Clinical trial NCT05244473: A Safety Study of Brentuximab Vedotin in Participants With HIV
Official title: 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)
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Human Immunodeficiency Virus
Keywords: HIV
Immunological Nonresponder
Seattle Genetics
Lead sponsor: Seagen Inc.
Sponsor class: INDUSTRY
First posted: 2022-02-17
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of participants with adverse events (AEs)
timeFrame: Through 30 days after last study treatment
measure: Number of participants with laboratory abnormalities
timeFrame: Approximately 1 year
measure: Number of participants with dose-limiting toxicities (DLTs) by dose level
timeFrame: Up to 30 days
Secondary outcomes:
measure: Area under the concentration-time curve (AUC)
timeFrame: Approximately 4 months
measure: Maximum concentration (Cmax)
timeFrame: Approximately 4 months
measure: Time to maximum concentration (Tmax)
timeFrame: Approximately 4 months
measure: Apparent terminal half-life (t1/2)
timeFrame: Approximately 4 months
measure: Trough concentration (Ctrough)
timeFrame: Approximately 4 months
measure: Incidence of antidrug antibodies (ADAs)
timeFrame: Approximately 4 months
measure: Proportion of participants with CD4+ T-cell lymphocyte count >200 cells/µL
timeFrame: Approximately 1 year
measure: Proportion of participants with CD4+ T-cell lymphocyte count >200 cells/µL, with a minimum increase of 50 cells/µL
timeFrame: Approximately 1 year
measure: Duration of CD4+ T-cell lymphocyte count increases >200 cells/µL
timeFrame: Approximately 1 year
measure: Duration of CD4+ T-cell lymphocyte count increases >200 cells/µL with a minimum increase of 50 cells/µL
timeFrame: Approximately 1 year
measure: Change from baseline in CD4+ T-cell lymphocyte counts
timeFrame: Approximately 1 year
measure: Change from baseline in CD4+ T cell percentage
timeFrame: Approximately 1 year
measure: Change from baseline in CD8+ T-cell lymphocyte counts
timeFrame: Approximately 1 year
measure: Change from baseline in CD4:CD8 ratio
timeFrame: Approximately 1 year
measure: Change from baseline in Treg and other T-cell subsets
timeFrame: Approximately 6 months
measure: Proportion of subjects with HIV viral load <50 copies/mL
timeFrame: Approximately 1 year
measure: Proportion of subjects with fatal or non-fatal acquired immunodeficiency syndrome (AIDS) related opportunistic disease or death from any cause
timeFrame: Approximately 1 year
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California at San Francisco
state: California
city: Chicago
country: United States
facility: University of Illinois at Chicago
state: Illinois
Study officials:
affiliation: Seagen Inc.
name: Andrei Shustov, MD
role: STUDY_DIRECTOR
References: