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

NCT05388474 | Active Not Recruiting FDA Drug

• 1 other identifier: TH-IBA-CTR-1003
• Study Type: observational
• Target: 168
• Locations: 1 country
• Sites: 36

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.

Conditions

HIV Infections; Multi-Antiviral Resistance

Keywords

HIV; Drug resistance

Outcome Measures

Primary Outcomes (3)

• 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

Other Outcomes (4)

• Secondary Outcome measures

  Maximum 36 months

• Secondary Outcome measures

  Maximum 36 months

• Secondary Outcome measures

  Maximum 36 months

Study Arms (2)

Cohort 1 (No ibalizumab or Pre-ibalizumab treatment):

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

Cohort 2 (On ibalizumab treatment):

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

Interventions

No ibalizumab or Pre-ibalizumab treatment OTHER

Patient registry

Also known as: Ibalizumab

Cohort 1 (No ibalizumab or Pre-ibalizumab treatment):

On ibalizumab treatment BIOLOGICAL

Patient registry

Also known as: Ibalizumab

Cohort 2 (On ibalizumab treatment):

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Theratechnologies: lead
• Excelsus Statistics Inc.: collaborator
• Health Psychology Research Group (HPR): collaborator
• ICON Clinical Research: collaborator

Study Sites (36)

Ruane Clinical Research

Los Angeles, California, 90036, United States

Location

Mills Clinical Research

Los Angeles, California, 90046, United States

Location

BIOS Clinical Research

Palm Springs, California, 92262, United States

Location

UC San Diego Owen Clinic

San Diego, California, 92103, United States

Location

Yale University

New Haven, Connecticut, 06520, United States

Location

Circle Care Center

Stamford, Connecticut, 06850, United States

Location

Waterbury Hospital

Waterbury, Connecticut, 06702, United States

Location

Whitman Walker Health

Washington D.C., District of Columbia, 20005, United States

Location

Georgetown University Medical Center

Washington D.C., District of Columbia, 20007, United States

Location

Aids Healthcare Foundation

Fort Lauderdale, Florida, 33308, United States

Location

Gary J. Richmond, M.D., PA

Fort Lauderdale, Florida, 33316, United States

Location

Midway Specialty Care Center Miami Beach

Miami Beach, Florida, 33140, United States

Location

Orlando Immunology Center (OIC)

Orlando, Florida, 32803, United States

Location

Bliss Health

Orlando, Florida, 32806, United States

Location

Can Community Health

Tampa, Florida, 33614, United States

Location

St-Joseph's Comprehensive Research

Tampa, Florida, 33614, United States

Location

CAN Community Health

Tampa, Florida, 34232, United States

Location

Triple O Research Institute PA

West Palm Beach, Florida, 33407, United States

Location

Indiana University Health Inc.

Bloomington, Indiana, 47405, United States

Location

University of Maryland School of Medicine

Baltimore, Maryland, 21201, United States

Location

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

The Research Institute

Springfield, Massachusetts, 01105, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

Las Vegas Research Center

Las Vegas, Nevada, 89106, United States

Location

I.D. Care Associates, PA

Hillsborough, New Jersey, 08844, United States

Location

Prime Healthcare Services - St Michael's Medical Center

Newark, New Jersey, 07102, United States

Location

SUNY Upstate Medical Center

Syracuse, New York, 13210, United States

Location

Amity Medical Group

Charlotte, North Carolina, 28215, United States

Location

The Roper St. Francis Ryan White Wellness Center

Charleston, South Carolina, 29407, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Prism Health North Texas

Dallas, Texas, 75204, United States

Location

North Texas Infectious Diseases Consultants, P.A

Dallas, Texas, 75246, United States

Location

Therapeutic Concepts, PA

Houston, Texas, 77004, United States

Location

UT Health Houston

Houston, Texas, 77030, United States

Location

St. Hope Foundation

Houston, Texas, 77036, United States

Location

Legacy Community Pharmacy Services

Houston, Texas, 77074, United States

Location

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• Armenia D, Di Carlo D, Flandre P, Bouba Y, Borghi V, Forbici F, Bertoli A, Gori C, Fabeni L, Gennari W, Pinnetti C, Mondi A, Cicalini S, Gagliardini R, Vergori A, Bellagamba R, Malagnino V, Montella F, Colafigli M, Latini A, Marocco R, Licthner M, Andreoni M, Mussini C, Ceccherini-Silberstein F, Antinori A, Perno CF, Santoro MM. HIV MDR is still a relevant issue despite its dramatic drop over the years. J Antimicrob Chemother. 2020 May 1;75(5):1301-1310. doi: 10.1093/jac/dkz554.

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• Burkly LC, Olson D, Shapiro R, Winkler G, Rosa JJ, Thomas DW, Williams C, Chisholm P. Inhibition of HIV infection by a novel CD4 domain 2-specific monoclonal antibody. Dissecting the basis for its inhibitory effect on HIV-induced cell fusion. J Immunol. 1992 Sep 1;149(5):1779-87.

  PMID: 1380539 BACKGROUND

• Freeman MM, Seaman MS, Rits-Volloch S, Hong X, Kao CY, Ho DD, Chen B. Crystal structure of HIV-1 primary receptor CD4 in complex with a potent antiviral antibody. Structure. 2010 Dec 8;18(12):1632-41. doi: 10.1016/j.str.2010.09.017.

  PMID: 21134642 BACKGROUND

• Gathe JC, Hardwicke RL, Garcia F, Weinheimer S, Lewis ST, Cash RB. Efficacy, Pharmacokinetics, and Safety Over 48 Weeks With Ibalizumab-Based Therapy in Treatment-Experienced Adults Infected With HIV-1: A Phase 2a Study. J Acquir Immune Defic Syndr. 2021 Apr 1;86(4):482-489. doi: 10.1097/QAI.0000000000002591.

  PMID: 33427765 BACKGROUND

• Kilby JM, Eron JJ. Novel therapies based on mechanisms of HIV-1 cell entry. N Engl J Med. 2003 May 29;348(22):2228-38. doi: 10.1056/NEJMra022812. No abstract available.

  PMID: 12773651 BACKGROUND

• Moore JP, Sattentau QJ, Klasse PJ, Burkly LC. A monoclonal antibody to CD4 domain 2 blocks soluble CD4-induced conformational changes in the envelope glycoproteins of human immunodeficiency virus type 1 (HIV-1) and HIV-1 infection of CD4+ cells. J Virol. 1992 Aug;66(8):4784-93. doi: 10.1128/JVI.66.8.4784-4793.1992.

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• Pearce N. Analysis of matched case-control studies. BMJ. 2016 Feb 25;352:i969. doi: 10.1136/bmj.i969.

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• Reimann KA, Burkly LC, Burrus B, Waite BC, Lord CI, Letvin NL. In vivo administration to rhesus monkeys of a CD4-specific monoclonal antibody capable of blocking AIDS virus replication. AIDS Res Hum Retroviruses. 1993 Mar;9(3):199-207. doi: 10.1089/aid.1993.9.199.

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• Reimann KA, Lin W, Bixler S, Browning B, Ehrenfels BN, Lucci J, Miatkowski K, Olson D, Parish TH, Rosa MD, Oleson FB, Hsu YM, Padlan EA, Letvin NL, Burkly LC. A humanized form of a CD4-specific monoclonal antibody exhibits decreased antigenicity and prolonged plasma half-life in rhesus monkeys while retaining its unique biological and antiviral properties. AIDS Res Hum Retroviruses. 1997 Jul 20;13(11):933-43. doi: 10.1089/aid.1997.13.933.

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• Raymond S, Piffaut M, Bigot J, Cazabat M, Montes B, Bertrand K, Martin-Blondel G, Izopet J, Delobel P. Sexual transmission of an extensively drug-resistant HIV-1 strain. Lancet HIV. 2020 Aug;7(8):e529-e530. doi: 10.1016/S2352-3018(20)30205-8. No abstract available.

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• Reimann KA, Khunkhun R, Lin W, Gordon W, Fung M. A humanized, nondepleting anti-CD4 antibody that blocks virus entry inhibits virus replication in rhesus monkeys chronically infected with simian immunodeficiency virus. AIDS Res Hum Retroviruses. 2002 Jul 20;18(11):747-55. doi: 10.1089/08892220260139486.

  PMID: 12167266 BACKGROUND

• Sattentau QJ, Moore JP. The role of CD4 in HIV binding and entry. Philos Trans R Soc Lond B Biol Sci. 1993 Oct 29;342(1299):59-66. doi: 10.1098/rstb.1993.0136.

  PMID: 7904348 BACKGROUND

• Song R, Franco D, Kao CY, Yu F, Huang Y, Ho DD. Epitope mapping of ibalizumab, a humanized anti-CD4 monoclonal antibody with anti-HIV-1 activity in infected patients. J Virol. 2010 Jul;84(14):6935-42. doi: 10.1128/JVI.00453-10. Epub 2010 May 12.

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  PMID: 24141714 BACKGROUND

• Zhang XQ, Sorensen M, Fung M, Schooley RT. Synergistic in vitro antiretroviral activity of a humanized monoclonal anti-CD4 antibody (TNX-355) and enfuvirtide (T-20). Antimicrob Agents Chemother. 2006 Jun;50(6):2231-3. doi: 10.1128/AAC.00761-05.

  PMID: 16723592 BACKGROUND

Related Links

• EACS (2019). European Aids Clinical Society (EACS) Guidelines version 10.
• UNAIDS, 2019. Global AIDS Update 2019. Communities at the centre. Defending rights, breaking barriers, reaching people with HIV services

MeSH Terms

Conditions

HIV Infections

Interventions

ibalizumab

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Officials

• Princy N Kumar, MD

  Georgetown University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 1, 2022
• First Posted: May 24, 2022
• Study Start: March 22, 2022
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: January 2, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (36)