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

HIV-1 Infection Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03060447
• Other study ID #: GS-US-382-3961
• Status: Completed
• Phase: Phase 1
• Start date: May 9, 2017
• Est. completion date: February 13, 2020

Study information

• Verified date: March 2021
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: February 13, 2020
• Est. primary completion date: February 13, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• HIV-1 Infection

Intervention

Drug:
• Vesatolimod
Tablets Administered orally
• Placebo
Tablets Administered orally
• 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.

Locations

Country	Name	City	State
United States	Central Texas Clinical Research	Austin	Texas
United States	Midway Immunology & Research Center	Fort Pierce	Florida
United States	Mills Clinical Research	Los Angeles	California
United States	Orlando Immunology Center	Orlando	Florida
United States	Zuckerberg San Francisco General	San Francisco	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)

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.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	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
Secondary	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.	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
Secondary	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.	From Week 1 up to Week 24
Secondary	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.	Pre-ART (Initial Screening Visit) and 24 weeks plus 6 months following virologic re-suppression on ART (maximum 33 months and 5 days)
Secondary	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).	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)
Secondary	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.	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)
Secondary	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.	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)
Secondary	Pharmacokinetic (PK) Parameter: Cmax of Vesatolimod	Cmax is defined as the maximum concentration of drug.	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.
Secondary	PK Parameter: AUClast of Vesatolimod	AUClast is defined as the concentration of drug from time zero to the last observable concentration.	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.
Secondary	PK Parameter: AUCinf of Vesatolimod	AUCinf was defined as the concentration of drug extrapolated to infinite time.	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.
Secondary	PK Parameter: %AUCexp of Vesatolimod	%AUCexp is defined as the percentage of AUC extrapolated between AUClast and AUCinf.	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.
Secondary	PK Parameter: Tmax of Vesatolimod	Tmax is defined as the time (observed time point) of Cmax.	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.