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

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ClinicalTrials.gov Identifier: NCT02858401

Recruitment Status : Completed

First Posted : August 8, 2016

Results First Posted : February 21, 2020

Last Update Posted : February 21, 2020

Sponsor:

Information provided by (Responsible Party):

Gilead Sciences

Tracking Information

First Submitted Date ^ICMJE

July 26, 2016

First Posted Date ^ICMJE

August 8, 2016

Results First Submitted Date ^ICMJE

February 7, 2020

Results First Posted Date ^ICMJE

February 21, 2020

Last Update Posted Date

February 21, 2020

Actual Study Start Date ^ICMJE

January 29, 2015

Actual Primary Completion Date

February 14, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures ^ICMJE

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.

Original Primary Outcome Measures ^ICMJE

Incidence of treatment-emergent serious adverse events (SAEs) and all treatment-emergent adverse events [ Time Frame: Up to 101 days ]
Maximum change from baseline in plasma log10 HIV-1 RNA at any postdose timepoint up to Day 81 [ Time Frame: Up to 81 days ]

Change History

Current Secondary Outcome Measures ^ICMJE

Change From Baseline in Plasma Log10 HIV-1 RNA at Day 2 [ Time Frame: 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 3 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 11 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 22 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 36 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 45 [ Time Frame: 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 47 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 58 [ Time Frame: 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 59 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 78 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 106 [ Time Frame: 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 [ Time Frame: 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 115 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 129 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Postdose 1 on Day 1 ]
Percentage of Participants With Plasma HIV-1 RNA ≥ 50 Copies/mL at PostDose 2 on Day 15 [ Time Frame: PostDose 2 on Day 15 ]
Percentage of Participants With Plasma HIV-1 RNA ≥ 50 Copies/mL at PostDose 3 on Day 29 [ Time Frame: PostDose 3 on Day 29 ]
Percentage of Participants With Plasma HIV-1 RNA ≥ 50 Copies/mL at PostDose 4 on Day 43 [ Time Frame: PostDose 4 on Day 43 ]
Percentage of Participants With Plasma HIV-1 RNA ≥ 50 Copies/mL at PostDose 5 on Day 57 [ Time Frame: PostDose 5 on Day 57 ]
Percentage of Participants With Plasma HIV-1 RNA ≥ 50 Copies/mL at PostDose 6 on Day 71 [ Time Frame: PostDose 6 on Day 71 ]
Percentage of Participants With Plasma HIV-1 RNA ≥ 50 Copies/mL at PostDose 7 on Day 85 [ Time Frame: PostDose 7 on Day 85 ]
Percentage of Participants With Plasma HIV-1 RNA ≥ 50 Copies/mL at PostDose 8 on Day 99 [ Time Frame: PostDose 8 on Day 99 ]
Percentage of Participants With Plasma HIV-1 RNA ≥ 50 Copies/mL at PostDose 9 on Day 113 [ Time Frame: PostDose 9 on Day 113 ]
Percentage of Participants With Plasma HIV-1 RNA ≥ 50 Copies/mL at PostDose 10 on Day 127 [ Time Frame: PostDose 10 on Day 127 ]

Original Secondary Outcome Measures ^ICMJE

Change from baseline in plasma log10 HIV-1 RNA at post-baseline visits [ Time Frame: Up to 101 days ]
Proportion of participants with plasma HIV-1 RNA > 50 copies/mL at any postdose timepoint [ Time Frame: Up to 81 days ]
Change in single copy assay (SCA) from predose to 2 days postdose [ Time Frame: Predose to 2 days postdose ]
Change in cell-associated HIV-1 RNA from predose to 2 days postdose [ Time Frame: Predose to 2 days postdose ]

Current Other Pre-specified Outcome Measures

Not Provided

Original Other Pre-specified Outcome Measures

Not Provided

Descriptive Information

Brief Title ^ICMJE

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

Official Title ^ICMJE

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

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 Provided

Study Type ^ICMJE

Interventional

Study Phase ^ICMJE

Phase 1

Study Design ^ICMJE

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment

Condition ^ICMJE

HIV-1 Infection

Intervention ^ICMJE

Drug: Vesatolimod
Tablet(s) administered orally once every 2 weeks

Other Name: GS-9620
Drug: Placebo
Tablet(s) administered orally once every 2 weeks
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.

Study Arms ^ICMJE

Experimental: Vesatolimod 1 mg (Cohort 1)
Vesatolimod 1 mg for 71 days, while continuing their existing ARV regimen
Interventions:
- Drug: Vesatolimod
- Drug: ARV regimen
Experimental: Vesatolimod 2 mg (Cohort 2)
Vesatolimod 2 mg for 71 days, while continuing their existing ARV regimen
Interventions:
- Drug: Vesatolimod
- Drug: ARV regimen
Experimental: Vesatolimod 4 mg (Cohort 3)
Vesatolimod 4 mg for 71 days, while continuing their existing ARV regimen
Interventions:
- Drug: Vesatolimod
- Drug: ARV regimen
Experimental: Vesatolimod 6 mg (Cohort 4)
Vesatolimod 6 mg for 127 days, while continuing their existing ARV regimen
Interventions:
- Drug: Vesatolimod
- Drug: ARV regimen
Experimental: Vesatolimod 8 mg (Cohort 5)
Vesatolimod 8 mg for 127 days administered following overnight fasting, while continuing their existing ARV regimen
Interventions:
- Drug: Vesatolimod
- Drug: ARV regimen
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)
Interventions:
- Drug: Vesatolimod
- Drug: ARV regimen
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
Interventions:
- Drug: Vesatolimod
- Drug: ARV regimen
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
Interventions:
- Drug: Vesatolimod
- Drug: ARV regimen
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
Interventions:
- Drug: Vesatolimod
- Drug: ARV regimen
Placebo Comparator: Placebo (Cohorts 1-9)
Placebo to match vesatolimod for 71 or 127 days, while continuing their existing ARV regimen
Interventions:
- Drug: Placebo
- Drug: ARV regimen

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 J, 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 with HIV-1. Clin Infect Dis. 2020 Oct 12. pii: ciaa1534. doi: 10.1093/cid/ciaa1534. [Epub ahead of print]

* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.

Recruitment Information

Recruitment Status ^ICMJE

Completed

Actual Enrollment ^ICMJE

Original Estimated Enrollment ^ICMJE

Actual Study Completion Date ^ICMJE

February 14, 2019

Actual Primary Completion Date

February 14, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria ^ICMJE

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.

Sex/Gender ^ICMJE

Sexes Eligible for Study:

All

Ages ^ICMJE

18 Years and older (Adult, Older Adult)

Accepts Healthy Volunteers ^ICMJE

Contacts ^ICMJE

Contact information is only displayed when the study is recruiting subjects

Listed Location Countries ^ICMJE

United States

Removed Location Countries

Administrative Information

NCT Number ^ICMJE

NCT02858401

Other Study ID Numbers ^ICMJE

GS-US-382-1450

Has Data Monitoring Committee

Yes

U.S. FDA-regulated Product

Studies a U.S. FDA-regulated Drug Product:	Yes
Studies a U.S. FDA-regulated Device Product:	No

IPD Sharing Statement ^ICMJE

Plan to Share IPD:

Responsible Party

Gilead Sciences

Study Sponsor ^ICMJE

Gilead Sciences

Collaborators ^ICMJE

Not Provided

Investigators ^ICMJE

Study Director:

Gilead Study Director

Gilead Sciences

PRS Account

Gilead Sciences

Verification Date

February 2020

^ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

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