{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T16:25:50Z","timestamp":1785860750878,"version":"3.56.0"},"reference-count":18,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:00:00Z","timestamp":1760400000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:00:00Z","timestamp":1760400000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Bepirovirsen, an antisense oligonucleotide in development for the treatment of chronic hepatitis B virus (HBV) infection, is administered from glass vials as a subcutaneous (SC) injection by healthcare professionals (HCPs). A ready\u2010to\u2010use prefilled syringe (PFS) assembled with a safety syringe device (SSD) has been developed to make administration more convenient and facilitate patient self\u2010administration. This Phase 1, open\u2010label, randomized, parallel\u2010group study evaluated the relative bioavailability of bepirovirsen delivered from a vial or PFS SSD, assessed the viability of PFS SSD self\u2010administration, and evaluated the safety and tolerability of SC bepirovirsen in healthy participants. Participants (N = 159) received a single 300 mg SC dose of bepirovirsen administered by a HCP (vial [n = 46] or PFS SSD [n = 49]), or self\u2010administered (PFS SSD, with [n = 32] or without [n = 32] training from a HCP). Relative bioavailability (primary endpoint) of HCP\u2010administered bepirovirsen delivered by vial versus PFS SSD was assessed using maximum observed plasma concentration (C\n                    <jats:sub>max<\/jats:sub>\n                    ) and area under the concentration\u2013time curve from time zero extrapolated to infinity (AUC\n                    <jats:sub>(0\u2010inf)<\/jats:sub>\n                    ). Participants were monitored for adverse events. Bepirovirsen exposure was bioequivalent when HCP\u2010administered either by vial or PFS SSD; the 90% confidence intervals (CIs) for the geometric mean ratios (GMRs) were within the standard bioequivalence reference range, 0.80\u20101.25, for both C\n                    <jats:sub>max<\/jats:sub>\n                    (1.02 [0.91\u20101.14]) and AUC\n                    <jats:sub>(0\u2010inf)<\/jats:sub>\n                    (1.05 [0.96\u20101.15]). Self\u2010administration using PFS SSD achieved bioequivalence for bepirovirsen exposure compared with HCP administration. No new safety concerns were identified. These findings confirm that PFS SSD is a viable alternative to vials for bepirovirsen administration, when HCP\u2010 or self\u2010administered, for the treatment of chronic HBV.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Clinical trial identifier<\/jats:bold>\n                    : NCT06058390\n                  <\/jats:p>","DOI":"10.1002\/cpdd.1615","type":"journal-article","created":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T13:19:51Z","timestamp":1760447991000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Phase 1, Randomized, Open\u2010Label, Parallel Group Study to Evaluate the Relative Bioavailability and Safety of Subcutaneous Bepirovirsen when Delivered from a Vial or Prefilled Syringe Fitted with a Safety Syringe Device in Healthy Adult Participants"],"prefix":"10.1002","volume":"15","author":[{"given":"Amir S.","family":"Youssef","sequence":"first","affiliation":[{"name":"Clinical Pharmacology and Quantitative Medicine GSK  Collegeville Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Poonam","family":"Shah","sequence":"additional","affiliation":[{"name":"Clinical Development GSK  Stevenage UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maxwell","family":"Hu","sequence":"additional","affiliation":[{"name":"Research and Development GSK  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helene","family":"Plein","sequence":"additional","affiliation":[{"name":"Safety Evaluation and Risk Management GSK  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhishek","family":"Roy","sequence":"additional","affiliation":[{"name":"Development Biostatistics GSK  Bangalore India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ravi","family":"Sharma","sequence":"additional","affiliation":[{"name":"Development Biostatistics GSK  Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Mole","sequence":"additional","affiliation":[{"name":"Clinical Development GSK  Stevenage UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Blazejczyk","sequence":"additional","affiliation":[{"name":"Safety Evaluation and Risk Management GSK  Warsaw Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy","family":"Cross","sequence":"additional","affiliation":[{"name":"Medicine Development Industrialisation GSK  Stevenage UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian","family":"Spears","sequence":"additional","affiliation":[{"name":"Clinical Research \u2010 Early Clinical Development PPD  Austin Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel","family":"Pak","sequence":"additional","affiliation":[{"name":"Clinical Research \u2010 Early Clinical Development PPD  Las Vegas Nevada USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rejbinder","family":"Kaur","sequence":"additional","affiliation":[{"name":"Development Global Clinical Operations GSK  Stevenage UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Elston","sequence":"additional","affiliation":[{"name":"Clinical Development GSK  Stevenage UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dickens","family":"Theodore","sequence":"additional","affiliation":[{"name":"Clinical Development GSK  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjan","family":"Hezareh","sequence":"additional","affiliation":[{"name":"Clinical Development GSK  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Nader","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Quantitative Medicine GSK  Collegeville Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,10,14]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-1253(23)00197-8"},{"key":"e_1_2_11_3_1","unstructured":"WHO.Hepatitis B factsheet.Accessed September 30 2025.https:\/\/www.who.int\/news\u2010room\/fact\u2010sheets\/detail\/hepatitis\u2010b."},{"key":"e_1_2_11_4_1","unstructured":"WHO.Global hepatitis report 2024.Accessed September 30 2025.https:\/\/www.who.int\/publications\/i\/item\/9789240091672"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01513-4"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2210027"},{"key":"e_1_2_11_7_1","unstructured":"ClinicalTrials.gov.Study of bepirovirsen in nucleos(t)ide analogue\u2010treated participants with chronic hepatitis B (B\u2010Well 1) (B\u2010Well 1). Accessed September 30 2025.https:\/\/clinicaltrials.gov\/study\/NCT05630807"},{"key":"e_1_2_11_8_1","unstructured":"ClinicalTrials.gov.Study of bepirovirsen in nucleos(t)ide analogue\u2010treated participants with chronic hepatitis B (B\u2010Well 2) (B\u2010Well 2). Accessed September 30 2025.https:\/\/clinicaltrials.gov\/study\/NCT05630820"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2024.08.010"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2023.06.002"},{"key":"e_1_2_11_11_1","unstructured":"LimS AsselahT DiaconescuGI et\u00a0al.Evidence of durable response to bepirovirsen in B\u2010clear on\u2010NA responders: B\u2010sure second report (poster #5047\u2010C). Paper presented at: American Association for the Study of Liver Disease (AASLD) The Liver Meeting; 21\u201324 June 2023;Boston MA."},{"key":"e_1_2_11_12_1","unstructured":"XieQ ArbuneA AtsukawaM et\u00a0al.Evidence of durable response to bepirovirsen in B\u2010clear not\u2010on\u2010NA responders: B\u2010sure second report (poster #5046\u2010C). Paper presented at: American Association for the Study of Liver Disease (AASLD) The Liver Meeting; 21\u201324 June 2023;Boston MA."},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-022-03227-0"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/psrh.12278"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.2147\/DHPS.S290771"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.4103\/2230-973X.93004"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1089\/nat.2017.0693"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40121-024-01066-2"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1586\/14760584.2015.1081067"}],"container-title":["Clinical Pharmacology in Drug Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpdd.1615","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cpdd.1615","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpdd.1615","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T11:39:55Z","timestamp":1772969995000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/cpdd.1615"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,14]]},"references-count":18,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,2]]}},"alternative-id":["10.1002\/cpdd.1615"],"URL":"https:\/\/doi.org\/10.1002\/cpdd.1615","archive":["Portico"],"relation":{},"ISSN":["2160-763X","2160-7648"],"issn-type":[{"value":"2160-763X","type":"print"},{"value":"2160-7648","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,14]]},"assertion":[{"value":"2025-05-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-22","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-10-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e1615"}}