Study of the Efficacy and Safety of Apricitabine, a New NRTI, to Treat Drug-resistant HIV Infection

This study has been terminated.
(Sponsor decision)
Sponsor:
Information provided by (Responsible Party):
Avexa
ClinicalTrials.gov Identifier:
NCT00612898
First received: January 30, 2008
Last updated: January 19, 2012
Last verified: January 2012
  Purpose

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.


Condition Intervention Phase
HIV Infections
Drug: apricitabine
Drug: lamivudine
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Avexa:

Primary Outcome Measures:
  • Proportion of patients with plasma HIV-1 RNA <50 copies/mL at W24 [ Time Frame: week 24 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to loss of virological response (TLOVR analysis; FDA algorithm) at W12, W24 and W48 (<50 copies/mL) [ Time Frame: week 12, 24, and 48 ] [ Designated as safety issue: No ]
  • Proportion of patients with plasma HIV-1 RNA <50 copies/mL at W48 [ Time Frame: week 48 ] [ Designated as safety issue: No ]

Enrollment: 239
Study Start Date: February 2008
Study Completion Date: January 2010
Primary Completion Date: January 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
800mg BID apricitabine plus optimised background
Drug: apricitabine
800mg BID apricitabine orally for 48 weeks
Other Name: AVX754
Active Comparator: 2
150mg BID lamivudine plus optimised background
Drug: lamivudine
150mg BID lamivudine orally for 48 weeks
Other Name: 3TC

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00612898

  Hide Study Locations
Locations
United States, Alabama
UAB, 845 19th St South, South Beville Biomedical Research Building
Birmingham, Alabama, United States, 35294-2170
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294-2170
United States, Arizona
Southwest Center for HIV/AIDS
Phoenix, Arizona, United States, 85006
United States, California
Living Hope Clinical Foundation, Inc
Long Beach, California, United States, 90813
Kaiser Permanente Medical Center
San Francisco, California, United States, 94115
AIDS Research Alliance
West Hollywood, California, United States, 90069
United States, Colorado
Denver Health & Hospital Authority
Denver, Colorado, United States, 80204
United States, District of Columbia
Georgetown University
Washington, District of Columbia, United States, 20007
George Washington University
Washington, District of Columbia, United States, 20037
United States, Florida
Gary Richmond, MD
Fort Lauderdale, Florida, United States, 33316
Orlando Immunology Center
Orlando, Florida, United States, 32803
Infectious Disease Research Institute, Inc
Tampa, Florida, United States, 33614
Treasure Coast Infectious Diseases Consultants
Vero Beach, Florida, United States, 32960
United States, Georgia
Aids Research Consortium Of Atlanta Inc.
Atlanta, Georgia, United States, 30308
Atlanta Infectious Disease Group, PC
Atlanta, Georgia, United States, 30309
United States, Hawaii
University of Hawaii
Honolulu, Hawaii, United States, 96816-2333
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611
United States, Kansas
University of Kansas School of Medicine
Wichita, Kansas, United States, 67214
United States, Massachusetts
Fenway Community Health Center
Boston, Massachusetts, United States, 02115
Community Research Intiative of New England
Boston, Massachusetts, United States, 02215-3319
United States, New Jersey
I.D. Care, Inc.
Hillsborough, New Jersey, United States, 08844-4254
Saint Michael's Medical Center
Newark, New Jersey, United States, 07102
United States, Ohio
Summa Health System
Akron, Ohio, United States, 44304-1430
United States, Oregon
The Research & Education Institute
Portland, Oregon, United States, 97209
United States, Texas
Central Texas Clinical Research
Austin, Texas, United States, 78705
Nicholaos C Bellos, MD, PA
Dallas, Texas, United States, 75204
North Texas Infectious Diseases Consultants, P.A.
Dallas, Texas, United States, 75246
Tarrant County Infection Disease Associates
Fort Worth, Texas, United States, 76104
University of Texas Medical Brach
Galveston, Texas, United States, 77555-0435
Therapeutic Concepts
Houston, Texas, United States, 77004
Resarch Access Network
Houston, Texas, United States, 77098
DCOL Center for Clinical Research
Longview, Texas, United States, 75605
United States, Washington
Swedish Medical Center
Seattle, Washington, United States, 98104
Australia, New South Wales
407 Doctors
Darlinghurst, New South Wales, Australia, 2010
Parramatta Sexual Health Clinic
Parramatta, New South Wales, Australia, 2150
Westmead Hospital
Westmead, New South Wales, Australia, 2145
Australia, Victoria
Carlton Clinic
Carlton, Victoria, Australia, 3053
Melbourne Sexual Health Centre
Carlton, Victoria, Australia, 3053
The Alfred
Melbourne, Victoria, Australia
Royal Melbourne Hospital
Parkville, Victoria, Australia, 3050
Prahran Market Clinic
South Yarra, Victoria, Australia, 3141
Belgium
Prins Leopold Institute voor Tropische Geneeskunde
Antwerpen, Belgium, 2000
Hopitaux IRIS Sud
Bruxelles, Belgium, 1000
Cliniques Universitaires Saint-Luc
Bruxelles, Belgium, 1200
Canada, British Columbia
Ubc Downtown I.D. Clinic
Vancouver, British Columbia, Canada, V6Z 2C7
Canada, Ontario
Hamilton Health Sciences Corporation
Hamilton, Ontario, Canada, L8N 3Z5
Sunnybrook Health Sciences Centre
Toronto, Ontario, Canada, M4N 3M5
University Health Network
Toronto, Ontario, Canada, H5G 2C4
Canada
Centre Hospitalier Universitaire de Quebec
Quebec, Canada, G1V 4G2
Germany
EPIMED GmbH
Berlin, Germany, 12157
Charite-Universitatsmedizin Berlin
Berlin, Germany, 13353
Ruhr-Universitat Bochum
Bochum, Germany, 44791
Universitatsklinikum Bonn
Bonn, Germany, 53105
Klinikum Dortmund gGmbH
Dortmund, Germany, 44137
Universitatsklinikum Essen
Essen, Germany, 45122
Klinikum der Johann-Wolfgang Goethe-Universitat
Frankfurt, Germany, 60590
Praxis fuer Innere Medizin
Freiburg, Germany, 79098
Praxis Dr.Schneider
Furth, Germany, 90762
Dr. med. Birger Kuhlmann
Hannover, Germany, 30159
Klinikum der Universitat Munchen - Innenstadt
Munchen, Germany, 80336
Praxis Dres. Ulmer, Frietsch, Muller
Stuttgart, Germany, 70197
Gemeinschaftspraxis E. Schnaitmann, Dr. med. A. Schaffert, Dr. med. A. Trein, Dr. med. E. Ibler
Stuttgart, Germany, 70197
Israel
Soroka University Medical Center
Beer-Sheva, Israel, 84101
Rambam Medical Center
Haifa, Israel, 31096
Hadassah University Hospital Ein Kerem
Jerusalem, Israel, 91120
The Chaim Sheba Medical Center
Ramat-Gan, Israel, 52621
Kaplan Medical Center
Rehovot, Israel, 76100
Tel-Aviv Sourasky Medical Center
Tel Aviv, Israel, 64239
Italy
Ospedale S.Maria Annunziata
Antella, Italy, 50011
Azienda Ospedaliera Universitaria di Ferrara Arcispedale S.Anna
Ferrara, Italy, 44100
Azienda Ospedaliera Universitaria San Martino
Genova, Italy, 16132
Ospedale Luigi Sacco
Milano, Italy, 20157
Fondazione Centro San Raffaele del Monte Tabor
Milano, Italy, 20127
Azienda Ospedaliero-Universitaria di Modena Policlinico
Modena, Italy, 41100
Azienda Ospedaliera Cotugno
Napoli, Italy, 80131
Azienda Ospedaliera di Padova
Padova, Italy, 35128
Istituto Nazionale Malattie Infettive "Lazzaro Spallanzani" IRCCS
Roma, Italy, 149
Comprensorio Amedeo di Savoia - Birago Di Vische
Torino, Italy, 10149
Peru
Hospital Nacional CASE-EsSalud
Arequipa, Peru, 0
Investigaciones Medicas en Salud
Lima, Peru, 14
Edgardo Rebagliati Hospital
Lima, Peru
Via Libre
Lima, Peru, 1
Hospital Nacional Cayetano Heredia
Lima, Peru, 31
Hospital Dos de Mayo
Lima, Peru, 1
Puerto Rico
Instituto De Investigacion Cientifica
Ponce, Puerto Rico, 731
Hope Clinical Research
San Juan, Puerto Rico, 909
University of Puerto Rico
San Juan, Puerto Rico, 00936-5067
Thailand
Pharmongkutklao Hospital
Bangkok, Thailand, 10330
Sirraj Hospital, Mahidol Universoty
Bangkok, Thailand, 10700
The HIV Netherlands Australia Thailand Research Collaboration (HIV-NAT)
Bangkok, Thailand, 10330
Ramathibodi Hospital, Mahidol University
Bangkok, Thailand, 10400
Mahidol University Hospital for Tropical Diseases
Bangkok, Thailand, 10270
Maharaj Nakorn Chiang Mai, Chiang Mai University
Chiang Mai, Thailand, 50002
Khon Kaen University
Khon Kaen, Thailand, 40002
Bamrasnaradura Institution
Nonthaburi, Thailand, 11000
United Kingdom
Birmingham Heartlands Hospital
Birmingham, United Kingdom, B9 5SS
Royal Free Hospital
London, United Kingdom, NW3 2QG
Guy's King's & St. Thomas' School of Medicine
London, United Kingdom, SE5 9RJ
St Mary's Hospital
London, United Kingdom, W2 1NY
St Bartholomew's Hospital
London, United Kingdom, EC1A 7BE
Sponsors and Collaborators
Avexa
Investigators
Study Director: Susan W Cox, Ph D Avexa Ltd
Principal Investigator: Michael Saag, MD UAB Center for AIDS Research
  More Information

No publications provided

Responsible Party: Avexa
ClinicalTrials.gov Identifier: NCT00612898     History of Changes
Other Study ID Numbers: AVX-301
Study First Received: January 30, 2008
Last Updated: January 19, 2012
Health Authority: United States: Food and Drug Administration
Argentina: Human Research Bioethics Committee
Australia: Human Research Ethics Committee
Belgium: Federal Agency for Medicines and Health Products, FAMHP
Brazil: Ministry of Health
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
Germany: Ministry of Health
Portugal: Ethics Committee for Clinical Research
South Africa: Department of Health
United Kingdom: Medicines and Healthcare Products Regulatory Agency
Italy: The Italian Medicines Agency
Israel: Ministry of Health
Canada: Health Canada
Guatemala: Health ministry
India: Ministry of Health
Russia: Pharmacological Committee, Ministry of Health
Thailand: Food and Drug Administration
Peru: Ministry of Health
Mexico: Ministry of Health
Uganda: Ministry of Health

Keywords provided by Avexa:
HIV infection
Drug resistance
Reverse transcriptase inhibitor
Nucleoside analogue
treatment experienced

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Lamivudine
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on April 16, 2014