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

HIV-1 Infection Clinical Trial

Official title:

A Phase 1b, Randomized, Blinded, Placebo-Controlled Dose-Escalation Study of the Safety and Biological Activity of GS-9620 in HIV-1 Infected, Virologically Suppressed Adults

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02858401
• Other study ID #: GS-US-382-1450
• Status: Completed
• Phase: Phase 1
• Start date: January 29, 2015
• Est. completion date: February 14, 2019

Study information

• Verified date: February 2020
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: February 14, 2019
• Est. primary completion date: February 14, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key 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

Key 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

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Related Conditions & MeSH terms

• HIV-1 Infection

Intervention

Drug:
• Vesatolimod
Tablet(s) administered orally once every 2 weeks
• Placebo
Tablet(s) administered orally once every 2 weeks
• 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.

Locations

Country	Name	City	State
United States	Central Texas Clinical Research	Austin	Texas
United States	Ohio State University Infectious Diseases Research	Columbus	Ohio
United States	Midway Immunology & Research Center	Fort Pierce	Florida
United States	Mills Clinical Research	Los Angeles	California
United States	Orlando Immunology Center Recruiting	Orlando	Florida
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	UCSD Antiviral Research Center (AVRC)	San Diego	California
United States	Peter Shalit, MD	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Country where clinical trial is conducted

United States, 

References & Publications (1)

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,

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants Experiencing Treatment-Emergent Serious Adverse Events (SAEs) and Any Treatment-Emergent Adverse Events (AEs).		For Cohorts 1 to 3: First dose date up to 71 days plus 30 days; For Cohorts 4 to 6: First dose date up to 127 days plus 30 days; For placebo: First dose date up to 71 days plus 30 days or first dose date up to 127 days plus 30 days
Primary	Maximum Change From Baseline in Plasma Log10 HIV-1 RNA at Any Postdose Timepoint	The maximum change from baseline in plasma Log10 HIV-1 RNA refers to the maximum change at any postdose timepoint up to Day 81 or Day 134 for placebo, Day 81 for Cohorts 1 to 3, and Day 134 for Cohorts 4 to 6.	For Cohorts 1 to 3: Baseline to Day 81; For Cohorts 4 to 6: Baseline to Day 134; For placebo: Baseline to Day 81 or Baseline to Day 134
Secondary	Change From Baseline in Plasma Log10 HIV-1 RNA at Day 2	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 2.	Baseline; Day 2
Secondary	Change From Baseline in Plasma Log10 HIV-1 RNA at Day 3	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 3.	Baseline; Day 3
Secondary	Change From Baseline in Plasma Log10 HIV-1 RNA at Day 5	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 5.	Baseline; Day 5
Secondary	Change From Baseline in Plasma Log10 HIV-1 RNA at Day 8	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 8.	Baseline; Day 8
Secondary	Change From Baseline in Plasma Log10 HIV-1 RNA at Day 11	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 11.	Baseline; Day 11
Secondary	Change From Baseline in Plasma Log10 HIV-1 RNA at Day 15	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 15.	Baseline; Day 15
Secondary	Change From Baseline in Plasma Log10 HIV-1 RNA at Day 17	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 17.	Baseline; Day 17
Secondary	Change From Baseline in Plasma Log10 HIV-1 RNA at Day 19	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 19.	Baseline; Day 19
Secondary	Change From Baseline in Plasma Log10 HIV-1 RNA at Day 22	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 22.	Baseline; Day 22
Secondary	Change From Baseline in Plasma Log10 HIV-1 RNA at Day 25	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 25.	Baseline; Day 25
Secondary	Change From Baseline in Plasma Log10 HIV-1 RNA at Day 29	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 29.	Baseline; Day 29
Secondary	Change From Baseline in Plasma Log10 HIV-1 RNA at Day 31	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 31.	Baseline; Day 31
Secondary	Change From Baseline in Plasma Log10 HIV-1 RNA at Day 33	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 33.	Baseline; Day 33
Secondary	Change From Baseline in Plasma Log10 HIV-1 RNA at Day 36	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 36	Baseline; Day 36
Secondary	Change From Baseline in Plasma Log10 HIV-1 RNA at Day 39	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 39	Baseline; Day 39
Secondary	Change From Baseline in Plasma Log10 HIV-1 RNA at Day 43	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 43	Baseline; Day 43
Secondary	Change From Baseline in Plasma Log10 HIV-1 RNA at Day 45	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit pn Day 45	Baseline; Day 45
Secondary	Change From Baseline in Plasma Log10 HIV-1 RNA at Day 47	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 47	Baseline; Day 47
Secondary	Change From Baseline in Plasma Log10 HIV-1 RNA at Day 50	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 50.	Baseline; Day 50
Secondary	Change From Baseline in Plasma Log10 HIV-1 RNA at Day 53	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 53	Baseline; Day 53
Secondary	Change From Baseline in Plasma Log10 HIV-1 RNA at Day 57	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 57.	Baseline; Day 57
Secondary	Change From Baseline in Plasma Log10 HIV-1 RNA at Day 58	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 58.	Baseline; Day 58
Secondary	Change From Baseline in Plasma Log10 HIV-1 RNA at Day 59	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 59.	Baseline; Day 59
Secondary	Change From Baseline in Plasma Log10 HIV-1 RNA at Day 61	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 61.	Baseline; Day 61
Secondary	Change From Baseline in Plasma Log10 HIV-1 RNA at Day 64	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 64.	Baseline; Day 64
Secondary	Change From Baseline in Plasma Log10 HIV-1 RNA at Day 67	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 67.	Baseline; Day 67
Secondary	Change From Baseline in Plasma Log10 HIV-1 RNA at Day 71	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 71.	Baseline; Day 71
Secondary	Change From Baseline in Plasma Log10 HIV-1 RNA at Day 73	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 73.	Baseline; Day 73
Secondary	Change From Baseline in Plasma Log10 HIV-1 RNA at Day 75	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 75.	Baseline; Day 75
Secondary	Change From Baseline in Plasma Log10 HIV-1 RNA at Day 78	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 78.	Baseline; Day 78
Secondary	Change From Baseline in Plasma Log10 HIV-1 RNA at Day 81	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 81.	Baseline; Day 81
Secondary	Change From Baseline in Plasma Log10 HIV-1 RNA at Day 85	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 85.	Baseline; Day 85
Secondary	Change From Baseline in Plasma Log10 HIV-1 RNA at Day 87	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 87.	Baseline; Day 87
Secondary	Change From Baseline in Plasma Log10 HIV-1 RNA at Day 92	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 92.	Baseline; Day 92
Secondary	Change From Baseline in Plasma Log10 HIV-1 RNA at Day 99	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 99.	Baseline; Day 99
Secondary	Change From Baseline in Plasma Log10 HIV-1 RNA at Day 101	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 101.	Baseline; Day 101
Secondary	Change From Baseline in Plasma Log10 HIV-1 RNA at Day 106	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 106.	Baseline; Day 106
Secondary	Change From Baseline in Plasma Log10 HIV-1 RNA at Day 113	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 113.	Baseline; Day 113
Secondary	Change From Baseline in Plasma Log10 HIV-1 RNA at Day 115	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 115.	Baseline; Day 115
Secondary	Change From Baseline in Plasma Log10 HIV-1 RNA at Day 120	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 120.	Baseline; Day 120
Secondary	Change From Baseline in Plasma Log10 HIV-1 RNA at Day 127	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 127.	Baseline; Day 127
Secondary	Change From Baseline in Plasma Log10 HIV-1 RNA at Day 128	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 128.	Baseline; Day 128
Secondary	Change From Baseline in Plasma Log10 HIV-1 RNA at Day 129	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 129.	Baseline; Day 129
Secondary	Change From Baseline in Plasma Log10 HIV-1 RNA at Day 134	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 134.	Baseline; Day 134
Secondary	Change From Baseline in Plasma Log10 HIV-1 RNA at Day 157	Change from baseline in plasma log10 HIV-1 RNA refers to change from baseline at a postbaseline visit on Day 157.	Baseline; Day 157
Secondary	Percentage of Participants With Plasma HIV-1 RNA = 50 Copies/mL at Postdose 1 on Day 1		Postdose 1 on Day 1
Secondary	Percentage of Participants With Plasma HIV-1 RNA = 50 Copies/mL at PostDose 2 on Day 15		PostDose 2 on Day 15
Secondary	Percentage of Participants With Plasma HIV-1 RNA = 50 Copies/mL at PostDose 3 on Day 29		PostDose 3 on Day 29
Secondary	Percentage of Participants With Plasma HIV-1 RNA = 50 Copies/mL at PostDose 4 on Day 43		PostDose 4 on Day 43
Secondary	Percentage of Participants With Plasma HIV-1 RNA = 50 Copies/mL at PostDose 5 on Day 57		PostDose 5 on Day 57
Secondary	Percentage of Participants With Plasma HIV-1 RNA = 50 Copies/mL at PostDose 6 on Day 71		PostDose 6 on Day 71
Secondary	Percentage of Participants With Plasma HIV-1 RNA = 50 Copies/mL at PostDose 7 on Day 85		PostDose 7 on Day 85
Secondary	Percentage of Participants With Plasma HIV-1 RNA = 50 Copies/mL at PostDose 8 on Day 99		PostDose 8 on Day 99
Secondary	Percentage of Participants With Plasma HIV-1 RNA = 50 Copies/mL at PostDose 9 on Day 113		PostDose 9 on Day 113
Secondary	Percentage of Participants With Plasma HIV-1 RNA = 50 Copies/mL at PostDose 10 on Day 127		PostDose 10 on Day 127