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

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ClinicalTrials.gov Identifier: NCT02858401
Recruitment Status : Active, not recruiting
First Posted : August 8, 2016
Last Update Posted : November 8, 2018
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Brief Summary:
The primary objectives of this study are to evaluate the safety and tolerability of vesatolimod (formerly GS-9620) at escalating, multiple doses of vesatolimod 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.

Condition or disease Intervention/treatment Phase
HIV-1 Infection Drug: Vesatolimod Drug: Placebo Drug: ARV regimen Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 56 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
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
Actual Study Start Date : January 29, 2015
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : June 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: HIV/AIDS

Arm Intervention/treatment
Experimental: Vesatolimod 1 mg (Cohort 1)
Vesatolimod 1 mg for 71 days, while continuing their existing ARV regimen
Drug: Vesatolimod
Tablet(s) administered orally once every 2 weeks
Other Name: GS-9620

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.

Experimental: Vesatolimod 2 mg (Cohort 2)
Vesatolimod 2 mg for 71 days, while continuing their existing ARV regimen
Drug: Vesatolimod
Tablet(s) administered orally once every 2 weeks
Other Name: GS-9620

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.

Experimental: Vesatolimod 4 mg (Cohort 3)
Vesatolimod 4 mg for 71 days, while continuing their existing ARV regimen
Drug: Vesatolimod
Tablet(s) administered orally once every 2 weeks
Other Name: GS-9620

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.

Experimental: Vesatolimod 6 mg (Cohort 4)
Vesatolimod 6 mg for 127 days, while continuing their existing ARV regimen
Drug: Vesatolimod
Tablet(s) administered orally once every 2 weeks
Other Name: GS-9620

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.

Experimental: Vesatolimod 8 mg (Cohort 5)
Vesatolimod 8 mg for 127 days administered following overnight fasting, while continuing their existing ARV regimen
Drug: Vesatolimod
Tablet(s) administered orally once every 2 weeks
Other Name: GS-9620

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.

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

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.

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

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.

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

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.

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

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.

Placebo Comparator: Placebo (Cohorts 1-9)
Placebo to match vesatolimod for 71 or 127 days, while continuing their existing ARV regimen
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.




Primary Outcome Measures :
  1. Incidence of treatment-emergent serious adverse events (SAEs) and all treatment-emergent adverse events [ Time Frame: Up to 157 days ]
  2. Maximum change from baseline in plasma log10 HIV-1 RNA at any postdose timepoint [ Time Frame: Up to Day 81 (Cohorts 1 to 3) or up to Day 134 (Cohorts 4 to 9) ]

Secondary Outcome Measures :
  1. Change from baseline in plasma log10 HIV-1 RNA at post-baseline visits [ Time Frame: Up to 157 days ]
  2. Proportion of participants with plasma HIV-1 RNA > 50 copies/mL at any postdose timepoint [ Time Frame: Up to Day 81 (Cohorts 1 to 3) or up to Day 134 (Cohorts 4 to 9) ]
  3. Change in single copy assay (SCA) from predose to 2 days postdose [ Time Frame: Predose to 2 days postdose ]
  4. Change in cell-associated HIV-1 RNA from predose to 2 days postdose [ Time Frame: Predose to 2 days postdose ]
  5. Change in HIV-1 reservoir measured by cell (PBMC) associated DNA from pre-dose to 2 days post-dose (Cohorts 1 to 9) [ Time Frame: Predose to 2 days postdose ]
  6. Change in HIV-1 reservoir measured by by use of a second assay using stored PBMC samples from pre-dose to 2 days post-dose (Cohorts 4 to 9) [ Time Frame: Predose to 2 days postdose ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02858401


Locations
United States, California
Mills Clinical Research
Los Angeles, California, United States, 90069
UCSD Antiviral Research Center (AVRC)
San Diego, California, United States, 92103
United States, Florida
Midway Immunology & Research Center
Fort Pierce, Florida, United States, 34982
Orlando Immunology Center Recruiting
Orlando, Florida, United States, 32803
United States, Ohio
Ohio State University Infectious Diseases Research
Columbus, Ohio, United States, 43210
United States, Pennsylvania
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
United States, Texas
Central Texas Clinical Research
Austin, Texas, United States, 78705
United States, Washington
Peter Shalit, MD
Seattle, Washington, United States, 98104
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Gilead Study Director Gilead Sciences

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT02858401     History of Changes
Other Study ID Numbers: GS-US-382-1450
First Posted: August 8, 2016    Key Record Dates
Last Update Posted: November 8, 2018
Last Verified: November 2018

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