10th Conference on Retroviruses and Opportunistic Infections


Boston, MA USA - February 10 -14, 2003

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Safety and Preliminary Anti-HIV Activity of an Anti-CD4 mAb (TNX-355; Formerly Hu5A8) in HIV-infected Patients.

Conf Retroviruses Opportunistic Infect 2003 Feb 10-14;10th: abstract no. 13
D. R. Kuritzkes1, J. M. Jacobson2, W. Powderly3, E. Godofsky4, E. DeJesus5, F. Haas6, K. A. Reimann7, P. Yarbough8, V. R. Curt8, W. R. Shanahan8
1Brigham and Women's Hosp, Boston, MA; 2Beth Israel Med Ctr, New York, NY; 3Washington Univ in St Louis, MO; 4Bach and Godofsky, Bradenton, FL; 5Infectious Disease Clin Res Initiative, Altamonte Springs, FL; 6Assoc in Med and Mental Hlth, Tulsa, OK; 7Beth Israel Deaconess Med Ctr, Boston, MA; and 8Tanox, Inc, Houston, TX

Background: TNX-355, a humanized IgG4 anti-CD4 domain 2 mAb, has potent anti-HIV-1 activity in vitro. In vivo studies in rhesus macaques and in vitro studies with human peripheral blood lymphocytes show that TNX-355 is not immunosuppressive. This study was performed to determine the safety and preliminary anti-HIV activity of a single dose of TNX-355 in HIV-infected subjects.

Study design: 5 Five (5) sequential cohorts of six 6 HIV-1-infected subjects received single IV doses of TNX-355 in an open-label dose-escalation study (0.3, 1, 3, 10, and 25 mg/kg). Eligible patients (pts) had stable viral load (VL) ≥5,000 copies/mL, CD4 count ≥100/mm3, and stable or no ARV therapy for ≥2 months (mos) prior to dosing. Data collected included change in VL, CD4 count, % coating of CD4+ cells, and serum TNX-355 levels.

Results: Mean baseline CD4 count (354 cells/mm3) and VL (5.1 log10 copies/mL) were similar across treatment groups. All patients were HAART-experienced and 19/30 were on failing HAART at entry. Mean peak decreases in VL of 0.2, 0.68, 1.48, and 1.09 log10, occurred on days 2, 4, 14, and 21 for the 1, 3, 10, and 25 mg/kg dose cohorts, respectively. Duration of complete CD4 cell coating with TNX-355, ranging from 1-2 days at 1 mg/kg to 15-27 days at 25 mg/kg, correlated with day of VL nadir. TNX-355 was well tolerated. No SAEs were reported. CD4 cell depletion was not observed in any cohort.

COHORT CD4+
CELL COATING
WITH TNX-355		 VIRAL LOAD
Dose Level Duration of
Complete Coating		 Cohort Nadir
Achieved on		 Mean Change
from Baseline to
Cohort Nadir
(Range)		 No. of Patients
Achieving > 1.0 log10 Decrease
from Baseline
(Range)
1.0 mg/kg 1-2 days Day 2 -0.2 log10
(+0.4 to -0.68)		 0 of 6
(+0.16 to -0.68)
3.0 mg/kg 3-4 days Day 4 -0.68 log10
(-0.23 to -1.20)		 2 of 6
(-0.23 to -1.20)
10.0 mg/kg 8-13 days Day 14 -1.48 log10
(-0.98 to -2.10)		 5 of 6
(-0.98 to -2.10)
25.0 mg/kg 15-27 days Day 21 -1.09 log10
(+0.26 to -2.33)		 5 of 6
(-0.90 to -2.33)

Conclusion: Single doses of the novel entry inhibitor TNX-355 were well tolerated and acutely reduced viral load in HIV-1-infected patients. Further assessment of therapeutic potential awaits data from longer duration trials; a phase 1b multiple-dose study is planned.

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Copyright © 2003 - Foundation for Retrovirology and Human Health. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed (AIDSLINE) from National Library of Medicine.