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Trial record 1 of 1 for:    GS-US-382-3961
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Study to Evaluate the Safety and Efficacy of Vesatolimod in Antiretroviral Treated Human Immunodeficiency Virus (HIV-1) Infected Controllers

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ClinicalTrials.gov Identifier: NCT03060447
Recruitment Status : Completed
First Posted : February 23, 2017
Results First Posted : April 21, 2021
Last Update Posted : April 21, 2021
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Tracking Information
First Submitted Date  ICMJE February 17, 2017
First Posted Date  ICMJE February 23, 2017
Results First Submitted Date  ICMJE February 10, 2021
Results First Posted Date  ICMJE April 21, 2021
Last Update Posted Date April 21, 2021
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: March 29, 2021)
Percentage of Participants Experiencing Treatment Emergent Serious Adverse Events (TESAEs) and Treatment Emergent Adverse Events (TEAEs) [ Time Frame: From first dose up to 30 days after permanent discontinuation of study drug (assessed maximum up to 33 months and 5 days) ]
AE was any untoward medical occurrence in a clinical study participant administered a medicinal product (MP), which did not necessarily had a causal relationship with treatment. AE was therefore any unfavorable and/or unintended sign, symptom, or disease temporally associated with use of MP, whether or not considered related to MP. TEAEs: AE with an onset date on or after the study drug start date and no later than 30 days after study drug stop date; or any AE leading to study drug discontinuation. TESAEs: event that resulted in following: death; life-threatening situation; in-patient hospitalization or prolongation of existing hospitalization; persistent or significant disability or incapacity; congenital anomaly or birth defect; medically important event or reaction: such events might not have been immediately life-threatening or resulted in death or hospitalization but may jeopardize participant or may require intervention to prevent one of the other outcomes constituting SAEs.
Original 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 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 29, 2021)
  • Change From Baseline in Plasma Log 10 HIV-1 RNA by Taqman 2.0 [ Time Frame: Baseline and Dose 1: Days 2,8; Dose 2: Days 1,8; Dose 3: Days 1,8; Dose 4: Days 1,2,4,8; Dose 5: Day 1,8; Dose 6: Days 1,4,8; Dose 7: Days 1,8; Dose 8: Days 1,8; Dose 9: Days 1,8; Dose 10: Days 1,2,4,8,14 ]
    Plasma log 10 HIV-1 RNA was measured using Taqman version 2.0 assay with limit of quantification of 20 copies/mL.
  • Time to Virologic Rebound [ Time Frame: From Day 1 (Period 1) up to 24 weeks of Period 2 plus 6 months following virologic re-suppression on ART, an average of 17 months ]
    Time to virologic rebound was analyzed using the Kaplan-Meier method at two cut-off values; ≥ 50 copies/mL and ≥ 200 copies/mL. Virologic rebound at ≥ 50 copies/mL was defined as 2 consecutive HIV-1 RNA measurements ≥ 50 copies/mL. Virologic rebound at ≥ 200 copies/mL was defined as 2 consecutive HIV-1 RNA measurements ≥ 200 copies/mL. The date of rebound was the first time HIV-1 RNA measurement ≥ 50 copies/mL or ≥ 200 respectively.
  • Peak HIV-1 Viral Load During Period 2 [ Time Frame: From Week 1 up to Week 24 ]
    For participants who did not restart ART, the maximum value of HIV-1 RNA measurements during ATI was used as the peak value and for participants who restarted ART, the maximum value of HIV-1 RNA measurements during ATI before the restart of ART was used as the peak value.
  • Change in Plasma Viral Load Set-Point Following ATI [ Time Frame: Pre-ART (Initial Screening Visit) and 24 weeks plus 6 months following virologic re-suppression on ART (maximum 33 months and 5 days) ]
    Plasma viral load set-point values were calculated at pre-ART stage and following ATI. Change in plasma viral load set-point following ATI = viral set-point following ATI minus pre-ART set point. The plasma viral set-point following ATI was calculated as the geometric mean of all the HIV-1 RNA measurements between a start date and an end date. The start date and end date was provided by clinical based on blinded individual participant's data review.
  • Change From Baseline in Levels of Serum Cytokines [ Time Frame: Baseline and Dose 1: Day 2,8; Dose 4: Days 1,2,8; Dose 10: Days 1,2,8; ATI Remission Visit (12 weeks post ATI Visit: evaluated at maximum of 24 weeks); Early study drug discontinuation (7 days post- last ATI visit at Week 24) ]
    Following Serum Cytokines Levels were evaluated: interferon-a (IFN-a), interleukin-1 receptor antagonist (IL-1RA), inducible protein-10 (IP-10) and inducible T cell alpha chemoattractant (ITAC).
  • Fold Change in Messenger Ribonucleic Acid (mRNA) of Interferon-Stimulated Genes (ISGs) in Whole Blood [ Time Frame: Baseline and Dose 1: Day 2; Dose 4: Days 1,2; Dose 10: Day 1,2; Early Study Drug Discontinuation (7 days post- last ATI visit at Week 24) ]
    Following ISGs Levels were evaluated: Interferon-stimulated Gene 15 (ISG15), Oligoadenylate synthase-1 (OAS-1), and interferon-induced guanosine triphosphate-binding protein MX1. Fold change was calculated as postbaseline value divided by baseline value.
  • Change From Baseline in Immune Cell Activation [ Time Frame: Baseline and Dose 4: Days 1,2,4; Dose 6: Days 1,4; Dose 10: Days 1,2,4,14; ATI Remission Visit (12 weeks post ATI Visit: evaluated at maximum of 24 weeks) ]
    Activation of Immune cells (T cells: CD4/CD38/HLADR, CD8/CD38/HLADR and NK cells: CD69+CD56+CD16+, CD69+CD56dimCD16neg, CD69+CD56brCD16dim) was measured by cytometry.
  • Pharmacokinetic (PK) Parameter: Cmax of Vesatolimod [ Time Frame: Pre-dose (≤ 5 minutes prior to dosing), 0.5, 1, 2, 4, 6, 8, 10, and 24 hours post dose at Dose 1-Day 1 visit. ]
    Cmax is defined as the maximum concentration of drug.
  • PK Parameter: AUClast of Vesatolimod [ Time Frame: Pre-dose (≤ 5 minutes prior to dosing), 0.5, 1, 2, 4, 6, 8, 10, and 24 hours post dose at Dose 1-Day 1 visit. ]
    AUClast is defined as the concentration of drug from time zero to the last observable concentration.
  • PK Parameter: AUCinf of Vesatolimod [ Time Frame: Pre-dose (≤ 5 minutes prior to dosing), 0.5, 1, 2, 4, 6, 8, 10, and 24 hours post dose at Dose 1-Day 1 visit. ]
    AUCinf was defined as the concentration of drug extrapolated to infinite time.
  • PK Parameter: %AUCexp of Vesatolimod [ Time Frame: Pre-dose (≤ 5 minutes prior to dosing), 0.5, 1, 2, 4, 6, 8, 10, and 24 hours post dose at Dose 1-Day 1 visit. ]
    %AUCexp is defined as the percentage of AUC extrapolated between AUClast and AUCinf.
  • PK Parameter: Tmax of Vesatolimod [ Time Frame: Pre-dose (≤ 5 minutes prior to dosing), 0.5, 1, 2, 4, 6, 8, 10, and 24 hours post dose at Dose 1-Day 1 visit. ]
    Tmax is defined as the time (observed time point) of Cmax.
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 Study to Evaluate the Safety and Efficacy of Vesatolimod in Antiretroviral Treated Human Immunodeficiency Virus (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
    Tablets Administered orally
    Other Name: GS-9620
  • Drug: Placebo
    Tablets Administered orally
  • Drug: ART
    ART regimens administered in accordance with their prescribing information. The following agents are allowed as part of the ART regimen: nucleoside reverse transcriptase inhibitors, raltegravir, dolutegravir (DTG), rilpivirine, and maraviroc.
Study Arms  ICMJE
  • Experimental: Vesatolimod
    Participants in Period 1 will receive 10 doses of vesatolimod (4 mg to 8 mg) once every 14 days over a 20-week period along with their prescribed ART. Participants in Period 2 (ATI) will discontinue ART and vesatolimod and will be monitored for rebound in HIV-1 plasma viremia for 24 weeks. Participants who restart ART during Period 2 due to virologic rebound will complete the ART Re-Initiation Visits, and then Post-ART Re-suppression Visits monthly for 6 additional months. Participants who complete 24 Weeks of ATI without restarting ART will move onto Period 3 and have 2 options. They can remain off ART for up to an additional 24 weeks. Those who restart ART at the start of Period 3 will complete ART Re-initiation Visits and then Post-ART Re-suppression Visits monthly for 6 additional months.
    Interventions:
    • Drug: Vesatolimod
    • Drug: ART
  • Experimental: Placebo
    Participants in Period 1 will receive 10 doses of placebo matched to vesatolimod once every 14 days over a 20-week period along with their prescribed ART. Participants in Period 2 (ATI) will discontinue ART and placebo and will be monitored for rebound in HIV-1 plasma viremia for 24 weeks. Participants who restart ART during Period 2 due to virologic rebound will complete the ART Re-Initiation Visits, and then Post-ART Re-suppression Visits monthly for 6 additional months. Participants who complete 24 Weeks of ATI without restarting ART will move onto Period 3 and have 2 options. They can remain off ART for up to an additional 24 weeks. Those who restart ART at the start of Period 3 will complete ART Re-initiation Visits and then Post-ART Re-suppression Visits monthly for 6 additional months.
    Interventions:
    • Drug: Placebo
    • Drug: ART
Publications * SenGupta D, Ramgopal M, Brinson C, DeJesus E, Mills A, Shalit P, et al. Safety and Analytic Treatment Interruption Outcomes of Vesatolimod in HIV Controllers. Oral Presentation at CROI 2020, Boston, USA. Abstract 3982.

*   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: March 29, 2021)
25
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 ribonucleic acid (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 consecutive 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
  • Cluster of Differentiation 4 (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 March 2021

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