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

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

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.

Study Overview

• Status: Completed
• Conditions: HIV
• Intervention / Treatment: Drug: ibalizumab; Drug: Optimized Background Regimen

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.

• Study Type: Interventional
• Enrollment (Actual): 79
• Phase: Phase 3

Contacts and Locations

Study Locations

• Puerto Rico
  • San Juan, Puerto Rico, 00909
    • Clinical Research PR, Inc.
• United States
  • California
    • Long Beach, California, United States, 90813
      • Long Beach Education and Research Consultants
    • Los Angeles, California, United States, 90027
      • Southern California Permanente Medical Group
    • Los Angeles, California, United States, 90036
      • Ruane Clinical Research Institute Inc.
    • Los Angeles, California, United States, 90059
      • Charles R. Drew University of Medicine and Science, Clinical and Translational Research Center
    • Los Angeles, California, United States, 90069
      • Anthony Mills MD Inc.
    • Palm Springs, California, United States, 92262
      • Palmtree Clinical Research, Inc.
    • San Francisco, California, United States, 94118
      • Kaiser Foundation Research Institute
    • San Francisco, California, United States, 94115
      • eStudy Site
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale University
  • District of Columbia
    • Washington, District of Columbia, United States, 20007
      • Georgetown University School of Medicine
  • Florida
    • Fort Lauderdale, Florida, United States, 33316
      • Gary Richmond, MD, PA
    • Miami, Florida, United States, 33133
      • AIDS Healthcare Foundation - Kinder Medical Group
    • Miami, Florida, United States, 33140
      • AIDS Healthcare Foundation - South Beach
    • Orlando, Florida, United States, 32803
      • Orlando Immunology Center
    • West Palm Beach, Florida, United States, 33401
      • Triple O Research Institute
  • Georgia
    • Atlanta, Georgia, United States, 30312
      • AIDS Research Consortium of Atlanta
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • University of Hawaii - John A. Burns School of Medicine
  • Illinois
    • Chicago, Illinois, United States, 60613
      • Howard Brown Health Center
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • National Institute of Allergy & Infectious Diseases
  • Massachusetts
    • Springfield, Massachusetts, United States, 01105
      • ID Research Institute
  • Missouri
    • Saint Louis, Missouri, United States, 63108
      • Central West Clinical Research
  • New York
    • Bronx, New York, United States, 10461
      • Jacobi Medical Center
    • New York, New York, United States, 10001
      • AIDS Healthcare Foundation - Manhattan Midtown HCC
    • New York, New York, United States, 10011
      • Chelsea Village Medical
  • North Carolina
    • Greenville, North Carolina, United States, 27834
      • East Carolina University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Philadelphia FIGHT
  • Tennessee
    • Memphis, Tennessee, United States, 38105
      • St. Jude's Children's Research Hospital
  • Texas
    • Bellaire, Texas, United States, 77401
      • St. Hope Foundation Community Health Center
    • Dallas, Texas, United States, 75246
      • North Texas Infectious Disease Consultants
    • Houston, Texas, United States, 77098
      • Research Access Network
    • Houston, Texas, United States, 77098
      • Crofoot Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Drug: 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; Other Names: TNX-355, Hu5A8; Drug: 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).; Other Names: antiretroviral therapy
Experimental: 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	Drug: 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; Other Names: TNX-355, Hu5A8; Drug: 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).; Other Names: antiretroviral therapy

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: TaiMed Biologics Inc.
• Collaborators: Westat
• Investigators: Principal Investigator: Stanley T. Lewis, MD, MPH, TaiMed Biologics Inc.

Study record dates

Study Major Dates

• Study Start: March 1, 2016
• Primary Completion (Actual): November 1, 2018
• Study Completion (Actual): November 1, 2018

Study Registration Dates

• First Submitted: March 8, 2016
• First Submitted That Met QC Criteria: March 11, 2016
• First Posted (Estimate): March 14, 2016

Study Record Updates

• Last Update Posted (Actual): March 11, 2021
• Last Update Submitted That Met QC Criteria: February 18, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: HIV; antibody; AIDS; Resistant; Salvage; ibalizumab
• Additional Relevant MeSH Terms: Anti-Infective Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; Ibalizumab
• Other Study ID Numbers: TMB-311

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No