Ibalizumab Plus Optimized Background Regimen in Patient With Multi-Drug Resistant HIV

A Phase 3, Single Arm, 24-Week, Multicenter Study of Ibalizumab Plus an Optimized Background Regimen (OBR) in Treatment-Experienced Patients Infected With Multi-Drug Resistant HIV-1

This Phase 3, single arm, multicenter study will evaluate the safety and effectiveness of ibalizumab in treatment-experienced patients infected with multi-drug resistant HIV-1.

Study Overview

• Status: Completed
• Conditions: HIV
• Intervention / Treatment: Biological: ibalizumab; Drug: Optimized Background Regimen (OBR)

Detailed Description

This Phase 3, single arm, multicenter study will evaluate the safety and effectiveness of ibalizumab in treatment-experienced patients infected with multi-drug resistant HIV-1. Patients must have been treated with HAART for at least 6 months and be failing or have recently failed (i.e., in the last 8 weeks) therapy to determine baseline viral load.

Days 0-6 of the study will be a "control period." During Days 0 through 6 patients will be monitored on current failing therapy (or no therapy, if the patient has failed and discontinued treatment within the 8 weeks preceding Screening).

Days 7-13 of the study will be an "essential monotherapy period." During Days 7 through 13 patients will continue on current failing therapy and receive one 2000 mg dose (loading dose) of ibalizumab on Day 7. Day 7 is Baseline for the treatment period (Day 7-Week 25).

Day 14-Week 25 of the study will be the "maintenance period." On Day 14 (primary endpoint), the OBR will be initiated and must include at least one agent to which the patient's virus is susceptible. Beginning at Day 21, 800 mg of ibalizumab will be administered every 2 weeks through Week 23.

End of Study evaluations will be performed at Week 25, and a follow-up visit will be conducted at Week 29.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 3

Contacts and Locations

Study Locations

• Puerto Rico
  • San Juan, Puerto Rico, 75246
    • Clinical Research PR, Inc
• Taiwan
  • Kaohsiung, Taiwan, 82445
    • E-DA Hospital
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital
• 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, 90069
      • Anthony Mills, MD, Inc.
    • Los Angeles, California, United States, 90008
      • W King Health Care Group
    • Los Angeles, California, United States, 90036
      • Ruane Medical and Clinical Research Institute
    • Los Angeles, California, United States, 90059
      • Charles R. Drew Univ. of Med. & Science Clinical and Translational Research Center
    • Los Angeles, California, United States, 90211
      • AIDS Healthcare Foundation
    • Palm Springs, California, United States, 92262
      • Palmtree Clinical Research Inc.
    • San Francisco, California, United States, 94115
      • Quest Clinical Research
    • San Francisco, California, United States, 94118
      • Kaiser Foundation Research Institute
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale University
    • Norwalk, Connecticut, United States, 06850
      • Circle CARE Center, LLC
  • 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
    • Fort Pierce, Florida, United States, 34982
      • Midway Immunology and Research Center
    • Miami, Florida, United States, 33136
      • University of Miami
    • 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
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland, Institute of Human Virology
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health Systems
    • Southfield, Michigan, United States, 48075
      • St. John Hospital and Medical Center
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center
    • New York, New York, United States, 10018
      • ACRIA
  • North Carolina
    • Charlotte, North Carolina, United States, 28232
      • Carolinas Healthcare System
  • Texas
    • Dallas, Texas, United States, 75246
      • North Texas Infectious Disease Consultants
    • Houston, Texas, United States, 77098
      • Research Access Network

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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
• Have no acquired immunodeficiency syndrome (AIDS)-defining events in the 3 months before Screening, other than cutaneous Kaposi's sarcoma or wasting syndrome due to HIV
• Are able and willing to comply with all protocol requirements and procedures
• Have a life expectancy that is >6 months.
• 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 resistance testing
• Have a history of at least 6 months on antiretroviral treatment
• Are receiving a stable highly active antiretroviral regimen for at least 8 weeks before Screening and are willing to continue that regimen until Day 14, OR (in the past 8 weeks) have failed and are off therapy and are willing to stay off therapy until Day 14
• Have full viral sensitivity/susceptibility to at least one antiretroviral agent, other than ibalizumab, as determined by the screening resistance tests 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 screening resistance tests 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:

• Any active AIDS-defining illness per Category C conditions according to the Centers for Disease Control and Prevention (CDC) Classification System for HIV Infection, with the following exceptions: cutaneous Kaposi's sarcoma and wasting syndrome due to HIV
• 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 initial administration of study drug
• 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 12 weeks before Enrollment
• Any prior exposure to ibalizumab (formerly TNX-355 and Hu5A8)
• Any vaccination within 7 days before Enrollment
• 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
• Any Grade 3 or 4 laboratory abnormality according to the Division of AIDS 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: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Open-Label Ibalizumab plus OBR; 2000 mg intravenous ibalizumab (loading dose) on Day 7 followed in 14 days (on Day 21) by 800 mg intravenous ibalizumab administered once every two weeks, plus an Optimized Background Regimen (OBR) beginning on Day 14.

Biological: ibalizumab; 2000mg intravenous ibalizumab (loading dose), followed 14 days later by 800mg intravenous ibalizumab every 2 weeks; Other Names: TNX-355; Hu1A8; Drug: Optimized Background Regimen (OBR); All participants will be prescribed an Optimized Background Regimen of antiretroviral medications selected on the basis of treatment history and the results of Screening viral resistance and tropism testing. The prescribed regimen must contain at least one agent to which the participant's virus is known to be sensitive.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy: Proportion of Participants Achieving a Viral Load Reduction of at Least 0.5 Log 10: ITT-MEF	Proportion of participants (%) achieving a viral load reduction of at least 0.5 log from baseline (Day 7)	Day 14
Efficacy: Proportion of Subjects With a Viral Load Decrease of at Least 0.5 Log 10 - Protocol Correct	Proportion of patients (%) with a viral load decrease of at least 0.5 log 10 from baseline (day 7)	Day 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy: Proportion of Patients With Undetectable Viral Load: ITT-MEF	Proportion of patients with undetectable Viral Load (<50 copies/mL, and <400 copies/mL)	Week 25 /end of study
Efficacy: Proportion of Patients With Undetectable HIV-RNA Levels: Protocol Correct	Proportion of patients (%) with HIV-RNA levels < 50 copies/mL and < 400 copies/mL at Week 25/End of Study	Week 25/End of Study
Mean Change in Viral Load as a Measure of Efficacy - ITT-MEF	Mean change from Day 7/Baseline in log 10 vial load measured at Day 14	Day 7 and Day 14
Mean Change in Viral Load as a Measure of Efficacy - Protocol Correct	Mean change from Day 7/Baseline in Log 10 viral load measured at Day 14	Day 7 and Day 14
End of Study Viral Load Reductions as a Measure of Efficacy - Intent to Treat Analysis	Proportion of patients achieving a >/= 0.5 log10 and >/= 1.0 log10 decrease from Day 7/Baseline in viral load at Week 25/End of Study	at Week 25/End of Study
End of Study Viral Load Reductions as a Measure of Efficacy - Protocol Correct Analysis	Proportion of patients achieving a >/= 0.5 log10 and >/= 1.0 log10 decrease from Day 7/Baseline in viral load at Week 25/End of Study	at Week 25/End of Study
Mean Change in CD4+ Cell Count as a Measure of Efficacy and Safety - ITT	Mean change from Day 7/Baseline in CD4+ cell count at Week 25/End of Study	Day 7 and Week 25/End of Study
Mean Change in CD4+ Cell Count as a Measure of Efficacy and Safety - Protocol Correct	Mean change from Day 7/Baseline in CD4+ cell count at Week 25/End of Study	Day 7 and Week 25/End of Study
Safety: Proportion of Participants Experiencing Adverse Events	Proportion of participants experiencing at least one treatment emergent adverse event to week 25/End of Study	Through Week 25/End of Study
Proportion of Participants Experiencing Adverse Event Related to Study Drug as a Measure of Safety and Tolerability	Proportion of participants experiencing a treatment emergent adverse event determined by the investigator to be related to study drug	Through Week 25/End of Study
Proportion of Participants Experiencing Serious Adverse Event as a Measure of Safety and Tolerability	Proportion of participants experiencing at least one serious treatment emergent adverse event, excluding death	Through Week 25/End of Study
Proportion of Participants Discontinuing Study Drug Due to Adverse Event	Proportion of participants discontinuing study drug due to occurrence of treatment emergent adverse event	Through Week 25/End of Study
Proportion of Participants Experiencing Adverse Event Grade 3 and Higher as a Measure of Safety and Tolerability	Proportion of participants experiencing treatment emergent adverse event Grade 3 and higher	Through Week 25/End of Study
Proportion of Participants Experiencing Adverse Event With Death as Outcome as a Measure of Safety and Tolerability	Proportion of participants experiencing treatment emergent adverse event with death as the outcome, regardless of relationship to study drug	Through Week 25/End of Study
Proportion of Participants Experiencing New AIDS-defining Adverse Event According to CDC Criteria as a Measure of Safety and Tolerability	Proportion of participants experiencing treatment emergent adverse event that is AIDS-defining by the CDC adverse event classification criteria for HIV infection	Through Week 25/End of Study

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacodynamics: CD4 Receptor Occupancy	% of CD receptors occupied by ibalizumab on CD4+ T-cells	At Week 25/End of Study

Collaborators and Investigators

• Sponsor: TaiMed Biologics Inc.

Publications and helpful links

General Publications

• Emu B, Fessel J, Schrader S, Kumar P, Richmond G, Win S, Weinheimer S, Marsolais C, Lewis S. Phase 3 Study of Ibalizumab for Multidrug-Resistant HIV-1. N Engl J Med. 2018 Aug 16;379(7):645-654. doi: 10.1056/NEJMoa1711460.

Study record dates

Study Major Dates

• Study Start: August 1, 2015
• Primary Completion (Actual): October 1, 2016
• Study Completion (Actual): December 1, 2016

Study Registration Dates

• First Submitted: June 11, 2015
• First Submitted That Met QC Criteria: June 18, 2015
• First Posted (Estimate): June 19, 2015

Study Record Updates

• Last Update Posted (Actual): March 19, 2020
• Last Update Submitted That Met QC Criteria: March 10, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Anti-Infective Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; Ibalizumab
• Other Study ID Numbers: TMB-301