ABX464 in Fully Controlled HIV Infected Patients Treated With Boosted Protease Inhibitor Treatment - Full Text View

Purpose

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	Intervention	Phase
HIV Infection	Drug: ABX464 Drug: Placebo	Phase 2


Study Type:	Interventional
Study Design:	Allocation: Randomized Intervention Model: Parallel Assignment Masking: 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).

Resource links provided by NLM:

MedlinePlus related topics: HIV/AIDS

U.S. FDA Resources

Further study details as provided by Abivax S.A.:

Primary Outcome Measures:

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:

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


Enrollment:	30
Study Start Date:	May 2016
Study Completion Date:	June 2017
Primary Completion Date:	May 2017 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

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


Ages Eligible for Study:	18 Years to 65 Years (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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02735863

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


Responsible Party:	Abivax S.A.
ClinicalTrials.gov Identifier:	NCT02735863 History of Changes
Other Study ID Numbers:	ABX464-004
Study First Received:	April 8, 2016
Last Updated:	June 19, 2017

Additional relevant MeSH terms:


HIV Infections Lentivirus Infections Retroviridae Infections RNA Virus Infections Virus Diseases Sexually Transmitted Diseases, Viral Sexually Transmitted Diseases Immunologic Deficiency Syndromes Immune System Diseases Ritonavir Darunavir	HIV Protease Inhibitors Cobicistat Protease Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-HIV Agents Anti-Retroviral Agents Antiviral Agents Anti-Infective Agents Cytochrome P-450 CYP3A Inhibitors Cytochrome P-450 Enzyme Inhibitors

ClinicalTrials.gov processed this record on July 17, 2017