10E8.4/iMab Bispecific Antibody in HIV-uninfected and HIV-infected Adults

Summary

Many HIV-infected individuals mount a broad neutralizing serologic response 2-3 years after infection. Broadly neutralizing antibodies might play an important role in protection from acquisition of HIV infection because they can protect macaques from infection, and the presence of anti-HIV antibodies was the only positive correlate of protection in an HIV vaccine efficacy trial (RV144 trial). HIV neutralizing antibodies also have the potential to alter the course of HIV infection in humans. Therefore, these antibodies might be useful to both prevent and treat HIV-1 infection. This is a phase 1 dose escalating clinical trial to evaluate the safety, tolerability, pharmacokinetics and the antiretroviral effects of a novel bispecific monoclonal antibody 10E8.4/iMab in HIV-infected and HIV-uninfected individuals. The study will be conducted as a multi-center study at the Columbia University Medical Center in New York City and the Orlando Immunology Center in Orlando, Florida.

Timeline

Start

2019-04-08

Primary completion

2022-03-23

Completion

2022-03-23

Outcome

Met primary endpoint

paper The primary objective of the study to evaluate the safety/tolerability of 10E8.4/iMab was met. PMID 42414619 ↗

Publications

• Background Hraber P, Seaman MS, Bailer RT, Mascola JR, Montefiori DC, Korber BT. Prevalence of broadly neutralizing antibody responses during chronic HIV-1 infection. AIDS. 2014 Jan 14;28(2):163-9. doi: 10.1097/QAD.0000000000000106.
• Background Haynes BF, Gilbert PB, McElrath MJ, Zolla-Pazner S, Tomaras GD, Alam SM, Evans DT, Montefiori DC, Karnasuta C, Sutthent R, Liao HX, DeVico AL, Lewis GK, Williams C, Pinter A, Fong Y, Janes H, DeCamp A, Huang Y, Rao M, Billings E, Karasavvas N, Robb ML, Ngauy V, de Souza MS, Paris R, Ferrari G, Bailer RT, Soderberg KA, Andrews C, Berman PW, Frahm N, De Rosa SC, Alpert MD, Yates NL, Shen X, Koup RA, Pitisuttithum P, Kaewkungwal J, Nitayaphan S, Rerks-Ngarm S, Michael NL, Kim JH. Immune-correlates analysis of an HIV-1 vaccine efficacy trial. N Engl J Med. 2012 Apr 5;366(14):1275-86. doi: 10.1056/NEJMoa1113425.
• Weiner JA, Banks LA, Natarajan H, Lin S, Sami S, Kovacikova G, Carpenter MC, Ackerman ME. Drawing a line in the sand: impact of analytical choices on anti-drug antibody cut-points and testing outcomes. Bioanalysis. 2026 Jul 14:1-12. doi: 10.1080/17576180.2026.2698615. Online ahead of print.
• Theodore DA, Mayer BT, Rolle CP, DeJesus E, Ackerman ME, Seaman MS, Weiner JA, Mohri H, Huang Y, Gray B, Chang J, Gerber MW, Yu J, Luo Y, Padte NN, Yin MT, Barin B, Greene R, Palmer S, Pazmino A, Benitez J, Dorr C, McNairy M, DiRenzo J, Orzell CV, Ho DD, Hyrien O, Sobieszczyk ME. Bispecific 10E8.4/iMab broadly neutralizing antibody in people with or without HIV-1: a partially randomized phase 1 trial. Nat Med. 2026 Jul 7. doi: 10.1038/s41591-026-04472-w. Online ahead of print.

Drugs

Indications