A Safety Study of Brentuximab Vedotin in Participants With HIV

Study Overview
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Brief Summary
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This study will test brentuximab vedotin to see if it is safe for people with human immunodeficiency virus (HIV) who have low CD4+ and have received antiretroviral therapy (ART) treatment. It will also see if brentuximab vedotin raises CD4+ counts. It will study the side effects of this drug as well. A side effect is anything a drug does to the body besides treating the disease. In this study participants will be assigned randomly to a group. Participants will get either brentuximab vedotin or placebo. A placebo looks like the drug but does not contain any medicine in it. All participants will keep getting ART during the study.

Official Title
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A Phase 1, Single-blind, Dose-escalation Study to Assess the Safety and Tolerability of Brentuximab Vedotin (ADCETRIS®) in Subjects With Human Immunodeficiency Virus (HIV)

Conditions
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Human Immunodeficiency Virus

Intervention / Treatment
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* Drug: brentuximab vedotin
* Drug: Placebo
* Drug: ART


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV-1 seropositive with documentation of infection Immunological nonresponder, defined as: Has been on ART with an HIV viral load <50 copies/mL for at least 24 months Has a CD4+ T-cell lymphocyte count between 51 to 200 cells/µL Life expectancy of >9 months. Participant is negative for hepatitis B, or if infected with hepatitis B, receiving anti-hepatitis B therapy Participants with a history of hepatitis C virus (HCV) are eligible if they have completed therapy for HCV and show sustained virologic remission (12 weeks or more) Exclusion Criteria: Any currently active AIDS-defining illness per Category C conditions according to the CDC Classification System for HIV Infection, with the following exceptions: Limited cutaneous Kaposi's sarcoma not currently requiring systemic therapy Wasting syndrome due to HIV or any other AIDS-defining illness for which no therapeutic treatment is required OR the required treatment is not included in the list of prohibited medications Acute liver disease or any other active infection secondary to HIV requiring acute therapy History of progressive multifocal leukoencephalopathy (PML) Prior clinical John Cunningham virus (JCV) infection, history of JCV identified in cerebrospinal fluid, or presence of JCV antibodies at screening Cirrhosis secondary to any cause Any immunomodulating therapy (excluding premedication steroid) within 4 weeks prior to the screening visit Prior malignancy within 2 years other than cutaneous basal cell or squamous cell carcinoma, carcinoma in situ of the cervix, anal intraepithelial neoplasia, or cutaneous Kaposi's sarcoma

Ages Eligible for Study
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Minimum Age: 18 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: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Brentuximab vedotin + ART<br>Brentuximab vedotin given on Day 1 and Day 15. ART will be given throughout the study. | Drug: brentuximab vedotin<br>* Given into the vein (IV; intravenously)<br>* Other names: ADCETRIS;Drug: ART<br>* Daily use of a combination of HIV medicines<br>|
| Placebo Comparator: Placebo + ART<br>Placebo given on Day 1 and Day 15. ART will be given throughout the study. | Drug: Placebo<br>* Given by IV<br>Drug: ART<br>* Daily use of a combination of HIV medicines<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events (AEs) | Any untoward medical occurrence in a clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment | Through 30 days after last study treatment | 
| Number of participants with laboratory abnormalities |  | Approximately 1 year | 
| Number of participants with dose-limiting toxicities (DLTs) by dose level |  | Up to 30 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the concentration-time curve (AUC) | Pharmacokinetic (PK) Parameter | Approximately 4 months | 
| Maximum concentration (Cmax) | PK Parameter | Approximately 4 months | 
| Time to maximum concentration (Tmax) | PK Parameter | Approximately 4 months | 
| Apparent terminal half-life (t1/2) | PK Parameter | Approximately 4 months | 
| Trough concentration (Ctrough) | PK Parameter | Approximately 4 months | 
| Incidence of antidrug antibodies (ADAs) |  | Approximately 4 months | 
| Proportion of participants with CD4+ T-cell lymphocyte count >200 cells/µL |  | Approximately 1 year | 
| Proportion of participants with CD4+ T-cell lymphocyte count >200 cells/µL, with a minimum increase of 50 cells/µL |  | Approximately 1 year | 
| Duration of CD4+ T-cell lymphocyte count increases >200 cells/µL | The time from start of the first occurrence of CD4+ T-cell count increases to the level >200 cells/µL to the first occurrence of CD4+ T-cell count to the level <200 cells/µL | Approximately 1 year | 
| Duration of CD4+ T-cell lymphocyte count increases >200 cells/µL with a minimum increase of 50 cells/µL | The time from start of the first occurrence of CD4+ T-cell count increases to the level >200 cells/µL to the first occurrence of CD4+ T-cell count to the level <200 cells/µL with a minimum increase of 50 cells/µL | Approximately 1 year | 
| Change from baseline in CD4+ T-cell lymphocyte counts | The change from baseline in CD4+ T-cell lymphocyte counts will be summarized based on observed values. | Approximately 1 year | 
| Change from baseline in CD4+ T cell percentage | The change from baseline in CD4+ T cell percentage will be summarized based on observed values. | Approximately 1 year | 
| Change from baseline in CD8+ T-cell lymphocyte counts | The change from baseline CD8+ T-cell lymphocyte counts will be summarized based on observed values. | Approximately 1 year | 
| Change from baseline in CD4:CD8 ratio | The change from baseline in CD4:CD8 ratio will be summarized. | Approximately 1 year | 
| Change from baseline in Treg and other T-cell subsets |  | Approximately 6 months | 
| Proportion of subjects with HIV viral load <50 copies/mL | The proportion of subjects with HIV viral load <50 copies/mL will be summarized. | Approximately 1 year | 
| Proportion of subjects with fatal or non-fatal acquired immunodeficiency syndrome (AIDS) related opportunistic disease or death from any cause |  | Approximately 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, Immunological Nonresponder, Seattle Genetics