A Study of AL-034 to Evaluate the Safety, Tolerability and Pharmacokinetics of Single and Multiple Doses in Healthy Participants

Summary

This is a Phase 1 first-in-human (FIH) study evaluating single and multiple dose administration of AL-034 in healthy adult participants. The aim is to examine the safety (including pharmacodynamic \[PD\] biomarker assessments), tolerability, and pharmacokinetics (PK) of increasing single ascending doses (SADs) (Part 1) and multiple ascending doses (MADs) (Part 2) of AL-034. The potential food effect will be investigated in healthy adult participants at one or optionally 2 single dose level(s).

Timeline

Start

2017-09-07

Primary completion

2018-11-14

Completion

2018-11-14

Publications

• Background Bazett HC. An analysis of the time-relationship of electrocardiograms. Heart. 1920; 7:353 380.
• Background Di Bisceglie AM. Hepatitis B and hepatocellular carcinoma. Hepatology. 2009 May;49(5 Suppl):S56-60. doi: 10.1002/hep.22962.
• Background Chang TT, Gish RG, de Man R, Gadano A, Sollano J, Chao YC, Lok AS, Han KH, Goodman Z, Zhu J, Cross A, DeHertogh D, Wilber R, Colonno R, Apelian D; BEHoLD AI463022 Study Group. A comparison of entecavir and lamivudine for HBeAg-positive chronic hepatitis B. N Engl J Med. 2006 Mar 9;354(10):1001-10. doi: 10.1056/NEJMoa051285.
• Background Cohen C, Holmberg SD, McMahon BJ, Block JM, Brosgart CL, Gish RG, London WT, Block TM. Is chronic hepatitis B being undertreated in the United States? J Viral Hepat. 2011 Jun;18(6):377-83. doi: 10.1111/j.1365-2893.2010.01401.x. Epub 2010 Dec 8.
• Background European Association For The Study Of The Liver. EASL clinical practice guidelines: Management of chronic hepatitis B virus infection. J Hepatol. 2012 Jul;57(1):167-85. doi: 10.1016/j.jhep.2012.02.010. Epub 2012 Mar 20. No abstract available.
• Background Fridericia LS. Die Systolendauer im Elektrokardiogramm bei normalen Menschen und bei Herzkranken. Acta Med Scand 1920; 53: 469-486
• Background Investigator's Brochure: JNJ 64794964 (AL-034). Edition 1. Janssen Research & Development (May 2017).
• Background Lai CL, Shouval D, Lok AS, Chang TT, Cheinquer H, Goodman Z, DeHertogh D, Wilber R, Zink RC, Cross A, Colonno R, Fernandes L; BEHoLD AI463027 Study Group. Entecavir versus lamivudine for patients with HBeAg-negative chronic hepatitis B. N Engl J Med. 2006 Mar 9;354(10):1011-20. doi: 10.1056/NEJMoa051287.
• Background Liang TJ. Hepatitis B: the virus and disease. Hepatology. 2009 May;49(5 Suppl):S13-21. doi: 10.1002/hep.22881.
• Background Lok AS, McMahon BJ, Brown RS Jr, Wong JB, Ahmed AT, Farah W, Almasri J, Alahdab F, Benkhadra K, Mouchli MA, Singh S, Mohamed EA, Abu Dabrh AM, Prokop LJ, Wang Z, Murad MH, Mohammed K. Antiviral therapy for chronic hepatitis B viral infection in adults: A systematic review and meta-analysis. Hepatology. 2016 Jan;63(1):284-306. doi: 10.1002/hep.28280. Epub 2015 Nov 13.
• Background Lucifora J, Protzer U. Attacking hepatitis B virus cccDNA--The holy grail to hepatitis B cure. J Hepatol. 2016 Apr;64(1 Suppl):S41-S48. doi: 10.1016/j.jhep.2016.02.009.
• Background Marcellin P, Lau GK, Bonino F, Farci P, Hadziyannis S, Jin R, Lu ZM, Piratvisuth T, Germanidis G, Yurdaydin C, Diago M, Gurel S, Lai MY, Button P, Pluck N; Peginterferon Alfa-2a HBeAg-Negative Chronic Hepatitis B Study Group. Peginterferon alfa-2a alone, lamivudine alone, and the two in combination in patients with HBeAg-negative chronic hepatitis B. N Engl J Med. 2004 Sep 16;351(12):1206-17. doi: 10.1056/NEJMoa040431.
• Background Phyo WW, Soh AY, Lim SG, Lee GH. Search for a cure for chronic hepatitis B infection: How close are we? World J Hepatol. 2015 May 28;7(9):1272-81. doi: 10.4254/wjh.v7.i9.1272.
• Background Poggio ED, Wang X, Greene T, Van Lente F, Hall PM. Performance of the modification of diet in renal disease and Cockcroft-Gault equations in the estimation of GFR in health and in chronic kidney disease. J Am Soc Nephrol. 2005 Feb;16(2):459-66. doi: 10.1681/ASN.2004060447. Epub 2004 Dec 22.
• Background Schweitzer A, Horn J, Mikolajczyk RT, Krause G, Ott JJ. Estimations of worldwide prevalence of chronic hepatitis B virus infection: a systematic review of data published between 1965 and 2013. Lancet. 2015 Oct 17;386(10003):1546-55. doi: 10.1016/S0140-6736(15)61412-X. Epub 2015 Jul 28.
• Background Williamson DF. Descriptive epidemiology of body weight and weight change in U.S. adults. Ann Intern Med. 1993 Oct 1;119(7 Pt 2):646-9. doi: 10.7326/0003-4819-119-7_part_2-199310011-00004.
• Background World Health Organization (WHO). Hepatitis B Fact Sheet. Available at: http://www.who.int/mediacentre/factsheets/fs204/en/. Accessed 31 January 2017

Drugs

Indications