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

• ClinicalTrials.gov Identifier: NCT02475629
• Recruitment Status: Completed
• First Posted: June 19, 2015
• Results First Posted: March 19, 2020
• Last Update Posted: March 19, 2020
• Sponsor: TaiMed Biologics Inc.
• Information provided by (Responsible Party): TaiMed Biologics Inc.

Tracking Information

• First Submitted Date: June 11, 2015
• First Posted Date: June 19, 2015
• Results First Submitted Date: February 7, 2020
• Results First Posted Date: March 19, 2020
• Last Update Posted Date: March 19, 2020
• Study Start Date: August 2015
• Actual Primary Completion Date: October 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 10, 2020)

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

Original Primary Outcome Measures (submitted: June 18, 2015)

Day 14 Viral Load Reduction as a Measure of Efficacy [ Time Frame: at Day 14 ]

Proportion of patients achieving a >/= 0.5 log10 decrease from Day 7/Baseline Viral Load

Current Secondary Outcome Measures (submitted: March 10, 2020)

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

Original Secondary Outcome Measures (submitted: June 18, 2015)

• Undetectable Viral Load as a Measure of Efficacy [ Time Frame: at Week 25/End of Study ]
  Proportion of patients with HIV-RNA levels < 50 copies/mL and < 400 copies/mL at Week 25/End of Study
• Mean Change in Viral Load as a Measure of Efficacy [ Time Frame: at Day 14 and Week 25/End of Study ]
  Mean change from Day 7/Baseline in viral load at Day 14 and at Week 25/End of Study
• End of Study Viral Load Reductions as a Measure of Efficacy [ Time Frame: at Week 25/End of Study ]
  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
• Mean Change in CD4+ Cell Count as a Measure of Efficacy and Safety [ Time Frame: at Week 25/End of Study ]
  Mean change from Day 7/Baseline in CD4+ cell count at Week 25/End of Study
• Viral Sensitivity/Susceptibility Changes Associated with Virologic Failure after Administration of Ibalizumab as a Measure of Efficacy [ Time Frame: Through Week 25/End of Study ]
  HIV-1 sensitivity/susceptibility changes associated with virologic failure after administration of ibalizumab
• CD4 Receptor Density as a Measure of Pharmacodynamics [ Time Frame: Through Week 25/End of Study ]
  Density of CD4 receptors on CD4+ T-cells
• CD4 Receptor Occupancy as a Measure of Pharmacodynamics [ Time Frame: Through Week 25/End of Study ]
  Occupancy of CD4 receptors on CD4+ T-cells by ibalizumab
• Number of Participants with Physical Examination Abnormalities as a Measure of Safety and Tolerability [ Time Frame: Through Week 25/End of Study ]
  Number of participants with physical examination abnormalities associated with the administration of ibalizumab
• Number of Participants with Vital Sign Measurement Abnormalities as a Measure of Safety and Tolerability [ Time Frame: Through Week 25/End of Study ]
  Number of participants with abnormal vital sign measurements associated with administration of ibalizumab
• Number of Participants with 12-Lead Electrocardiogram Abnormalities as a Measure of Safety and Tolerability [ Time Frame: Through Week 25/End of Study ]
  Number of participants with abnormal electrocardiogram measurements associated with administration of ibalizumab
• Number of Participants with Abnormal Clinical Laboratory Parameters as a Measure of Safety and Tolerability [ Time Frame: Through Week 25/End of Study ]
  Number of participants with abnormal clinical laboratory parameters associated with administration of ibalizumab
• Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: Through Week 25/End of Study ]
  Number of participants with adverse events associated with administration of ibalizumab
• Number of Participants with Class C AIDS-Defining Events as a Measure of Safety and Tolerability [ Time Frame: Through Week 25/End of Study ]
  Number of participants with CDC Classification System "Class C" AIDS-defining events associated with administration of ibalizumab
• Immunogenicity of Ibalizumab as a Measure of Safety and Tolerability [ Time Frame: Through Week 25/End of Study ]
  Measured levels of anti-ibalizumab antibodies in participant blood samples

Current Other Pre-specified Outcome Measures (submitted: March 10, 2020)

Pharmacodynamics: CD4 Receptor Occupancy [ Time Frame: At Week 25/End of Study ]

% of CD receptors occupied by ibalizumab on CD4+ T-cells

Original Other Pre-specified Outcome Measures (submitted: June 18, 2015)

• Patient-Related Assessment - Quality of Life as a Measure of Tolerability [ Time Frame: Week 25/End of Study ]
  Functional Assessment of HIV Infection (FAHI) questionnaire to assess patients' quality of life prior to study drug administration and again at Week 25/End of Study
• Ibalizumab Serum Concentrations as a Measure of Pharmacokinetics [ Time Frame: Through Week 25/End of Study ]
  Peak and trough concentrations of ibalizumab measured in serum

Descriptive Information

• Brief Title: Ibalizumab Plus Optimized Background Regimen in Patient With Multi-Drug Resistant HIV
• Official Title: 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
• Brief Summary: 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.

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
• Study Phase: Phase 3
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: HIV

Intervention

• 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.

Study Arms

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.

Interventions:

• Biological: ibalizumab
• Drug: Optimized Background Regimen (OBR)

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 17, 2016): 40
• Original Estimated Enrollment (submitted: June 18, 2015): 30
• Actual Study Completion Date: December 2016
• Actual Primary Completion Date: October 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Puerto Rico, Taiwan, United States

Administrative Information

• NCT Number: NCT02475629
• Other Study ID Numbers: TMB-301
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: TaiMed Biologics Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: TaiMed Biologics Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: TaiMed Biologics Inc.
• Verification Date: February 2020