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
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Gilead Sciences
- Enrollment
- 48
- Locations
- 8
- Primary Endpoint
- Percentage of Participants Experiencing Treatment-Emergent Serious Adverse Events (SAEs) and Any Treatment-Emergent Adverse Events (AEs).
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
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.
Arms & Interventions
Vesatolimod 1 mg (Cohort 1)
Vesatolimod 1 mg for 71 days, while continuing their existing ARV regimen
Intervention: Vesatolimod (Drug)
Vesatolimod 1 mg (Cohort 1)
Vesatolimod 1 mg for 71 days, while continuing their existing ARV regimen
Intervention: ARV regimen (Drug)
Vesatolimod 2 mg (Cohort 2)
Vesatolimod 2 mg for 71 days, while continuing their existing ARV regimen
Intervention: Vesatolimod (Drug)
Vesatolimod 2 mg (Cohort 2)
Vesatolimod 2 mg for 71 days, while continuing their existing ARV regimen
Intervention: ARV regimen (Drug)
Vesatolimod 4 mg (Cohort 3)
Vesatolimod 4 mg for 71 days, while continuing their existing ARV regimen
Intervention: Vesatolimod (Drug)
Vesatolimod 4 mg (Cohort 3)
Vesatolimod 4 mg for 71 days, while continuing their existing ARV regimen
Intervention: ARV regimen (Drug)
Vesatolimod 6 mg (Cohort 4)
Vesatolimod 6 mg for 127 days, while continuing their existing ARV regimen
Intervention: Vesatolimod (Drug)
Vesatolimod 6 mg (Cohort 4)
Vesatolimod 6 mg for 127 days, while continuing their existing ARV regimen
Intervention: ARV regimen (Drug)
Vesatolimod 8 mg (Cohort 5)
Vesatolimod 8 mg for 127 days administered following overnight fasting, while continuing their existing ARV regimen
Intervention: Vesatolimod (Drug)
Vesatolimod 8 mg (Cohort 5)
Vesatolimod 8 mg for 127 days administered following overnight fasting, while continuing their existing ARV regimen
Intervention: ARV regimen (Drug)
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)
Intervention: Vesatolimod (Drug)
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)
Intervention: ARV regimen (Drug)
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
Intervention: Vesatolimod (Drug)
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
Intervention: ARV regimen (Drug)
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
Intervention: Vesatolimod (Drug)
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
Intervention: ARV regimen (Drug)
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
Intervention: Vesatolimod (Drug)
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
Intervention: ARV regimen (Drug)
Placebo (Cohorts 1-9)
Placebo to match vesatolimod for 71 or 127 days, while continuing their existing ARV regimen
Intervention: Placebo (Drug)
Placebo (Cohorts 1-9)
Placebo to match vesatolimod for 71 or 127 days, while continuing their existing ARV regimen
Intervention: ARV regimen (Drug)
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
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
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 Outcomes
- Change From Baseline in Plasma Log10 HIV-1 RNA at Day 2(Baseline; 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 at Day 15(Baseline; 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 at Day 19(Baseline; 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 at Day 5(Baseline; 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 at Day 22(Baseline; 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 at Day 29(Baseline; 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 at Day 33(Baseline; Day 33)
- Change From Baseline in Plasma Log10 HIV-1 RNA at Day 36(Baseline; 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 at Day 43(Baseline; Day 43)
- Change From Baseline in Plasma Log10 HIV-1 RNA at Day 45(Baseline; Day 45)
- Change From Baseline in Plasma Log10 HIV-1 RNA at Day 47(Baseline; 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 at Day 53(Baseline; 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 at Day 59(Baseline; 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 at Day 64(Baseline; 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 at Day 71(Baseline; 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 at Day 75(Baseline; 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 at Day 78(Baseline; 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 at Day 85(Baseline; 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 at Day 92(Baseline; 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 at Day 101(Baseline; 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 at Day 120(Baseline; 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 at Day 128(Baseline; 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 at Day 113(Baseline; 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 at Day 134(Baseline; Day 134)
- Change From Baseline in Plasma Log10 HIV-1 RNA at 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)