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A PHASE 2 OPEN-LABEL TRIAL OF ANTIBODY UB-421 MONOTHERAPY AS A SUBSTITUTE FOR HAART
Chang-Yi Wang1, Wingwai Wong2, Hung-Chin Tsai3, Yen-Hsu Chen4, Mei-June Liao5, Shugene Lynn6
1United Biomed, Inc, Hauppauge, NY, USA,2Taipei Veterans General Hosp, Taipei, Taiwan,3Kaohsiung Veterans General Hosp, Kaohsiung, Taiwan,4Kaohsiung Med Univ and Hosp, Kaohsiung, Taiwan,5United Biopharma, Inc, Hsinchu, Taiwan,6UBI Asia, Hsinchu, Taiwan
The antiviral activity of UB-421, a monoclonal antibody that binds to CD4 receptor to block HIV-1 entry, was demonstrated in a prior Phase 2a trial of 29 antiretroviral-naïve HIV-1(+) adults in Taiwan (Trial No. NCT01668043); the average (and SD) of maximum viral load (VL) reduction was 2.27 (0.6) and 2.45 (0.46) log10 copies/mL after 8-week monotherapy on 10mg/Kg/weekly or 25mg/Kg/biweekly, respectively.
Efficacy and safety of UB-421 monotherapy was examined in this Phase 2 trial among HAART-stabilized HIV-1(+) Asian adults whose VLs had been recorded as undetectable (< 50 copies/mL) at least twice in the past year (NCT02369146); 14 and 15 such adults interrupted HAART to receive 8 doses of UB-421 infusions on 10mg/Kg/weekly (Arm 1) or 25mg/Kg/biweekly (Arm 2) regimens, respectively, with prompt return to HAART if viral rebound (VR, > 400 copies/mL at 2 consecutive visits). Efficacy was assessed as the percentage of and the time to VR; changes in laboratory parameters were compared to baseline.
Twenty-seven of 29 enrolled subjects completed all 8 doses of UB-421 with no VR during the monotherapy period, which was 8-week for Arm 1 and 16-week for Arm 2. Two subjects in Arm 2 did not complete (1 lost to follow-up, 1 withdrew due to skin rash), but had undetectable VL for all trial visits. At the end of treatment (EOT), 22 subjects resumed HAART and were monitored for 8 weeks with continuous viral suppression. Five subjects (3 in Arm 1 and 2 in Arm 2) refused to resume the scheduled HAART, and viral rebound was detected 35-62 days after the last UB-421 dose; all 5 re-started HAART right after rebound, and their VL were monitored until undetectable. At the end of study for both arms, CD4+ T cell counts remained stable (p>0.17 Wilcoxon signed-rank (WSR) test), while CD8+ T cell counts increased (p<0.05). The 27 completers exhibited significant reductions (interquartile =1.7% - 3.1%) of CD4+ T regulatory cell percentage at EOT (p<0.001 WSR test). In 11 subjects with proviral DNA > 100 copies/106 PBMC at baseline, 10 showed a mean 2.24-fold reduction at EOT. The most common drug-related (possible or probable) adverse event (AE) was mild to moderate skin rash (48.3% of 29 subjects), and no death or drug-related SAE occurred.
No viral rebound occurred during the UB-421 monotherapy period; the regimen was safe and well tolerated. UB-421 warrants further evaluation for an indication as monotherapy for HAART substitution in virally suppressed HIV-1 adults.