CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

437 PRO140 SINGLE-AGENT MAINTENANCE THERAPY FOR HIV-1 INFECTION: A 2-YEAR UPDATE Jay Lalezari 1 , Kush Dhody 2 , Ula Kowalczyk 1 , Kazem Kazempour 2 , Nader Pourhassan 3 , Paul J. Maddon 4

1 Quest Clinical Rsr, San Francisco, CA, USA, 2 Amarex Clinical Rsr, LLC, Germantown, MD, USA, 3 CytoDyn Inc., Vancouver, WA, USA, 4 Maddon Advisors LLC, Scarsdale, NY, USA Background: PRO140 is a humanized CCR5 mAb with potent antiviral activity of ≥1.65 log10 mean viral load (VL) reduction as a weekly subcutaneous injection (SC) in patients infected with only CCR5-tropic HIV-1. This open-label, single-arm phase 2b extension study evaluated long-term suppression of HIV-1 replication by PRO140 SC monotherapy (MT) following initial antiretroviral therapy (ART). Methods: 42 adult patients on ART and infected with only CCR5-tropic HIV-1 (11-cohort 1, 28-cohort 2, 3-cohort 3) with VL <40 c/mL (LabCorp) were switched to weekly PRO140 350 mg SC MT. Following maintenance of viral suppression for 13 weeks, 17 subjects in cohort 2 and 3 were trained to self-administer PRO140 SC and offered continuation of MT in an ongoing extension study. Results: 16 eligible subjects (87.5%male, 19% non-white) with median age of 54.9 years (26-68) and median CD4 T-cell count of 593 cells/mm3 (365-1059) were enrolled. One patient discontinued at week 47 (with VL <40 c/mL) due to relocation and 5 subjects experienced virologic failure (VF) (2 consecutive VL ≥400 c/mL). The mean time to VF was 329 days (106-691). 10 subjects are currently on PRO140 SC MT of which 9 subjects have completed nearly 2 years of treatment (93–106 weeks). 7 patients reported single-copy HIV-1 RNA values of <1 c/mL; 3 subjects reported values of 4, 10, and 19 c/mL (bioMONTR Labs). Prior to study entry, all subjects were infected with only CCR5-tropic HIV-1 by Trofile® DNA Co-receptor Tropism Assay (LabCorp). Co-receptor tropismwas reassessed at VF by Trofile® RNA Assay and no change was reported. PhenoSense® Entry (LabCorp) results for PRO140, maraviroc, and AMD3100 showed no significant change in post-treatment IC50, IC90 and fold change values compared with baseline results in VF and non-VF group of subjects. Anti-PRO140 antibodies were not detected in any subject. PRO140 was generally well tolerated with no drug-related major adverse events or treatment discontinuation reported. Conclusion: In this phase 2b extension study, patients infected with only CCR5-tropic HIV-1 and virologically suppressed on ART were switched to weekly self-administered PRO140 350 mg SC MT. For nearly 2 years, PRO140 SC MT provided maximal virologic suppression, was well tolerated, and enabled the avoidance of potential toxicity of ART while preserving drug options. These results support further development of PRO140 SC as a simple, long-acting, single-agent maintenance therapy after initial ART in selected HIV-1 infected patients. 438 INTRAMUSCULAR IBALIZUMAB: PHARMACOKINETICS, SAFETY, AND EFFICACY VS IV ADMINISTRATION Hsi-Hsun Lin 1 , Susan Shin-Jung Lee 2 , Ning-Chi Wang 3 , YingAn Lai 4 , Kuei-Ling Kuo 4 , Steven Weinheimer 5 , Stanley Lewis 5 1 E-Da Hosp, Kaohsiung City, Taiwan, 2 Kaohsiung Veterans General Hosp, Kaohsiung, Taiwan, 3 Tri-Service General Hosp, Taipei City, Taiwan, 4 TaiMed Biologics, Taipei City, Taiwan, 5 TaiMed Biologics USA, Irvine, CA, USA Background: Ibalizumab (IBA) is a humanized monoclonal antibody that binds to a conformational epitope on the domain 2 region of human CD4 receptors thereby blocking entry of HIV into CD4 lymphocytes. It is a long-acting HIV entry inhibitor currently in Phase 3 development for the treatment of multi-drug resistant (MDR) HIV infection via intravenous (IV) administration. In this ongoing adaptive design study, we aimed to investigate the pharmacokinetics (PK), safety, antiretroviral activity, and pharmacodynamics (PD) of intramuscular (IM) administration of different doses of IBA. This report presents results of the 800 mg IM dose group as it offers the most direct comparison to the previous IV administration trial in patients with MDR HIV. Methods: A Phase 1/2, randomized study of IBA injection was conducted, which enrolled HIV positive patients with HIV-1 RNA ≥5000 copies/mL who have not received antiretroviral (ARV) treatment for the preceding year. Injections of 800 mg IBA were administrated intramuscularly every two weeks with no other ARVs on three occasions. Results: All eight patients enrolled in the 800 mg dose group were males with a mean age of 28 years. At Baseline (BL), mean viral load (VL) was 55,000 copies/mL and mean CD4+T cell count was 314 cells/µL. Starting ~3 days post-injection, after serum concentrations peaked, the PK profile of 800 mg IM IBA was comparable to that of IV IBA infusions (from study TMB-202, Figure 1). The terminal half-life (T1/2) was 0.86 day and distribution T1/2 was 3.47 days. The mean trough concentration was 5-14 µg/mL and the mean CD4 receptor occupancy (RO) was greater than 80% during the dosing period. The mean maximum VL reduction was 1.23 log10 at Day 7 following the first administration, followed by a return toward BL at the end of dosing. After three doses, CD4+ T cell counts were 51% higher than Baseline, on average. No serious adverse events or discontinuations were reported during the study period. No injection site reactions were reported. Conclusion: The PK profile of biweekly 800 mg IBA administered IM was comparable to the IV PK profile from a previous study. IBA at 800 mg was safe, well tolerated, and produced clinically significant viral load reductions at Day 7 as monotherapy.

Poster and Themed Discussion Abstracts

CROI 2017 182