This Phase 3, single arm, multicenter study will evaluate the safety and effectiveness of ibalizumab in treatment-experienced patients infected with multi-drug resistant HIV-1.
This Phase 3, single arm, multicenter study will evaluate the safety and effectiveness of ibalizumab in treatment-experienced patients infected with multi-drug resistant HIV-1. Patients must have been treated with HAART for at least 6 months and be failing or have recently failed (i.e., in the last 8 weeks) therapy to determine baseline viral load. Days 0-6 of the study will be a "control period." During Days 0 through 6 patients will be monitored on current failing therapy (or no therapy, if the patient has failed and discontinued treatment within the 8 weeks preceding Screening). Days 7-13 of the study will be an "essential monotherapy period." During Days 7 through 13 patients will continue on current failing therapy and receive one 2000 mg dose (loading dose) of ibalizumab on Day 7. Day 7 is Baseline for the treatment period (Day 7-Week 25). Day 14-Week 25 of the study will be the "maintenance period." On Day 14 (primary endpoint), the OBR will be initiated and must include at least one agent to which the patient's virus is susceptible. Beginning at Day 21, 800 mg of ibalizumab will be administered every 2 weeks through Week 23. End of Study evaluations will be performed at Week 25, and a follow-up visit will be conducted at Week 29.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
40
2000mg intravenous ibalizumab (loading dose), followed 14 days later by 800mg intravenous ibalizumab every 2 weeks
All participants will be prescribed an Optimized Background Regimen of antiretroviral medications selected on the basis of treatment history and the results of Screening viral resistance and tropism testing. The prescribed regimen must contain at least one agent to which the participant's virus is known to be sensitive.
Efficacy: Proportion of Participants Achieving a Viral Load Reduction of at Least 0.5 Log 10: ITT-MEF
Proportion of participants (%) achieving a viral load reduction of at least 0.5 log from baseline (Day 7)
Time frame: Day 14
Efficacy: Proportion of Subjects With a Viral Load Decrease of at Least 0.5 Log 10 - Protocol Correct
Proportion of patients (%) with a viral load decrease of at least 0.5 log 10 from baseline (day 7)
Time frame: Day 14
Efficacy: Proportion of Patients With Undetectable Viral Load: ITT-MEF
Proportion of patients with undetectable Viral Load (\<50 copies/mL, and \<400 copies/mL)
Time frame: Week 25 /end of study
Efficacy: Proportion of Patients With Undetectable HIV-RNA Levels: Protocol Correct
Proportion of patients (%) with HIV-RNA levels \< 50 copies/mL and \< 400 copies/mL at Week 25/End of Study
Time frame: Week 25/End of Study
Mean Change in Viral Load as a Measure of Efficacy - ITT-MEF
Mean change from Day 7/Baseline in log 10 vial load measured at Day 14
Time frame: Day 7 and Day 14
Mean Change in Viral Load as a Measure of Efficacy - Protocol Correct
Mean change from Day 7/Baseline in Log 10 viral load measured at Day 14
Time frame: Day 7 and Day 14
End of Study Viral Load Reductions as a Measure of Efficacy - Intent to Treat Analysis
Proportion of patients achieving a \>/= 0.5 log10 and \>/= 1.0 log10 decrease from Day 7/Baseline in viral load at Week 25/End of Study
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Long Beach Education and Research Consultants
Long Beach, California, United States
W King Health Care Group
Los Angeles, California, United States
Southern California Permanente Medical Group
Los Angeles, California, United States
Ruane Medical and Clinical Research Institute
Los Angeles, California, United States
Charles R. Drew Univ. of Med. & Science Clinical and Translational Research Center
Los Angeles, California, United States
Anthony Mills, MD, Inc.
Los Angeles, California, United States
AIDS Healthcare Foundation
Los Angeles, California, United States
Palmtree Clinical Research Inc.
Palm Springs, California, United States
Quest Clinical Research
San Francisco, California, United States
Kaiser Foundation Research Institute
San Francisco, California, United States
...and 20 more locations
Time frame: at Week 25/End of Study
End of Study Viral Load Reductions as a Measure of Efficacy - Protocol Correct Analysis
Proportion of patients achieving a \>/= 0.5 log10 and \>/= 1.0 log10 decrease from Day 7/Baseline in viral load at Week 25/End of Study
Time frame: at Week 25/End of Study
Mean Change in CD4+ Cell Count as a Measure of Efficacy and Safety - ITT
Mean change from Day 7/Baseline in CD4+ cell count at Week 25/End of Study
Time frame: Day 7 and Week 25/End of Study
Mean Change in CD4+ Cell Count as a Measure of Efficacy and Safety - Protocol Correct
Mean change from Day 7/Baseline in CD4+ cell count at Week 25/End of Study
Time frame: Day 7 and Week 25/End of Study
Safety: Proportion of Participants Experiencing Adverse Events
Proportion of participants experiencing at least one treatment emergent adverse event to week 25/End of Study
Time frame: Through Week 25/End of Study
Proportion of Participants Experiencing Adverse Event Related to Study Drug as a Measure of Safety and Tolerability
Proportion of participants experiencing a treatment emergent adverse event determined by the investigator to be related to study drug
Time frame: Through Week 25/End of Study
Proportion of Participants Experiencing Serious Adverse Event as a Measure of Safety and Tolerability
Proportion of participants experiencing at least one serious treatment emergent adverse event, excluding death
Time frame: Through Week 25/End of Study
Proportion of Participants Discontinuing Study Drug Due to Adverse Event
Proportion of participants discontinuing study drug due to occurrence of treatment emergent adverse event
Time frame: Through Week 25/End of Study
Proportion of Participants Experiencing Adverse Event Grade 3 and Higher as a Measure of Safety and Tolerability
Proportion of participants experiencing treatment emergent adverse event Grade 3 and higher
Time frame: Through Week 25/End of Study
Proportion of Participants Experiencing Adverse Event With Death as Outcome as a Measure of Safety and Tolerability
Proportion of participants experiencing treatment emergent adverse event with death as the outcome, regardless of relationship to study drug
Time frame: Through Week 25/End of Study
Proportion of Participants Experiencing New AIDS-defining Adverse Event According to CDC Criteria as a Measure of Safety and Tolerability
Proportion of participants experiencing treatment emergent adverse event that is AIDS-defining by the CDC adverse event classification criteria for HIV infection
Time frame: Through Week 25/End of Study