Ibalizumab Plus Optimized Background Regimen in Treatment-Experienced Patients With Multi-Drug Resistant HIV-1

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Phase 3, Multicenter, Expanded Access Study of Ibalizumab Plus an Optimized Background Regimen (OBR) in Treatment-Experienced Patients Infected With Multi-Drug Resistant (MDR) HIV-1

Conditions
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HIV

Intervention / Treatment
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* Drug: ibalizumab
* Drug: Optimized Background Regimen


Participation Criteria
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Eligibility Criteria
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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 Exclusion Criteria for patients meeting the Inclusion Criteria for Cohort 1 (Cohort 2) Eligible for participation in other TaiMed-sponsored clinical trials of ibalizumab 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 Any significant acute illness within 1 week before the first administration of investigational medication on this study 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. Any immunomodulating therapy (including interferon), systemic steroids, or systemic chemotherapy within 4 weeks before Day 0 Any prior exposure to ibalizumab (formerly TNX-355 and Hu5A8) Any vaccination within 7 days before Day 0 Any female patient who either is pregnant, intends to become pregnant, or is currently breastfeeding 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 Any previous clinically significant allergy or hypersensitivity to any excipient in the ibalizumab formulation Any radiation therapy during the 28 days before first administration of investigational medication on this study Any clinically significant Grade 3 or 4 laboratory abnormality according to the Division of AIDS (DAIDS) grading scale, except for the following asymptomatic Grade 3 events: triglyceride elevation total cholesterol elevation

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>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 | Drug: ibalizumab<br>* 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<br>* Other names: TNX-355, Hu5A8;Drug: Optimized Background Regimen<br>* 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).<br>* Other names: antiretroviral therapy;|
| Experimental: Cohort 2<br>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 | Drug: ibalizumab<br>* 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<br>* Other names: TNX-355, Hu5A8;Drug: Optimized Background Regimen<br>* 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).<br>* Other names: antiretroviral therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability of Ibalizumab + OBR | Number of participants with Grade 3/4 adverse events possibly, probably, or definitely due to ibalizumab | Through 48 weeks | 
| 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 | 48 weeks | 
| 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 | 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 48 weeks | 
| 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 | 48 weeks | 
| 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 | 48 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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AIDS, HIV, Resistant, Salvage, ibalizumab, antibody