Study of Darunavir/r + Tenofovir/Emtricitabine vs. Darunavir/r + Raltegravir in HIV-infected Antiretroviral naïve Subjects

HIV Infections Clinical Trial

— ANRS 143  

Official title:

An Open-label Randomised Two-year Trial Comparing Two First-line Regimens in HIV-infected Antiretroviral naïve Subjects: Darunavir/r + Tenofovir/Emtricitabine vs. Darunavir/r + Raltegravir (ANRS 143/NEAT 001)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01066962
• Other study ID #: 2009-015113-44
• Secondary ID: 2009-015113-44
• Status: Completed
• Phase: Phase 3
• First received: February 9, 2010
• Last updated: November 5, 2013
• Start date: August 2010
• Est. completion date: October 2013

Study information

• Verified date: November 2013
• Source: French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
• Contact: n/a
• Is FDA regulated: No
• Health authority: Austria: Federal Ministry for Health and WomenBelgium: Federal Agency for Medicinal Products and Health ProductsDenmark: Danish Medicines AgencyFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: Federal Institute for Drugs and Medical DevicesGreece: National Organization of MedicinesHungary: National Institute of PharmacyIreland: Irish Medicines BoardItaly: The Italian Medicines AgencyNetherlands: The Central Committee on Research Involving Human Subjects (CCMO)Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsPortugal: National Pharmacy and Medicines InstituteSpain: Spanish Agency of MedicinesSweden: Medical Products AgencyUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

The triple therapy darunavir/r + tenofovir/emtricitabine is likely to become a relevant first-line treatment option in the years to come. The dual combination of boosted darunavir + raltegravir is an innovative treatment option that combines two potent new antiretroviral drugs, one of which belongs to a new drug class (integrase inhibitor). The expected efficacy profile of this combination is promising. Moreover, this combination might have a better tolerance profile and has the advantage of sparing the NRTI class.

In the context of tenofovir/emtricitabine currently being a reference backbone in first-line antiretroviral regimens, we hypothesise that, in combination with darunavir/r, raltegravir may be an alternative option if its efficacy is non-inferior to tenofovir/emtricitabine.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 800
• Est. completion date: October 2013
• Est. primary completion date: October 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patient with confirmed HIV infection

• Age = 18 years

• Written informed consent

• Male patient or non-pregnant, non-lactating female

• No previous treatment with any antiretroviral drugs

• HIV-1 RNA > 1000 copies/ml

• Indication to start an antiretroviral treatment as long as subject has also a CD4 cell count = 500/mm3 either at screening or on a sample taken within 3 months before screening

• No major IAS-USA mutations on genotypic testing at the screening visit or on any historical genotype, if available

Non-inclusion Criteria:

• Woman without effective contraception method (recommended contraception during the trial is mechanical + a second method other than an oral contraceptive)

• Pregnant or breastfeeding woman

• Woman expecting to conceive during the study

• HIV-2 co-infection

• Creatinine clearance < 60 ml/mn (Cockcroft & Gault equation), alkaline phosphatase, ASAT, or ALAT = 5 ULN

• Patient with significant impairment of hepatic function, defined as serum albumin < 2.8 g/dl or INR > 1.7 or presence of ascites, in the absence of another explanation for the abnormal finding

• CD4 > 500/mm3 at screening, except in case of symptomatic HIV disease (defined by conditions qualifying for CDC category B or C) or CD4 = 500/mm3 on a sample taken within 3 months before screening.

• Any major IAS-USA mutation conferring resistance to one or more of reverse transcriptase or protease inhibitors on genotypic testing at screening

• Mycobacteriosis under treatment

• Malignancy requiring chemotherapy or radiotherapy

• Positive HBs Ag

• HCV infection for which specific treatment is ongoing or planned during the first year on trial treatment

• Known hypersensitivity to one of the trial drugs or its excipients

• Contraindicated concomitant treatment

• Anticipated non-compliance with the protocol

• Participation in another clinical trial with an on-going exclusion period at screening

• Subject under legal guardianship or incapacitation

• Subject, who in the opinion of the investigator, is unable to complete the study period

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• darunavir/ritonavir QD + raltegravir BID
darunavir 800 mg, i.e. 2 tablets of 400 mg once daily (QD) ritonavir 100 mg, 1 tablet once daily (QD) raltegravir 400 mg, 1 tablet twice daily (BID)
• darunavir/r QD + tenofovir/emtricitabine QD (fixed dose combination)
darunavir 800 mg, i.e. 2 tablets of 400 mg once daily (QD) ritonavir 100 mg, 1 tablet once daily (QD) tenofovir/emtricitabine 245/200 mg, fixed dose combination, 1 tablet once daily (QD)

Locations

Country	Name	City	State
Austria	Allgemeines Krankenhaus der Stadt Wien	Wien
Austria	Otto Wagner Spital mit Pflegezentrum	Wien
Belgium	ITZ Antwerpen	Antwerpen
Belgium	CHU Saint Pierre	Brussels
Belgium	UZ Gent	Gent
Denmark	Rigshospitalet	Copenhagen
Denmark	Hvidovre Hospital	Hvidovre
France	Hôpital Pellegrin	Bordeaux
France	Hôpital Saint André	Bordeaux
France	Hôpital Henri Mondor	Créteil
France	Hôpital du Bocage	Dijon
France	Hôpital Pierre Zobda-Quitman	Fort de France
France	CHD de la Roche sur Yon	La Roche sur Yon
France	Hôpital Bicêtre	Le Kremlin Bicêtre
France	Hôpital Gui de Chauliac	Montpellier
France	Hôpital de l'Hôtel Dieu	Nantes
France	Hôpital Bichat	Paris
France	Hôpital Européen Georges Pompidou (HEGP)	Paris
France	Hôpital La Pitié Salpétrière	Paris
France	Hôpital Saint Antoine	Paris
France	Hôpital Saint Louis	Paris
France	Hôpital Pontchaillou	Rennes
France	Hôpital Foch	Suresnes
France	Hôpital Purpan	Toulouse
France	Hôpital Gustave Dron	Tourcoing
Germany	Gemeinschaftspraxis Jessen-Jessen-Stein	Berlin
Germany	Med. Universitätsklinik I	Bonn
Germany	Universitätsklinikum Essen	Essen
Germany	Klinikum der Johann Wolfgang Goethe Universität	Frankfurt
Germany	Asklepios-Klinik St. Georg	Hamburg
Germany	ICH study centre	Hamburg
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Universitätsklinik Köln	Köln
Greece	Attikon University Hospital	Athens
Greece	Evaggelismos General Hospital	Athens
Greece	Laikon General Hospital	Athens
Hungary	Saint Laszlo Hospital	Budapest
Ireland	Mater Misericordiae	Dublin
Ireland	St James's Hospital	Dublin
Italy	University of Brescia	Brescia
Italy	Ospedale Santa Maria Annunziata	Florence
Italy	Fondazione Centro San Raffaele del Monte Tabor	Milan
Italy	San Paolo Hospital	Milan
Italy	Luigi Sacco Hospital	Milano
Italy	Istituto Naziona e per le Malattie "Lazzaro Spallanzani"	Rome
Italy	Sapienza Universita di Roma	Rome
Italy	Torvergata University	Rome
Italy	Ospedale "Amedeo di Savoia"	Turin
Netherlands	AMC	Amsterdam
Netherlands	Jan van Goyen Medical Center	Amsterdam
Netherlands	Rijnstate Hospital	Arnhem
Poland	Hospital of Infectious Diseases of Warsaw	Warsaw
Portugal	Hospital de Curry Cabral	Lisbon
Portugal	Hospital Santa Maria	Lisbon
Portugal	Hospital de Joaquim Urbano	Porto
Spain	Hospital General Universitario de Alicante	Alicante
Spain	Hospital Clinic	Barcelona
Spain	Hospital de la Santa Creu I Sant Pau.	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	Hospital Germans Trias i Pujol	Barcelona
Spain	Hospital Carlos III	Madrid
Spain	Hospital Clinico San Carlos	Madrid
Spain	Hospital Gregorio Marañon	Madrid
Spain	Hospital Universitario La Paz	Madrid
Spain	Hospital Universitario Virgen de la Victoria	Malaga
Spain	Hospital Universitario La Fe	Valencia
Sweden	Sahlgrenska hospital	Gothenburg
Sweden	Karolinska hospital	Stockholm
Sweden	Venhälsan hospital	Stockholm
United Kingdom	Royal Bournemouth Hospital	Bournemouth
United Kingdom	Southmead Hospital	Bristol
United Kingdom	Western General Hospital	Edinburgh
United Kingdom	Mortimer market centre	London
United Kingdom	Royal Free Hospital	London
United Kingdom	Saint Mary's hospital	London
United Kingdom	Saint Stephen's Centre	London
United Kingdom	Saint Thomas hospital	London

Sponsors (2)

Lead Sponsor	Collaborator
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)	NEAT - European AIDS Treatment Network

Countries where clinical trial is conducted

Austria,  Belgium,  Denmark,  France,  Germany,  Greece,  Hungary,  Ireland,  Italy,  Netherlands,  Poland,  Portugal,  Spain,  Sweden,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time to virologic or clinical failure, as the first occurrence of one of six protocol-defined components		minimum 2 years	No