A Prospective and Retrospective Observational Study of Multidrug-Resistant Patient Outcomes With and Without Ibalizumab

Study Overview
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Brief Summary
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The virological efficacy of ibalizumab has been clearly demonstrated in multiple clinical trials. This study will expand ibalizumab's clinical data set and allow a better understanding of the virologic response durability on ARV regimens with or without ibalizumab in a heterogeneous real-world patient population. Additional data on the efficacy and safety of ibalizumab and its impact on patient reported outcomes will be captured until study end. Primary Objective: To evaluate the long-term efficacy, safety, and durability of ibalizumab in combination with other ARVs by comparing the virologic, immunologic and clinical outcomes of patients receiving ibalizumab treatment versus patients not receiving ibalizumab. Secondary Objective: To assess the efficacy of ibalizumab in combination with other antiretrovirals by comparing the virologic, immunologic, clinical and patient reported outcomes of patients before and after they receive ibalizumab treatment. To assess the long-term safety and tolerability of ibalizumab. Other Objectives: To assess risk factors/predictors of virologic and immunologic response. To assess efficacy and safety in special populations that enroll.

Detailed Description
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Antiretroviral therapy (ART) for treatment of human immunodeficiency virus (HIV) has evolved tremendously over recent years. Newer medications have superior efficacy and tolerability, affording more convenient treatment regimens. The proportion of patients receiving antiretroviral (ARV) treatment that maintain viral suppression is approximately 85% in the United States. However, some patients may not be able to adhere to the prescribed ARV regimen or harbour strains of HIV that are resistant to most currently available therapies. Multi-drug resistant (MDR) HIV may be transmitted or result from incomplete viral suppression, which leads to accumulation of mutations in the viral genome over time. Patients with MDR HIV infection have significantly fewer available treatment options to construct a fully suppressive regimen. This ultimately results in shorter life expectancy, greater potential for transmission of MDR virus, increased morbidity and greater use of health resources. These comparisons are valid for the general population as well as people infected with non-MDR virus. Ibalizumab, a humanized IgG4 monoclonal antibody that binds to a conformational epitope on domain 2 of the extracellular portion of the CD4 receptor, belongs to a new class of ARVs, CD4-directed post-attachment HIV-1 inhibitors, Ibalizumab exhibits no known cross-resistance with other ARV medications. Ibalizumab was approved by the FDA on March 6, 2018 and is indicated in combination with other ARVs for the treatment of HIV-1 infection in heavily treatment-experienced adults with MDR HIV-1 infection failing their current ARV regimen. It has been available commercially from April 2018. The safety, efficacy and durability of response to ibalizumab treatment in combination with other ARVs have been demonstrated in clinical trials. This registry is designed to better understand the long-term efficacy and safety outcomes of MDR patients with and without ibalizumab in a real-world scenario.

Official Title
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A Prospective and Retrospective Observational Study of Multidrug-Resistant Patient Outcomes With and Without Ibalizumab in a Real-World Setting: United States

Conditions
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HIV Infections, Multi-Antiviral Resistance

Intervention / Treatment
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* Other: No ibalizumab or Pre-ibalizumab treatment
* Biological: On ibalizumab treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The patient is Heavily treatment-experienced (HTE), with limited treatment options and a history of treatment failure; Based on recent or historical resistance assays and ARV history, patients must have documented Multi Drug Resistant (MDR) HIV-1 (e.g., laboratory report and documented past ARV treatment); Received an appropriate HIV-1 resistance assay (genotypic or phenotypic testing) to devise an OBR (which may include an investigational ARV treatment) or will receive an appropriate resistance assay prior to initiating ibalizumab treatment; Provide signed and dated informed consent to the Investigator, indicating that the patient (or, legally acceptable representative) has been informed of all pertinent aspects of the study, and is capable of understanding and willing to comply with the registry requirements. The consent will request to access the patient's medical, hospital, pharmacy, and vital statistics records as appropriate, as well as historical medical data for the full retrospective time period (01 May 2018 to enrollment). Further, consent will be provided for access to all available historical resistance and ARV treatment data; ≥18 years of age or older at the time of screening; Provide information on at least one alternate contact person of their choice (primary care physician, close relative or emergency contact) who can be contacted, should the patient be lost to follow-up over the course of the study; Acknowledgement that in the event of their death, additional information can be obtained by contacting their primary care physician, a close relative, emergency contact or by consulting public or external databases (death registries, obituary listings) when available and verifiable. This is to be done in accordance with local regulatory requirements and laws; Exceptionally, patients who may have started ibalizumab outside of the approved indication can also be included in Cohort 2 of the registry at the discretion of the investigator, provided they determine clinical utility. Exclusion Criteria: Pregnant or breastfeeding; Unable to provide informed consent; Hypersensitivity to ibalizumab or any of the excipients in ibalizumab; Previous ibalizumab experience (Cohort 1 only) Previously enrolled in Cohort 2 of this registry.

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Cohort 1 (No ibalizumab or Pre-ibalizumab treatment):<br>This cohort will be comprised of Heavily treatment-experienced (HTE) patients with Multi Drug Resistant (MDR) HIV who are not receiving ibalizumab. These patients will roll-over into cohort 2 if a change to their ARV regimen is made to include ibalizumab. | Other: No ibalizumab or Pre-ibalizumab treatment<br>* Patient registry<br>* Other names: Ibalizumab;|
| Cohort 2 (On ibalizumab treatment):<br>This cohort will be comprised of Heavily Treatment-Experienced patients (HTE) with Multi Drug Resistant (MDR) HIV who are starting treatment with an ARV regimen that includes ibalizumab. Patients already receiving ibalizumab prior to study entry may also be included in Cohort 2 if baseline viral load (VL) and cluster of differentiation 4 (CD4) count data are available prior to ibalizumab treatment. Recruited patients will be required to consent to provide their full retrospective ARV treatment and drug resistance history, as well as retrospective historical data from their medical records from 01 May 2018 to enrollment. | Biological: On ibalizumab treatment<br>* Patient registry<br>* Other names: Ibalizumab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Outcome measures | To compare the virologic, immunologic and clinical outcomes of patients receiving ibalizumab treatment vs. matched patients not receiving ibalizumab. And to evaluate the long-term efficacy and durability of ibalizumab in combination with other antiretrovirals. The following data will be collected: RELEVANT DISEASE AND PATIENT CHARACTERISTICS: HIV Type Duration of HIV infection Gender Age Race/ethnicity Vital signs (weight (kilograms), height (meters), systolic and diastolic blood pressure (mmHg)) Geographic location AIDS-defining illnesses (CDC classification) Comorbidities and other diagnoses Concomitant medications | Maximum 36 months | 
| Primary Outcome measures | BASELINE DISEASE CHARACTERISTICS: Pre-enrolment Viral Load (copies/ml) Pre-enrolment CD4 count (cells/mm3) Laboratory parameters: Hepatitis serology, CD4 (cells/mm3), CD8 (cells/mm3), HIV-RNA, HIV subtype Historic Antiretroviral treatment (three years prior to enrolment) Previous (three years prior to enrolment) and ongoing antiretroviral treatment Genotypic and phenotypic resistance data and complete history HIV subtype when available for patient | Maximum 36 months | 
| Primary Outcome measures | ON-TREATMENT INFORMATION: CD4 count (cells/mm3) Viral Load (copies/ml) Weight (kilograms) HIV subtype when available for patient Concomitant medication review Resistance testing review Optimized Background Regimen review New AIDS-Defining Events (CDC classification) Adverse Reactions/Serious Adverse reactions review Hospitalizations review Ibalizumab discontinuation date and reason (e.g., lost to follow-up, death). | Maximum 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, Drug resistance