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

NCT02990325 | Completed Phase 1 Results DMC

• 1 other identifier: ABX464-005
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

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.

Conditions

HIV Infections; Health Volunteers

Keywords

ABX464, HIV infection

Outcome Measures

Primary Outcomes (10)

• 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 Outcomes (3)

• Mean Change From Baseline in Plasma Viral Load (Ultrasensitive Assay)

  Day 28, Day 56, Day 84 and Day 112

• CD4+ Counts (Cell/mm^3)

  Day 28, Day 35, Day 56, Day 84, Day 91 and Day 112

• Total HIV-1 DNA Reservoir in Peripheral Blood Mononuclear Cells (PBMC)

  Day 28, Day 56, Day 84 and Day 112

Study Arms (3)

ABX464 150mg

EXPERIMENTAL

ABX464, 50mg per Capsule Three Capsules per day for 28 days

Drug: ABX464 150mg

ABX464 50mg for 28 days

EXPERIMENTAL

ABX464, 50mg per Capsule One Capsule per day for 28 days

Drug: ABX464 50mg

ABX464 50mg for 84 days

EXPERIMENTAL

ABX464, 50mg per Capsule One Capsule per day for 84 days

Drug: ABX464 50mg

Interventions

ABX464 150mg DRUG

ABX464 given orally at 150 mg per day from Day 0 to Day 28 (Cohort 1/ HIV infected subjects)

ABX464 150mg

ABX464 50mg DRUG

ABX464 given orally at 50 mg per day from Day 0 to Day 28 (Cohort 2 / non HIV infected subjects)

ABX464 50mg for 28 days

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• 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;

Sponsors & Collaborators

• Abivax S.A.: lead

Study Sites (1)

Hospital Universitari Germans Trias i Pujol

Badalona, Catalonia, 08916, Spain

Location

Related Publications (1)

• 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.

  PMID: 34436569 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

ABX464

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; 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

Results Point of Contact

• Title: Sophie Biguenet
• Organization: Abivax

sophie.biguenet@abivax.com

+33 (0) 1 53 83 08 41

Study Officials

• Paul GINESTE, PhD

  Abivax S.A.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 7, 2016
• First Posted: December 13, 2016
• Study Start: March 27, 2017
• Primary Completion: December 27, 2018
• Study Completion: October 21, 2019
• Last Updated: March 31, 2023
• Results First Posted: March 31, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)