Dataset Information

Safety, Pharmacokinetics, and Antiviral Activity of a Novel HIV Antiviral, ABX464, in Treatment-Naive HIV-Infected Subjects in a Phase 2 Randomized, Controlled Study.

ABSTRACT: We investigated the safety and antiviral effects of an anti-HIV compound (ABX464) with a unique mechanism of viral replication inhibition. This was a randomized, double-blind, placebo-controlled, dose-ranging study in treatment-naive HIV-infected patients. Participants were assigned to eight groups; each group included eight subjects receiving either the study compound, ABX464 (n = 6), or the corresponding placebo (n = 2), according to a randomization code. The first dose administered was 25 mg, given once or 3 times a day over a 2- to 3-week period. Ascending doses of up to 150 mg were delivered after review of the safety data. The primary objective of the study was to assess the safety and tolerability of ABX464 after repeated oral administrations in subjects infected by HIV. Sixty-six subjects were enrolled and were randomized. Sixty-three subjects completed the study according to the study protocol. Twenty-one adverse events (AEs) were reported by 7 subjects out of 16 (44%) who received placebo, and 158 AEs were reported by 39 subjects out of 50 (78%) who received the study drug. In the ABX464 treatment group, all of these adverse events were mild to moderate. No subjects discontinued treatment due to drug-related AEs. Administration of ABX464 at up to 150 mg once a day was safe and well tolerated in HIV-infected subjects. An efficacy signal with respect to a reduction of the viral load by ABX464 was detected, mainly in subjects treated at the highest dose. Further studies will be required to demonstrate antiviral effects in HIV-infected subjects in combination with other antiretroviral therapies. (This study is registered on the ClinicalTrials.gov website under registration no. NCT02452242.).

SUBMITTER: Steens JM

PROVIDER: S-EPMC5487684 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Safety, Pharmacokinetics, and Antiviral Activity of a Novel HIV Antiviral, ABX464, in Treatment-Naive HIV-Infected Subjects in a Phase 2 Randomized, Controlled Study.

Steens Jean-Marc JM Scherrer Didier D Gineste Paul P Barrett P Noel PN Khuanchai Supparatpino S Winai Ratanasuwan R Ruxrungtham Kiat K Tazi Jamal J Murphy Robert R Ehrlich Hartmut H

Antimicrobial agents and chemotherapy 20170627 7

We investigated the safety and antiviral effects of an anti-HIV compound (ABX464) with a unique mechanism of viral replication inhibition. This was a randomized, double-blind, placebo-controlled, dose-ranging study in treatment-naive HIV-infected patients. Participants were assigned to eight groups; each group included eight subjects receiving either the study compound, ABX464 (<i>n</i> = 6), or the corresponding placebo (<i>n</i> = 2), according to a randomization code. The first dose administe ...[more]

PMID: 28507108

Similar Datasets

Project description:Objectives:To assess the safety and tolerability as well as antiretroviral impact of ABX464, an oral investigational drug with a novel mechanism of HIV-1 inhibition (ClinicalTrials.gov NCT02735863). Methods:Randomised, double-blind, placebo-controlled, Phase IIa study in individuals living with HIV-1 on antiretroviral therapy at six clinical centres in Spain, France and Belgium. ABX464 was administered once a day to 22 fully controlled HIV-1-positive participants at two doses (50?mg, n=6 and 150?mg, n=16) versus placebo, which was given to eight participants for 28 days in combination with a boosted protease inhibitor (darunavir/ritonavir or darunavir/cobicistat). The primary objective of the study was to assess ABX464 safety and tolerability when used in combination with darunavir boosted therapy. The secondary objective was to study antiretroviral efficacy on viral reservoirs using time to viral rebound following treatment interruption. The impact of ABX464 on HIV-1 reservoirs was further assessed by measuring levels of total HIV-1 in peripheral blood mononuclear cells (PBMCs) in the intervention arm versus placebo. A positive response was defined as an absolute reduction in HIV-1 DNA of at least 50 copies/106 PBMCs and a relative decrease >25% of HIV-1 DNA level. Results:Twenty-six of the 30 randomly allocated participants completed the study according to the study protocol. ABX464 was found to be safe and well tolerated with the majority of adverse events (AEs) being mild or moderate. Of the participants, 22 (73.3%) experienced treatment-associated AEs (93.8%, 66.7%, 37.5% in the ABX464 150-mg, 50-mg dose and placebo arms, respectively). Percentages for combined grade 3/4 AEs for the three arms were 6.3%, 0% and 12.5%, respectively. Median time (Kaplan-Meier estimates) to viral rebound for ABX464 150-mg, 50-mg and placebo arms were 12.0 (95% confidence interval [CI]: 10-15), 15.5 (95% CI 14-22) and 15.5 (95% CI 1-22) days, respectively with no significant difference between the 150-mg treatment arm and placebo. Median changes in total HIV-1 DNA copies/106 PBMCs for ABX464 150-mg, 50-mg and placebo arms after 28 days of treatment were -40 (range -434 to +194), -115 (range -116 to -114) and 25 (range -35 to +218), respectively, showing a decrease in the intervention arms. There were 6/14, 2/2, and 0/4 responders for ABX464 150?mg, 50?mg and placebo, respectively. No significant difference was seen between treatment arms and placebo with respect to these virological parameters. Conclusions:This small controlled study confirmed the good safety and tolerability of ABX464 and provides some evidence of a potential reduction of the HIV-1 reservoir in terms of HIV-1 DNA levels in PBMCs when it was added to an HIV-1 protease inhibitor-based regimen. These results will need to be confirmed in a larger study.

Project description:Ibrexafungerp (code name in China: HS-10366) is a first-in-class and orally active triterpenoid antifungal agent with broad antifungal activity against Candida spp., Aspergillus spp., and other fungal pathogens. It was approved by the U.S. Food and Drug Administration for the treatment of vulvovaginal candidiasis. The study aimed to evaluate the safety, tolerability, and pharmacokinetic (PK) characteristics of oral ibrexafungerp in healthy Chinese adults. A single-center, randomized, double-blind, placebo-controlled single ascending dose (SAD, n = 42), and multiple ascending dose (MAD, n = 28) study was conducted in healthy Chinese subjects from March to October 2022. There were three cohorts in the SAD stage (300, 600, and 1,500 mg) and two cohorts in the MAD stage [450 mg once daily (QD) for 7 days; a loading dose of 750 mg twice daily (BID) for the first 2 days followed by a maintenance dose of 750 mg QD for consecutive 5 days]. Eligible participants in each cohort were randomly assigned in a 6:1 ratio to receive either ibrexafungerp or placebo orally. The primary objectives were to evaluate the safety and tolerability. The secondary objective was to evaluate PK parameters, including Cmax, AUC, and t1/2. A total of 70 healthy Chinese subjects were enrolled in the study. The mean (SD) age was 29.0 (6.32), and 55.7% were male. All treatment-emergent adverse events (TEAEs) were mild or moderate. There were no serious adverse events, and no subjects were discontinued from the study due to TEAEs. All TEAEs were recovered or resolved. The most common TEAEs were diarrhea, abdominal pain, and nausea. In the SAD stage, Cmax, and AUC increased in an approximately dose-proportional manner in the dose range of 300-1,500 mg. The mean t1/2 was within 18.29-21.30 hours. In the MAD stage, an accumulation of exposure (Cmax and AUC) was observed following multiple doses. This phase 1 study demonstrates a favorable safety, tolerability, and PK profile of ibrexafungerp in healthy Chinese subjects.

Dataset Information

Safety, Pharmacokinetics, and Antiviral Activity of a Novel HIV Antiviral, ABX464, in Treatment-Naive HIV-Infected Subjects in a Phase 2 Randomized, Controlled Study.

Publications

Safety, Pharmacokinetics, and Antiviral Activity of a Novel HIV Antiviral, ABX464, in Treatment-Naive HIV-Infected Subjects in a Phase 2 Randomized, Controlled Study.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets