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

HIV Infection Clinical Trial

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).

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02735863
• Other study ID #: ABX464-004
• Status: Completed
• Phase: Phase 2
• First received: April 8, 2016
• Last updated: June 19, 2017
• Start date: May 2016
• Est. completion date: June 2017

Study information

• Verified date: June 2017
• Source: Abivax S.A.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: June 2017
• Est. primary completion date: May 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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;

Related Conditions & MeSH terms

• HIV Infection
• HIV Infections

Intervention

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

Locations

Country	Name	City	State
Belgium	C.H.U. Saint-Pierre	Bruxelles
Belgium	Ghent University Hospital	Ghent
Belgium	CHU Sart Tilman	Liège
France	CHU de Montpellier - Hôpital Gui de Chauliac	Montpellier
Spain	Hospital Clinic	Barcelona
Spain	Hospital Universitari Germans Trias i Pujo	Barcelona

Sponsors (1)

Lead Sponsor	Collaborator
Abivax S.A.

Countries where clinical trial is conducted

Belgium,  France,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frequency of Adverse Reactions graded according to the "Division of AIDS table for grading the severity of adult and pediatric adverse events" (Version 2.0 November 2014)		Up to 4 months
Secondary	Time to Viral Rebound	Time To Viral Rebound is defined as the time between treatment stop (i.e. day 29) and viral rebound detection	Up to 3 months