Dose-Response Study of Ibalizumab (Monoclonal Antibody) Plus Optimized Background Regimen in Patients With HIV-1
Condition: HIV
Intervention: Ibalizumab; Ibalizumab
Intervention description: Ibalizumab 800 mg IV every 2 weeks; Ibalizumab 2000 mg IV every 4 weeks
Intervention MeSH terms: Ibalizumab; Antibodies, Monoclonal
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 113.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: HIV; CD4; experienced; resistant; resistance; monoclonal; antibody; infusion; ibalizumab; TNX355; TNX-355; TMB355; TMB-355

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).
    

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