Clinical trial NCT02735863: ABX464 in Fully Controlled HIV Infected Patients Treated With Boosted Protease Inhibitor Treatment
Official title: A Multi-center, Randomized, Double-blind, Placebo-controlled Phase IIa Trial to Compare the Safety of ABX464 Given at a Fixed Dose to Placebo in Fully Controlled HIV Infected Patients Treated With Boosted Protease Inhibitor Treatment (Darunavir/Ritonavir or Darunavir/Cobicistat).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infection
Lead sponsor: Abivax S.A.
Sponsor class: INDUSTRY
First posted: 2016-04-13
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study is a placebo-controlled study aimed at assessing the safety of ABX464 administered at 50 mg and 150 mg o.d. versus placebo in HIV infected patients who are treated with darunavir + ritonavir (DRV/RTV) or darunavir + cobicistat (DRV/COBI).

Detailed description: 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.

Eligibility criteria: 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;

Primary outcomes:
measure: Number of Participants With Adverse Events
timeFrame: Up to 4 months
Secondary outcomes:
measure: Time to Viral Rebound
timeFrame: Up to 3 months
Other outcomes:
Locations:
city: Bruxelles
country: Belgium
facility: C.H.U. Saint-Pierre
city: Ghent
country: Belgium
facility: Ghent University Hospital
city: Liège
country: Belgium
facility: CHU Sart Tilman
city: Lyon
country: France
facility: Hôpital de la Croix Rousse
city: Montpellier
country: France
facility: CHU de Montpellier - Hôpital Gui de Chauliac
city: Barcelona
country: Spain
facility: Hospital Clinic
city: Barcelona
country: Spain
facility: Hospital Universitari de Bellvitge
city: Barcelona
country: Spain
facility: Hospital Universitari Germans Trias i Pujo
Study officials:
References:
citation: 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.