A Safety Study of Brentuximab Vedotin in Participants With HIV

Sponsor

Seagen Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05244473

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

2.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Human Immunodeficiency Virus	Drug: brentuximab vedotin Drug: Placebo Drug: ART	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

48 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Participant)

Primary Purpose:

Treatment

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)

Anticipated Study Start Date :

Aug 31, 2022

Anticipated Primary Completion Date :

May 31, 2024

Anticipated Study Completion Date :

May 31, 2024

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: Brentuximab vedotin + ART

Brentuximab vedotin given on Day 1 and Day 15. ART will be given throughout the study.

Drug: brentuximab vedotin

Given into the vein (IV; intravenously)

Other Names:

ADCETRIS

Drug: ART

Daily use of a combination of HIV medicines

Placebo Comparator: Placebo + ART

Placebo given on Day 1 and Day 15. ART will be given throughout the study.

Drug: Placebo

Given by IV

Drug: ART

Daily use of a combination of HIV medicines

Outcome Measures

Primary Outcome Measures

Number of participants with adverse events (AEs) [Through 30 days after last study treatment]
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
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

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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