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

NCT03060447 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: GS-US-382-3961
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 6

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.

Conditions

HIV-1 Infection

Outcome Measures

Primary Outcomes (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.

  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)

• Change From Baseline in Plasma Log 10 HIV-1 RNA by Taqman 2.0

  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

• Time to Virologic Rebound

  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

• Peak HIV-1 Viral Load During Period 2

  From Week 1 up to Week 24

• Change in Plasma Viral Load Set-Point Following ATI

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

• Change From Baseline in Levels of Serum Cytokines

  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)

Study Arms (2)

Vesatolimod

EXPERIMENTAL

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.

Drug: Vesatolimod; Drug: ART

Placebo

EXPERIMENTAL

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.

Drug: Placebo; Drug: ART

Interventions

Vesatolimod DRUG

Tablets Administered orally

Also known as: GS-9620

Vesatolimod

Placebo DRUG

Tablets Administered orally

Placebo

ART DRUG

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.

Placebo; Vesatolimod

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (6)

Mills Clinical Research

Los Angeles, California, 90069, United States

Location

Zuckerberg San Francisco General

San Francisco, California, 94110, United States

Location

Midway Immunology & Research Center

Ft. Pierce, Florida, 34982, United States

Location

Orlando Immunology Center

Orlando, Florida, 32803, United States

Location

Central Texas Clinical Research

Austin, Texas, 78705, United States

Location

Peter Shalit, MD

Seattle, Washington, 98104, United States

Location

Related Publications (1)

• 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.

  RESULT

MeSH Terms

Interventions

vesatolimod

Results Point of Contact

• Title: Gilead Clinical Study Information Center
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

1-833-445-3230 (GILEAD-0)

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 17, 2017
• First Posted: February 23, 2017
• Study Start: May 9, 2017
• Primary Completion: February 13, 2020
• Study Completion: February 13, 2020
• Last Updated: April 21, 2021
• Results First Posted: April 21, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)