HIV
Conditions
Keywords
HIV, Resistant, Salvage, ibalizumab, antibody, AIDS
Brief summary
Ibalizumab is a monoclonal antibody that works by blocking HIV entry into the immune system cells (CD4+ or T-cells) the virus typically infects. Ibalizumab is intended for use in combination with other anti-HIV drugs in people with multi-drug resistant HIV and limited treatment options. This study will collect further information on the safety and tolerability of intravenously administered (IV) ibalizumab combined with an optimized background regimen for treating multi-drug resistant HIV-1 infection, and will provide continuing access to ibalizumab for patients completing a prior ibalizumab clinical trial.
Detailed description
Participants will enroll into one of two study cohorts. Cohort 1 will provide continued administration of IV ibalizumab for patients completing a prior ibalizumab clinical trial (TaiMed-sponsored or Investigator-Sponsored). Patients will continue to receive IV infusions of ibalizumab at the dosage assigned in the previous study - either 800 mg once every two weeks, or 2000 mg once every four weeks. Cohort 2 will provide IV ibalizumab, 800 mg once every two weeks, for qualifying patients with multi-drug resistant HIV-1 and limited treatment options who have never previously received ibalizumab. Participants may continue in this study for 48 weeks, or until ibalizumab becomes commercially available, whichever occurs first.
Interventions
DRUGibalizumab
Intravenous infusion of humanized monoclonal antibody binding with a region of Domain 2 of CD4 receptor, blocking post-attachment conformational changes necessary for HIV cell entry
An investigator-selected, standard-of-care combination regimen of antiretroviral agents for treating HIV-1 infection, selected based upon patient treatment history and the results of previous viral resistance testing. The combination must contain at least one agent other than ibalizumab to which the patient's virus is sensitive (susceptible).
Sponsors
Westat
TaiMed Biologics Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
(Cohort 1) * Currently receiving ibalizumab via other TaiMed-sponsored or investigator-Sponsored protocol * Are capable of understanding and have voluntarily signed the informed consent document (Cohort 2) * 18 years of age or older * Are capable of understanding and have voluntarily signed the informed consent document * Have documented HIV-1 infection by official, signed, written history (e.g., laboratory report), otherwise an HIV-antibody test will be performed * Are able and willing to comply with all protocol requirements and procedures * 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 previous viral resistance testing (resistance testing is not provided by the study for qualification purposes) * Have a history of at least 6 months on antiretroviral treatment * Are receiving a failing antiretroviral regimen OR have failed and are off therapy * Have viral sensitivity/susceptibility to at least one antiretroviral agent, other than ibalizumab, as determined by previous resistance test performed within 6 months of screening 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 resistance tests used for screening as a component of OBR * 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
Exclusion criteria
(Cohort 1) * There are no
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability of Ibalizumab + OBR | Through 48 weeks | Number of participants with Grade 3/4 adverse events possibly, probably, or definitely due to ibalizumab |
| Discontinuations Due to Adverse Events Related to Ibalizumab | 48 weeks | number of participants discontinuing ibalizumab treatment due to adverse events probably, possibly, or definitely related to ibalizumab |
| Effectiveness of Ibalizumab + OBR (Cohort 2 Only) | 7 days | Number of patients in Cohort 2 achieving at least a 0.5 log change from Baseline in viral load at Day 7 of the study |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Suppression to <50 Copies With Ibalizumab + OBR (Cohort 2 Only) | 48 weeks | Number of patients in Cohort 2 with HIV-1 RNA levels \<50 copies/mL at week 48 |
| Suppression to <400 Copies by Ibalizumab + OBR (Cohort 2 Only) | 48 weeks | Number of patients in Cohort 2 with HIV-1 RNA levels \<400 copies/mL at week 48 |
| Effectiveness of Ibalizumab + OBR by 1.0 Log10 Decrease in Viral Load From Baseline (Cohort 2 Only) | 48 weeks | Number of patients in Cohort 2 achieving at least a 1.0 log10 decrease in viral load from Baseline measurement at all assessment time points |
Countries
Puerto Rico, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1 IV ibalizumab (combined with optimized background regimen):
800 mg once every two weeks for patients receiving that dosage on prior, successfully completed ibalizumab clinical trial
OR
2000 mg once every four weeks for patients receiving that dosage on prior, successfully completed ibalizumab clinical trial
Administered for 48 weeks, or until ibalizumab becomes commercially available
ibalizumab: Intravenous infusion of humanized monoclonal antibody binding with a region of Domain 2 of CD4 receptor, blocking post-attachment conformational changes necessary for HIV cell entry
Optimized Background Regimen: An investigator-selected, standard-of-care combination regimen of antiretroviral agents for treating HIV-1 infection, selected based upon patient treatment history and the results of previous viral resistance testing. The combination must contain at least one agent other than ibalizumab to which the patient's virus is sensitive (susceptible). | 41 |
| Cohort 2 IV ibalizumab (combined with optimized background regimen):
800 mg once every two weeks for qualifying patients who have never received ibalizumab
Administered for 48 weeks, or until ibalizumab becomes commercially available
ibalizumab: Intravenous infusion of humanized monoclonal antibody binding with a region of Domain 2 of CD4 receptor, blocking post-attachment conformational changes necessary for HIV cell entry
Optimized Background Regimen: An investigator-selected, standard-of-care combination regimen of antiretroviral agents for treating HIV-1 infection, selected based upon patient treatment history and the results of previous viral resistance testing. The combination must contain at least one agent other than ibalizumab to which the patient's virus is sensitive (susceptible). | 38 |
| Total | 79 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 3 |
| Overall Study | Death | 5 | 2 |
| Overall Study | Lack of Efficacy | 0 | 2 |
| Overall Study | Lost to Follow-up | 1 | 3 |
| Overall Study | Physician Decision | 1 | 4 |
| Overall Study | Went onto commercial drug | 30 | 23 |
| Overall Study | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | Total | Cohort 2 | Cohort 1 |
|---|---|---|---|
| Age, Continuous | 51.9 years STANDARD_DEVIATION 10.4 | 49.9 years STANDARD_DEVIATION 11.7 | 52.8 years STANDARD_DEVIATION 9.07 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 20 Participants | 8 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 59 Participants | 30 Participants | 29 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Number of Study Participants Enrolled | 79 Participants | 38 Participants | 41 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 28 Participants | 16 Participants | 12 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) White | 47 Participants | 20 Participants | 27 Participants |
| Region of Enrollment Puerto Rico | 6 participants | 4 participants | 2 participants |
| Region of Enrollment United States | 73 participants | 34 participants | 39 participants |
| Sex: Female, Male Female | 8 Participants | 4 Participants | 4 Participants |
| Sex: Female, Male Male | 71 Participants | 34 Participants | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 5 / 41 | 2 / 38 |
| other Total, other adverse events | 39 / 41 | 37 / 38 |
| serious Total, serious adverse events | 16 / 41 | 15 / 38 |
Outcome results
Primary
Discontinuations Due to Adverse Events Related to Ibalizumab
number of participants discontinuing ibalizumab treatment due to adverse events probably, possibly, or definitely related to ibalizumab
Time frame: 48 weeks
Population: intent-to -treat
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 | Discontinuations Due to Adverse Events Related to Ibalizumab | 0 Participants |
| Cohort 2 | Discontinuations Due to Adverse Events Related to Ibalizumab | 3 Participants |
Primary
Effectiveness of Ibalizumab + OBR (Cohort 2 Only)
Number of patients in Cohort 2 achieving at least a 0.5 log change from Baseline in viral load at Day 7 of the study
Time frame: 7 days
Population: As treated analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 2 | Effectiveness of Ibalizumab + OBR (Cohort 2 Only) | 28 participants |
Primary
Safety and Tolerability of Ibalizumab + OBR
Number of participants with Grade 3/4 adverse events possibly, probably, or definitely due to ibalizumab
Time frame: Through 48 weeks
Population: intent-to-treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1 | Safety and Tolerability of Ibalizumab + OBR | 8 participants |
| Cohort 2 | Safety and Tolerability of Ibalizumab + OBR | 9 participants |
Secondary
Effectiveness of Ibalizumab + OBR by 1.0 Log10 Decrease in Viral Load From Baseline (Cohort 2 Only)
Number of patients in Cohort 2 achieving at least a 1.0 log10 decrease in viral load from Baseline measurement at all assessment time points
Time frame: 48 weeks
Population: as treated analysis
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 1 | Effectiveness of Ibalizumab + OBR by 1.0 Log10 Decrease in Viral Load From Baseline (Cohort 2 Only) | 0 Participants |
| Cohort 2 | Effectiveness of Ibalizumab + OBR by 1.0 Log10 Decrease in Viral Load From Baseline (Cohort 2 Only) | 11 Participants |
Secondary
Suppression to <400 Copies by Ibalizumab + OBR (Cohort 2 Only)
Number of patients in Cohort 2 with HIV-1 RNA levels \<400 copies/mL at week 48
Time frame: 48 weeks
Population: as-treated-analysis
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 2 | Suppression to <400 Copies by Ibalizumab + OBR (Cohort 2 Only) | 10 Participants |
Secondary
Suppression to <50 Copies With Ibalizumab + OBR (Cohort 2 Only)
Number of patients in Cohort 2 with HIV-1 RNA levels \<50 copies/mL at week 48
Time frame: 48 weeks
Population: as-treated-population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort 2 | Suppression to <50 Copies With Ibalizumab + OBR (Cohort 2 Only) | 11 Participants |