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

A Phase 1b, Randomized, Blinded, Placebo-Controlled Dose-Escalation Study of the Safety and Biological Activity of GS-9620 in HIV-1 Infected, Virologically Suppressed Adults

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 Overview

• Status: Completed
• Conditions: HIV-1 Infection
• Intervention / Treatment: Drug: Vesatolimod; Drug: ARV regimen; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90069
      • Mills Clinical Research
    • San Diego, California, United States, 92103
      • UCSD Antiviral Research Center (AVRC)
  • Florida
    • Fort Pierce, Florida, United States, 34982
      • Midway Immunology & Research Center
    • Orlando, Florida, United States, 32803
      • Orlando Immunology Center Recruiting
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Ohio State University Infectious Diseases Research
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh
  • Texas
    • Austin, Texas, United States, 78705
      • Central Texas Clinical Research
  • Washington
    • Seattle, Washington, United States, 98104
      • Peter Shalit, MD

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

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

10

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Vesatolimod 1 mg (Cohort 1); Vesatolimod 1 mg for 71 days, while continuing their existing ARV regimen	Drug: Vesatolimod; Tablet(s) administered orally once every 2 weeks; Other Names: GS-9620; Drug: ARV regimen; 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.
EXPERIMENTAL: Vesatolimod 2 mg (Cohort 2); Vesatolimod 2 mg for 71 days, while continuing their existing ARV regimen	Drug: Vesatolimod; Tablet(s) administered orally once every 2 weeks; Other Names: GS-9620; Drug: ARV regimen; 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.
EXPERIMENTAL: Vesatolimod 4 mg (Cohort 3); Vesatolimod 4 mg for 71 days, while continuing their existing ARV regimen	Drug: Vesatolimod; Tablet(s) administered orally once every 2 weeks; Other Names: GS-9620; Drug: ARV regimen; 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.
EXPERIMENTAL: Vesatolimod 6 mg (Cohort 4); Vesatolimod 6 mg for 127 days, while continuing their existing ARV regimen	Drug: Vesatolimod; Tablet(s) administered orally once every 2 weeks; Other Names: GS-9620; Drug: ARV regimen; 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.
EXPERIMENTAL: Vesatolimod 8 mg (Cohort 5); Vesatolimod 8 mg for 127 days administered following overnight fasting, while continuing their existing ARV regimen	Drug: Vesatolimod; Tablet(s) administered orally once every 2 weeks; Other Names: GS-9620; Drug: ARV regimen; 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.
EXPERIMENTAL: Vesatolimod 10 or 12 mg (Cohort 6); Vesatolimod 10 or 12 mg for 127 days administered following overnight fasting, while continuing their existing ARV regimen. Participants will receive 3 administrations of 10 mg, followed by 7 administrations of 12 mg (after review of 10 mg safety data)	Drug: Vesatolimod; Tablet(s) administered orally once every 2 weeks; Other Names: GS-9620; Drug: ARV regimen; 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.
EXPERIMENTAL: Vesatolimod 12 mg (Optional Cohort 7); Vesatolimod up to 12 mg for up to 127 days for up to 10 total doses administered following overnight fasting, while continuing their existing ARV regimen	Drug: Vesatolimod; Tablet(s) administered orally once every 2 weeks; Other Names: GS-9620; Drug: ARV regimen; 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.
EXPERIMENTAL: Vesatolimod 6 mg with an acidic solution (Optional Cohort 8); Vesatolimod 6 mg for 127 days for up to 10 total doses administered with an acidic solution (cranberry juice), while continuing their existing ARV regimen	Drug: Vesatolimod; Tablet(s) administered orally once every 2 weeks; Other Names: GS-9620; Drug: ARV regimen; 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.
EXPERIMENTAL: Vesatolimod up to 12 mg (Cohort 9); Vesatolimod up to 12 mg for 127 days for up to 10 total doses administered following a moderate-fat meal, after the review of the data from the highest tolerated fasted dose cohort while continuing their existing ARV regimen	Drug: Vesatolimod; Tablet(s) administered orally once every 2 weeks; Other Names: GS-9620; Drug: ARV regimen; 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.
PLACEBO_COMPARATOR: Placebo (Cohorts 1-9); Placebo to match vesatolimod for 71 or 127 days, while continuing their existing ARV regimen	Drug: ARV regimen; 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.; Drug: Placebo; Tablet(s) administered orally once every 2 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Experiencing Treatment-Emergent Serious Adverse Events (SAEs) and Any Treatment-Emergent Adverse Events (AEs).		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.	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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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	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	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	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	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	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.	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	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	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.	Baseline; Day 157
Percentage of Participants With Plasma HIV-1 RNA ≥ 50 Copies/mL at Postdose 1 on Day 1		Postdose 1 on Day 1
Percentage of Participants With Plasma HIV-1 RNA ≥ 50 Copies/mL at PostDose 2 on Day 15		PostDose 2 on Day 15
Percentage of Participants With Plasma HIV-1 RNA ≥ 50 Copies/mL at PostDose 3 on Day 29		PostDose 3 on Day 29
Percentage of Participants With Plasma HIV-1 RNA ≥ 50 Copies/mL at PostDose 4 on Day 43		PostDose 4 on Day 43
Percentage of Participants With Plasma HIV-1 RNA ≥ 50 Copies/mL at PostDose 5 on Day 57		PostDose 5 on Day 57
Percentage of Participants With Plasma HIV-1 RNA ≥ 50 Copies/mL at PostDose 6 on Day 71		PostDose 6 on Day 71
Percentage of Participants With Plasma HIV-1 RNA ≥ 50 Copies/mL at PostDose 7 on Day 85		PostDose 7 on Day 85
Percentage of Participants With Plasma HIV-1 RNA ≥ 50 Copies/mL at PostDose 8 on Day 99		PostDose 8 on Day 99
Percentage of Participants With Plasma HIV-1 RNA ≥ 50 Copies/mL at PostDose 9 on Day 113		PostDose 9 on Day 113
Percentage of Participants With Plasma HIV-1 RNA ≥ 50 Copies/mL at PostDose 10 on Day 127		PostDose 10 on Day 127

Collaborators and Investigators

• Sponsor: Gilead Sciences

Publications and helpful links

General Publications

• Riddler S, Para M, Benson C, et al. Vesatolimod (GS-9620) is safe and pharmacodynamically active in HIV infected individuals [Oral presentation WEAA0304]. 10th International AIDS Society Conference on HIV Science (IAS 2019), 22-23 July 2019, Mexico City, Mexico
• Riddler SA, Para M, Benson CA, Mills A, Ramgopal M, DeJesus E, Brinson C, Cyktor J, Jacobs J, Koontz D, Mellors JW, Laird GM, Wrin T, Patel H, Guo S, Wallin J, Boice J, Zhang L, Humeniuk R, Begley R, German P, Graham H, Geleziunas R, Brainard DM, SenGupta D. Vesatolimod, a Toll-like Receptor 7 Agonist, Induces Immune Activation in Virally Suppressed Adults Living With Human Immunodeficiency Virus-1. Clin Infect Dis. 2021 Jun 1;72(11):e815-e824. doi: 10.1093/cid/ciaa1534.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 29, 2015
• Primary Completion (ACTUAL): February 14, 2019
• Study Completion (ACTUAL): February 14, 2019

Study Registration Dates

• First Submitted: July 26, 2016
• First Submitted That Met QC Criteria: August 3, 2016
• First Posted (ESTIMATE): August 8, 2016

Study Record Updates

• Last Update Posted (ACTUAL): February 21, 2020
• Last Update Submitted That Met QC Criteria: February 7, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Anti-Infective Agents; Antiviral Agents; Vesatolimod
• Other Study ID Numbers: GS-US-382-1450

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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