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

Study Overview
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Brief Summary
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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.

Official Title
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A Phase IIa, Open-label, Multiple-Dose Trial to Investigate the Safety and Efficacy of the UB-421 in Asymptomatic HIV-1 Infected Adults

Conditions
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HIV-1 Infection in Adults

Intervention / Treatment
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* Drug: Antibody UB-421


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Antibody UB-421 Cohort 1<br>10 mg/kg BW, 8 weekly doses for 8-week treatment period | Drug: Antibody UB-421<br>* UB-421 is administered by intravenous infusion<br>|
| Experimental: Antibody UB-421 Cohort 2<br>25 mg/kg BW, 4 biweekly doses for 8-week treatment period | Drug: Antibody UB-421<br>* UB-421 is administered by intravenous infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To evaluate safety and tolerability of multiple intravenous infusions of two dose cohorts of UB-421 | 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. | 16-week study period | 
| To evaluate efficacy by measurement of individual maximal viral load reduction and mean maximal viral load reduction of two dose cohorts of UB-421. | 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. | 16-week study period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To determine pharmacokinetic parameters of two dose cohorts of UB-421. | 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. | 16-week study period | 
| To determine the anti-UB-421 antibody concentration in serum of two dose cohorts of UB-421 | 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. | 16-week study period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV-1, CD4, antibody, immunotherapy