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

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

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.

Study Overview

• Status: Completed
• Conditions: HIV Infections; Health Volunteers
• Intervention / Treatment: Drug: ABX464 150mg; Drug: ABX464 50mg; Drug: ABX464 50mg

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 Type: Interventional
• Enrollment (Actual): 36
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Spain
  • Catalogna
    • Badalona, Catalogna, Spain, 08916
      • Hospital Universitari Germans Trias i Pujol

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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;

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Abivax S.A.
• Investigators: Study Director: Paul GINESTE, PhD, Abivax S.A.

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): March 27, 2017
• Primary Completion (Actual): December 27, 2018
• Study Completion (Actual): October 21, 2019

Study Registration Dates

• First Submitted: December 7, 2016
• First Submitted That Met QC Criteria: December 8, 2016
• First Posted (Estimate): December 13, 2016

Study Record Updates

• Last Update Posted (Actual): March 31, 2023
• Last Update Submitted That Met QC Criteria: March 30, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: ABX464, HIV infection
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections
• Other Study ID Numbers: ABX464-005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No