Clinical trial NCT00612898: Study of the Efficacy and Safety of Apricitabine, a New NRTI, to Treat Drug-resistant HIV Infection
Official title: A Phase 2b/3, Randomized, Double Blind, Dose Confirming Study of the Safety, Efficacy and Tolerability of Apricitabine Versus Lamivudine in Treatment-experienced HIV-1 Infected Patients With the M184V/I Mutation in Reverse Transcriptase
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: HIV Infections
Keywords: HIV infection
Drug resistance
Reverse transcriptase inhibitor
Nucleoside analogue
treatment experienced
Lead sponsor: Avexa
Sponsor class: INDUSTRY
First posted: 2008-02-12
Enrollment: 239
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Apricitabine is a new NRTI which is active against drug-resistant HIV. NRTIs are often included as part of patients' treatment, but many HIV-infected patients develop resistance to commonly used NRTIs such as lamivudine (3TC) and emtricitabine (FTC). This study will examine whether including apricitabine as part of patients' treatment is more effective than including lamivudine,when patients change treatment because of drug resistance.

Detailed description: ATC has potent antiviral activity both in vitro (against wild-type HIV-1 and HIV-1 with mutations in reverse transcriptase that confer resistance to NRTIs), and in clinical studies in both treatment-naïve and treatment-experienced patients with M184V, including in the presence of additional NRTI mutations in reverse transcriptase.

The M184V mutation is most commonly present amongst patients failing regimens containing either of the two deoxycytidine analogs lamivudine and emtricitabine. Whilst lamivudine therapy is often maintained in patients harboring the M184V mutation in some settings, there are no deoxycytidine analogs currently available that effectively suppress replication of HIV-1 containing the M184V/I mutation, particularly in the presence of other additional NRTI mutations.

The purpose of this study is to extend the efficacy and safety established in study AVX-201 of ATC in patients who are HIV-1 infected and have failed treatment with lamivudine or emtricitabine and have confirmed M184V/I mutation. Patients to be enrolled will be failing their current lamivudine- or emtricitabine-containing regimen and therefore have limited remaining NRTI treatment options. This study will investigate whether it is possible to improve control of HIV-1 viral replication by including ATC within a treatment experienced patient's new optimized background regimen following ART treatment failure.

Eligibility criteria: Inclusion Criteria:

* HIV-1 positive with M184V/I mutation in reverse transcriptase;
* 18 years of age or older;
* Currently taking lamivudine (3TC) or emtricitabine (FTC)

Exclusion Criteria:

* Female patients who are pregnant or breastfeeding;
* Current hepatitis B virus (HBV) infection;
* Current treatment for hepatitis C virus infection;
* Renal function not adequate

Primary outcomes:
measure: Proportion of patients with plasma HIV-1 RNA <50 copies/mL at W24
timeFrame: week 24
Secondary outcomes:
measure: Time to loss of virological response (TLOVR analysis; FDA algorithm) at W12, W24 and W48 (<50 copies/mL)
timeFrame: week 12, 24, and 48
measure: Proportion of patients with plasma HIV-1 RNA <50 copies/mL at W48
timeFrame: week 48
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: UAB, 845 19th St South, South Beville Biomedical Research Building
state: Alabama
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: Phoenix
country: United States
facility: Southwest Center for HIV/AIDS
state: Arizona
city: Long Beach
country: United States
facility: Living Hope Clinical Foundation, Inc
state: California
city: San Francisco
country: United States
facility: Kaiser Permanente Medical Center
state: California
city: West Hollywood
country: United States
facility: AIDS Research Alliance
state: California
city: Denver
country: United States
facility: Denver Health & Hospital Authority
state: Colorado
city: Washington
country: United States
facility: Georgetown University
state: District of Columbia
city: Washington
country: United States
facility: George Washington University
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: Gary Richmond, MD
state: Florida
city: Orlando
country: United States
facility: Orlando Immunology Center
state: Florida
city: Tampa
country: United States
facility: Infectious Disease Research Institute, Inc
state: Florida
city: Vero Beach
country: United States
facility: Treasure Coast Infectious Diseases Consultants
state: Florida
city: Atlanta
country: United States
facility: Aids Research Consortium Of Atlanta Inc.
state: Georgia
city: Atlanta
country: United States
facility: Atlanta Infectious Disease Group, PC
state: Georgia
city: Honolulu
country: United States
facility: University of Hawaii
state: Hawaii
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Wichita
country: United States
facility: University of Kansas School of Medicine
state: Kansas
city: Boston
country: United States
facility: Fenway Community Health Center
state: Massachusetts
city: Boston
country: United States
facility: Community Research Intiative of New England
state: Massachusetts
city: Hillsborough
country: United States
facility: I.D. Care, Inc.
state: New Jersey
city: Newark
country: United States
facility: Saint Michael's Medical Center
state: New Jersey
city: Akron
country: United States
facility: Summa Health System
state: Ohio
city: Portland
country: United States
facility: The Research & Education Institute
state: Oregon
city: Austin
country: United States
facility: Central Texas Clinical Research
state: Texas
city: Dallas
country: United States
facility: Nicholaos C Bellos, MD, PA
state: Texas
city: Dallas
country: United States
facility: North Texas Infectious Diseases Consultants, P.A.
state: Texas
city: Fort Worth
country: United States
facility: Tarrant County Infection Disease Associates
state: Texas
city: Galveston
country: United States
facility: University of Texas Medical Brach
state: Texas
city: Houston
country: United States
facility: Therapeutic Concepts
state: Texas
city: Houston
country: United States
facility: Resarch Access Network
state: Texas
city: Longview
country: United States
facility: DCOL Center for Clinical Research
state: Texas
city: Seattle
country: United States
facility: Swedish Medical Center
state: Washington
city: Darlinghurst
country: Australia
facility: 407 Doctors
state: New South Wales
city: Parramatta
country: Australia
facility: Parramatta Sexual Health Clinic
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Carlton
country: Australia
facility: Carlton Clinic
state: Victoria
city: Carlton
country: Australia
facility: Melbourne Sexual Health Centre
state: Victoria
city: Melbourne
country: Australia
facility: The Alfred
state: Victoria
city: Parkville
country: Australia
facility: Royal Melbourne Hospital
state: Victoria
city: South Yarra
country: Australia
facility: Prahran Market Clinic
state: Victoria
city: Antwerpen
country: Belgium
facility: Prins Leopold Institute voor Tropische Geneeskunde
city: Bruxelles
country: Belgium
facility: Hopitaux IRIS Sud
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Vancouver
country: Canada
facility: Ubc Downtown I.D. Clinic
state: British Columbia
city: Hamilton
country: Canada
facility: Hamilton Health Sciences Corporation
state: Ontario
city: Toronto
country: Canada
facility: University Health Network
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Quebec
country: Canada
facility: Centre Hospitalier Universitaire de Quebec
city: Berlin
country: Germany
facility: EPIMED GmbH
city: Berlin
country: Germany
facility: Charite-Universitatsmedizin Berlin
city: Bochum
country: Germany
facility: Ruhr-Universitat Bochum
city: Bonn
country: Germany
facility: Universitatsklinikum Bonn
city: Dortmund
country: Germany
facility: Klinikum Dortmund gGmbH
city: Essen
country: Germany
facility: Universitatsklinikum Essen
city: Frankfurt
country: Germany
facility: Klinikum der Johann-Wolfgang Goethe-Universitat
city: Freiburg
country: Germany
facility: Praxis fuer Innere Medizin
city: Furth
country: Germany
facility: Praxis Dr.Schneider
city: Hannover
country: Germany
facility: Dr. med. Birger Kuhlmann
city: Munchen
country: Germany
facility: Klinikum der Universitat Munchen - Innenstadt
city: Stuttgart
country: Germany
facility: Gemeinschaftspraxis E. Schnaitmann, Dr. med. A. Schaffert, Dr. med. A. Trein, Dr. med. E. Ibler
city: Stuttgart
country: Germany
facility: Praxis Dres. Ulmer, Frietsch, Muller
city: Beer-Sheva
country: Israel
facility: Soroka University Medical Center
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Jerusalem
country: Israel
facility: Hadassah University Hospital Ein Kerem
city: Ramat-Gan
country: Israel
facility: The Chaim Sheba Medical Center
city: Rehovot
country: Israel
facility: Kaplan Medical Center
city: Tel Aviv
country: Israel
facility: Tel-Aviv Sourasky Medical Center
city: Antella
country: Italy
facility: Ospedale S.Maria Annunziata
city: Ferrara
country: Italy
facility: Azienda Ospedaliera Universitaria di Ferrara Arcispedale S.Anna
city: Genova
country: Italy
facility: Azienda Ospedaliera Universitaria San Martino
city: Milano
country: Italy
facility: Fondazione Centro San Raffaele del Monte Tabor
city: Milano
country: Italy
facility: Ospedale Luigi Sacco
city: Modena
country: Italy
facility: Azienda Ospedaliero-Universitaria di Modena Policlinico
city: Napoli
country: Italy
facility: Azienda Ospedaliera Cotugno
city: Padova
country: Italy
facility: Azienda Ospedaliera di Padova
city: Roma
country: Italy
facility: Istituto Nazionale Malattie Infettive "Lazzaro Spallanzani" IRCCS
city: Torino
country: Italy
facility: Comprensorio Amedeo di Savoia - Birago Di Vische
city: Arequipa
country: Peru
facility: Hospital Nacional CASE-EsSalud
city: Lima
country: Peru
facility: Investigaciones Medicas en Salud
city: Lima
country: Peru
facility: Hospital Dos de Mayo
city: Lima
country: Peru
facility: Via Libre
city: Lima
country: Peru
facility: Hospital Nacional Cayetano Heredia
city: Lima
country: Peru
facility: Edgardo Rebagliati Hospital
city: Ponce
country: Puerto Rico
facility: Instituto De Investigacion Cientifica
city: San Juan
country: Puerto Rico
facility: University of Puerto Rico
city: San Juan
country: Puerto Rico
facility: Hope Clinical Research
city: Bangkok
country: Thailand
facility: Mahidol University Hospital for Tropical Diseases
city: Bangkok
country: Thailand
facility: Pharmongkutklao Hospital
city: Bangkok
country: Thailand
facility: The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT)
city: Bangkok
country: Thailand
facility: Ramathibodi Hospital, Mahidol University
city: Bangkok
country: Thailand
facility: Sirraj Hospital, Mahidol Universoty
city: Chiang Mai
country: Thailand
facility: Maharaj Nakorn Chiang Mai, Chiang Mai University
city: Khon Kaen
country: Thailand
facility: Khon Kaen University
city: Nonthaburi
country: Thailand
facility: Bamrasnaradura Institution
city: Birmingham
country: United Kingdom
facility: Birmingham Heartlands Hospital
city: London
country: United Kingdom
facility: St Bartholomew's Hospital
city: London
country: United Kingdom
facility: Royal Free Hospital
city: London
country: United Kingdom
facility: Guy's King's & St. Thomas' School of Medicine
city: London
country: United Kingdom
facility: St Mary's Hospital
Study officials:
affiliation: Avexa Ltd
name: Susan W Cox, Ph D
role: STUDY_DIRECTOR
affiliation: UAB Center for AIDS Research
name: Michael Saag, MD
role: PRINCIPAL_INVESTIGATOR
References: