Study to Evaluate the Safety and Efficacy of Vesatolimod in Antiretroviral Treated Human Immunodeficiency Virus (HIV-1) Infected Controllers

NCT ID: NCT03060447

Last Updated: 2021-04-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 25 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-05-09
• Study Completion Date: 2020-02-13

Brief Summary

The primary objective of this study is to evaluate the safety and tolerability of a 10-dose regimen of vesatolimod in HIV-1 infected controllers on antiretroviral treatment (ART) and during analytical treatment interruption (ATI) following vesatolimod dosing.

Conditions

HIV-1 Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Vesatolimod

Participants in Period 1 will receive 10 doses of vesatolimod (4 mg to 8 mg) once every 14 days over a 20-week period along with their prescribed ART. Participants in Period 2 (ATI) will discontinue ART and vesatolimod and will be monitored for rebound in HIV-1 plasma viremia for 24 weeks. Participants who restart ART during Period 2 due to virologic rebound will complete the ART Re-Initiation Visits, and then Post-ART Re-suppression Visits monthly for 6 additional months. Participants who complete 24 Weeks of ATI without restarting ART will move onto Period 3 and have 2 options. They can remain off ART for up to an additional 24 weeks. Those who restart ART at the start of Period 3 will complete ART Re-initiation Visits and then Post-ART Re-suppression Visits monthly for 6 additional months.

Group Type: EXPERIMENTAL

Vesatolimod

Intervention Type: DRUG

Tablets Administered orally

ART

Intervention Type: DRUG

ART regimens administered in accordance with their prescribing information. The following agents are allowed as part of the ART regimen: nucleoside reverse transcriptase inhibitors, raltegravir, dolutegravir (DTG), rilpivirine, and maraviroc.

Placebo

Participants in Period 1 will receive 10 doses of placebo matched to vesatolimod once every 14 days over a 20-week period along with their prescribed ART. Participants in Period 2 (ATI) will discontinue ART and placebo and will be monitored for rebound in HIV-1 plasma viremia for 24 weeks. Participants who restart ART during Period 2 due to virologic rebound will complete the ART Re-Initiation Visits, and then Post-ART Re-suppression Visits monthly for 6 additional months. Participants who complete 24 Weeks of ATI without restarting ART will move onto Period 3 and have 2 options. They can remain off ART for up to an additional 24 weeks. Those who restart ART at the start of Period 3 will complete ART Re-initiation Visits and then Post-ART Re-suppression Visits monthly for 6 additional months.

Group Type: EXPERIMENTAL

Placebo

Intervention Type: DRUG

Tablets Administered orally

ART

Intervention Type: DRUG

ART regimens administered in accordance with their prescribing information. The following agents are allowed as part of the ART regimen: nucleoside reverse transcriptase inhibitors, raltegravir, dolutegravir (DTG), rilpivirine, and maraviroc.

Interventions

Vesatolimod

Tablets Administered orally

Intervention Type: DRUG

Placebo

Tablets Administered orally

Intervention Type: DRUG

ART

ART regimens administered in accordance with their prescribing information. The following agents are allowed as part of the ART regimen: nucleoside reverse transcriptase inhibitors, raltegravir, dolutegravir (DTG), rilpivirine, and maraviroc.

Intervention Type: DRUG

Other Intervention Names

GS-9620

Eligibility Criteria

Inclusion Criteria

• Plasma HIV-1 ribonucleic acid (RNA) levels < 50 copies/mL at screening
• Chronic HIV-1 infection (for ≥ 6 months) prior to ART initiation
• Pre-ART Plasma HIV-1 RNA set point between 50 and ≤ 5,000 copies/mL measured within two years prior to ART initiation
• On ART for ≥ 6 consecutive months prior to screening
• Documented plasma HIV-1 RNA < 50 copies/mL for ≥ 6 months preceding the screening visit (or undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is ≥ 50 copies/mL). Unconfirmed virologic elevations of ≥ 50 copies/mL (transient detectable viremia, or "blip") prior to screening are acceptable.
• No documented history of resistance to any components of the current ART regimen
• Availability of a fully active alternative ART regimen, in the opinion of the Investigator, in the event of discontinuation of the current ART regimen with development of resistance.
• Hemoglobin ≥ 11.5 g/dL (males) or ≥ 11 g/dL (females)
• White Blood Cells ≥ 2,500 cells/μL
• Platelets ≥ 125,000/mL
• Absolute Neutrophil Counts ≥ 1000 cells/μL
• Cluster of Differentiation 4 (CD4)+ count ≥ 500 cells/μL
• Alanine aminotransferase (ALT), aspartate aminotransferase (AST) or bilirubin ≤ 2 × upper limit of normal (ULN)
• Estimated glomerular filtration rate ≥ 60 mL/min
• No autoimmune disease requiring on-going immunosuppression
• No evidence of current hepatitis B virus (HBV) infection
• No evidence of current hepatitis C virus (HCV) infection (positive anti-HCV antibody and negative HCV polymerase chain reaction (PCR) results are acceptable)
• No documented history of pre-ART CD4 nadir < 200 cells/μL (unknown pre-ART CD4 nadir is acceptable)
• No history of opportunistic illness indicative of stage 3 HIV
• No acute febrile illness within 35 days prior to Pre-Baseline/ Day -13

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gilead Sciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

Mills Clinical Research

Los Angeles, California, United States

Zuckerberg San Francisco General

San Francisco, California, United States

Midway Immunology & Research Center

Ft. Pierce, Florida, United States

Orlando Immunology Center

Orlando, Florida, United States

Central Texas Clinical Research

Austin, Texas, United States

Peter Shalit, MD

Seattle, Washington, United States

Countries

United States

References

SenGupta D, Ramgopal M, Brinson C, DeJesus E, Mills A, Shalit P, et al. Safety and Analytic Treatment Interruption Outcomes of Vesatolimod in HIV Controllers. Oral Presentation at CROI 2020, Boston, USA. Abstract 3982.

Reference Type: RESULT

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Document Type: Study Protocol

View Document

Other Identifiers

GS-US-382-3961

Identifier Type: -

Identifier Source: org_study_id