Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Dose-Response Study of Ibalizumab (Monoclonal Antibody) Plus Optimized Background Regimen in Patients With HIV-1 (TMB-202)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
TaiMed Biologics Inc.
ClinicalTrials.gov Identifier:
NCT00784147
First received: October 30, 2008
Last updated: April 17, 2014
Last verified: April 2014

October 30, 2008
April 17, 2014
August 2008
April 2011   (final data collection date for primary outcome measure)
The Proportion of Patients Achieving Undetectable Viral Loads at Week 24. [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
For the primary efficacy analysis, "undetectable" was defined as having HIV-1 RNA below the limit of assay detection at <50 copies/mL. The primary efficacy endpoint was analyzed using Fisher exact test. The primary analysis was performed using the ITT population and both the missing data equals treatment failure (MEF) and last observation carried forward (LOCF) methods. The more conservative MEF results are recorded here.
The primary evaluation of effectiveness will be based on the proportion of patients achieving undetectable viral loads at Week 24. [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
Complete list of historical versions of study NCT00784147 on ClinicalTrials.gov Archive Site
  • Mean Change From Baseline in Viral Load (log10) at Week 24/EOS [ Time Frame: Week 24 / End of Study ] [ Designated as safety issue: No ]
    The mean change in HIV-1 RNA (log10) from the Baseline measurement was analyzed at Week 24/End of Study using a generalized linear model at each scheduled study visit.
  • Mean Change From Baseline in CD4+ T-Cell Count at Week 24/EOS [ Time Frame: Week 24 / End of Study ] [ Designated as safety issue: No ]
    The mean change in CD4+ T-cell count from the Baseline measurement at Week 24/End of Study was summarized at each scheduled time point by treatment group.
Evaluate changes in viral load, CD4+ cell counts,TOLVR; pharmacokinetic sensitivity, susceptibility, & presence of antibodies to ibalizumab; impact of ibalizumab on quality of life [ Time Frame: 48 weeks ] [ Designated as safety issue: Yes ]
  • Proportion of Patients With Viral Load <200 Copies/mL at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    This measure was assessed in the same manner as the primary efficacy analysis for the proportion of patients achieving HIV-1 RNA levels below 200 copies/mL at Week 24 of the study.
  • Proportion of Patients With Viral Load <400 Copies/mL at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    This efficacy measure was assessed in the same manner as the primary efficacy analysis to determine the proportion of the total population achieving HIV-1 RNA levels <400 copies at Week 24 of the study.
  • Proportion of Patients With a 1.0 log10 or Greater Reduction in Viral Load at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    This efficacy assessment was performed in the same manner as the primary efficacy analysis for the proportion of the total population achieving at least a 1.0 log10 reduction from Baseline in HIV-1 RNA.
  • Proportion of Patients With a 0.5 log10 or Greater Reduction in Viral Load at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    This efficacy assessment was performed in the same manner as the primary efficacy analysis for the proportion of the total population achieving at least a 0.5 log10 reduction from the Baseline measurement in HIV-1 RNA at Week 24 of the study.
Not Provided
 
Dose-Response Study of Ibalizumab (Monoclonal Antibody) Plus Optimized Background Regimen in Patients With HIV-1
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)

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).

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
Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
HIV
  • Drug: Ibalizumab
    Ibalizumab 800 mg IV every 2 weeks
    Other Name: TNX-355; Hu5A8
  • Drug: Ibalizumab
    Ibalizumab 2000 mg IV every 4 weeks
    Other Name: TNX-355; Hu5A8
  • Active Comparator: Ibalizumab 800 mg
    every 2 weeks, combined with an Optimized Background Regimen
    Intervention: Drug: Ibalizumab
  • Active Comparator: Ibalizumab 2000 mg
    every 4 weeks, combined with an Optimized Background Regimen
    Intervention: Drug: Ibalizumab
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
113
April 2011
April 2011   (final data collection date for primary outcome measure)

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
Both
18 Years to 70 Years
No
Contact information is only displayed when the study is recruiting subjects
United States,   Puerto Rico
 
NCT00784147
TMB-202 Amendment 2
Yes
TaiMed Biologics Inc.
TaiMed Biologics Inc.
Not Provided
Study Director: Stanley T. Lewis, MD TaiMed Biologics Inc.
TaiMed Biologics Inc.
April 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP