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

• ClinicalTrials.gov Identifier: NCT01668043
• Recruitment Status: Completed
• First Posted: August 17, 2012
• Last Update Posted: August 20, 2014
• Sponsor: United Biomedical
• Collaborators: Taipei Veterans General Hospital, Taiwan; Kaohsiung Veterans General Hospital.; UBI Asia in Taiwan
• Information provided by (Responsible Party): United Biomedical

Tracking Information

• First Submitted Date: August 1, 2012
• First Posted Date: August 17, 2012
• Last Update Posted Date: August 20, 2014
• Study Start Date: September 2012
• Actual Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 15, 2012)

• To evaluate safety and tolerability of multiple intravenous infusions of two dose cohorts of UB-421 [ Time Frame: 16-week study period ]
  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 ]
  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.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: August 15, 2012)

• To determine pharmacokinetic parameters of two dose cohorts of UB-421. [ Time Frame: 16-week study period ]
  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 ]
  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.

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: September 20, 2012)

• To determine pharmacokinetic parameters of two dose cohorts of UB-421 [ Time Frame: 16-week study period ]
  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 ]
  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 ]
  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).

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study to Evaluate Safety and Efficacy of UB-421 Antibody in HIV-1 Infected Adults
• 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
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: HIV-1 Infection in Adults

Intervention

Drug: Antibody UB-421

UB-421 is administered by intravenous infusion

Study Arms

• Experimental: Antibody UB-421 Cohort 1
  10 mg/kg BW, 8 weekly doses for 8-week treatment period
  Intervention: Drug: Antibody UB-421
• Experimental: Antibody UB-421 Cohort 2
  25 mg/kg BW, 4 biweekly doses for 8-week treatment period
  Intervention: Drug: Antibody UB-421

Publications *

• 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.
• 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

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 18, 2014): 29
• Original Estimated Enrollment (submitted: August 15, 2012): 20
• Actual Study Completion Date: March 2014
• Actual Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 20 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Taiwan

Administrative Information

• NCT Number: NCT01668043
• Other Study ID Numbers: UBI Protocol A201; Protocol A201-HIV ( Other Identifier: UBI Asia )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: United Biomedical
• Original Responsible Party: Same as current
• Current Study Sponsor: United Biomedical
• Original Study Sponsor: Same as current

Collaborators

• 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)

• PRS Account: United Biomedical
• Verification Date: August 2014