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

Phase 1

Completed

Conditions: HIV-1 Infection

Interventions: Drug: Vesatolimod
Drug: Placebo
Drug: ARV regimen

Registration Number: NCT02858401

Lead Sponsor: Gilead Sciences

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 48

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Vesatolimod 2 mg (Cohort 2)	Vesatolimod	Vesatolimod 2 mg for 71 days, while continuing their existing ARV regimen
Vesatolimod 4 mg (Cohort 3)	ARV regimen	Vesatolimod 4 mg for 71 days, while continuing their existing ARV regimen
Vesatolimod 6 mg (Cohort 4)	ARV regimen	Vesatolimod 6 mg for 127 days, while continuing their existing ARV regimen
Vesatolimod 8 mg (Cohort 5)	ARV regimen	Vesatolimod 8 mg for 127 days administered following overnight fasting, while continuing their existing ARV regimen
Vesatolimod 2 mg (Cohort 2)	ARV regimen	Vesatolimod 2 mg for 71 days, while continuing their existing ARV regimen
Vesatolimod 10 or 12 mg (Cohort 6)	ARV regimen	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)
Vesatolimod 12 mg (Optional Cohort 7)	ARV regimen	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
Vesatolimod up to 12 mg (Cohort 9)	ARV regimen	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
Placebo (Cohorts 1-9)	Placebo	Placebo to match vesatolimod for 71 or 127 days, while continuing their existing ARV regimen
Vesatolimod 1 mg (Cohort 1)	ARV regimen	Vesatolimod 1 mg for 71 days, while continuing their existing ARV regimen
Vesatolimod 6 mg with an acidic solution (Optional Cohort 8)	ARV regimen	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
Placebo (Cohorts 1-9)	ARV regimen	Placebo to match vesatolimod for 71 or 127 days, while continuing their existing ARV regimen
Vesatolimod 1 mg (Cohort 1)	Vesatolimod	Vesatolimod 1 mg for 71 days, while continuing their existing ARV regimen
Vesatolimod 6 mg (Cohort 4)	Vesatolimod	Vesatolimod 6 mg for 127 days, while continuing their existing ARV regimen
Vesatolimod 4 mg (Cohort 3)	Vesatolimod	Vesatolimod 4 mg for 71 days, while continuing their existing ARV regimen
Vesatolimod 8 mg (Cohort 5)	Vesatolimod	Vesatolimod 8 mg for 127 days administered following overnight fasting, while continuing their existing ARV regimen
Vesatolimod 10 or 12 mg (Cohort 6)	Vesatolimod	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)
Vesatolimod 12 mg (Optional Cohort 7)	Vesatolimod	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
Vesatolimod 6 mg with an acidic solution (Optional Cohort 8)	Vesatolimod	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
Vesatolimod up to 12 mg (Cohort 9)	Vesatolimod	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

Primary Outcome Measures

Name	Time	Method
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	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	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.

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in Plasma Log10 HIV-1 RNA at Day 2	Baseline; Day 2	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 2.
Change From Baseline in Plasma Log10 HIV-1 RNA at Day 11	Baseline; Day 11	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 11.
Change From Baseline in Plasma Log10 HIV-1 RNA at Day 15	Baseline; Day 15	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 15.
Change From Baseline in Plasma Log10 HIV-1 RNA at Day 17	Baseline; Day 17	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 17.
Change From Baseline in Plasma Log10 HIV-1 RNA at Day 19	Baseline; Day 19	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 19.
Change From Baseline in Plasma Log10 HIV-1 RNA at Day 3	Baseline; Day 3	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 3.
Change From Baseline in Plasma Log10 HIV-1 RNA at Day 5	Baseline; Day 5	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 5.
Change From Baseline in Plasma Log10 HIV-1 RNA at Day 8	Baseline; Day 8	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 8.
Change From Baseline in Plasma Log10 HIV-1 RNA at Day 22	Baseline; Day 22	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 22.
Change From Baseline in Plasma Log10 HIV-1 RNA at Day 25	Baseline; Day 25	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 25.
Change From Baseline in Plasma Log10 HIV-1 RNA at Day 29	Baseline; Day 29	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 29.
Change From Baseline in Plasma Log10 HIV-1 RNA at Day 31	Baseline; Day 31	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 31.
Change From Baseline in Plasma Log10 HIV-1 RNA at Day 33	Baseline; Day 33	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 33.
Change From Baseline in Plasma Log10 HIV-1 RNA at Day 45	Baseline; Day 45	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit pn Day 45
Change From Baseline in Plasma Log10 HIV-1 RNA at Day 36	Baseline; Day 36	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 36
Change From Baseline in Plasma Log10 HIV-1 RNA at Day 39	Baseline; Day 39	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 39
Change From Baseline in Plasma Log10 HIV-1 RNA at Day 43	Baseline; Day 43	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 43
Change From Baseline in Plasma Log10 HIV-1 RNA at Day 47	Baseline; Day 47	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 47
Change From Baseline in Plasma Log10 HIV-1 RNA at Day 50	Baseline; Day 50	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 50.
Change From Baseline in Plasma Log10 HIV-1 RNA at Day 53	Baseline; Day 53	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 53
Change From Baseline in Plasma Log10 HIV-1 RNA at Day 57	Baseline; Day 57	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 57.
Change From Baseline in Plasma Log10 HIV-1 RNA at Day 59	Baseline; Day 59	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 59.
Change From Baseline in Plasma Log10 HIV-1 RNA at Day 61	Baseline; Day 61	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 61.
Change From Baseline in Plasma Log10 HIV-1 RNA at Day 64	Baseline; Day 64	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 64.
Change From Baseline in Plasma Log10 HIV-1 RNA at Day 67	Baseline; Day 67	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 67.
Change From Baseline in Plasma Log10 HIV-1 RNA at Day 71	Baseline; Day 71	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 71.
Change From Baseline in Plasma Log10 HIV-1 RNA at Day 73	Baseline; Day 73	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 73.
Change From Baseline in Plasma Log10 HIV-1 RNA at Day 75	Baseline; Day 75	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 75.
Change From Baseline in Plasma Log10 HIV-1 RNA at Day 58	Baseline; Day 58	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 58.
Change From Baseline in Plasma Log10 HIV-1 RNA at Day 78	Baseline; Day 78	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 78.
Change From Baseline in Plasma Log10 HIV-1 RNA at Day 81	Baseline; Day 81	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 81.
Change From Baseline in Plasma Log10 HIV-1 RNA at Day 85	Baseline; Day 85	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 85.
Change From Baseline in Plasma Log10 HIV-1 RNA at Day 87	Baseline; Day 87	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 87.
Change From Baseline in Plasma Log10 HIV-1 RNA at Day 92	Baseline; Day 92	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 92.
Change From Baseline in Plasma Log10 HIV-1 RNA at Day 99	Baseline; Day 99	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 99.
Change From Baseline in Plasma Log10 HIV-1 RNA at Day 101	Baseline; Day 101	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 101.
Change From Baseline in Plasma Log10 HIV-1 RNA at Day 115	Baseline; Day 115	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 115.
Change From Baseline in Plasma Log10 HIV-1 RNA at Day 120	Baseline; Day 120	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 120.
Change From Baseline in Plasma Log10 HIV-1 RNA at Day 127	Baseline; Day 127	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 127.
Change From Baseline in Plasma Log10 HIV-1 RNA at Day 128	Baseline; Day 128	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 128.
Change From Baseline in Plasma Log10 HIV-1 RNA at Day 106	Baseline; Day 106	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 106.
Change From Baseline in Plasma Log10 HIV-1 RNA at Day 113	Baseline; Day 113	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 113.
Change From Baseline in Plasma Log10 HIV-1 RNA at Day 129	Baseline; Day 129	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 129.
Change From Baseline in Plasma Log10 HIV-1 RNA at Day 134	Baseline; Day 134	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 134.
Change From Baseline in Plasma Log10 HIV-1 RNA at Day 157	Baseline; Day 157	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on 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

Trial Locations

Locations (8): Midway Immunology & Research Center
🇺🇸
Fort Pierce, Florida, United States
University of Pittsburgh
🇺🇸
Pittsburgh, Pennsylvania, United States
Mills Clinical Research
🇺🇸
Los Angeles, California, United States
UCSD Antiviral Research Center (AVRC)
🇺🇸
San Diego, California, United States
Orlando Immunology Center Recruiting
🇺🇸
Orlando, Florida, United States
Ohio State University Infectious Diseases Research
🇺🇸
Columbus, Ohio, United States
Peter Shalit, MD
🇺🇸
Seattle, Washington, United States
Central Texas Clinical Research
🇺🇸
Austin, Texas, United States