;Klamm K.;Suyumova I.;Kooienga L. A.;Janko C.;Rizk D.;Julian B.;Caster D.;Perez E.;Garg G.;Gowda N.;Udani S.;Mandayam S.;Workeneh B.;Assefi A.;Greco B.;Germain M.;Patel J.;Quinn S.;Sullivan J.;Glaze J.;Madonia P.;McMahon K.;Giles H.;Adler S.;Dai T.
2023-01-01
Abstract
Background: Sparsentan is a novel, non-immunosuppressive, single-molecule, dual endothelin and angiotensin receptor antagonist being examined in an ongoing phase 3 trial in adults with IgA nephropathy. We report the prespecified interim analysis of the primary proteinuria efficacy endpoint, and safety. Methods: PROTECT is an international, randomised, double-blind, active-controlled study, being conducted in 134 clinical practice sites in 18 countries. The study examines sparsentan versus irbesartan in adults (aged ≥18 years) with biopsy-proven IgA nephropathy and proteinuria of 1·0 g/day or higher despite maximised renin-angiotensin system inhibitor treatment for at least 12 weeks. Participants were randomly assigned in a 1:1 ratio to receive sparsentan 400 mg once daily or irbesartan 300 mg once daily, stratified by estimated glomerular filtration rate at screening (30 to <60 mL/min per 1·73 m2 and ≥60 mL/min per 1·73 m2) and urine protein excretion at screening (≤1·75 g/day and >1·75 g/day). The primary efficacy endpoint was change from baseline to week 36 in urine protein-creatinine ratio based on a 24-h urine sample, assessed using mixed model repeated measures. Treatment-emergent adverse events (TEAEs) were safety endpoints. All endpoints were examined in all participants who received at least one dose of randomised treatment. The study is ongoing and is registered with ClinicalTrials.gov, NCT03762850. Findings: Between Dec 20, 2018, and May 26, 2021, 404 participants were randomly assigned to sparsentan (n=202) or irbesartan (n=202) and received treatment. At week 36, the geometric least squares mean percent change from baseline in urine protein-creatinine ratio was statistically significantly greater in the sparsentan group (-49·8%) than the irbesartan group (-15·1%), resulting in a between-group relative reduction of 41% (least squares mean ratio=0·59; 95% CI 0·51-0·69; p<0·0001). TEAEs with sparsentan were similar to irbesartan. There were no cases of severe oedema, heart failure, hepatotoxicity, or oedema-related discontinuations. Bodyweight changes from baseline were not different between the sparsentan and irbesartan groups. Interpretation: Once-daily treatment with sparsentan produced meaningful reduction in proteinuria compared with irbesartan in adults with IgA nephropathy. Safety of sparsentan was similar to irbesartan. Future analyses after completion of the 2-year double-blind period will show whether these beneficial effects translate into a long-term nephroprotective potential of sparsentan. Funding: Travere Therapeutics.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11571/1479026
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simulazione ASN
Il report seguente simula gli indicatori relativi alla propria produzione scientifica in relazione alle soglie ASN 2023-2025 del proprio SC/SSD. Si ricorda che il superamento dei valori soglia (almeno 2 su 3) è requisito necessario ma non sufficiente al conseguimento dell'abilitazione. La simulazione si basa sui dati IRIS e sugli indicatori bibliometrici alla data indicata e non tiene conto di eventuali periodi di congedo obbligatorio, che in sede di domanda ASN danno diritto a incrementi percentuali dei valori. La simulazione può differire dall'esito di un’eventuale domanda ASN sia per errori di catalogazione e/o dati mancanti in IRIS, sia per la variabilità dei dati bibliometrici nel tempo. Si consideri che Anvur calcola i valori degli indicatori all'ultima data utile per la presentazione delle domande.
La presente simulazione è stata realizzata sulla base delle specifiche raccolte sul tavolo ER del Focus Group IRIS coordinato dall’Università di Modena e Reggio Emilia e delle regole riportate nel DM 589/2018 e allegata Tabella A. Cineca, l’Università di Modena e Reggio Emilia e il Focus Group IRIS non si assumono alcuna responsabilità in merito all’uso che il diretto interessato o terzi faranno della simulazione. Si specifica inoltre che la simulazione contiene calcoli effettuati con dati e algoritmi di pubblico dominio e deve quindi essere considerata come un mero ausilio al calcolo svolgibile manualmente o con strumenti equivalenti.
