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HIV-1 InfectionPhase 1NCT03060447

Study to Evaluate the Safety and Efficacy of Vesatolimod in Antiretroviral Treated Human Immunodeficiency Virus (HIV-1) Infected Controllers

A Phase 1 study testing Vesatolimod and ART in people with HIV-1 Infection, run by Gilead Sciences at 6 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
HIV-1 Infection
What is being tested?
Vesatolimod and ART
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
25 participants
Where
6 sitesUnited States
Study dates
9 May 2017to 13 Feb 2020
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 21Show fewer
  • 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.

Who cannot join

None listed.

Trial locations and contacts

6 sites in 1 country.

6 sites in 1 country

United States6 sites
  • Central Texas Clinical Research

    Austin, Texas, 78705

  • Midway Immunology & Research Center

    Ft. Pierce, Florida, 34982

  • Mills Clinical Research

    Los Angeles, California, 90069

  • Orlando Immunology Center

    Orlando, Florida, 32803

  • Zuckerberg San Francisco General

    San Francisco, California, 94110

  • Peter Shalit, MD

    Seattle, Washington, 98104

Other trials in United States

About this study

Official title: 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

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.

Conditions
HIV-1 Infection
Being tested
Vesatolimod, Placebo, ART

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • VesatolimodDrug

    Also called GS-9620

    Tablets Administered orally

  • PlaceboDrug

    Tablets Administered orally

  • ARTDrug

    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 groups in NCT03060447
Study groupRoleWhat they receive
VesatolimodExperimentalParticipants 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.
Receives: Drug: Vesatolimod; Drug: ART
PlaceboExperimentalParticipants 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.
Receives: Drug: Placebo; Drug: ART

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Participants Experiencing Treatment Emergent Serious Adverse Events (TESAEs) and Treatment Emergent Adverse Events (TEAEs)

    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.

    Measured: From first dose up to 30 days after permanent discontinuation of study drug (assessed maximum up to 33 months and 5 days)

Secondary outcomes (12)
  1. Change From Baseline in Plasma Log 10 HIV-1 RNA by Taqman 2.0

    Plasma log 10 HIV-1 RNA was measured using Taqman version 2.0 assay with limit of quantification of 20 copies/mL.

    Measured: 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

  2. Time to Virologic Rebound

    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.

    Measured: 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

  3. Peak HIV-1 Viral Load During Period 2

    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.

    Measured: From Week 1 up to Week 24

  4. Change in Plasma Viral Load Set-Point Following ATI

    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.

    Measured: Pre-ART (Initial Screening Visit) and 24 weeks plus 6 months following virologic re-suppression on ART (maximum 33 months and 5 days)

  5. Change From Baseline in Levels of Serum Cytokines

    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).

    Measured: 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)

  6. Fold Change in Messenger Ribonucleic Acid (mRNA) of Interferon-Stimulated Genes (ISGs) in Whole Blood

    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.

    Measured: 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)

  7. Change From Baseline in Immune Cell Activation

    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.

    Measured: 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)

  8. Pharmacokinetic (PK) Parameter: Cmax of Vesatolimod

    Cmax is defined as the maximum concentration of drug.

    Measured: 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.

  9. PK Parameter: AUClast of Vesatolimod

    AUClast is defined as the concentration of drug from time zero to the last observable concentration.

    Measured: 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.

  10. PK Parameter: AUCinf of Vesatolimod

    AUCinf was defined as the concentration of drug extrapolated to infinite time.

    Measured: 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.

  11. PK Parameter: %AUCexp of Vesatolimod

    %AUCexp is defined as the percentage of AUC extrapolated between AUClast and AUCinf.

    Measured: 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.

  12. PK Parameter: Tmax of Vesatolimod

    Tmax is defined as the time (observed time point) of Cmax.

    Measured: 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.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Feb 2017
  2. Study start9 May 2017
  3. Primary completion13 Feb 2020
  4. Study completion13 Feb 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
25 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03060447
Sponsor's protocol ID
GS-US-382-3961
Status last verified
Mar 2021
First submitted
17 Feb 2017
Last updated
21 Apr 2021
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

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.

  • Abdel-Mohsen M, Deeks S, Giron L, Hong KY, Goldman A, Zhang L, Huang SSY, Verrill D, Guo S, Selzer L, de Vries CR, Vendrame E, SenGupta D, Wallin JJ, Cai Y. Circulating immune and plasma biomarkers of time to HIV rebound in HIV controllers treated with vesatolimod. Front Immunol. 2024 Jun 24;15:1405348. doi: 10.3389/fimmu.2024.1405348. eCollection 2024.

    PubMed 38979421

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Vesatolimod and ART in people with HIV-1 Infection, run by Gilead Sciences at 6 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 21 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 21 Apr 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03060447, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Apr 2021.

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