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

Phase 1

Completed

• Conditions: HIV Infections; Health Volunteers
• Interventions: Drug: ABX464 50mg; Drug: ABX464 150mg

• Registration Number: NCT02990325
• Lead Sponsor: Abivax S.A.

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.

Study Timeline

• Study First Submitted: 2016-12-07
• Study First Submitted QC: 2016-12-08
• Study First Posted: 2016-12-13
• Study Start: 2017-03-27
• Primary Completion: 2018-12-27
• Study Completion: 2019-10-21
• Results First Submitted: 2022-06-01
• Status Verified: 2023-03
• Results First Submitted QC: 2023-03-30
• Last Update Submitted: 2023-03-30
• Results First Posted: 2023-03-31
• Last Update Posted: 2023-03-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 36

Inclusion Criteria

Not provided

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;

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ABX464 50mg for 84 days	ABX464 50mg	ABX464, 50mg per Capsule One Capsule per day for 84 days
ABX464 150mg	ABX464 150mg	ABX464, 50mg per Capsule Three Capsules per day for 28 days
ABX464 50mg for 28 days	ABX464 50mg	ABX464, 50mg per Capsule One Capsule per day for 28 days

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Hospital Universitari Germans Trias i Pujol; 🇪🇸 Badalona, Catalogna, Spain