Conditions: HIV
Keywords: HIV CD4 experienced resistant resistance monoclonal antibody infusion ibalizumab TNX355 TNX-355 TMB355 TMB-355
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 113
Healthy volunteers: no

Brief summary:
The investigational product, ibalizumab, is a humanized IgG4 monoclonal antibody administered via intravenous infusion at 800 mg every 2 weeks or at 2000 mg every 4 weeks. In addition to study drug, all patients will receive an optimized background regimen (OBR), which is a standard-of-care regimen selected by the investigator prior to randomization that is comprised of 2-4 antiretroviral agents. These agents must have been approved by the local regulatory agency or be available through expanded-access programs for treatment of human immunodeficiency virus (HIV).

Detailed description:
The primary objectives of this study are to:

* Evaluate the dose-response relationship of antiviral activity of the ibalizumab dose regimens at Week 24 in order to determine the optimal dose and regimen. The primary evaluation of effectiveness will be based on the proportion of patients achieving undetectable viral loads at Week 24.
* Evaluate the safety and tolerability of two dose regimens of ibalizumab for dose selection

The secondary objectives of this study are to:

* Evaluate changes from Baseline in viral load, CD4+ cell counts, and time to loss of virologic response (TLOVR)
* Characterize HIV-1 sensitivity/susceptibility changes associated with ibalizumab administration in combination with OBR
* Determine the presence and significance of anti-ibalizumab antibodies, if any (immunogenicity of ibalizumab)
* Assess CD4 receptor density and occupancy
* Determine the impact of ibalizumab on quality of life as assessed by patient-reported outcomes on questionnaires
* Evaluate the pharmacokinetic profile of two dose regimens of ibalizumab at steady state

Arms:
arm 1: every 2 weeks, combined with an Optimized Background Regimen arm 2: every 4 weeks, combined with an Optimized Background Regimen

Interventions: intervention 1: Ibalizumab intervention 2: Ibalizumab
Intervention descriptions: intervention 1: Ibalizumab 800 mg IV every 2 weeks intervention 2: Ibalizumab 2000 mg IV every 4 weeks

Protocol document: