First in Human Study of TLC-ART 101 (ACTU 2001)

Summary

This study is a prospective, open-label, single-site, first-in-human study of a long-acting, injectable combination antiretroviral therapy platform, with a pharmacologically-guided adaptive design for dose escalation, de-escalation, and study duration. The study is designed to learn whether the formulation can be used as a platform for other drugs for treatment of HIV. The formulation is a drug combination nanoparticle (DCNP). The study will be conducted by UW Positive Research. The sample size for this study is 12-16. The study population consists of healthy adults without HIV. The study duration is 57 days per participant at the start of the study.

Timeline

Start

2023-04-01

Primary completion

2024-06-28

Completion

2024-06-28

Publications

• Background Freeling JP, Koehn J, Shu C, Sun J, Ho RJ. Anti-HIV drug-combination nanoparticles enhance plasma drug exposure duration as well as triple-drug combination levels in cells within lymph nodes and blood in primates. AIDS Res Hum Retroviruses. 2015 Jan;31(1):107-14. doi: 10.1089/aid.2014.0210.
• Background McConnachie LA, Kinman LM, Koehn J, Kraft JC, Lane S, Lee W, Collier AC, Ho RJY. Long-Acting Profile of 4 Drugs in 1 Anti-HIV Nanosuspension in Nonhuman Primates for 5 Weeks After a Single Subcutaneous Injection. J Pharm Sci. 2018 Jul;107(7):1787-1790. doi: 10.1016/j.xphs.2018.03.005. Epub 2018 Mar 13.
• Background Kraft JC, McConnachie LA, Koehn J, Kinman L, Collins C, Shen DD, Collier AC, Ho RJ. Long-acting combination anti-HIV drug suspension enhances and sustains higher drug levels in lymph node cells than in blood cells and plasma. AIDS. 2017 Mar 27;31(6):765-770. doi: 10.1097/QAD.0000000000001405.
• Background Kraft JC, Treuting PM, Ho RJY. Indocyanine green nanoparticles undergo selective lymphatic uptake, distribution and retention and enable detailed mapping of lymph vessels, nodes and abnormalities. J Drug Target. 2018 Jun-Jul;26(5-6):494-504. doi: 10.1080/1061186X.2018.1433681. Epub 2018 Feb 12.
• Background Perazzolo S, Shireman LM, McConnachie LA, Koehn J, Kinman L, Lee W, Lane S, Collier AC, Shen DD, Ho RJY. Integration of Computational and Experimental Approaches to Elucidate Mechanisms of First-Pass Lymphatic Drug Sequestration and Long-Acting Pharmacokinetics of the Injectable Triple-HIV Drug Combination TLC-ART 101. J Pharm Sci. 2020 May;109(5):1789-1801. doi: 10.1016/j.xphs.2020.01.016. Epub 2020 Jan 29.
• Background Perazzolo S, Shireman LM, Shen DD, Ho RJY. Physiologically Based Pharmacokinetic Modeling of 3 HIV Drugs in Combination and the Role of Lymphatic System after Subcutaneous Dosing. Part 1: Model for the Free-Drug Mixture. J Pharm Sci. 2022 Feb;111(2):529-541. doi: 10.1016/j.xphs.2021.10.007. Epub 2021 Oct 19.
• Background Perazzolo S, Shen DD, Ho RJY. Physiologically Based Pharmacokinetic Modeling of 3 HIV Drugs in Combination and the Role of Lymphatic System after Subcutaneous Dosing. Part 2: Model for the Drug-combination Nanoparticles. J Pharm Sci. 2022 Mar;111(3):825-837. doi: 10.1016/j.xphs.2021.10.009. Epub 2021 Oct 19.

Drugs

Indications