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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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HIV-1 Infection

Intervention / Treatment
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* Drug: Vesatolimod
* Drug: Placebo
* Drug: ARV regimen


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vesatolimod 1 mg (Cohort 1)<br>Vesatolimod 1 mg for 71 days, while continuing their existing ARV regimen | Drug: Vesatolimod<br>* Tablet(s) administered orally once every 2 weeks<br>* Other names: GS-9620;Drug: ARV regimen<br>* 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.<br>|
| Experimental: Vesatolimod 2 mg (Cohort 2)<br>Vesatolimod 2 mg for 71 days, while continuing their existing ARV regimen | Drug: Vesatolimod<br>* Tablet(s) administered orally once every 2 weeks<br>* Other names: GS-9620;Drug: ARV regimen<br>* 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.<br>|
| Experimental: Vesatolimod 4 mg (Cohort 3)<br>Vesatolimod 4 mg for 71 days, while continuing their existing ARV regimen | Drug: Vesatolimod<br>* Tablet(s) administered orally once every 2 weeks<br>* Other names: GS-9620;Drug: ARV regimen<br>* 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.<br>|
| Experimental: Vesatolimod 6 mg (Cohort 4)<br>Vesatolimod 6 mg for 127 days, while continuing their existing ARV regimen | Drug: Vesatolimod<br>* Tablet(s) administered orally once every 2 weeks<br>* Other names: GS-9620;Drug: ARV regimen<br>* 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.<br>|
| Experimental: Vesatolimod 8 mg (Cohort 5)<br>Vesatolimod 8 mg for 127 days administered following overnight fasting, while continuing their existing ARV regimen | Drug: Vesatolimod<br>* Tablet(s) administered orally once every 2 weeks<br>* Other names: GS-9620;Drug: ARV regimen<br>* 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.<br>|
| Experimental: Vesatolimod 10 or 12 mg (Cohort 6)<br>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<br>* Tablet(s) administered orally once every 2 weeks<br>* Other names: GS-9620;Drug: ARV regimen<br>* 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.<br>|
| Experimental: Vesatolimod 12 mg (Optional Cohort 7)<br>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<br>* Tablet(s) administered orally once every 2 weeks<br>* Other names: GS-9620;Drug: ARV regimen<br>* 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.<br>|
| Experimental: Vesatolimod 6 mg with an acidic solution (Optional Cohort 8)<br>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<br>* Tablet(s) administered orally once every 2 weeks<br>* Other names: GS-9620;Drug: ARV regimen<br>* 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.<br>|
| Experimental: Vesatolimod up to 12 mg (Cohort 9)<br>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<br>* Tablet(s) administered orally once every 2 weeks<br>* Other names: GS-9620;Drug: ARV regimen<br>* 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.<br>|
| Placebo Comparator: Placebo (Cohorts 1-9)<br>Placebo to match vesatolimod for 71 or 127 days, while continuing their existing ARV regimen | Drug: Placebo<br>* Tablet(s) administered orally once every 2 weeks<br>Drug: ARV regimen<br>* 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.<br>|

What is the study measuring?
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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 |