Multi-Drug Resistant HIV-1

The primary objective of this study is to:  Demonstrate the antiviral activity of ibalizumab at Day 14 and at Week 25/ End of Study (EOS) The secondary objectives of this study are to:  Assess the safety and tolerability of ibalizumab through Week 25/EOS  Assess the mean change from Baseline/Day 7 in CD4+ cell count at Week 25/EOS  Characterize human immunodeficiency virus type-1 (HIV-1) sensitivity/susceptibility changes associated with protocol-defined virologic failure after 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

ibalizumab

ibalizumab

vial

1.33ml/vial (150mg/ml)

Primary effectiveness variable:
 Proportion of patients achieving a ≥ 0.5 log10 decrease from
Day 7/Baseline in viral load at Day 14
Secondary effectiveness variables:
 Proportion of patients with HIV-1 RNA levels <50 copies/mL
and <400 copies/mL at Week 25/EOS
 Mean change from Day 7/Baseline in viral load at Day 14 and
Week 25/EOS
 Proportion of patients achieving a ≥ 0.5 log10 and ≥1.0 log10
decrease from Day 7/Baseline in viral load at Week 25/EOS
 Safety and tolerability of ibalizumab
 Mean change from Day 7/Baseline in CD4+ cell count at Week
25/EOS
 HIV-1 sensitivity/susceptibility changes associated with virologic
failure after administration of ibalizumab
 CD4 receptor density and occupancy

Patients must meet all of the following criteria to be included in the
study:
1. Are capable of understanding and have voluntarily signed the
informed consent document
2. Have documented HIV-1 infection by official, signed, written
history (e.g., laboratory report), otherwise an HIV-antibody test will
be performed
3. Have no acquired immunodeficiency syndrome (AIDS)-defining
events in the 3 months before Screening, other than cutaneous
Kaposi’s sarcoma or wasting syndrome due to HIV
4. Are able and willing to comply with all protocol requirements and
procedures
5. Are 18 years of age or older
6. Have a life expectancy that is >6 months.
7. Have a viral load >1,000 copies/mL and documented resistance to
at least one antiretroviral medication from each of three classes of
antiretroviral medications as measured by resistance testing
8. Have a history of at least 6 months on antiretroviral treatment
9. Are receiving a stable highly active antiretroviral regimen for at least
8 weeks before Screening and are willing to continue that regimen
until Day 14, OR (in the past 8 weeks) have failed and are off
therapy and are willing to stay off therapy until Day 14
10. Have full viral sensitivity/susceptibility to at least one antiretroviral
agent, other than ibalizumab, as determined by the screening
resistance tests and be willing and able to be treated with at least one
agent to which the patient’s viral isolate is fully sensitive/susceptible
according to the screening resistance tests as a component of OBR
11. If sexually active, are willing to use an effective method of
contraception during the study and for 30 days after the last
administration of the study drug

Patients having or meeting any of the following conditions or
characteristics will be excluded from the study:
1. Any active AIDS-defining illness per Category C conditions
according to the Centers for Disease Control and Prevention (CDC)
Classification System for HIV Infection, with the following
exceptions: cutaneous Kaposi’s sarcoma and wasting syndrome due
to HIV
2. Any significant diseases (other than HIV-1 infection) or clinically
significant findings, including psychiatric and behavioral problems,
determined from screening, medical history and/or physical
examination that, in the investigator’s opinion, would preclude the
patient from participating in this study
3. Any significant acute illness within 1 week before the initial
administration of study drug
4. Any active infection secondary to HIV requiring acute therapy;
however, patients that require maintenance therapy (i.e., secondary
prophylaxis for opportunistic infections) will be eligible for the
study.
5. Any immunomodulating therapy (including interferon), systemic
steroids, or systemic chemotherapy within 12 weeks before
Enrollment
6. Any prior exposure to ibalizumab (formerly TNX-355 and Hu5A8)
7. Any vaccination within 7 days before Enrollment
8. Any female patient who either is pregnant, intends to become
pregnant, or is currently breastfeeding
9. Any current alcohol or illicit drug use that, in the investigator’s
opinion, will interfere with the patient’s ability to comply with the
study schedule and protocol evaluations
10. Any previous clinically significant allergy or hypersensitivity to any
excipient in the ibalizumab formulation
11. Any radiation therapy during the 28 days before first administration
of investigational medication
12. Any Grade 3 or 4 laboratory abnormality according to the Division
of AIDS grading scale, except for the following asymptomatic
grading scale, except for the following asymptomatic Grade 3
events:
 triglyceride elevation
 total cholesterol elevation