Maraviroc Switch Collaborative Study

HIV Clinical Trial

— MARCH  

Official title:

Randomised, Openlabel Study Evaluating Efficacy and Safety of Maraviroc as a Switch for Either NRTI or PI/r in HIV-1 Infected Individuals With Stable, Well‐Controlled Plasma HIV‐RNA While Taking Their First N(t)RTI + PI/r Regimen of cART

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01384682
• Other study ID #: 2011-01-MAR
• Status: Completed
• Phase: Phase 4
• First received: June 28, 2011
• Last updated: January 18, 2016
• Start date: August 2011
• Est. completion date: December 2015

Study information

• Verified date: January 2016
• Source: Kirby Institute
• Contact: n/a
• Is FDA regulated: No
• Health authority: Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia MedicaAustralia: Department of Health and Ageing Therapeutic Goods AdministrationCanada: Health CanadaChile: Ministry of HealthFrance: Agence Nationale de Sécurité du Médicament et des produits de santéGermany: Ministry of HealthIreland: Irish Medicines BoardJapan: Ministry of Health, Labor and WelfareMexico: Ministry of HealthSpain: Agencia Española de Medicamentos y Productos SanitariosThailand: Ministry of Public HealthUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyPoland: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

MARCH is an international, multicentre trial planning to enroll 380 HIV-1 infected patients who are currently on 2N(t)RTI + PI/r regimen and virologically suppressed. Participants will be randomized (1:2:2) to one of three treatment groups: to continue their current treatment regimen, maraviroc dose at 150 mg twice daily with PI/r, or maraviroc at 300 mg twice daily with 2N(t)RTI. As the participants population have HIV RNA <200 copies/mL, the phenotypic assessment of tropism cannot be used to determine tropism, instead we will employ the genotypic assessment of tropism by sequencing the V3 loop of the HIV envelope. The main aim of this study is to investigate whether switching to maraviroc, in combination with either RTI or PI/r, is as good at keeping the HIV viral load undetectable as the combination of RTI with PI/r. The other aim is to see if switching to these combinations with maraviroc will improve some of the side effects that can be seen when people take combination therapy including RTI and PI/r.

The study hypothesis is that in stable, virologically suppressed (plasma HIV-RNA <200 copies/mL) patients with no history of prior virological failure, a switch to either MVC dosed at 300mg twice daily (bid) combined with the same 2N(t)RTI backbone regimen or MVC dosed at 150mg twice daily (bid) with the current PI/r (or 300mg bid at the discretion of the investigator if the PI/r is fosamprenavir/r) provides similar (non-inferior) antiretroviral efficacy compared to continuation of the current 2N(t)RTI + PI/r regimen.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 399
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Documented HIV-1 infection by a licensed diagnostic test at any time prior to study entry

• Age >18 years

• HIV-1 RNA <200 copies/mL plasma for at least 24 weeks

• Stable (>24 weeks) ART including two N(t)RTIs and a PI/r

• No evidence of any primary HIV genotypic mutations in HIV reverse transcriptase or protease for all patients with available resistance testing results conducted prior to cART and/or during viral rebound/failure

• Provision of written, informed consent.

Exclusion Criteria:

• CXCR4 or CCR5/CXCR4 dual tropic HIV tropism or a non-reportable tropism result based on assessment using proviral DNA

• Anticipated need to modify current cART regimen for toxicity management in the next 6 months

• The following laboratory criteria,

1. absolute neutrophil count (ANC) <750 cells/µL

2. haemoglobin <8.0 g/dL

3. platelet count <50,000 cells/µL

4. serum AST, ALT >5 x upper limit of normal (ULN)

• Active hepatitis B co-infection

• Pregnant women or nursing mothers

• Current use of any prohibited medications as described in product specific information.

• Hypersensitivity to soy or peanuts

• Acute therapy for serious infection or other serious medical illness (in the judgement of the site Principal Investigator) requiring systemic treatment and/or hospitalisation

• Use of immunomodulators (e.g. systemic corticosteroids, recombinant interleukin-2, interferon) within 30 days prior to screening

• Patients with current alcohol or illicit substance use that in the opinion of the site Principal Investigator would conflict with any aspect of the conduct of the study

• Patients unlikely to be able to remain in follow-up for the protocol-defined period

• Prisoners or subjects who are compulsorily detained (involuntary incarcerated).

Study Design

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

Related Conditions & MeSH terms

• HIV

Intervention

Drug:
• Maraviroc
Maraviroc is a marketed drug for the treatment of HIV-infection. Maraviroc will be supplied in two different oral dose forms, 150mg and 300mg given twice a day. The drug will be dosed according to the recommendations in the product label i.e. with PI/r the dose is 150mg bid except, Maraviroc 300mg bid can be used at the discretion of the investigator if the PI/r is fosamprenavir/r; those randomised to the 2N(t)RTI arm, will receive Maraviroc 300mg bid. Patients randomised to receive Maraviroc will be provided with bottles of Maraviroc which contain a 30-day supply.

Locations

Country	Name	City	State
Argentina	FUNCEI	Buenos Aires	Ciudad de Buenos Aires
Argentina	Fundacion IDEAA	Buenos Aires
Argentina	Hospital G de Agudos JM Ramos Mejia	Buenos Aires	Ciudad de Buenos Aires
Argentina	Hospital Italiano de Buenos Aires	Buenos Aires	Ciudad de Buenos Aires
Argentina	Hospital Privado- Centro Medico Cordoba	Cordoba
Argentina	Hospital Nacional Prof Alejandro Posadas	El Palomar	Provincia de Buenos Aires
Argentina	Hospital Dr Diego Paroissien	Isidro Casanova	Provincia de Buenos Aires
Argentina	CAICI	Rosario	Provincia de Santa Fe
Australia	O'Brien Street Practice	Adelaide	South Australia
Australia	Gladstone Road Medical Centre	Bisbane	Queensland
Australia	Brisbane Sexual Health and HIV Service (formerly AMU)	Brisbane	Queensland
Australia	Alfred Hospital	Melbourne	Victoria
Australia	Monash Medical Centre	Melbourne	Victoria
Australia	Nambour General Hospital	Nambour	Queensland
Australia	Holdsworth House Medical Practice	Sydney	New South Wales
Australia	Royal Prince Alfred Hospital	Sydney	New South Wales
Australia	St. Vincent's Hospital	Sydney	New South Wales
Australia	Westmead Hospital	Sydney	New South Wales
Canada	Southern Alberta Clinic	Calgary	Alberta
Canada	Clinic Opus/Lori	Montreal	Quebec
Canada	Canadian Immunodeficiency Research Collaborative (CIRC) lnc (Maple Leaf Clinic)	Toronto	Ontario
Canada	University Health Network/Toronto General Hospital	Toronto	Ontario
Chile	Fundación Arriarán	Santiago	Santiago RM
France	Service Maladies infectieuses et Tropicales CHR ORLEANS La SOURCE	Orleans
Germany	Dienstleistung centre ID (Baumgarten, MIB medical center for infectious diseases)	Berlin
Germany	Gemeinschaftspraxis Jessen Jessen Stein	Berlin
Germany	University of Bonn, Med J. Immunologische Siudienzenirale	Bonn
Germany	Klinikum der Universitat Zu Koln	Cologne
Germany	Universitätsklinikum Düsseldorf, Klinik für Gastroenterologie, Hepatologie und Infektiologie-MX- Amb	Düsseldorf
Germany	Johann Wolfgang Goethe-University Hospital, Medical HIVCENTER	Frankfurt	Frankfurt am Main
Germany	Klinik für Immunologie und Rheumatologie, Medzinische Hochschule Hannover	Hannover
Ireland	Mater Misericordiae University Hospital	Dublin
Japan	Nagoya Medical Center	Nagoya
Mexico	Hospital Civil de Guadalajara	Guadalajara	Jalisco
Mexico	Hospital General de Leon	Leon
Mexico	INCMNSZ	Mexico City
Poland	Wojewodzki Szpital Zakazny Centrum Diagnostyki i Terapii AIDS	Warsaw
Spain	Hospital Germans Trias i Pujol	Badalona	Catalonia
Spain	Hospital Clínic de Barcelona	Barcelona	Catalonia
Spain	Hospital de la Santa Creu i Sant Pau	Barcelona	Catalonia
Spain	Hospital La Paz,	Madrid
Spain	Hospital Principe de Asturias	Madrid
Spain	Hospital Regional Carlos Haya de Málaga	Malaga
Spain	Virgen Del Rocio University Hospital	Seville
Spain	Hospital Universitari i Politecnic La Fe	Valencia
Thailand	Chulalongkorn University Hospital	Bangkok
United Kingdom	Brighton & Sussex University NHS Trust	Brighton	Sussex
United Kingdom	Coventry and Warwickshire Partnership Trust	Coventry	Warwickshire
United Kingdom	Western General Hospital	Edinburgh	Lothian
United Kingdom	St. Mary's Hospital, Imperial College	London
United Kingdom	St. Thomas's Hospital	London

Sponsors (3)

Lead Sponsor	Collaborator
Kirby Institute	Pfizer, ViiV Healthcare

Countries where clinical trial is conducted

Argentina,  Australia,  Canada,  Chile,  France,  Germany,  Ireland,  Japan,  Mexico,  Poland,  Spain,  Thailand,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The comparison of the switch arms to control arm of proportions of participants with HIV RNA <200 copies/mL 48 weeks after randomisation.		48 weeks after randomization	Yes
Secondary	Virological endpoints: proportion of participants with plasma HIV-1 RNA<50 copies/ml	A number of secondary endpoints will be examined at or through to week 48 in this protocol. These will include, but not be limited to the following: Virologic; Immunologic and biomarkers; Clinical; Metabolic and body composition; Safety; Adherence; Quality of Life and Resistance endpoints.	48 weeks from randomization	Yes

External Links

•   Kirby Institute for infection and immunity in society homepage - click here for more information on the MARCH study.