A Safety, Pharmacokinetics, and Pharmacodynamics Study of ABX464 in HIV-1 Seronegative and Seropositive Adults

Study Overview
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Brief Summary
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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
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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.

Official Title
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An Open-Label Study of the Safety, Pharmacokinetics, and Pharmacodynamics of ABX464 in HIV-1 Seronegative and Seropositive Adults

Conditions
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HIV Infections, Health Volunteers

Intervention / Treatment
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* Drug: ABX464 150mg
* Drug: ABX464 50mg
* Drug: ABX464 50mg


Participation Criteria
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Eligibility Criteria
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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;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ABX464 150mg<br>ABX464, 50mg per Capsule Three Capsules per day for 28 days | Drug: ABX464 150mg<br>* ABX464 given orally at 150 mg per day from Day 0 to Day 28 (Cohort 1/ HIV infected subjects)<br>|
| Experimental: ABX464 50mg for 28 days<br>ABX464, 50mg per Capsule One Capsule per day for 28 days | Drug: ABX464 50mg<br>* ABX464 given orally at 50 mg per day from Day 0 to Day 28 (Cohort 2 / non HIV infected subjects)<br>|
| Experimental: ABX464 50mg for 84 days<br>ABX464, 50mg per Capsule One Capsule per day for 84 days | Drug: ABX464 50mg<br>* ABX464 given orally at 50 mg per day from Day 0 to Day 84 (Cohort 3 / HIV infected subjects)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Curve (AUC) of ABX464 in Sera | Pharmacokinetic parameters | Day 1, Day 28 and Day 84 | 
| Maximum Observed Concentration (Cmax) of ABX464 in Sera | Pharmacokinetic parameters | Day 1, Day 28 and day 84 | 
| Area Under the Curve (AUC) of ABX464 Metabolite (ABX464-N-Glucuronide) in Sera | Pharmacokinetics parameters | Day 1, Day 28 and Day 84 | 
| Maximum Observed Concentration (Cmax) of ABX464 Metabolite (ABX464-N-Glucuronide) in Sera | Pharmacokinetic parameters | Day 1, Day 28 and Day 84 | 
| Maximum Observed Concentration (Cmax) of ABX464 in Peripheral Blood Mononuclear Cells (PBMC) | Pharmacokinetic parameters | Day 1, Day 28 and Day 84 | 
| Area Under the Curve (AUC) of ABX464 in Peripheral Blood Mononuclear Cells (PBMC) | Pharmacokinetic parameters | Day 1, Day 28 and Day 84 | 
| Maximum Observed Concentration (Cmax) of ABX464 Metabolite (ABX464-N-Glucuronide) in Peripheral Blood Mononuclear Cells (PBMC) | Pharmacokinetic parameters | Day 1, Day 28 and Day 84 | 
| Area Under the Curve (AUC) of ABX464 Metabolite (ABX464-N-Glucuronide) in Peripheral Blood Mononuclear Cells (PBMC) | Pharmacokinetic parameters | Day 1, Day 28 and Day 84 | 
| Concentration of ABX464 in Rectal Tissue (Measured Only at Pre-infusion Timepoint) | Pharmacokinetic parameters | Day 1, Day 28, Day 56, Day 84 and Day 112 | 
| Concentration of ABX464 Metabolite (ABX464-N-Glucuronide) in Rectal Tissue (Measured Only at Pre-infusion Timepoint) | Pharmacokinetic parameters | Day 1, Day 28, Day 56, Day 84 and Day 112 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline in Plasma Viral Load (Ultrasensitive Assay) | Viral Load Assessments (HIV-1 RNA copies/ml) | Day 28, Day 56, Day 84 and Day 112 | 
| CD4+ Counts (Cell/mm^3) | T-cell determinations | Day 28, Day 35, Day 56, Day 84, Day 91 and Day 112 | 
| Total HIV-1 DNA Reservoir in Peripheral Blood Mononuclear Cells (PBMC) | HIV reservoir cells (CD4+) | Day 28, Day 56, Day 84 and Day 112 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ABX464, HIV infection