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

NCT ID: NCT02858401

Last Updated: 2020-02-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-01-29
• Study Completion Date: 2019-02-14

Brief Summary

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

Conditions

HIV-1 Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Vesatolimod 1 mg (Cohort 1)

Vesatolimod 1 mg for 71 days, while continuing their existing ARV regimen

Group Type: EXPERIMENTAL

Vesatolimod

Intervention Type: DRUG

Tablet(s) administered orally once every 2 weeks

ARV regimen

Intervention Type: DRUG

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.

Vesatolimod 2 mg (Cohort 2)

Vesatolimod 2 mg for 71 days, while continuing their existing ARV regimen

Group Type: EXPERIMENTAL

Vesatolimod

Intervention Type: DRUG

Tablet(s) administered orally once every 2 weeks

ARV regimen

Intervention Type: DRUG

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.

Vesatolimod 4 mg (Cohort 3)

Vesatolimod 4 mg for 71 days, while continuing their existing ARV regimen

Group Type: EXPERIMENTAL

Vesatolimod

Intervention Type: DRUG

Tablet(s) administered orally once every 2 weeks

ARV regimen

Intervention Type: DRUG

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.

Vesatolimod 6 mg (Cohort 4)

Vesatolimod 6 mg for 127 days, while continuing their existing ARV regimen

Group Type: EXPERIMENTAL

Vesatolimod

Intervention Type: DRUG

Tablet(s) administered orally once every 2 weeks

ARV regimen

Intervention Type: DRUG

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.

Vesatolimod 8 mg (Cohort 5)

Vesatolimod 8 mg for 127 days administered following overnight fasting, while continuing their existing ARV regimen

Group Type: EXPERIMENTAL

Vesatolimod

Intervention Type: DRUG

Tablet(s) administered orally once every 2 weeks

ARV regimen

Intervention Type: DRUG

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.

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)

Group Type: EXPERIMENTAL

Vesatolimod

Intervention Type: DRUG

Tablet(s) administered orally once every 2 weeks

ARV regimen

Intervention Type: DRUG

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.

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

Group Type: EXPERIMENTAL

Vesatolimod

Intervention Type: DRUG

Tablet(s) administered orally once every 2 weeks

ARV regimen

Intervention Type: DRUG

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.

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

Group Type: EXPERIMENTAL

Vesatolimod

Intervention Type: DRUG

Tablet(s) administered orally once every 2 weeks

ARV regimen

Intervention Type: DRUG

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.

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

Group Type: EXPERIMENTAL

Vesatolimod

Intervention Type: DRUG

Tablet(s) administered orally once every 2 weeks

ARV regimen

Intervention Type: DRUG

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 (Cohorts 1-9)

Placebo to match vesatolimod for 71 or 127 days, while continuing their existing ARV regimen

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Tablet(s) administered orally once every 2 weeks

ARV regimen

Intervention Type: DRUG

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.

Interventions

Vesatolimod

Tablet(s) administered orally once every 2 weeks

Intervention Type: DRUG

Placebo

Tablet(s) administered orally once every 2 weeks

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

GS-9620

Eligibility Criteria

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

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gilead Sciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

Mills Clinical Research

Los Angeles, California, United States

UCSD Antiviral Research Center (AVRC)

San Diego, California, United States

Midway Immunology & Research Center

Ft. Pierce, Florida, United States

Orlando Immunology Center Recruiting

Orlando, Florida, United States

Ohio State University Infectious Diseases Research

Columbus, Ohio, United States

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Central Texas Clinical Research

Austin, Texas, United States

Peter Shalit, MD

Seattle, Washington, United States

Countries

United States

References

Riddler S, Para M, Benson C, et al. Vesatolimod (GS-9620) is safe and pharmacodynamically active in HIV infected individuals [Oral presentation WEAA0304]. 10th International AIDS Society Conference on HIV Science (IAS 2019), 22-23 July 2019, Mexico City, Mexico

Reference Type: RESULT

Riddler SA, Para M, Benson CA, Mills A, Ramgopal M, DeJesus E, Brinson C, Cyktor J, Jacobs J, Koontz D, Mellors JW, Laird GM, Wrin T, Patel H, Guo S, Wallin J, Boice J, Zhang L, Humeniuk R, Begley R, German P, Graham H, Geleziunas R, Brainard DM, SenGupta D. Vesatolimod, a Toll-like Receptor 7 Agonist, Induces Immune Activation in Virally Suppressed Adults Living With Human Immunodeficiency Virus-1. Clin Infect Dis. 2021 Jun 1;72(11):e815-e824. doi: 10.1093/cid/ciaa1534.

Reference Type: DERIVED

PMID: 33043969 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

GS-US-382-1450

Identifier Type: -

Identifier Source: org_study_id