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

HIV Infections Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00612898
• Other study ID #: AVX-301
• Status: Terminated
• Phase: Phase 2/Phase 3
• First received: January 30, 2008
• Last updated: January 19, 2012
• Start date: February 2008
• Est. completion date: January 2010

Study information

• Verified date: January 2012
• Source: Avexa
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationArgentina: Human Research Bioethics CommitteeAustralia: Human Research Ethics CommitteeBelgium: Federal Agency for Medicines and Health Products, FAMHPBrazil: Ministry of HealthFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)Germany: Ministry of HealthPortugal: Ethics Committee for Clinical ResearchSouth Africa: Department of HealthUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyItaly: The Italian Medicines AgencyIsrael: Ministry of HealthCanada: Health CanadaGuatemala: Health ministryIndia: Ministry of HealthRussia: Pharmacological Committee, Ministry of HealthThailand: Food and Drug AdministrationPeru: Ministry of HealthMexico: Ministry of HealthUganda: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 239
• Est. completion date: January 2010
• Est. primary completion date: January 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• HIV Infections
• Infection

Intervention

Drug:
• apricitabine
800mg BID apricitabine orally for 48 weeks
• lamivudine
150mg BID lamivudine orally for 48 weeks

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Avexa

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Germany,  Israel,  Italy,  Peru,  Puerto Rico,  Thailand,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients with plasma HIV-1 RNA <50 copies/mL at W24		week 24	No
Secondary	Time to loss of virological response (TLOVR analysis; FDA algorithm) at W12, W24 and W48 (<50 copies/mL)		week 12, 24, and 48	No
Secondary	Proportion of patients with plasma HIV-1 RNA <50 copies/mL at W48		week 48	No