Clinical trial NCT02475629: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV
Lead sponsor: TaiMed Biologics Inc.
Sponsor class: INDUSTRY
First posted: 2015-06-19
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Efficacy: Proportion of Participants Achieving a Viral Load Reduction of at Least 0.5 Log 10: ITT-MEF
timeFrame: Day 14
measure: Efficacy: Proportion of Subjects With a Viral Load Decrease of at Least 0.5 Log 10 - Protocol Correct
timeFrame: Day 14
Secondary outcomes:
measure: Efficacy: Proportion of Patients With Undetectable Viral Load: ITT-MEF
timeFrame: Week 25 /end of study
measure: Efficacy: Proportion of Patients With Undetectable HIV-RNA Levels: Protocol Correct
timeFrame: Week 25/End of Study
measure: Mean Change in Viral Load as a Measure of Efficacy - ITT-MEF
timeFrame: Day 7 and Day 14
measure: Mean Change in Viral Load as a Measure of Efficacy - Protocol Correct
timeFrame: Day 7 and Day 14
measure: End of Study Viral Load Reductions as a Measure of Efficacy - Intent to Treat Analysis
timeFrame: at Week 25/End of Study
measure: End of Study Viral Load Reductions as a Measure of Efficacy - Protocol Correct Analysis
timeFrame: at Week 25/End of Study
measure: Mean Change in CD4+ Cell Count as a Measure of Efficacy and Safety - ITT
timeFrame: Day 7 and Week 25/End of Study
measure: Mean Change in CD4+ Cell Count as a Measure of Efficacy and Safety - Protocol Correct
timeFrame: Day 7 and Week 25/End of Study
measure: Safety: Proportion of Participants Experiencing Adverse Events
timeFrame: Through Week 25/End of Study
measure: Proportion of Participants Experiencing Adverse Event Related to Study Drug as a Measure of Safety and Tolerability
timeFrame: Through Week 25/End of Study
measure: Proportion of Participants Experiencing Serious Adverse Event as a Measure of Safety and Tolerability
timeFrame: Through Week 25/End of Study
measure: Proportion of Participants Discontinuing Study Drug Due to Adverse Event
timeFrame: Through Week 25/End of Study
measure: Proportion of Participants Experiencing Adverse Event Grade 3 and Higher as a Measure of Safety and Tolerability
timeFrame: Through Week 25/End of Study
measure: Proportion of Participants Experiencing Adverse Event With Death as Outcome as a Measure of Safety and Tolerability
timeFrame: Through Week 25/End of Study
measure: Proportion of Participants Experiencing New AIDS-defining Adverse Event According to CDC Criteria as a Measure of Safety and Tolerability
timeFrame: Through Week 25/End of Study
Other outcomes:
measure: Pharmacodynamics: CD4 Receptor Occupancy
timeFrame: At Week 25/End of Study
Locations:
city: Long Beach
country: United States
facility: Long Beach Education and Research Consultants
state: California
city: Los Angeles
country: United States
facility: W King Health Care Group
state: California
city: Los Angeles
country: United States
facility: Southern California Permanente Medical Group
state: California
city: Los Angeles
country: United States
facility: Ruane Medical and Clinical Research Institute
state: California
city: Los Angeles
country: United States
facility: Charles R. Drew Univ. of Med. & Science Clinical and Translational Research Center
state: California
city: Los Angeles
country: United States
facility: Anthony Mills, MD, Inc.
state: California
city: Los Angeles
country: United States
facility: AIDS Healthcare Foundation
state: California
city: Palm Springs
country: United States
facility: Palmtree Clinical Research Inc.
state: California
city: San Francisco
country: United States
facility: Quest Clinical Research
state: California
city: San Francisco
country: United States
facility: Kaiser Foundation Research Institute
state: California
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Norwalk
country: United States
facility: Circle Care Center, LLC
state: Connecticut
city: Washington
country: United States
facility: Georgetown University School of Medicine
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: Gary Richmond, MD, PA
state: Florida
city: Fort Pierce
country: United States
facility: Midway Immunology and Research Center
state: Florida
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Orlando
country: United States
facility: Orlando Immunology Center
state: Florida
city: West Palm Beach
country: United States
facility: Triple O Research Institute
state: Florida
city: Atlanta
country: United States
facility: AIDS Research Consortium of Atlanta
state: Georgia
city: Baltimore
country: United States
facility: University of Maryland, Institute of Human Virology
state: Maryland
city: Detroit
country: United States
facility: Henry Ford Health Systems
state: Michigan
city: Southfield
country: United States
facility: St. John Hospital and Medical Center
state: Michigan
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: New York
country: United States
facility: ACRIA
state: New York
city: Charlotte
country: United States
facility: Carolinas HealthCare System
state: North Carolina
city: Dallas
country: United States
facility: North Texas Infectious Disease Consultants
state: Texas
city: Houston
country: United States
facility: Research Access Network
state: Texas
city: San Juan
country: Puerto Rico
facility: Clinical Research PR, Inc
city: Kaohsiung
country: Taiwan
facility: E-Da Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
Study officials:
References:
citation: 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.