Clinical trial NCT02858401: Safety and Biological Activity of Vesatolimod in HIV-1 Infected, Virologically Suppressed Adults
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV-1 Infection
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2016-08-08
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants Experiencing Treatment-Emergent Serious Adverse Events (SAEs) and Any Treatment-Emergent Adverse Events (AEs).
timeFrame: 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
measure: Maximum Change From Baseline in Plasma Log10 HIV-1 RNA at Any Postdose Timepoint
timeFrame: 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:
measure: Change From Baseline in Plasma Log10 HIV-1 RNA at Day 2
timeFrame: Baseline; Day 2
measure: Change From Baseline in Plasma Log10 HIV-1 RNA at Day 3
timeFrame: Baseline; Day 3
measure: Change From Baseline in Plasma Log10 HIV-1 RNA at Day 5
timeFrame: Baseline; Day 5
measure: Change From Baseline in Plasma Log10 HIV-1 RNA at Day 8
timeFrame: Baseline; Day 8
measure: Change From Baseline in Plasma Log10 HIV-1 RNA at Day 11
timeFrame: Baseline; Day 11
measure: Change From Baseline in Plasma Log10 HIV-1 RNA at Day 15
timeFrame: Baseline; Day 15
measure: Change From Baseline in Plasma Log10 HIV-1 RNA at Day 17
timeFrame: Baseline; Day 17
measure: Change From Baseline in Plasma Log10 HIV-1 RNA at Day 19
timeFrame: Baseline; Day 19
measure: Change From Baseline in Plasma Log10 HIV-1 RNA at Day 22
timeFrame: Baseline; Day 22
measure: Change From Baseline in Plasma Log10 HIV-1 RNA at Day 25
timeFrame: Baseline; Day 25
measure: Change From Baseline in Plasma Log10 HIV-1 RNA at Day 29
timeFrame: Baseline; Day 29
measure: Change From Baseline in Plasma Log10 HIV-1 RNA at Day 31
timeFrame: Baseline; Day 31
measure: Change From Baseline in Plasma Log10 HIV-1 RNA at Day 33
timeFrame: Baseline; Day 33
measure: Change From Baseline in Plasma Log10 HIV-1 RNA at Day 36
timeFrame: Baseline; Day 36
measure: Change From Baseline in Plasma Log10 HIV-1 RNA at Day 39
timeFrame: Baseline; Day 39
measure: Change From Baseline in Plasma Log10 HIV-1 RNA at Day 43
timeFrame: Baseline; Day 43
measure: Change From Baseline in Plasma Log10 HIV-1 RNA at Day 45
timeFrame: Baseline; Day 45
measure: Change From Baseline in Plasma Log10 HIV-1 RNA at Day 47
timeFrame: Baseline; Day 47
measure: Change From Baseline in Plasma Log10 HIV-1 RNA at Day 50
timeFrame: Baseline; Day 50
measure: Change From Baseline in Plasma Log10 HIV-1 RNA at Day 53
timeFrame: Baseline; Day 53
measure: Change From Baseline in Plasma Log10 HIV-1 RNA at Day 57
timeFrame: Baseline; Day 57
measure: Change From Baseline in Plasma Log10 HIV-1 RNA at Day 58
timeFrame: Baseline; Day 58
measure: Change From Baseline in Plasma Log10 HIV-1 RNA at Day 59
timeFrame: Baseline; Day 59
measure: Change From Baseline in Plasma Log10 HIV-1 RNA at Day 61
timeFrame: Baseline; Day 61
measure: Change From Baseline in Plasma Log10 HIV-1 RNA at Day 64
timeFrame: Baseline; Day 64
measure: Change From Baseline in Plasma Log10 HIV-1 RNA at Day 67
timeFrame: Baseline; Day 67
measure: Change From Baseline in Plasma Log10 HIV-1 RNA at Day 71
timeFrame: Baseline; Day 71
measure: Change From Baseline in Plasma Log10 HIV-1 RNA at Day 73
timeFrame: Baseline; Day 73
measure: Change From Baseline in Plasma Log10 HIV-1 RNA at Day 75
timeFrame: Baseline; Day 75
measure: Change From Baseline in Plasma Log10 HIV-1 RNA at Day 78
timeFrame: Baseline; Day 78
measure: Change From Baseline in Plasma Log10 HIV-1 RNA at Day 81
timeFrame: Baseline; Day 81
measure: Change From Baseline in Plasma Log10 HIV-1 RNA at Day 85
timeFrame: Baseline; Day 85
measure: Change From Baseline in Plasma Log10 HIV-1 RNA at Day 87
timeFrame: Baseline; Day 87
measure: Change From Baseline in Plasma Log10 HIV-1 RNA at Day 92
timeFrame: Baseline; Day 92
measure: Change From Baseline in Plasma Log10 HIV-1 RNA at Day 99
timeFrame: Baseline; Day 99
measure: Change From Baseline in Plasma Log10 HIV-1 RNA at Day 101
timeFrame: Baseline; Day 101
measure: Change From Baseline in Plasma Log10 HIV-1 RNA at Day 106
timeFrame: Baseline; Day 106
measure: Change From Baseline in Plasma Log10 HIV-1 RNA at Day 113
timeFrame: Baseline; Day 113
measure: Change From Baseline in Plasma Log10 HIV-1 RNA at Day 115
timeFrame: Baseline; Day 115
measure: Change From Baseline in Plasma Log10 HIV-1 RNA at Day 120
timeFrame: Baseline; Day 120
measure: Change From Baseline in Plasma Log10 HIV-1 RNA at Day 127
timeFrame: Baseline; Day 127
measure: Change From Baseline in Plasma Log10 HIV-1 RNA at Day 128
timeFrame: Baseline; Day 128
measure: Change From Baseline in Plasma Log10 HIV-1 RNA at Day 129
timeFrame: Baseline; Day 129
measure: Change From Baseline in Plasma Log10 HIV-1 RNA at Day 134
timeFrame: Baseline; Day 134
measure: Change From Baseline in Plasma Log10 HIV-1 RNA at Day 157
timeFrame: Baseline; Day 157
measure: Percentage of Participants With Plasma HIV-1 RNA ≥ 50 Copies/mL at Postdose 1 on Day 1
timeFrame: Postdose 1 on Day 1
measure: Percentage of Participants With Plasma HIV-1 RNA ≥ 50 Copies/mL at PostDose 2 on Day 15
timeFrame: PostDose 2 on Day 15
measure: Percentage of Participants With Plasma HIV-1 RNA ≥ 50 Copies/mL at PostDose 3 on Day 29
timeFrame: PostDose 3 on Day 29
measure: Percentage of Participants With Plasma HIV-1 RNA ≥ 50 Copies/mL at PostDose 4 on Day 43
timeFrame: PostDose 4 on Day 43
measure: Percentage of Participants With Plasma HIV-1 RNA ≥ 50 Copies/mL at PostDose 5 on Day 57
timeFrame: PostDose 5 on Day 57
measure: Percentage of Participants With Plasma HIV-1 RNA ≥ 50 Copies/mL at PostDose 6 on Day 71
timeFrame: PostDose 6 on Day 71
measure: Percentage of Participants With Plasma HIV-1 RNA ≥ 50 Copies/mL at PostDose 7 on Day 85
timeFrame: PostDose 7 on Day 85
measure: Percentage of Participants With Plasma HIV-1 RNA ≥ 50 Copies/mL at PostDose 8 on Day 99
timeFrame: PostDose 8 on Day 99
measure: Percentage of Participants With Plasma HIV-1 RNA ≥ 50 Copies/mL at PostDose 9 on Day 113
timeFrame: PostDose 9 on Day 113
measure: Percentage of Participants With Plasma HIV-1 RNA ≥ 50 Copies/mL at PostDose 10 on Day 127
timeFrame: PostDose 10 on Day 127
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Mills Clinical Research
state: California
city: San Diego
country: United States
facility: UCSD Antiviral Research Center (AVRC)
state: California
city: Fort Pierce
country: United States
facility: Midway Immunology & Research Center
state: Florida
city: Orlando
country: United States
facility: Orlando Immunology Center Recruiting
state: Florida
city: Columbus
country: United States
facility: Ohio State University Infectious Diseases Research
state: Ohio
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Austin
country: United States
facility: Central Texas Clinical Research
state: Texas
city: Seattle
country: United States
facility: Peter Shalit, MD
state: Washington
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
citation: 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
citation: 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.