Study to Evaluate Safety and Efficacy of UB-421 Antibody in HIV-1 Infected Adults

This study has been completed.
Sponsor:
Collaborators:
Taipei Veterans General Hospital, Taiwan
Kaohsiung Veterans General Hospital.
UBI Asia in Taiwan
Information provided by (Responsible Party):
United Biomedical
ClinicalTrials.gov Identifier:
NCT01668043
First received: August 1, 2012
Last updated: August 18, 2014
Last verified: August 2014
  Purpose

The purpose of this Phase IIa study is to determine whether the antibody (UB-421), targeting the HIV-1 receptor on the CD4 molecule of T-lymphocytes and monocytes, is safe and effective when multiple doses are administered by intravenous infusion to asymptomatic HIV-1 infected adults and to assess pharmacokinetic parameters of the antibody in blood and on cells. The neutralizing activity of UB-421 blocks HIV-1 from binding to its receptor on CD4-positive cells; thus, UB-421 functions as an immunotherapeutic intervention to prevent HIV-1 infection.


Condition Intervention Phase
HIV-1 Infection in Adults
Drug: Antibody UB-421
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase IIa, Open-label, Multiple-Dose Trial to Investigate the Safety and Efficacy of the UB-421 in Asymptomatic HIV-1 Infected Adults

Resource links provided by NLM:


Further study details as provided by United Biomedical:

Primary Outcome Measures:
  • To evaluate safety and tolerability of multiple intravenous infusions of two dose cohorts of UB-421 [ Time Frame: 16-week study period ] [ Designated as safety issue: Yes ]

    Safety evaluations include physical examination, measurement of vital signs, clinical chemistry and hematology tests at each visit (to assess changes from normal range), incidence of adverse event (AE) and serious AE (SAE) of two dose cohorts and are followed for 16 weeks (end of study).

    Overall treatment tolerability of UB-421 for each cohort is defined as the percentage of the number of actual infusion doses divided by number of actual infusion doses plus number of missed doses of subject(s) who drops out due to drug-related AE(s); calculation follows specific formula.


  • To evaluate efficacy by measurement of individual maximal viral load reduction and mean maximal viral load reduction of two dose cohorts of UB-421. [ Time Frame: 16-week study period ] [ Designated as safety issue: Yes ]
    Efficacy measurements include virologic responses and determination of the proportion of subjects with viral load <50 copies/mL or <200 copies/mL; viral load reduction >0.5 log10 copies/mL or >1.0 log10 copies/mL; viral rebound over 0.5 log10 increase in viral load from the nadir value during 8-week treatment period, suggesting presence of study drug resistance mutants. HIV-1 viral load is determined at each blood collection during 16-week study period.


Secondary Outcome Measures:
  • To determine pharmacokinetic parameters of two dose cohorts of UB-421. [ Time Frame: 16-week study period ] [ Designated as safety issue: Yes ]
    Pharmacokinetic analyses are calculated at each visit during 8-week treatment period to determine the serum concentration before and after each infusion of UB-421 and during the 8-week follow-up period to determine the clearance of study drug in circulation.

  • To determine the anti-UB-421 antibody concentration in serum of two dose cohorts of UB-421 [ Time Frame: 16-week study period ] [ Designated as safety issue: Yes ]
    Immunogenicity of the study drug is measured by analytical ELISA test at each visit to determine if the anti-UB-421 antibody concentration is increased above the pre-treatment baseline level.


Other Outcome Measures:
  • To determine pharmacokinetic parameters of two dose cohorts of UB-421 [ Time Frame: 16-week study period ] [ Designated as safety issue: Yes ]
    Pharmacokinetic analyses are calculated at each visit during 8-week treatment period to determine the percentage of CD4+ T lymphocytes binding to the UB-421 study drug before each infusion and during the 8-week follow-up period to determine the duration of study drug bound to the CD4+ cells in circulation

  • To evaluate safety of multiple intravenous infusions of two dose cohorts of UB-421 [ Time Frame: 16-week study period ] [ Designated as safety issue: Yes ]
    Safety evaluations include evaluation of peripheral blood mononuclear cell proliferation and expression of Th1 and Th2 cytokines in the presence of study drug before the first and last UB-421 infusions during 8-week treatment period and at the end of follow-up period.

  • To evaluate efficacy by measurement of individual viral load samples for appearance of drug resistance mutants in the two dose cohorts of UB-421 [ Time Frame: 16-week period ] [ Designated as safety issue: Yes ]
    Efficacy measurements include virologic responses and determination of the proportion of subjects (if any) with viral load rebound during 8-week treatment period, suggesting emergence of study drug resistance mutants. Samples with viral load rebound will be characterized further to identify virus mutation(s).


Enrollment: 29
Study Start Date: September 2012
Study Completion Date: March 2014
Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Antibody UB-421 Cohort 1
10 mg/kg BW, 8 weekly doses for 8-week treatment period
Drug: Antibody UB-421
UB-421 is administered by intravenous infusion
Experimental: Antibody UB-421 Cohort 2
25 mg/kg BW, 4 biweekly doses for 8-week treatment period
Drug: Antibody UB-421
UB-421 is administered by intravenous infusion

  Eligibility

Ages Eligible for Study:   20 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Asymptomatic, treatment-naive, HIV-1 seropositive
  • CD4+ T cell count >350 cells/cubic millimeter
  • HIV-1 viral load >5,000 copies/mL
  • Other inclusion criteria apply

Exclusion Criteria:

  • Active infection requiring immediate therapy (except HIV-1)
  • Previous exposure to monoclonal antibody (including UB-421)
  • Prior participation in any HIV vaccine trial
  • Use of immunomodulating drugs or systemic chemotherapy
  • Other exclusion criteria apply
  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: NCT01668043

Locations
Taiwan
Taipei Veterans General Hospital (TVGH)
Taipei City, Beitou District, Taiwan, 11217
Kaohsiung Veterans General Hospital (KVGH)
Kaohsiung City, Zuoying District, Taiwan, 81362
Sponsors and Collaborators
United Biomedical
Taipei Veterans General Hospital, Taiwan
Kaohsiung Veterans General Hospital.
UBI Asia in Taiwan
Investigators
Principal Investigator: Wing Wai Wong, M.D. Taipei Veterans General Hospital (TVGH)
Principal Investigator: Hung Chin Tsai, M.D. Kaohsiung Veterans General Hospital (KVGH)
  More Information

Publications:
Responsible Party: United Biomedical
ClinicalTrials.gov Identifier: NCT01668043     History of Changes
Other Study ID Numbers: UBI Protocol A201, Protocol A201-HIV
Study First Received: August 1, 2012
Last Updated: August 18, 2014
Health Authority: Taiwan: Department of Health
Taiwan: Institutional Review Board

Keywords provided by United Biomedical:
HIV-1
CD4
antibody
immunotherapy

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

ClinicalTrials.gov processed this record on August 28, 2014