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Clinical Trials

Date: 2017-09-28

Type of information: Interim results

phase: 1-2

Announcement: interim results

Company: Abivax (France)

Product: ABX464

Action mechanism:

  • splice modulating agent. ABX464 is a first-in-class, small molecule inhibiting HIV replication through the inhibition of the Rev protein activity and modulation of RNA splicing. In collaboration with the team of Professor Jamal Tazi at the CNRS in Montpellier, France, Abivax designed ABX464 to lead to a clinically relevant improvement in HIV therapy. Preclinical data in humanized mice demonstrated that ABX464 monotherapy had an antiviral effect that was sustained following treatment interruption (Campos et al, Retrovirology 2015 12:30). A prior food-effect study demonstrated a three-fold increase in parent drug exposure when administered with food, without a significant impact on active glucuronide metabolite.

Disease: HIV infection

Therapeutic area: Infectious diseases

Country: Spain

Trial details:

  • 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. (NCT02990325)

Latest news:

  • • On September 28, 2017, Abivax announced top-line results from the first cohort of its Phase 2a trial, ABX464-005, demonstrating that ABX464 significantly reduced the HIV viral reservoir in blood in patients with HIV. The data confirm and extend the HIV reservoir reduction by ABX464 seen in ABIVAX’s previous Phase 2a trial, ABX464-004.
  • In the first cohort, 11 patients with HIV infection received 150mg ABX464 for 28 days in addition to their antiretroviral treatment. Blood samples and rectal biopsies were collected at pre-specified time intervals, allowing quantification of changes in the viral reservoir and mucosal inflammation over time. Two patients discontinued the study due to grade 1/2 adverse events, which resolved upon a maximum of 6 days after ABX464 interruption. Nine patients from the first cohort completed the study. Eight of these nine patients showed a decrease between day 0 and day 28 in HIV DNA in peripheral blood CD4+ T cells. The median for all nine patients decreased from 191 copies / million CD4+ T cells to 116 copies / million CD4 + T cells, resulting in a statistically significant decrease (p<0.01) in HIV DNA in CD4+ peripheral blood T cells. Because of low quality and quantity of cells isolated from the rectal biopsies, no reliable HIV DNA data from this tissue were obtained for this cohort.  Procedures will be changed for the ongoing second cohort to ensure that enough high quality viral DNA is available for the generation of the appropriate data.
  • • On September 18, 2017, Abivax announced that the first patient has been dosed in the second cohort of the Phase 2a ABX464-005 clinical trial.  In the first cohort, 12 patients with HIV infection received 150mg of ABX464 for 28 days in addition to their antiretroviral treatment. Rectal biopsies were collected at pre-specified intervals to quantify the change in viral load and level of inflammation in those HIV reservoirs over time. Initial results of the first cohort are expected in the first week of October. The second cohort of 12 patients will receive 50mg of ABX464 for three months in addition to their antiretroviral treatment. Similar to the first cohort, patients will undergo rectal biopsies at prespecified intervals to quantify the change in viral load and level of inflammation over the three-month time period. The first patient of the second cohort was dosed at the Germans Trias i Pujol University Hospital Badalona in Barcelona. Initial results of the second cohort are expected in the second quarter of 2018.
  • • On April 4, 2017, Abivax announced that the first patient has been enrolled, effectively launching the study, for which it has obtained regulatory and ethical clearance. This study in 24 HIV patients (ABX464-005) and 12 healthy volunteers (control arm) will examine the pharmacokinetics (PK) of ABX464 in HIV cellular reservoirs. Given its goal for ABX464 to pursue a functional cure of patients with HIV-infection, Abivax focuses on studying the impact of the drug candidate in the various reservoir locations where the virusis hiding during effective antiretroviral therapy. These reservoirs include the blood, which is being evaluated in the almost completed study ABX464-004, and the gut, which is the main focus of ABX464-005.
  • The ABX464-005 study, which will be conducted at the Germans Trias i Pujol University Hospital Badalona (Barcelona, Spain), has enrolled the first patient. These patients will receive ABX464 for 28 days in addition to their antiretroviral treatment. Rectal biopsies will be collected at certain intervals, allowing quantification of the viral load and the level of inflammation in this reservoir over time. The study may therefore provide a better understanding of the biological mechanism driving the long-term efficacy on the viral load rebound observed in preclinical models with ABX464. Initial results of the ABX464-005 study are expected in Q3 2017.

Is general: Yes