Clinical trial NCT03060447: Study to Evaluate the Safety and Efficacy of Vesatolimod in Antiretroviral Treated Human Immunodeficiency Virus (HIV-1) Infected Controllers
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV-1 Infection
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2017-02-23
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants Experiencing Treatment Emergent Serious Adverse Events (TESAEs) and Treatment Emergent Adverse Events (TEAEs)
timeFrame: From first dose up to 30 days after permanent discontinuation of study drug (assessed maximum up to 33 months and 5 days)
Secondary outcomes:
measure: Change From Baseline in Plasma Log 10 HIV-1 RNA by Taqman 2.0
timeFrame: 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
measure: Time to Virologic Rebound
timeFrame: 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
measure: Peak HIV-1 Viral Load During Period 2
timeFrame: From Week 1 up to Week 24
measure: Change in Plasma Viral Load Set-Point Following ATI
timeFrame: Pre-ART (Initial Screening Visit) and 24 weeks plus 6 months following virologic re-suppression on ART (maximum 33 months and 5 days)
measure: Change From Baseline in Levels of Serum Cytokines
timeFrame: 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)
measure: Fold Change in Messenger Ribonucleic Acid (mRNA) of Interferon-Stimulated Genes (ISGs) in Whole Blood
timeFrame: 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)
measure: Change From Baseline in Immune Cell Activation
timeFrame: 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)
measure: Pharmacokinetic (PK) Parameter: Cmax of Vesatolimod
timeFrame: 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.
measure: PK Parameter: AUClast of Vesatolimod
timeFrame: 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.
measure: PK Parameter: AUCinf of Vesatolimod
timeFrame: 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.
measure: PK Parameter: %AUCexp of Vesatolimod
timeFrame: 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.
measure: PK Parameter: Tmax of Vesatolimod
timeFrame: 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.
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Mills Clinical Research
state: California
city: San Francisco
country: United States
facility: Zuckerberg San Francisco General
state: California
city: Fort Pierce
country: United States
facility: Midway Immunology & Research Center
state: Florida
city: Orlando
country: United States
facility: Orlando Immunology Center
state: Florida
city: Austin
country: United States
facility: Central Texas Clinical Research
state: Texas
city: Seattle
country: United States
facility: Peter Shalit, MD
state: Washington
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
citation: 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.