ABX464 in Fully Controlled HIV Infected Patients Treated With Boosted Protease Inhibitor Treatment

This study is a placebo-controlled study aimed at assessing the safety of ABX464 administered at 50 mg o.d. and 150 mg versus placebo in HIV infected patients who are treated with darunavir + ritonavir (DRV/RTV) or darunavir + cobicistat (DRV/COBI). Eligible patients should be treated with darunavir + ritonavir or darunavir + cobicistat as monotherapy for at least 8 weeks prior to baseline. Patients should be fully suppressed (< 50 copies/mL) at least during the last 6 months prior to enrolment.

Upon screening visit, eligible patients will continue DRV/RTV or DRV/COBI single regimen given respectively at 800 mg of darunavir with 100 mg of ritonavir or 150 mg of cobicistat once a day with food in the morning.

At Day 0, study drug (ABX464 or its matching placebo) will be added on top of this background therapy for the next 28 days. ABX464 or its matching placebo will be given once a day at 50 mg or 150 mg.

At day 29, DRV/RTV or DRV/COBI and ABX464 or its matching placebo (i.e. all treatments) will be stopped. The viral load will be monitored twice a week during the first three weeks and weekly during the next weeks. In case of Viral Rebound (VR; defined below), ART will be resumed.

A 3:1 randomization ratio will be applied meaning that, per treatment block, 3 patients will receive ABX464 on top of DRV/RTV or DRV/COBI and 1 patient will receive placebo on top of DRV/RTV or DRV/COBI.

Dose limiting toxicity (DLT) is defined as a grade 3 or higher adverse event as defined by the "Division of AIDS table for grading the severity of adult and pediatric adverse events" (including signs/symptoms, lab toxicities and/or clinical events) considered by the Data Safety Monitoring Board as probably or definitely related to study treatment.

If more than 2 DLTs occur during the treatment period of the first four treated patients, then the enrolment of additional patients will be stopped. In addition, in case of a life threatening (grade 4) adverse reaction enrolment and treatment of ongoing patients will be immediately discontinued. In both cases, enrolment will only be resumed upon the decision of the sponsor if the Data Safety Monitoring Board can conclude that the causality of the event was unrelated or unlikely related to study treatment.

Thorough pharmacokinetics analysis will be performed to characterize potential drug-drug interactions between ABX464 and DRV/RTV-COBI.

• ABX464 (Drug): 50 mg or 150mg once daily for 28 days
• Placebo (Drug): ABX464 matching placebo

Primary outcomes

• Number of Participants With Adverse Events [Up to 4 months]: Patients who had received at least one dose of the study drug, and who had at least one baseline value. An AE was classified as a TEAE if it started, or increased in severity, on or after the first date and time of medication dosing (from Day 1 up to Day 28). Any AE which occurred after Day 28 was classified as post-treatment-emergent. Events were graded according to the "Division of AIDS table for grading the severity of adult and pediatric adverse events" (Version 2.0 November 2014).

Secondary outcomes

• Time to Viral Rebound [Up to 3 months]: Time To Viral Rebound is defined as the time between treatment stop (i.e. day 29) and viral rebound detection

Sex: All, ages: 18 Years to 65 Years

Inclusion Criteria:

* Patients infected with HIV;
* Patients with HIV plasma viral load ≤ 50 copies mL-1 during the 6 months prior to screening with a maximum of 2 blips during this period;
* Patients treated by DRV/RTV or DRV/COBI as a monotherapy for at least 8 weeks prior to baseline;
* Patients' HIV plasma viral load ≤100,000 copies mL-1 at any time (apart from primary infection if recorded);
* Patients' CD4+ T cells count ≥ 250 cells per mm3 at any time since diagnosis;
* Patients with CD4+ T cells count ≥ 600 cells per mm3 at screening;
* Man or woman aged 18-65 years;

Exclusion Criteria:

* Patient displaying any HIV protease inhibitor resistance mutation as listed in the current version of the HIV drug resistance database (Stanford University);
* Patient having had previously a viral load ≥ 500 copies mL-1 confirmed by a second measure since the initiation of the current ART;
* History of an AIDS-defining clinical illness;
* Concomitant AIDS-related opportunistic infection;

Participant flow

Outcome results

• Number of Participants With Adverse Events (Primary), Count of participants, Participants: ABX464 50mg 5; ABX464 150mg 15; ABX464 Matching Placebo 7
• Time to Viral Rebound (Secondary), Mean, days: ABX464 50mg 17.2 +/- 3.4; ABX464 150mg 14.4 +/- 7.4; ABX464 Matching Placebo 14.4 +/- 7.3 (p 0.5352)

Adverse events

Time frame: Up to 4 months

Serious adverse events by term

Other adverse events by term

• Results publication: Rutsaert S, Steens JM, Gineste P, Cole B, Kint S, Barrett PN, Tazi J, Scherrer D, Ehrlich HJ, Vandekerckhove L. Safety, tolerability and impact on viral reservoirs of the addition to antiretroviral therapy of ABX464, an investigational antiviral drug, in individuals living with HIV-1: a Phase IIa randomised controlled study. J Virus Erad. 2019 Jan 1;5(1):10-22. doi: 10.1016/S2055-6640(20)30273-9. PMID 30800421

• Study Protocol (PDF, 2016-11-07)
• Statistical Analysis Plan (PDF, 2017-07-03)