Clinical trial NCT02990325: A Safety, Pharmacokinetics, and Pharmacodynamics Study of ABX464 in HIV-1 Seronegative and Seropositive Adults
Official title: An Open-Label Study of the Safety, Pharmacokinetics, and Pharmacodynamics of ABX464 in HIV-1 Seronegative and Seropositive Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: HIV Infections
Health Volunteers
Keywords: ABX464, HIV infection
Lead sponsor: Abivax S.A.
Sponsor class: INDUSTRY
First posted: 2016-12-13
Enrollment: 36
Sex: MALE
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of the ABX464-005 study is to characterize the systemic and mucosal immunological sequelae associated with exposure to ABX464 and to explore selected immunological endpoints, compartmental pharmacokinetics, and pharmacodynamics.

Detailed description: The purpose of the ABX464-005 study is to characterize the systemic and mucosal immunological sequelae associated with exposure to ABX464 and to explore selected immunological endpoints, compartmental pharmacokinetics, and pharmacodynamics. The site will screen and enroll 12 HIV-infected subjects who will receive 150 mg ABX464 orally once daily for 28 days (Cohort 1). Following completion of this cohort a further 24 subjects will be enrolled: 12 HIV-uninfected subjects will receive 50 mg ABX464 orally once daily for 28 days (Cohort 2) and 12 HIV-infected subjects (Cohort 3) who will 50 mg ABX464 orally once daily for 84 days.

Eligibility criteria: Inclusion criteria:

* Males aged 18-65 years;
* Subjects with adequate hematological and biochemical laboratory parameters
* Subjects should be able and willing to comply with study visits and procedures as per protocol;
* Subjects should understand, sign and date the written voluntary informed consent form at the screening visit prior to any protocol-specific procedures being performed;
* Subjects must agree to use in addition to the condom, a second highly effective method (one for the subject and one for the partner) of contraception (defined as per the Clinical Trials Facilitation and Coordination Group (CTFG) Guidance).

For HIV positive Subjects

* Subjects with a positive HIV-1 serology at any time before the study entry.
* Subjects treated for at least 12 months prior to screening with Dolutegravir or Raltegravir combined with either Tenofovir + Emtricitabine (TDF/FTC) or Abacavir + Lamivudine (ABC/3TC);
* Subjects with HIV plasma viral load ≤ 50 copies/mL during the 6 months prior to screening with a maximum of 2 blips ≤ 1000 copies during this period;
* Subjects' HIV-1 plasma viral load to be ≤ 100,000 copies/mL at any time beyond 6 months after the estimated date of primary infection;

Exclusion Criteria:

* History of allergic disease, anaphylaxis or reactions likely to be triggered or exacerbated by any component of investigational products;
* Acute or chronic infectious disease other than HIV infection (include but not limited to viral hepatitis such as hepatitis B, hepatitis C, active tuberculosis, active syphilis \[i.e. currently treated\].
* Acute, chronic or history of clinically relevant pulmonary, cardiovascular, gastrointestinal, hepatic, pancreatic or renal functional abnormality, encephalopathy, neuropathy or unstable Central Nervous System (CNS) pathology, angina or cardiac arrhythmias, or any other clinically significant medical problems as determined by physical examination and/or laboratory screening tests and/or medical history;
* Severe hepatic impairment;
* Acute, chronic or history of immunodeficiency or autoimmune disease other than HIV infection;

Primary outcomes:
measure: Area Under the Curve (AUC) of ABX464 in Sera
timeFrame: Day 1, Day 28 and Day 84
measure: Maximum Observed Concentration (Cmax) of ABX464 in Sera
timeFrame: Day 1, Day 28 and day 84
measure: Area Under the Curve (AUC) of ABX464 Metabolite (ABX464-N-Glucuronide) in Sera
timeFrame: Day 1, Day 28 and Day 84
measure: Maximum Observed Concentration (Cmax) of ABX464 Metabolite (ABX464-N-Glucuronide) in Sera
timeFrame: Day 1, Day 28 and Day 84
measure: Maximum Observed Concentration (Cmax) of ABX464 in Peripheral Blood Mononuclear Cells (PBMC)
timeFrame: Day 1, Day 28 and Day 84
measure: Area Under the Curve (AUC) of ABX464 in Peripheral Blood Mononuclear Cells (PBMC)
timeFrame: Day 1, Day 28 and Day 84
measure: Maximum Observed Concentration (Cmax) of ABX464 Metabolite (ABX464-N-Glucuronide) in Peripheral Blood Mononuclear Cells (PBMC)
timeFrame: Day 1, Day 28 and Day 84
measure: Area Under the Curve (AUC) of ABX464 Metabolite (ABX464-N-Glucuronide) in Peripheral Blood Mononuclear Cells (PBMC)
timeFrame: Day 1, Day 28 and Day 84
measure: Concentration of ABX464 in Rectal Tissue (Measured Only at Pre-infusion Timepoint)
timeFrame: Day 1, Day 28, Day 56, Day 84 and Day 112
measure: Concentration of ABX464 Metabolite (ABX464-N-Glucuronide) in Rectal Tissue (Measured Only at Pre-infusion Timepoint)
timeFrame: Day 1, Day 28, Day 56, Day 84 and Day 112
Secondary outcomes:
measure: Mean Change From Baseline in Plasma Viral Load (Ultrasensitive Assay)
timeFrame: Day 28, Day 56, Day 84 and Day 112
measure: CD4+ Counts (Cell/mm^3)
timeFrame: Day 28, Day 35, Day 56, Day 84, Day 91 and Day 112
measure: Total HIV-1 DNA Reservoir in Peripheral Blood Mononuclear Cells (PBMC)
timeFrame: Day 28, Day 56, Day 84 and Day 112
Other outcomes:
Locations:
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol
state: Catalogna
Study officials:
affiliation: Abivax S.A.
name: Paul GINESTE, PhD
role: STUDY_DIRECTOR
References:
citation: Moron-Lopez S, Bernal S, Wong JK, Martinez-Picado J, Yukl SA. ABX464 Decreases the Total Human Immunodeficiency Virus (HIV) Reservoir and HIV Transcription Initiation in CD4+ T Cells From Antiretroviral Therapy-Suppressed Individuals Living With HIV. Clin Infect Dis. 2022 Jun 10;74(11):2044-2049. doi: 10.1093/cid/ciab733.