A Safety Study of Brentuximab Vedotin in Participants With HIV

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)

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.

Study Overview

• Status: Withdrawn
• Conditions: Human Immunodeficiency Virus
• Intervention / Treatment: Drug: brentuximab vedotin; Drug: ART; Drug: Placebo

• Study Type: Interventional
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94110
      • University of California at San Francisco
      • Contact: Sadie Munter; Phone Number: 628-206-4981; Email: Sadie.Munter@ucsf.edu
      • Principal Investigator: Timothy Henrich, MD
  • Illinois
    • Chicago, Illinois, United States, 60612
      • University of Illinois at Chicago
      • Principal Investigator: Paul Rubinstein, MD
      • Contact: Annette Kinsella; Phone Number: 312-996-5931; Email: annettek@uic.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / 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: ART; Daily use of a combination of HIV medicines; Drug: Placebo; Given by IV

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Seagen Inc.

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): December 31, 2022
• Primary Completion (ANTICIPATED): May 31, 2024
• Study Completion (ANTICIPATED): May 31, 2024

Study Registration Dates

• First Submitted: February 7, 2022
• First Submitted That Met QC Criteria: February 16, 2022
• First Posted (ACTUAL): February 17, 2022

Study Record Updates

• Last Update Posted (ESTIMATE): February 14, 2023
• Last Update Submitted That Met QC Criteria: February 10, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: HIV; Seattle Genetics; Immunological Nonresponder
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immune System Diseases; Slow Virus Diseases; HIV Infections; Acquired Immunodeficiency Syndrome; Immunologic Deficiency Syndromes; Antineoplastic Agents; Antineoplastic Agents, Immunological; Brentuximab Vedotin
• Other Study ID Numbers: SGN35-035

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No