A Safety Study of Brentuximab Vedotin in Participants With HIV

Phase 1

Withdrawn

• Conditions: Human Immunodeficiency Virus
• Interventions: Drug: Placebo; Drug: brentuximab vedotin; Drug: ART

• Registration Number: NCT05244473
• Lead Sponsor: Seagen Inc.

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-02-07
• Study First Submitted QC: 2022-02-16
• Study First Posted: 2022-02-17
• Study Start: 2022-12-31
• Status Verified: 2023-02
• Last Update Submitted: 2023-02-10
• Last Update Posted: 2023-02-14
• Primary Completion: 2024-05-31
• Study Completion: 2024-05-31

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo + ART	Placebo	Placebo given on Day 1 and Day 15. ART will be given throughout the study.
Brentuximab vedotin + ART	ART	Brentuximab vedotin given on Day 1 and Day 15. ART will be given throughout the study.
Placebo + ART	ART	Placebo given on Day 1 and Day 15. ART will be given throughout the study.
Brentuximab vedotin + ART	brentuximab vedotin	Brentuximab vedotin given on Day 1 and Day 15. ART will be given throughout the study.

Primary Outcome Measures

Name	Time	Method
Number of participants with laboratory abnormalities	Approximately 1 year
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 dose-limiting toxicities (DLTs) by dose level	Up to 30 days

Secondary Outcome Measures

Name	Time	Method
Proportion of participants with CD4+ T-cell lymphocyte count >200 cells/µL, with a minimum increase of 50 cells/µL	Approximately 1 year
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.
Apparent terminal half-life (t1/2)	Approximately 4 months	PK Parameter
Change from baseline in CD4:CD8 ratio	Approximately 1 year	The change from baseline in CD4:CD8 ratio will be summarized.
Maximum concentration (Cmax)	Approximately 4 months	PK Parameter
Proportion of participants with CD4+ T-cell lymphocyte count >200 cells/µL	Approximately 1 year
Trough concentration (Ctrough)	Approximately 4 months	PK Parameter
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
Change from baseline in Treg and other T-cell subsets	Approximately 6 months
Proportion of subjects with fatal or non-fatal acquired immunodeficiency syndrome (AIDS) related opportunistic disease or death from any cause	Approximately 1 year
Area under the concentration-time curve (AUC)	Approximately 4 months	Pharmacokinetic (PK) Parameter
Time to maximum concentration (Tmax)	Approximately 4 months	PK Parameter
Incidence of antidrug antibodies (ADAs)	Approximately 4 months
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.
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.
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

Trial Locations

Locations (2)

University of California at San Francisco; 🇺🇸 San Francisco, California, United States

University of Illinois at Chicago; 🇺🇸 Chicago, Illinois, United States