<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01668043</url>
  </required_header>
  <id_info>
    <org_study_id>UBI Protocol A201</org_study_id>
    <secondary_id>Protocol A201-HIV</secondary_id>
    <nct_id>NCT01668043</nct_id>
  </id_info>
  <brief_title>Study to Evaluate Safety and Efficacy of UB-421 Antibody in HIV-1 Infected Adults</brief_title>
  <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</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>United Biomedical</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Taipei Veterans General Hospital, Taiwan</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Kaohsiung Veterans General Hospital.</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>UBI Asia in Taiwan</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>United Biomedical</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this Phase IIa study is to determine whether the antibody (UB-421), targeting&#xD;
      the HIV-1 receptor on the CD4 molecule of T-lymphocytes and monocytes, is safe and effective&#xD;
      when multiple doses are administered by intravenous infusion to asymptomatic HIV-1 infected&#xD;
      adults and to assess pharmacokinetic parameters of the antibody in blood and on cells. The&#xD;
      neutralizing activity of UB-421 blocks HIV-1 from binding to its receptor on CD4-positive&#xD;
      cells; thus, UB-421 functions as an immunotherapeutic intervention to prevent HIV-1&#xD;
      infection.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">March 2014</completion_date>
  <primary_completion_date type="Actual">March 2014</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>To evaluate safety and tolerability of multiple intravenous infusions of two dose cohorts of UB-421</measure>
    <time_frame>16-week study period</time_frame>
    <description>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).&#xD;
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.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>To evaluate efficacy by measurement of individual maximal viral load reduction and mean maximal viral load reduction of two dose cohorts of UB-421.</measure>
    <time_frame>16-week study period</time_frame>
    <description>Efficacy measurements include virologic responses and determination of the proportion of subjects with viral load &lt;50 copies/mL or &lt;200 copies/mL; viral load reduction &gt;0.5 log10 copies/mL or &gt;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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>To determine pharmacokinetic parameters of two dose cohorts of UB-421.</measure>
    <time_frame>16-week study period</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>To determine the anti-UB-421 antibody concentration in serum of two dose cohorts of UB-421</measure>
    <time_frame>16-week study period</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>To determine pharmacokinetic parameters of two dose cohorts of UB-421</measure>
    <time_frame>16-week study period</time_frame>
    <description>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</description>
  </other_outcome>
  <other_outcome>
    <measure>To evaluate safety of multiple intravenous infusions of two dose cohorts of UB-421</measure>
    <time_frame>16-week study period</time_frame>
    <description>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.</description>
  </other_outcome>
  <other_outcome>
    <measure>To evaluate efficacy by measurement of individual viral load samples for appearance of drug resistance mutants in the two dose cohorts of UB-421</measure>
    <time_frame>16-week period</time_frame>
    <description>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).</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">29</enrollment>
  <condition>HIV-1 Infection in Adults</condition>
  <arm_group>
    <arm_group_label>Antibody UB-421 Cohort 1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>10 mg/kg BW, 8 weekly doses for 8-week treatment period</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Antibody UB-421 Cohort 2</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>25 mg/kg BW, 4 biweekly doses for 8-week treatment period</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Antibody UB-421</intervention_name>
    <description>UB-421 is administered by intravenous infusion</description>
    <arm_group_label>Antibody UB-421 Cohort 1</arm_group_label>
    <arm_group_label>Antibody UB-421 Cohort 2</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Asymptomatic, treatment-naive, HIV-1 seropositive&#xD;
&#xD;
          -  CD4+ T cell count &gt;350 cells/cubic millimeter&#xD;
&#xD;
          -  HIV-1 viral load &gt;5,000 copies/mL&#xD;
&#xD;
          -  Other inclusion criteria apply&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Active infection requiring immediate therapy (except HIV-1)&#xD;
&#xD;
          -  Previous exposure to monoclonal antibody (including UB-421)&#xD;
&#xD;
          -  Prior participation in any HIV vaccine trial&#xD;
&#xD;
          -  Use of immunomodulating drugs or systemic chemotherapy&#xD;
&#xD;
          -  Other exclusion criteria apply&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Wing Wai Wong, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Taipei Veterans General Hospital (TVGH)</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Hung Chin Tsai, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Kaohsiung Veterans General Hospital (KVGH)</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Taipei Veterans General Hospital (TVGH)</name>
      <address>
        <city>Taipei City</city>
        <state>Beitou District</state>
        <zip>11217</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kaohsiung Veterans General Hospital (KVGH)</name>
      <address>
        <city>Kaohsiung City</city>
        <state>Zuoying District</state>
        <zip>81362</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <reference>
    <citation>Wang CY, Sawyer LS, Murthy KK, Fang X, Walfield AM, Ye J, Wang JJ, Chen PD, Li ML, Salas MT, Shen M, Gauduin MC, Boyle RW, Koup RA, Montefiori DC, Mascola JR, Koff WC, Hanson CV. Postexposure immunoprophylaxis of primary isolates by an antibody to HIV receptor complex. Proc Natl Acad Sci U S A. 1999 Aug 31;96(18):10367-72. doi: 10.1073/pnas.96.18.10367.</citation>
    <PMID>10468614</PMID>
  </reference>
  <reference>
    <citation>Lynn S and Wang CY. Designed deimmunied monoclonal antibodies for protection against HIV exposure and treatment of HIV infection. U.S. Patent No. 7,501,494. http://patft.uspto.gov/netahtml/PTO/srchnum.htm</citation>
  </reference>
  <verification_date>August 2014</verification_date>
  <study_first_submitted>August 1, 2012</study_first_submitted>
  <study_first_submitted_qc>August 15, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 17, 2012</study_first_posted>
  <last_update_submitted>August 18, 2014</last_update_submitted>
  <last_update_submitted_qc>August 18, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 20, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>HIV-1</keyword>
  <keyword>CD4</keyword>
  <keyword>antibody</keyword>
  <keyword>immunotherapy</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>UB-421</mesh_term>
    <mesh_term>Antibodies</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01668043
org study id: UBI Protocol A201
secondary id: Protocol A201-HIV
nct id: NCT01668043
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
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.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: To evaluate safety and tolerability of multiple intravenous infusions of two dose cohorts of UB-421
time frame: 16-week study period
description: 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.
measure: 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
description: 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.
measure: To determine pharmacokinetic parameters of two dose cohorts of UB-421.
time frame: 16-week study period
description: 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.
measure: To determine the anti-UB-421 antibody concentration in serum of two dose cohorts of UB-421
time frame: 16-week study period
description: 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.
measure: To determine pharmacokinetic parameters of two dose cohorts of UB-421
time frame: 16-week study period
description: 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
measure: To evaluate safety of multiple intravenous infusions of two dose cohorts of UB-421
time frame: 16-week study period
description: 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.
measure: 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
description: 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).
arm group label: Antibody UB-421 Cohort 1
arm group type: Experimental
description: 10 mg/kg BW, 8 weekly doses for 8-week treatment period
arm group label: Antibody UB-421 Cohort 2
arm group type: Experimental
description: 25 mg/kg BW, 4 biweekly doses for 8-week treatment period
intervention type: Drug
intervention name: Antibody UB-421
description: UB-421 is administered by intravenous infusion
arm group label: Antibody UB-421 Cohort 1
arm group label: Antibody UB-421 Cohort 2
criteria: 
gender: All
minimum age: 20 Years
maximum age: N/A
healthy volunteers: No
last name: Wing Wai Wong, M.D.
role: Principal Investigator
affiliation: Taipei Veterans General Hospital (TVGH)
last name: Hung Chin Tsai, M.D.
role: Principal Investigator
affiliation: Kaohsiung Veterans General Hospital (KVGH)
facility: 
facility: 
country: Taiwan
citation: Wang CY, Sawyer LS, Murthy KK, Fang X, Walfield AM, Ye J, Wang JJ, Chen PD, Li ML, Salas MT, Shen M, Gauduin MC, Boyle RW, Koup RA, Montefiori DC, Mascola JR, Koff WC, Hanson CV. Postexposure immunoprophylaxis of primary isolates by an antibody to HIV receptor complex. Proc Natl Acad Sci U S A. 1999 Aug 31;96(18):10367-72. doi: 10.1073/pnas.96.18.10367.
PMID: 10468614
citation: Lynn S and Wang CY. Designed deimmunied monoclonal antibodies for protection against HIV exposure and treatment of HIV infection. U.S. Patent No. 7,501,494. http://patft.uspto.gov/netahtml/PTO/srchnum.htm
responsible party type: Sponsor
mesh term: UB-421
mesh term: Antibodies