First-In-Human Clinical Study of the C3 Complement Inhibitor AMY- 101 in Healthy Male Volunteers

Summary

Safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of a Single Ascending Dose (SAD) and a Multiple Dose (MD) of the complement inhibitor AMY-101. A prospective, single-center, open-label, First-In-Human (FIH) clinical study in healthy male volunteers.

Timeline

Start

2017-04-24

Primary completion

2017-11-30

Completion

2017-11-30

Publications

• Background Ricklin D, Lambris JD. Complement in immune and inflammatory disorders: therapeutic interventions. J Immunol. 2013 Apr 15;190(8):3839-47. doi: 10.4049/jimmunol.1203200.
• Background Ricklin D, Lambris JD. Complement in immune and inflammatory disorders: pathophysiological mechanisms. J Immunol. 2013 Apr 15;190(8):3831-8. doi: 10.4049/jimmunol.1203487.
• Background Mastellos DC, Yancopoulou D, Kokkinos P, Huber-Lang M, Hajishengallis G, Biglarnia AR, Lupu F, Nilsson B, Risitano AM, Ricklin D, Lambris JD. Compstatin: a C3-targeted complement inhibitor reaching its prime for bedside intervention. Eur J Clin Invest. 2015 Apr;45(4):423-40. doi: 10.1111/eci.12419. Epub 2015 Mar 9.
• Background Ricklin D, Lambris JD. Therapeutic control of complement activation at the level of the central component C3. Immunobiology. 2016 Jun;221(6):740-6. doi: 10.1016/j.imbio.2015.06.012. Epub 2015 Jun 10.
• Background Reis ES, Mastellos DC, Yancopoulou D, Risitano AM, Ricklin D, Lambris JD. Applying complement therapeutics to rare diseases. Clin Immunol. 2015 Dec;161(2):225-40. doi: 10.1016/j.clim.2015.08.009. Epub 2015 Sep 1.
• Background Mastellos DC, Ricklin D, Hajishengallis E, Hajishengallis G, Lambris JD. Complement therapeutics in inflammatory diseases: promising drug candidates for C3-targeted intervention. Mol Oral Microbiol. 2016 Feb;31(1):3-17. doi: 10.1111/omi.12129. Epub 2015 Oct 7.
• Background Reis ES, DeAngelis RA, Chen H, Resuello RR, Ricklin D, Lambris JD. Therapeutic C3 inhibitor Cp40 abrogates complement activation induced by modern hemodialysis filters. Immunobiology. 2015 Apr;220(4):476-82. doi: 10.1016/j.imbio.2014.10.026. Epub 2014 Nov 3.
• Background Mastellos DC, Ricklin D, Yancopoulou D, Risitano A, Lambris JD. Complement in paroxysmal nocturnal hemoglobinuria: exploiting our current knowledge to improve the treatment landscape. Expert Rev Hematol. 2014 Oct;7(5):583-98. doi: 10.1586/17474086.2014.953926. Epub 2014 Sep 2.
• Background Risitano AM, Ricklin D, Huang Y, Reis ES, Chen H, Ricci P, Lin Z, Pascariello C, Raia M, Sica M, Del Vecchio L, Pane F, Lupu F, Notaro R, Resuello RR, DeAngelis RA, Lambris JD. Peptide inhibitors of C3 activation as a novel strategy of complement inhibition for the treatment of paroxysmal nocturnal hemoglobinuria. Blood. 2014 Mar 27;123(13):2094-101. doi: 10.1182/blood-2013-11-536573. Epub 2014 Feb 4.
• Background Mastellos DC, Reis ES, Yancopoulou D, Hajishengallis G, Ricklin D, Lambris JD. From orphan drugs to adopted therapies: Advancing C3-targeted intervention to the clinical stage. Immunobiology. 2016 Oct;221(10):1046-57. doi: 10.1016/j.imbio.2016.06.013. Epub 2016 Jun 16.
• Background Maekawa T, Briones RA, Resuello RR, Tuplano JV, Hajishengallis E, Kajikawa T, Koutsogiannaki S, Garcia CA, Ricklin D, Lambris JD, Hajishengallis G. Inhibition of pre-existing natural periodontitis in non-human primates by a locally administered peptide inhibitor of complement C3. J Clin Periodontol. 2016 Mar;43(3):238-49. doi: 10.1111/jcpe.12507. Epub 2016 Mar 3.
• Background Hajishengallis G, Maekawa T, Abe T, Hajishengallis E, Lambris JD. Complement Involvement in Periodontitis: Molecular Mechanisms and Rational Therapeutic Approaches. Adv Exp Med Biol. 2015;865:57-74. doi: 10.1007/978-3-319-18603-0_4.
• Background Hajishengallis G, Hajishengallis E, Kajikawa T, Wang B, Yancopoulou D, Ricklin D, Lambris JD. Complement inhibition in pre-clinical models of periodontitis and prospects for clinical application. Semin Immunol. 2016 Jun;28(3):285-91. doi: 10.1016/j.smim.2016.03.006. Epub 2016 Mar 24.
• Background Zhang Y, Shao D, Ricklin D, Hilkin BM, Nester CM, Lambris JD, Smith RJ. Compstatin analog Cp40 inhibits complement dysregulation in vitro in C3 glomerulopathy. Immunobiology. 2015 Aug;220(8):993-8. doi: 10.1016/j.imbio.2015.04.001. Epub 2015 May 5.
• Background Mastellos DC, Reis ES, Ricklin D, Smith RJ, Lambris JD. Complement C3-Targeted Therapy: Replacing Long-Held Assertions with Evidence-Based Discovery. Trends Immunol. 2017 Jun;38(6):383-394. doi: 10.1016/j.it.2017.03.003. Epub 2017 Apr 14.
• Hajishengallis G, Hasturk H, Lambris JD; Contributing authors. C3-targeted therapy in periodontal disease: moving closer to the clinic. Trends Immunol. 2021 Oct;42(10):856-864. doi: 10.1016/j.it.2021.08.001. Epub 2021 Sep 2.

Drugs

Indications

No indication recorded.