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

• ClinicalTrials.gov Identifier: NCT02735863
• Recruitment Status: Completed
• First Posted: April 13, 2016
• Last Update Posted: June 20, 2017
• Sponsor: Abivax S.A.
• Information provided by (Responsible Party): Abivax S.A.

Study Description

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).

Condition or disease	Intervention/treatment	Phase
HIV Infection	Drug: ABX464; Drug: Placebo	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 30 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: 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 Start Date: May 2016
• Actual Primary Completion Date: May 2017
• Actual Study Completion Date: June 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: ABX464; Fixed dose of ABX464 50mg once daily given during 28 days in association with darunavir + ritonavir (DRV/RTV) or darunavir + cobicistat (DRV/COBI)	Drug: ABX464; 50 mg or 150mg once daily for 28 days
Placebo Comparator: ABX464 Matching placebo; Matching placebo of ABX464 given at 50mg once daily in association with darunavir + ritonavir (DRV/RTV) or darunavir + cobicistat (DRV/COBI)	Drug: Placebo; ABX464 matching placebo

Outcome Measures

Primary Outcome Measures :

1. 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) [ Time Frame: Up to 4 months ]

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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;

Contacts and Locations

Locations

Belgium

C.H.U. Saint-Pierre

Bruxelles, Belgium, 1000

Ghent University Hospital

Ghent, Belgium, 9000

CHU Sart Tilman

Liège, Belgium, 4000

France

CHU de Montpellier - Hôpital Gui de Chauliac

Montpellier, France, 34 295

Spain

Hospital Clinic

Barcelona, Spain, 08036

Hospital Universitari Germans Trias i Pujo

Barcelona, Spain, 08916

Sponsors and Collaborators

Abivax S.A.

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Abivax S.A.
• ClinicalTrials.gov Identifier: NCT02735863
• Other Study ID Numbers: ABX464-004
• First Posted: April 13, 2016
• Last Update Posted: June 20, 2017
• Last Verified: June 2017

Additional relevant MeSH terms:

HIV Infections; Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases