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Evaluate the Safety and Efficacy of Vesatolimod in Antiretroviral Treated HIV-1 Infected Controllers

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03060447
Recruitment Status : Completed
First Posted : February 23, 2017
Last Update Posted : March 2, 2020
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Tracking Information
First Submitted Date  ICMJE February 17, 2017
First Posted Date  ICMJE February 23, 2017
Last Update Posted Date March 2, 2020
Actual Study Start Date  ICMJE May 9, 2017
Actual Primary Completion Date February 13, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 17, 2017)
Overall Safety Profile as Assessed by Percentage of Participants Experiencing Treatment-Emergent Serious Adverse Events (SAEs) and all Treatment-Emergent Adverse Events. [ Time Frame: Up to 45 weeks plus 30 days ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 8, 2019)
  • Virology: Changes in Plasma HIV-1 RNA During the Dosing Period [ Time Frame: Up to 20 weeks ]
  • Virology: Time to Virologic Rebound and Plasma Viral Load Set-Point Following ATI [ Time Frame: Up to 25 weeks ]
  • Virology: Peak HIV-1 Viral Load During Period 2 [ Time Frame: Up to 25 weeks ]
  • Immunology/Pharmacodynamics: Changes in Serum/Plasma Cytokines in Whole Blood [ Time Frame: Up to 45 weeks ]
  • Immunology/Pharmacodynamics: Changes in mRNA of Interferon-Stimulated Genes (ISGs) in Whole Blood [ Time Frame: Up to 45 weeks ]
  • Immunology/Pharmacodynamics: Changes in Immune cell Activation in Whole Blood [ Time Frame: Up to 45 weeks ]
  • Pharmacokinetic (PK) Parameter: Cmax of Vesatolimod [ Time Frame: Up to 45 weeks ]
    Cmax is defined as maximum observed concentration of drug in plasma
  • PK Parameter: Ctau of Vesatolimod [ Time Frame: Up to 45 weeks ]
    Ctau is defined as the observed drug concentration at the end of the dosing interval (tau)
  • PK Parameter: AUCtau of Vesatolimod [ Time Frame: Up to 45 weeks ]
    AUCtau is defined as the area under the plasma concentration versus time curve over the dosing interval (tau)
Original Secondary Outcome Measures  ICMJE
 (submitted: February 17, 2017)
  • Virology: Changes in Plasma HIV-1 RNA and Cell Associated Viral RNA (CAVR) During the Dosing Period [ Time Frame: Up to 20 weeks ]
  • Virology: Changes in Peripheral Blood Mononuclear Cell (PBMC) HIV-1 Reservoir Between Baseline and Following GS-9620 Dosing [ Time Frame: Up to 45 weeks ]
  • Virology: Changes in Total CD4+ T Cell Reservoirs [ Time Frame: Up to 45 weeks ]
  • Virology: Time to Virologic Rebound and Plasma Viral Load Set-Point Following ATI [ Time Frame: Up to 25 weeks ]
  • Virology: Peak HIV-1 Viral Load During Period 2 [ Time Frame: Up to 25 weeks ]
  • Immunology/Pharmacodynamics: Changes in Serum/Plasma Cytokines [ Time Frame: Up to 45 weeks ]
  • Immunology/Pharmacodynamics: Changes in Plasma Kynurenine/ Tryptophan (K/T) [ Time Frame: Up to 45 weeks ]
  • Immunology/Pharmacodynamics: Changes in mRNA of Interferon-Stimulated Genes (ISGs) in Whole Blood [ Time Frame: Up to 45 weeks ]
  • Immunology/Pharmacodynamics: Changes in Immune cell Activation [ Time Frame: Up to 45 weeks ]
  • Immunology/Pharmacodynamics: Changes in HIV-1 Specific T cell Immune Responses [ Time Frame: Up to 45 weeks ]
  • Immunology/Pharmacodynamics: Changes in the Frequency of Regulatory T cells [ Time Frame: Up to 45 weeks ]
  • Immunology/Pharmacodynamics: Changes in the Quantity of HIV-Specific Antibodies [ Time Frame: Up to 45 weeks ]
  • Immunology/Pharmacodynamics: Changes in the Quality (Effector Functionality) of HIV-Specific Antibodies [ Time Frame: Up to 45 weeks ]
  • Immunology/Pharmacodynamics: Change in Plasma Inflammatory Markers [ Time Frame: Up to 45 weeks ]
  • Pharmacokinetic (PK) Parameter: Cmax of GS-9620 [ Time Frame: Up to 45 weeks ]
    Cmax is defined as maximum observed concentration of drug in plasma
  • PK Parameter: Ctau of GS-9620 [ Time Frame: Up to 45 weeks ]
    Ctau is defined as the observed drug concentration at the end of the dosing interval (tau)
  • PK Parameter: AUCtau of GS-9620 [ Time Frame: Up to 45 weeks ]
    AUCtau is defined as the area under the plasma concentration versus time curve over the dosing interval (tau)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Evaluate the Safety and Efficacy of Vesatolimod in Antiretroviral Treated HIV-1 Infected Controllers
Official Title  ICMJE A Phase 1b, Randomized, Double-Blind, Placebo-controlled Study to Evaluate the Safety and Efficacy of GS-9620 in Antiretroviral Treated HIV-1 Infected Controllers
Brief Summary The primary objective of this study is to evaluate the safety and tolerability of a 10-dose regimen of vesatolimod in HIV-1 infected controllers on antiretroviral treatment (ART) and during analytical treatment interruption (ATI) following vesatolimod dosing.
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
    8 mg dose administered as four 2 mg tablets orally every 14 days
    Other Name: GS-9620
  • Drug: Vesatolimod Placebo
    Tablet administered orally once every 14 days
  • Drug: ART
    ART regimens administered in accordance with their Prescribing Information
Study Arms  ICMJE
  • Experimental: Vesatolimod

    Period 1: Participants will receive up to 10 doses of vesatolimod. Participants will continue to take their prescribed ART during this period.

    Period 2: All participants will discontinue ART and be monitored for rebound in HIV-1 plasma viremia.

    Period 3: Participants may either enter in an optional analytical treatment interruption (ATI) extension period where they will continue to be off ART for up to an additional 6 months or restart ART and be monitored for additional 6 months.

    Interventions:
    • Drug: Vesatolimod
    • Drug: ART
  • Experimental: Vesatolimod placebo

    Period 1: Participants will receive up to 10 doses of vesatolimod placebo. Participants will continue to take their prescribed ART during this period.

    Period 2: All participants will discontinue ART and be monitored for rebound in HIV-1 plasma viremia.

    Period 3: Participants may either enter in an optional analytical treatment interruption (ATI) extension period where they will continue to be off ART for up to an additional 6 months or restart ART and be monitored for additional 6 months.

    Interventions:
    • Drug: Vesatolimod Placebo
    • Drug: ART
Publications * Not Provided

*   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
 (submitted: September 18, 2018)
28
Original Estimated Enrollment  ICMJE
 (submitted: February 17, 2017)
30
Actual Study Completion Date  ICMJE February 13, 2020
Actual Primary Completion Date February 13, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

  • Plasma HIV-1 RNA levels <50 copies/mL at screening
  • Chronic HIV-1 infection (for ≥ 6 months) prior to ART initiation
  • Pre-ART Plasma HIV-1 RNA set point between 50 and ≤ 5,000 copies/mL measured within two years prior to ART initiation
  • On ART for ≥ 6 months prior to screening
  • Documented plasma HIV-1 RNA < 50 copies/mL for ≥ 6 months preceding the screening visit (or undetectable HIV-1 RNA level according to the local assay being used if the limit of detection is ≥ 50 copies/mL). Unconfirmed virologic elevations of ≥ 50 copies/mL (transient detectable viremia, or "blip") prior to screening are acceptable.
  • No documented history of resistance to any components of the current ART regimen
  • Availability of a fully active alternative ART regimen, in the opinion of the Investigator, in the event of discontinuation of the current ART regimen with development of resistance.
  • Hemoglobin ≥ 11.5 g/dL (males) or ≥ 11 g/dL (females)
  • White Blood Cells ≥ 2,500 cells/μL
  • Platelets ≥ 125,000/mL
  • Absolute Neutrophil Counts ≥ 1000 cells/μL
  • CD4+ count ≥ 500 cells/μL
  • Alanine aminotransferase (ALT), aspartate aminotransferase (AST) or bilirubin ≤ 2 × upper limit of normal (ULN)
  • Estimated glomerular filtration rate ≥ 60 mL/min
  • No autoimmune disease requiring on-going immunosuppression
  • No evidence of current hepatitis B virus (HBV) infection
  • No evidence of current hepatitis C virus (HCV) infection (positive anti-HCV antibody and negative HCV polymerase chain reaction (PCR) results are acceptable)
  • No documented history of pre-ART CD4 nadir < 200 cells/μL (unknown pre-ART CD4 nadir is acceptable)
  • No history of opportunistic illness indicative of stage 3 HIV
  • No 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 No
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 NCT03060447
Other Study ID Numbers  ICMJE GS-US-382-3961
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: No
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