Agarwal, K

Ahn, S H

Brainard, D

Chen, C-H

Chen, C-Y

Chuang, W-L

Coffin, C S

Elkhashab, M

Flaherty, J F

Fournier, C

Gaggar, A

Gane, E

Heo, J

Huang, Y-H

Hui, A J

Jafri, Syed-Mohammed

Janssen, H L.A.

Lampertico, P

Lim, Y-S

Reggiani, G M

Suri, V

Tan, S

Tsang, T Y.O.

Zhao, Y

English

Henry Ford Health System Scholarly Commons

Henry Ford Health Henry Ford Health Scholarly Commons Gastroenterology Meeting Abstracts Gastroenterology 7-1-2021 Switching from tenofovir disoproxil fumarate and/or other oral antivirals to tenofovir alafenamide in virally suppressed CHB patients with moderate or severe renal impairment or ESRD on HD: final week 96 efficacy and safety results from a phase 2 study H L.A. Janssen P Lampertico C-H Chen J Heo C Fournier See next page for additional authors Follow this and additional works at: https://scholarlycommons.henryford.com/gastroenterology_mtgabstracts Recommended Citation Janssen HLA, Lampertico P, Chen C-H, Heo J, Fournier C, Ahn SH, Tsang TYO, Coffin CS, Huang Y-H, Reggiani GM, Hui AJ, Elkhashab M, Chen C-Y, Jafri S-M, Tan S, Zhao Y, Suri V, Flaherty JF, Gaggar A, Brainard D, Chuang W-L, Agarwal K, Gane E, and Lim Y-S. Switching from tenofovir disoproxil fumarate and/or other oral antivirals to tenofovir alafenamide in virally suppressed CHB patients with moderate or severe renal impairment or ESRD on HD: final week 96 efficacy and safety results from a phase 2 study. J Hepatol 2021; 75:S756-S757. This Conference Proceeding is brought to you for free and open access by the Gastroenterology at Henry Ford Health Scholarly Commons. It has been accepted for inclusion in Gastroenterology Meeting Abstracts by an authorized administrator of Henry Ford Health Scholarly Commons. Authors H L.A. Janssen, P Lampertico, C-H Chen, J Heo, C Fournier, S H. Ahn, T Y.O. Tsang, C S. Coffin, Y-H Huang, G M. Reggiani, A J. Hui, M Elkhashab, C-Y Chen, Syed-Mohammed Jafri, S Tan, Y Zhao, V Suri, J F. Flaherty, A Gaggar, D Brainard, W-L Chuang, K Agarwal, E Gane, and Y-S Lim This conference proceeding is available at Henry Ford Health Scholarly Commons: https://scholarlycommons.henryford.com/gastroenterology_mtgabstracts/122 [eGFRCG], serum creatinine) parameters, viral suppression, andserological and biochemical responses were serially assessed.Results: Of 31 patients enrolled, mean agewas 55 y (29% ≥60 y), 68%male, 81% Asian, and 90% HBeAg-negative; median (Q1, Q3) CTP andMELD scores were 6 (5, 8) and 10 (7.5, 14.2), respectively, medianeGFRCG 98.5 ml/min; 19% had osteoporosis on spine DXA. Twenty-five (81%) patients completed 96 weeks of TAF treatment (6discontinued early: 2-withdrew consent, 1-adverse event [AE;Grade 2 creatinine increase], 1-investigator decision, and 2-death[respiratory failure and aspiration pneumonia-both not treatment-related]). Week 96 efficacy/safety results are summarized in theTable. 96% of patients on TAF treatment had HBV DNA <20 IU/ml witha high proportion having normal ALT levels. Bone and renalparameters remained stable. TAF was well tolerated with no patientshaving a Grade 3 or 4 AE or a serious AE related to treatment.Conclusion: At 2 years, CHB patients with hepatic impairment whowere switched to TAF maintained high rates of viral suppression andnormal ALT values while bone and renal parameters remained stable.PO-2395Switching from tenofovir disoproxil fumarate and/or other oralantivirals to tenofovir alafenamide in virally suppressed CHBpatients with moderate or severe renal impairment or ESRD onHD: final week 96 efficacy and safety results from a phase 2 studyHarry LA Janssen1, Pietro Lampertico2, Chien-Hung Chen3,Jeong Heo4, Claire Fournier5, Sang Hoon Ahn6, Tak Yin Owen Tsang7,Carla S. Coffin8, Yi-Hsiang Huang9, Giulio Marchesini Reggiani10,Aric Josun Hui11, Magdy Elkhashab12, Chi-Yi Chen13,Syed-Mohammed Jafri14, Susanna Tan15, Yang Zhao15, Vithika Suri15,John F. Flaherty15, Anuj Gaggar15, Diana Brainard15,Wan-Long Chuang16, Kosh Agarwal17, Edward Gane18,Young-Suk Lim19. 1Erasmus Universiteit Rotterdam, Rotterdam,Netherlands; 2University of Milan, Milan, Italy; 3National TaiwanUniversity Hospital, Taipei City, Taiwan; 4Pusan National UniversitySchool of Medicine, Korea, Rep. of South; 5Service d’Hépatologie, CHUM,Canada; 6Yonsei University College of Medicine, Seoul, Korea, Rep. ofSouth; 7Chinese University of Hong Kong, Central Ave, Hong Kong;8University of Calgary; 9Taipei Veterans General Hospital, Taipei, Taiwan;10University of Bologna, Italy; 11Alice Ho Miu Ling Nethersole Hospital,Hong Kong; 12Toronto Liver Centre, Canada; 13Chia-Yi Christian Hospital,Taiwan; 14Henry Ford Health System, United States; 15Gilead SciencesInc., Foster City, United States; 16Kaohsiung Medical University Hospital,KaohsiungMedical University, Taiwan; 17Institute of Liver Studies, King’sCollege Hospital, United Kingdom; 18University of Auckland, NewZealand; 19Asan Medical Center, University of Ulsan College of Medicine,Korea, Rep. of SouthEmail: vithika.suri@gilead.comBackground and aims: We have previously shown in renallyimpaired (RI) chronic hepatitis B (CHB) patients, including thosewith end-stage renal disease (ESRD) on hemodialysis (HD), thatswitching to tenofovir alafenamide (TAF) from tenofovir disoproxilfumarate (TDF) and/or other oral antivirals (OAVs) maintains highrates of viral suppression with stable bone and renal safetyparameters at Week 48. Here we present the final Week 96 results.Method: In this Phase 2 study (NCT03180619), virally suppressedCHB patients (HBV DNA <LLOQ × ≥ 6 months and <20 IU/ml atscreening) with moderate or severe RI or with ESRD on HD atscreeningwhile receiving TDFand/or other OAVs for≥ 48weekswereenrolled and switched to TAF 25 mg QD for 96 weeks. Safetyassessments including adverse events (AEs) and changes in bone(hip and spine BMD) and renal (creatinine clearance by Cockcroft-Gault [eGFRCG], serum phosphorus, and serum creatinine -except inESRD patients) parameters, viral suppression, and serological andbiochemical responses were serially assessed.Results: Of 93 patients (mod-severe RI 78; ESRD on HD 15) enrolled,most (74%) were male and Asian (77%), with 51% ≥65 y, 83% HBeAg-negative, 34% with cirrhosis, and median ALT 17 U/L. Up to 24% hadosteoporosis at hip and/or spine, with most having comorbidities(HTN 60%, CV disease 22%, DM 25%). Twelve (13%; 11 mod-severe RIand 1 ESRD) patients discontinued the study early (5-withdrewconsent, 3-deaths [none treatment-related], 2-AE, and 2-investigatordecision). Key efficacy/safety results at Week 96 are summarized inthe Table. Viral suppression (HBV DNA<20IU/ml) was maintained inall patients remaining on treatment (i.e. missing equals excluded); aPOSTER PRESENTATIONSS756 Journal of Hepatology 2021 vol. 75(2) | S294–S803Downloaded for Anonymous User (n/a) at Henry Ford Hospital / Henry Ford Health System (CS North America) from ClinicalKey.com by Elsevier on August 25, 2021. For personal use only. No other uses without permission. Copyright ©2021. Elsevier Inc. All rights reserved.high proportion had target not detected. Overall, TAF was welltolerated with no Grade 3 or 4 AEs or serious AEs related to studytreatment. Relative to baseline levels, switching to TAF resulted insmallmedian % increases in hip/spine BMD in thosewithmoderate tosevere RI, and small median decreases in ESRD patients. 2 patientswith mod-severe RI had a bone fracture (ankle, rib). Median eGFRCGincreased while urinary markers of proximal tubular functionprogressively decreased in moderate to severe RI patients.Conclusion: Renally-impaired CHB patients, including ESRD patientson HD, who were switched to TAF from TDF and/or other OAVsmaintained high rates of viral suppression, and bone and renalparameters remained stable or slightly improved after 2 years oftreatment.PO-2422Safety, efficacy, and pharmacodynamic (PD) activity of 12 weekstreatment with oral RIG-I agonist, inarigivir (IRIG), plus 48 weeksof tenofovir alafenamide in adult patients with chronic hepatitisB: a phase 2 collaboration studyYoung-Suk Lim1, Aric J. Hui2, Jeong-Won Jang3, Won-Young Tak4,Sang Hoon Ahn5, Byoung Kuk Jang6, Tak Yin Owen Tsang7, Won Kim8,Jenny Yang9, Diana Chen9, Circe McDonald9, Liao Zhang9,Anuj Gaggar9, Bing Gao9, Kwan Soo Byun10, Kwan Sik Lee11,Hyung Joon Yim12, Henry L.Y. Chan13. 1Asan Medical Center, Universityof Ulsan College of Medicine Seoul-Korea, Seoul, Korea, Rep. of South;2Alice Ho Miu Ling Nethersole Hospital, Hong Kong; 3The CatholicUniversity of Korea, Seoul St. Mary’s Hospital, Korea, Rep. of South;4Kyungpook National University Hospital, Kyungpook NationalUniversity School of Medicine, Korea, Rep. of South; 5Yonsei UniversityCollege of Medicine, Korea, Rep. of South; 6Keimyung University DongSang Hospital, Korea, Rep. of South; 7Princess Margaret Hospital, HongKong; 8Seoul Metropolitan Government-Seoul National UniversityBoramae Medical Center, Korea, Rep. of South; 9Gilead Sciences Inc.,Foster City, United States; 10Korea University College of Medicine, KoreaUniversity Guro Hospital, Korea, Rep. of South; 11Gangnam SeveranceHospital, Yonsei University College of Medicine, Korea, Rep. of South;12Korea University Ansan Hospital, Ansan-si, Gyeonggi-do-Korea, Korea,Rep. of South; 13Prince of Wales Hospital, Hong KongEmail: jenny.yang@gilead.comBackground and aims: IRIG, RIG-I agonist, has demonstrated anti-viral activity in CHB patients. The MOA of IRIG suggests a directantiviral and an immune modulatory pathway. This study evaluatedsafety, efficacy, and PD activity of IRIG ≤400 mg ± TAF in CHB pts.Method: IACHB pts were enrolled into 4 cohorts: 48WK TAF alone orTAF+IRIG 50, 200, and 400 mg QD for 12WK; and virally suppressed(VS) cohort of 12WK IRIG 100 mg. Safety included AEs and lababnormalities. Primary obj: %pts with HBsAg ≥-0.5 log10 IU/ml atWK12. Secondary obj: change from BL in immune PD biomarkers.Final WK48 data and immunological characterization of 400 mgcohort to be presented.Results: 102 IA and 21 VS Asian CHB pts enrolled. Table shows BL andmean change at WK12 of viral markers. More TAF and IRIG 50 mg ptsat BL had GT C (≥75%), higher HBV DNA and ALT vs IRIG 200 mg and400 mg. No difference at WK12 in HBV DNA decline observed; TAFand IRIG 50 mg had numerically greater decline in HBsAg vs IRIG≥200 mg. In VS pts, no change in HBsAg with IRIG 100 mg observed.PrelimWK12 safety showed, no G4 AEs; 3 IRIG and 1 TAF pts had G3AEs. Majority of IRIG 400 mg pts had slight increase in ALT at WK16(mean (SD) change in ALT = 9 (65) U/L); similar trends were notobserved at lower doses. AEs reported by 41% (46/111) IRIG and 58%(7/12) TAF pts. Frequent (>1 pt) AE related to study drug were: ALTincrease (n = 5), constipation, dizziness, and headache (n = 2 each) allin IRIG pts. PD analysis demonstrates minimal changes to ISGexpression with IRIG 50 mg and 200 mg. Peripheral cytokine andHBV-specific Tcell responsewas similar between TAFand IRIG 50 mg.Conclusion:No dose dependent changes in HBV DNA or HBsAg wereobserved with IRIG ≤400 mg+NUC. IRIG was generally safe and welltolerated at doses ≤400 mg for 12WK. IRIG development has beendiscontinued due to IRIG-related hepatoxicity.Table: (abstract: PO-2422):TAF (N = 12)IRIG 50 mg (N =30)IRIG 200 mg(N = 30)IRIG 400 mg(N = 30)IRIG 100 mgVS Patients(N = 21)HBVDNA,meanlog10 IU/ml(range)7.1 (3.9–8.8) 7.1 (3.8–9.4) 6.3 (3.5–8.8) 6.6 (3.7–9.2) <1.3HBsAg, meanlog10 IU/ml(range)4.1 (2.8–4.8) 3.9 (2.2–5.1) 3.4 (1.9–4.9) 3.5 (1.5–5.1) 3.2 (2.1–4.2)ALT, mean U/ml(range)163 (48–630) 104 (31–439) 74 (25–154) 73 (26–461) 23 (8–52)Mean WK12Change (range)HBV DNA, log10IU/ml−4.2 (−6.4, −2.6) −4.2 (−6.4, −2.3) −4.0(−5.5, −1.7)−3.9 (−6.1,−2.4)N/AHBsAg, log10IU/ml−0.44 (−1.62,0.02)−0.24 (−0.96,0.08)0.02 (−0.46,1.02)−0.03(−0.86, 1.06)−0.02 (−0.12,0.06)ALT, U/L −117 (−611, 13) −57 (−403, 160) −38 (−135,46)−12 (−196,47)7 (−5, 50)PO-2429Safety and efficacy of oral TLR8 agonist, selgantolimod, in viremicadult patients with chronic hepatitis BHarry L.A. Janssen1, Young-Suk Lim2, Hyung Joon Kim3,Cheng-Hao Tseng4, Carla S. Coffin5, Magdy Elkashab6,Sang Hoon Ahn7, Anh-Hoa Nguyen8, Diana Chen8, Jeffrey Wallin8,Susanna Tan8, Jenny Yang8, Anuj Gaggar8, Diana Brainard8,Scott Fung1, Yoon Jun Kim9, Jia-Horng Kao10, Wan-Long Chuang11,Anna Brooks12,13, P. Rod Dunbar12,13. 1Toronto Centre for Liver Disease,Toronto General Hospital Research Institute, University Health Network,Canada; 2Asan Medical Center, University of Ulsan College of Medicine,Korea, Rep. of South; 3Chung-Ang University College of Medicine, Korea,Rep. of South; 4E-Da Hospital, Taiwan; 5University of Calgary, CummingSchool of Medicine, Canada; 6Toronto Liver Centre, Canada; 7YonseiUniversity College of Medicine, Korea, Rep. of South; 8Gilead SciencesInc., Foster City, United States; 9Seoul National University Hospital,Department of Internal Medicine and Liver Research Institute, Korea,Rep. of South; 10National Taiwan University Hospital, Taiwan;11Kaohsiung Medical University Hospital, Taiwan; 12School of BiologicalSciences, University of Auckland, Aukland, New Zealand; 13MauriceWilkins Centre Auckland, University of Auckland, Aukland, New ZealandEmail: harry.janssen@uhn.caBackground and aims: Selgantolimod (GS-9688, SLGN) is an oral,Toll-like receptor 8 agonist in clinical development for the treatmentof chronic hepatitis B (CHB). Here we present the results throughweek 48 on the safety and efficacy of 24 weeks of SLGN treatment inviremic CHB patients.Method: In this multicenter, double-blind, phase 2 study, viremicCHB patients were randomized (2:2:1) to SLGN 3 mg, 1.5 mg, andplacebo (PBO) once a week for 24 weeks in combination withtenofovir alafenamide. Safety assessments included monitoring oftreatment emergent adverse events (TEAE) and laboratory abnor-malities. The primary efficacy end point was the proportion ofpatients with ≥1 log10IU/ml decline in HBsAg levels from baseline atweek 24. Exploratory end points include changes in pharmacody-namic (PD) markers (e.g. IL-12p40 and IL-1RA) and changes inperipheral T- cell, myeloid and NK-cell subsets.Results: 67 patients (39 HBeAg-positive) were randomized. Baselinecharacteristics were similar across groups: majority were Asian(98.5%), male (58%) with a median (IQR) age of 47 (35–54) years,HBsAg level of 4.1 (3.5–4.7) log10IU/ml, andHBVDNA level of 7.5 (5.4–8.3) log10IU/ml. No patients achieved the primary end point of ≥1log10IU/ml decline in HBsAg levels at week 24; however, 3 (6%)patients in the SLGN-treated achieved HBsAg decline ≥0.5 log10IU/mlcompared to none in the placebo group. At week 48, 4 (7.4%) patientsPOSTER PRESENTATIONSS757Journal of Hepatology 2021 vol. 75(2) | S294–S803Downloaded for Anonymous User (n/a) at Henry Ford Hospital / Henry Ford Health System (CS North America) from ClinicalKey.com by Elsevier on August 25, 2021. For personal use only. No other uses without permission. Copyright ©2021. Elsevier Inc. All rights reserved.

Switching from tenofovir disoproxil fumarate and/or other oral antivirals to tenofovir alafenamide in virally suppressed CHB patients with moderate or severe renal impairment or ESRD on HD: final week 96 efficacy and safety results from a phase 2 study

https://scholarlycommons.henryford.com/cgi/viewcontent.cgi?article=1125&context=gastroenterology_mtgabstracts

Switching from tenofovir disoproxil fumarate and/or other oral antivirals to tenofovir alafenamide in virally suppressed CHB patients with moderate or severe renal impairment or ESRD on HD: final week 96 efficacy and safety results from a phase 2 study

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