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

• ClinicalTrials.gov Identifier: NCT02990325
• Recruitment Status: Completed
• First Posted: December 13, 2016
• Results First Posted: March 31, 2023
• Last Update Posted: March 31, 2023
• Sponsor: Abivax S.A.
• Information provided by (Responsible Party): Abivax S.A.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
HIV Infections; Health Volunteers	Drug: ABX464 150mg; Drug: ABX464 50mg	Phase 1; Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 36 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label Study of the Safety, Pharmacokinetics, and Pharmacodynamics of ABX464 in HIV-1 Seronegative and Seropositive Adults
• Actual Study Start Date: March 27, 2017
• Actual Primary Completion Date: December 27, 2018
• Actual Study Completion Date: October 21, 2019

Arms and Interventions

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)
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 84 (Cohort 3 / HIV infected subjects)

Outcome Measures

Primary Outcome Measures :

1. Area Under the Curve (AUC) of ABX464 in Sera [ Time Frame: Day 1, Day 28 and Day 84 ]
   Pharmacokinetic parameters
2. Maximum Observed Concentration (Cmax) of ABX464 in Sera [ Time Frame: Day 1, Day 28 and day 84 ]
   Pharmacokinetic parameters
3. Area Under the Curve (AUC) of ABX464 Metabolite (ABX464-N-Glucuronide) in Sera [ Time Frame: Day 1, Day 28 and Day 84 ]
   Pharmacokinetics parameters
4. Maximum Observed Concentration (Cmax) of ABX464 Metabolite (ABX464-N-Glucuronide) in Sera [ Time Frame: Day 1, Day 28 and Day 84 ]
   Pharmacokinetic parameters
5. Maximum Observed Concentration (Cmax) of ABX464 in Peripheral Blood Mononuclear Cells (PBMC) [ Time Frame: Day 1, Day 28 and Day 84 ]
   Pharmacokinetic parameters
6. Area Under the Curve (AUC) of ABX464 in Peripheral Blood Mononuclear Cells (PBMC) [ Time Frame: Day 1, Day 28 and Day 84 ]
   Pharmacokinetic parameters
7. Maximum Observed Concentration (Cmax) of ABX464 Metabolite (ABX464-N-Glucuronide) in Peripheral Blood Mononuclear Cells (PBMC) [ Time Frame: Day 1, Day 28 and Day 84 ]
   Pharmacokinetic parameters
8. Area Under the Curve (AUC) of ABX464 Metabolite (ABX464-N-Glucuronide) in Peripheral Blood Mononuclear Cells (PBMC) [ Time Frame: Day 1, Day 28 and Day 84 ]
   Pharmacokinetic parameters
9. Concentration of ABX464 in Rectal Tissue (Measured Only at Pre-infusion Timepoint) [ Time Frame: Day 1, Day 28, Day 56, Day 84 and Day 112 ]
   Pharmacokinetic parameters
10. Concentration of ABX464 Metabolite (ABX464-N-Glucuronide) in Rectal Tissue (Measured Only at Pre-infusion Timepoint) [ Time Frame: Day 1, Day 28, Day 56, Day 84 and Day 112 ]
    Pharmacokinetic parameters

Secondary Outcome Measures :

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

Eligibility Criteria

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

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;

Contacts and Locations

Locations

Spain

Hospital Universitari Germans Trias i Pujol

Badalona, Catalogna, Spain, 08916

Sponsors and Collaborators

Abivax S.A.

Investigators

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

  Study Documents (Full-Text)

Documents provided by Abivax S.A.:

Study Protocol  [PDF] September 4, 2018

Statistical Analysis Plan  [PDF] April 29, 2019

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Abivax S.A.
• ClinicalTrials.gov Identifier: NCT02990325
• Other Study ID Numbers: ABX464-005
• First Posted: December 13, 2016
• Results First Posted: March 31, 2023
• Last Update Posted: March 31, 2023
• Last Verified: March 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Abivax S.A.:

ABX464, HIV infection

Additional relevant MeSH terms:

HIV Infections; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases