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
  Purpose

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).


Condition Intervention Phase
HIV
Drug: Ibalizumab
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by TaiMed Biologics Inc.:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Other Outcome Measures:
  • 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.


Enrollment: 113
Study Start Date: August 2008
Study Completion Date: April 2011
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Ibalizumab 800 mg
every 2 weeks, combined with an Optimized Background Regimen
Drug: Ibalizumab
Ibalizumab 800 mg IV every 2 weeks
Other Name: TNX-355; Hu5A8
Active Comparator: Ibalizumab 2000 mg
every 4 weeks, combined with an Optimized Background Regimen
Drug: Ibalizumab
Ibalizumab 2000 mg IV every 4 weeks
Other Name: TNX-355; Hu5A8

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

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00784147

  Show 30 Study Locations
Sponsors and Collaborators
TaiMed Biologics Inc.
Investigators
Study Director: Stanley T. Lewis, MD TaiMed Biologics Inc.
  More Information

No publications provided

Responsible Party: TaiMed Biologics Inc.
ClinicalTrials.gov Identifier: NCT00784147     History of Changes
Other Study ID Numbers: TMB-202 Amendment 2
Study First Received: October 30, 2008
Results First Received: March 11, 2014
Last Updated: April 17, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by TaiMed Biologics Inc.:
HIV
CD4
experienced
resistant
resistance
monoclonal
antibody
infusion
ibalizumab
TNX355
TNX-355
TMB355
TMB-355

Additional relevant MeSH terms:
Antibodies, Monoclonal
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 29, 2014