Clinical trial NCT00784147: Dose-Response Study of Ibalizumab (Monoclonal Antibody) Plus Optimized Background Regimen in Patients With HIV-1
Official title: A Phase 2b, Randomized, Double-Blinded, 48-Week, Multicenter, Dose-Response Study of Ibalizumab Plus an Optimized Background Regimen in Treatment-Experienced Patients Infected With HIV-1(Amended to 24-Weeks)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV
Keywords: HIV
CD4
experienced
resistant
resistance
monoclonal
antibody
infusion
ibalizumab
TNX355
TNX-355
TMB355
TMB-355
Lead sponsor: TaiMed Biologics Inc.
Sponsor class: INDUSTRY
First posted: 2008-11-02
Enrollment: 113
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The investigational product, ibalizumab, is a humanized IgG4 monoclonal antibody administered via intravenous infusion at 800 mg every 2 weeks or at 2000 mg every 4 weeks. In addition to study drug, all patients will receive an optimized background regimen (OBR), which is a standard-of-care regimen selected by the investigator prior to randomization that is comprised of 2-4 antiretroviral agents. These agents must have been approved by the local regulatory agency or be available through expanded-access programs for treatment of human immunodeficiency virus (HIV).

Detailed description: The primary objectives of this study are to:

* Evaluate the dose-response relationship of antiviral activity of the ibalizumab dose regimens at Week 24 in order to determine the optimal dose and regimen. The primary evaluation of effectiveness will be based on the proportion of patients achieving undetectable viral loads at Week 24.
* Evaluate the safety and tolerability of two dose regimens of ibalizumab for dose selection

The secondary objectives of this study are to:

* Evaluate changes from Baseline in viral load, CD4+ cell counts, and time to loss of virologic response (TLOVR)
* Characterize HIV-1 sensitivity/susceptibility changes associated with ibalizumab administration in combination with OBR
* Determine the presence and significance of anti-ibalizumab antibodies, if any (immunogenicity of ibalizumab)
* Assess CD4 receptor density and occupancy
* Determine the impact of ibalizumab on quality of life as assessed by patient-reported outcomes on questionnaires
* Evaluate the pharmacokinetic profile of two dose regimens of ibalizumab at steady state

Eligibility criteria: Inclusion Criteria:

1. Are capable of understanding and have voluntarily signed the informed consent document
2. Have documented HIV-1 infection by official, signed, written history (eg, laboratory report), otherwise an HIV-antibody test will be performed
3. 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
4. Are able and willing to comply with all protocol requirements and procedures
5. Are 18 years of age or older
6. Have a life expectancy that is \>6 months.
7. Have a viral load \>1,000 copies/mL and documented decreased susceptibility to at least one NRTI, one NNRTI, and one PI, as measured by resistance testing
8. Are receiving a stable highly active antiretroviral regimen for at least 8 weeks before screening and are willing to continue that regimen until the baseline visit, OR (in the past 8 weeks) have failed and are off therapy and are willing to stay off therapy until the baseline visit
9. Have viral sensitivity/susceptibility to at least one agent (OSS criteria) 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 sensitive/susceptible according to the screening resistance tests as a component of OBR
10. 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:

1. Any active AIDS-defining illness per Category C conditions according to the Center for Disease Control (CDC) Classification System for HIV Infection, with the following exceptions: cutaneous Kaposi's sarcoma and wasting syndrome due to HIV
2. 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
3. Any significant acute illness within 1 week before the initial administration of study drug
4. Any active infection secondary to HIV requiring acute therapy; however, patients that require maintenance therapy (ie, secondary prophylaxis for opportunistic infections) will be eligible for the study
5. Any immunomodulating therapy (including interferon), systemic steroids, or systemic chemotherapy within 12 weeks before randomization
6. Any investigational therapy within 30 days before randomization, except for HIV-agents available in expanded-access programs
7. Any prior exposure to ibalizumab (formerly TNX-355 and Hu5A8)
8. Any vaccination within 21 days before randomization
9. Any female patient who either is pregnant, intends to become pregnant, or is currently breast-feeding
10. 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
11. Any previous clinically significant allergy or hypersensitivity to any excipient in the ibalizumab formulation
12. Any radiation therapy during the 28 days before first administration of investigational medication
13. Any grade 3 or 4 toxicity according to the Division of AIDS grading scale, except for the following asymptomatic grade 3 events: triglyceride elevation \& total cholesterol elevation

Primary outcomes:
measure: The Proportion of Patients Achieving Undetectable Viral Loads at Week 24.
timeFrame: 24 weeks
Secondary outcomes:
measure: Mean Change From Baseline in Viral Load (log10) at Week 24/EOS
timeFrame: Week 24 / End of Study
measure: Mean Change From Baseline in CD4+ T-Cell Count at Week 24/EOS
timeFrame: Week 24 / End of Study
Other outcomes:
measure: Proportion of Patients With Viral Load <200 Copies/mL at Week 24
timeFrame: Week 24
measure: Proportion of Patients With Viral Load <400 Copies/mL at Week 24
timeFrame: Week 24
measure: Proportion of Patients With a 1.0 log10 or Greater Reduction in Viral Load at Week 24
timeFrame: Week 24
measure: Proportion of Patients With a 0.5 log10 or Greater Reduction in Viral Load at Week 24
timeFrame: Week 24
Locations:
city: Beverly Hills
country: United States
facility: AIDS Health Care Foundation - Research
state: California
city: Long Beach
country: United States
facility: Living Hope Clinical Foundation
state: California
city: Los Angeles
country: United States
facility: Kaiser Permanente Medical Center
state: California
city: San Francisco
country: United States
facility: Quest Clinical Research
state: California
city: San Francisco
country: United States
facility: Kaiser Permanente Medical Center Research Unit
state: California
city: Denver
country: United States
facility: Kaiser Permanente of Colorado
state: Colorado
city: Denver
country: United States
facility: National Jewish Medical & Research Center
state: Colorado
city: Washington
country: United States
facility: Whitman-Walker Clinic
state: District of Columbia
city: Atlantis
country: United States
facility: South Florida Clinical Research
state: Florida
city: Miami
country: United States
facility: University of Miami, Miller School of Medicine
state: Florida
city: Orlando
country: United States
facility: Orlando Immunology Center
state: Florida
city: Port St. Lucie
country: United States
facility: Associates in Infectious Diseases
state: Florida
city: Vero Beach
country: United States
facility: Treasure Coast Infectious Disease Consultants
state: Florida
city: West Palm Beach
country: United States
facility: Triple O Medical Services, Inc.
state: Florida
city: Chicago
country: United States
facility: Northstar Medical Center
state: Illinois
city: Indianapolis
country: United States
facility: Indiana University School of Medicine - Wishard Memorial Hospital
state: Indiana
city: Newark
country: United States
facility: St. Michael's Medical Center
state: New Jersey
city: New York
country: United States
facility: AIDS Community Research Initiative of America
state: New York
city: Greenville
country: United States
facility: The Brody School of Medicine at ECU
state: North Carolina
city: Portland
country: United States
facility: The Research & Educational Group
state: Oregon
city: Austin
country: United States
facility: Central Texas Clinical Research
state: Texas
city: Dallas
country: United States
facility: North Texas Infectious Disease Consultants
state: Texas
city: Harlingen
country: United States
facility: Valley AIDS Council
state: Texas
city: Houston
country: United States
facility: Therapeutic Concepts
state: Texas
city: Houston
country: United States
facility: University of Texas Health Science Center
state: Texas
city: Houston
country: United States
facility: Nationsmed Clinical Research
state: Texas
city: Houston
country: United States
facility: Dr. Gordon E. Crofoot, MD, PA
state: Texas
city: Houston
country: United States
facility: Research Access Network
state: Texas
city: San Juan
country: Puerto Rico
facility: Clinical Research Puerto Rico
city: San Juan
country: Puerto Rico
facility: HOPE Clinical Research
Study officials:
affiliation: TaiMed Biologics Inc.
name: Stanley T. Lewis, MD
role: STUDY_DIRECTOR
References: