Safety and Biological Activity of Vesatolimod in HIV-1 Infected, Virologically Suppressed Adults

Gilead Sciences48 enrolled

Overview

The primary objectives of this study are to evaluate the safety and tolerability of escalating, multiple doses of vesatolimod (formerly GS-9620) in HIV-1 infected virologically suppressed adults on antiretroviral therapy (ART) and to evaluate the virologic effect of vesatolimod as measured by changes in plasma HIV-1 RNA.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

HIV-1 Infection

Interventions

VesatolimodDRUG

Tablet(s) administered orally once every 2 weeks

PlaceboDRUG

Tablet(s) administered orally once every 2 weeks

ARV regimenDRUG

Participants' current ARV regimen must be used in accordance with their prescribing information and may include the following: nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), raltegravir, dolutegravir, rilpivirine, and maraviroc.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Key Inclusion Criteria: * HIV-1 infection * Aged ≥ 18 years at Pre-baseline/Day -13 * On antiretroviral (ARV) treatment for ≥ 12 consecutive months prior to Pre-Baseline/Day -13 * The following agents are allowed as part of the current ARV regimen: NRTIs, raltegravir, dolutegravir, rilpivirine, and maraviroc * The following agents are NOT allowed as part of the current ARV regimen: HIV protease inhibitors (including low dose ritonavir), cobicistat-containing regimens, elvitegravir, efavirenz, etravirine, and nevirapine * A change in ARV regimen ≥ 45 days prior to baseline/Day 1 for reasons other than virologic failure (eg, tolerability, simplification, drug-drug interaction profile) is allowed * Plasma HIV-1 RNA \< 50 copies/mL at screening * Documented plasma HIV-1 RNA levels \< 50 copies/mL (according to the local assay being used) for ≥ 12 months preceding the screening visit (measured at least twice using a licensed assay with a lower limit of quantitation of at least 40 copies/mL) * Unconfirmed virologic elevations of ≥ 50 copies/mL (transient detectable viremia, or "blip") prior to screening are acceptable. (If the lower limit of detection of the local HIV-1 RNA assay is \< 50 copies/mL, the plasma HIV-1 RNA level cannot exceed 50 copies/mL on two consecutive HIV-1 RNA tests) * If ART regimen is changed ≥ 60 days prior to Pre-Baseline/Day -13, plasma HIV-1 RNA \<50 copies/mL at Pre-baseline/Day -13 visit is required * No documented history of resistance to any components of the current ARV regimen * Availability of a fully active alternative ARV regimen, in the opinion of the Investigator, in the event of discontinuation of the current ARV regimen with development of resistance * Hgb ≥ 11.5 g/dL (males) or ≥ 11 g/dL (females) * White blood cells (WBC) ≥ 4,000 cells/μL * Platelets ≥ 150,000/mL * Absolute neutrophil count (ANC) ≥ 1500 cells/μL * CD4 count ≥ 400 cells/μL * Albumin ≥ 3.9 g/dL * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2 × upper limit of the normal range (ULN) * Estimated glomerular filtration rate ≥ 60 mL/min * No autoimmune disease Key Exclusion Criteria: * Hepatitis B surface antigen (HBsAg) positive * Positive anti-HBs antibody and negative HBsAg results are acceptable * Hepatitis C antibody (HCVAb) positive * Positive anti-HCV antibody and negative HCV polymerase chain reaction (PCR) results are acceptable * Documented history of pre-ART CD4 nadir \< 200 cells/µL * Unknown pre-ART CD4 nadir is acceptable * A new AIDS-defining condition diagnosed within 90 days prior to screening * Acute febrile illness within 35 days prior to pre-baseline/Day -13 Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Locations (8)

Mills Clinical Research

Los Angeles, California, United States

UCSD Antiviral Research Center (AVRC)

San Diego, California, United States

Midway Immunology & Research Center

Ft. Pierce, Florida, United States

Orlando Immunology Center Recruiting

Outcomes

Primary Outcomes

Percentage of Participants Experiencing Treatment-Emergent Serious Adverse Events (SAEs) and Any Treatment-Emergent Adverse Events (AEs).

Time frame: For Cohorts 1 to 3: First dose date up to 71 days plus 30 days; For Cohorts 4 to 6: First dose date up to 127 days plus 30 days; For placebo: First dose date up to 71 days plus 30 days or first dose date up to 127 days plus 30 days

Maximum Change From Baseline in Plasma Log10 HIV-1 RNA at Any Postdose Timepoint

The maximum change from baseline in plasma Log10 HIV-1 RNA refers to the maximum change at any postdose timepoint up to Day 81 or Day 134 for placebo, Day 81 for Cohorts 1 to 3, and Day 134 for Cohorts 4 to 6.

Time frame: For Cohorts 1 to 3: Baseline to Day 81; For Cohorts 4 to 6: Baseline to Day 134; For placebo: Baseline to Day 81 or Baseline to Day 134

Secondary Outcomes

Change From Baseline in Plasma Log10 HIV-1 RNA at Day 2

Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 2.

Time frame: Baseline; Day 2

Change From Baseline in Plasma Log10 HIV-1 RNA at Day 3

Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 3.

Time frame: Baseline; Day 3

Change From Baseline in Plasma Log10 HIV-1 RNA at Day 5

Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 5.

Time frame: Baseline; Day 5

Change From Baseline in Plasma Log10 HIV-1 RNA at Day 8

Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 8.

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Orlando, Florida, United States

Ohio State University Infectious Diseases Research

Columbus, Ohio, United States

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Central Texas Clinical Research

Austin, Texas, United States

Peter Shalit, MD

Seattle, Washington, United States

Time frame: Baseline; Day 8

Change From Baseline in Plasma Log10 HIV-1 RNA at Day 11

Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 11.

Time frame: Baseline; Day 11

Change From Baseline in Plasma Log10 HIV-1 RNA at Day 15

Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 15.

Time frame: Baseline; Day 15

Change From Baseline in Plasma Log10 HIV-1 RNA at Day 17

Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 17.

Time frame: Baseline; Day 17

Change From Baseline in Plasma Log10 HIV-1 RNA at Day 19

Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 19.

Time frame: Baseline; Day 19

Change From Baseline in Plasma Log10 HIV-1 RNA at Day 22

Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 22.

Time frame: Baseline; Day 22

Change From Baseline in Plasma Log10 HIV-1 RNA at Day 25

Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 25.

Time frame: Baseline; Day 25

Change From Baseline in Plasma Log10 HIV-1 RNA at Day 29

Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 29.

Time frame: Baseline; Day 29

Change From Baseline in Plasma Log10 HIV-1 RNA at Day 31

Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 31.

Time frame: Baseline; Day 31

Change From Baseline in Plasma Log10 HIV-1 RNA at Day 33

Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 33.

Time frame: Baseline; Day 33

Change From Baseline in Plasma Log10 HIV-1 RNA at Day 36

Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 36

Time frame: Baseline; Day 36

Change From Baseline in Plasma Log10 HIV-1 RNA at Day 39

Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 39

Time frame: Baseline; Day 39

Change From Baseline in Plasma Log10 HIV-1 RNA at Day 43

Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 43

Time frame: Baseline; Day 43

Change From Baseline in Plasma Log10 HIV-1 RNA at Day 45

Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit pn Day 45

Time frame: Baseline; Day 45

Change From Baseline in Plasma Log10 HIV-1 RNA at Day 47

Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 47

Time frame: Baseline; Day 47

Change From Baseline in Plasma Log10 HIV-1 RNA at Day 50

Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 50.

Time frame: Baseline; Day 50

Change From Baseline in Plasma Log10 HIV-1 RNA at Day 53

Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 53

Time frame: Baseline; Day 53

Change From Baseline in Plasma Log10 HIV-1 RNA at Day 57

Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 57.

Time frame: Baseline; Day 57

Change From Baseline in Plasma Log10 HIV-1 RNA at Day 58

Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 58.

Time frame: Baseline; Day 58

Change From Baseline in Plasma Log10 HIV-1 RNA at Day 59

Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 59.

Time frame: Baseline; Day 59

Change From Baseline in Plasma Log10 HIV-1 RNA at Day 61

Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 61.

Time frame: Baseline; Day 61

Change From Baseline in Plasma Log10 HIV-1 RNA at Day 64

Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 64.

Time frame: Baseline; Day 64

Change From Baseline in Plasma Log10 HIV-1 RNA at Day 67

Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 67.

Time frame: Baseline; Day 67

Change From Baseline in Plasma Log10 HIV-1 RNA at Day 71

Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 71.

Time frame: Baseline; Day 71

Change From Baseline in Plasma Log10 HIV-1 RNA at Day 73

Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 73.

Time frame: Baseline; Day 73

Change From Baseline in Plasma Log10 HIV-1 RNA at Day 75

Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 75.

Time frame: Baseline; Day 75

Change From Baseline in Plasma Log10 HIV-1 RNA at Day 78

Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 78.

Time frame: Baseline; Day 78

Change From Baseline in Plasma Log10 HIV-1 RNA at Day 81

Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 81.

Time frame: Baseline; Day 81

Change From Baseline in Plasma Log10 HIV-1 RNA at Day 85

Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 85.

Time frame: Baseline; Day 85

Change From Baseline in Plasma Log10 HIV-1 RNA at Day 87

Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 87.

Time frame: Baseline; Day 87

Change From Baseline in Plasma Log10 HIV-1 RNA at Day 92

Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 92.

Time frame: Baseline; Day 92

Change From Baseline in Plasma Log10 HIV-1 RNA at Day 99

Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 99.

Time frame: Baseline; Day 99

Change From Baseline in Plasma Log10 HIV-1 RNA at Day 101

Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 101.

Time frame: Baseline; Day 101

Change From Baseline in Plasma Log10 HIV-1 RNA at Day 106

Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 106.

Time frame: Baseline; Day 106

Change From Baseline in Plasma Log10 HIV-1 RNA at Day 113

Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 113.

Time frame: Baseline; Day 113

Change From Baseline in Plasma Log10 HIV-1 RNA at Day 115

Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 115.

Time frame: Baseline; Day 115

Change From Baseline in Plasma Log10 HIV-1 RNA at Day 120

Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 120.

Time frame: Baseline; Day 120

Change From Baseline in Plasma Log10 HIV-1 RNA at Day 127

Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 127.

Time frame: Baseline; Day 127

Change From Baseline in Plasma Log10 HIV-1 RNA at Day 128

Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 128.

Time frame: Baseline; Day 128

Change From Baseline in Plasma Log10 HIV-1 RNA at Day 129

Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 129.

Time frame: Baseline; Day 129

Change From Baseline in Plasma Log10 HIV-1 RNA at Day 134

Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 134.

Time frame: Baseline; Day 134

Change From Baseline in Plasma Log10 HIV-1 RNA at Day 157

Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 157.

Time frame: Baseline; Day 157

Percentage of Participants With Plasma HIV-1 RNA ≥ 50 Copies/mL at Postdose 1 on Day 1

Time frame: Postdose 1 on Day 1

Percentage of Participants With Plasma HIV-1 RNA ≥ 50 Copies/mL at PostDose 2 on Day 15

Time frame: PostDose 2 on Day 15

Percentage of Participants With Plasma HIV-1 RNA ≥ 50 Copies/mL at PostDose 3 on Day 29

Time frame: PostDose 3 on Day 29

Percentage of Participants With Plasma HIV-1 RNA ≥ 50 Copies/mL at PostDose 4 on Day 43

Time frame: PostDose 4 on Day 43

Percentage of Participants With Plasma HIV-1 RNA ≥ 50 Copies/mL at PostDose 5 on Day 57

Time frame: PostDose 5 on Day 57

Percentage of Participants With Plasma HIV-1 RNA ≥ 50 Copies/mL at PostDose 6 on Day 71

Time frame: PostDose 6 on Day 71

Percentage of Participants With Plasma HIV-1 RNA ≥ 50 Copies/mL at PostDose 7 on Day 85

Time frame: PostDose 7 on Day 85

Percentage of Participants With Plasma HIV-1 RNA ≥ 50 Copies/mL at PostDose 8 on Day 99

Time frame: PostDose 8 on Day 99

Percentage of Participants With Plasma HIV-1 RNA ≥ 50 Copies/mL at PostDose 9 on Day 113

Time frame: PostDose 9 on Day 113

Percentage of Participants With Plasma HIV-1 RNA ≥ 50 Copies/mL at PostDose 10 on Day 127

Time frame: PostDose 10 on Day 127