Clinical trial NCT05388474: A Prospective and Retrospective Observational Study of Multidrug-Resistant Patient Outcomes With and Without Ibalizumab
Official title: A Prospective and Retrospective Observational Study of Multidrug-Resistant Patient Outcomes With and Without Ibalizumab in a Real-World Setting: United States
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: HIV Infections
Multi-Antiviral Resistance
Keywords: HIV
Drug resistance
Lead sponsor: Theratechnologies
Sponsor class: INDUSTRY
Collaborators: name: Excelsus Statistics Inc.
name: Health Psychology Research Group (HPR)
name: ICON Clinical Research
First posted: 2022-05-24
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The study will enroll Heavily treatment-experienced (HTE) adult patients infected with MDR HIV-1. For Cohort 2, the study will accept patients prescribed ibalizumab across study sites, including patients previously enrolled in Cohort 1 who subsequently initiated ibalizumab treatment. The decision to include ibalizumab in the treatment regimen will be clinical and independent of patient inclusion in the study.

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. The patient is Heavily treatment-experienced (HTE), with limited treatment options and a history of treatment failure;
2. 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);
3. 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;
4. 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;
5. ≥18 years of age or older at the time of screening;
6. 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;
7. 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;
8. 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:

1. Pregnant or breastfeeding;
2. Unable to provide informed consent;
3. Hypersensitivity to ibalizumab or any of the excipients in ibalizumab;
4. Previous ibalizumab experience (Cohort 1 only)
5. Previously enrolled in Cohort 2 of this registry.

Primary outcomes:
measure: Primary Outcome measures
timeFrame: Maximum 36 months
measure: Primary Outcome measures
timeFrame: Maximum 36 months
measure: Primary Outcome measures
timeFrame: Maximum 36 months
Secondary outcomes:
Other outcomes:
measure: Secondary Outcome measures
timeFrame: Maximum 36 months
measure: Secondary Outcome measures
timeFrame: Maximum 36 months
measure: Secondary Outcome measures
timeFrame: Maximum 36 months
measure: Secondary Outcome measures
timeFrame: Max 36 months
Locations:
city: Los Angeles
country: United States
facility: Ruane Clinical Research
state: California
city: Los Angeles
country: United States
facility: Mills Clinical Research
state: California
city: Palm Springs
country: United States
facility: BIOS Clinical Research
state: California
city: San Diego
country: United States
facility: UC San Diego Owen Clinic
state: California
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Stamford
country: United States
facility: Circle Care Center
state: Connecticut
city: Waterbury
country: United States
facility: Waterbury Hospital
state: Connecticut
city: Washington
country: United States
facility: Whitman Walker Health
state: District of Columbia
city: Washington
country: United States
facility: Georgetown University Medical Center
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: Aids Healthcare Foundation
state: Florida
city: Fort Lauderdale
country: United States
facility: Gary J. Richmond, M.D., PA
state: Florida
city: Miami Beach
country: United States
facility: Midway Specialty Care Center Miami Beach
state: Florida
city: Orlando
country: United States
facility: Orlando Immunology Center (OIC)
state: Florida
city: Orlando
country: United States
facility: Bliss Health
state: Florida
city: Tampa
country: United States
facility: Can Community Health
state: Florida
city: Tampa
country: United States
facility: St-Joseph's Comprehensive Research
state: Florida
city: Tampa
country: United States
facility: CAN Community Health
state: Florida
city: West Palm Beach
country: United States
facility: Triple O Research Institute PA
state: Florida
city: Bloomington
country: United States
facility: Indiana University Health Inc.
state: Indiana
city: Baltimore
country: United States
facility: University of Maryland School of Medicine
state: Maryland
city: Boston
country: United States
facility: Boston Medical Center
state: Massachusetts
city: Springfield
country: United States
facility: The Research Institute
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Las Vegas
country: United States
facility: Las Vegas Research Center
state: Nevada
city: Hillsborough
country: United States
facility: I.D. Care Associates, PA
state: New Jersey
city: Newark
country: United States
facility: Prime Healthcare Services - St Michael's Medical Center
state: New Jersey
city: Syracuse
country: United States
facility: SUNY Upstate Medical Center
state: New York
city: Charlotte
country: United States
facility: Amity Medical Group
state: North Carolina
city: Charleston
country: United States
facility: The Roper St. Francis Ryan White Wellness Center
state: South Carolina
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Dallas
country: United States
facility: Prism Health North Texas
state: Texas
city: Dallas
country: United States
facility: North Texas Infectious Diseases Consultants, P.A
state: Texas
city: Houston
country: United States
facility: Therapeutic Concepts, PA
state: Texas
city: Houston
country: United States
facility: UT Health Houston
state: Texas
city: Houston
country: United States
facility: St. Hope Foundation
state: Texas
city: Houston
country: United States
facility: Legacy Community Pharmacy Services
state: Texas
Study officials:
affiliation: Georgetown University
name: Princy N Kumar, MD
role: PRINCIPAL_INVESTIGATOR
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