Maraviroc Switch Collaborative Study

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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HIV

Intervention / Treatment
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* Drug: Maraviroc


Participation Criteria
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Eligibility Criteria
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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, absolute neutrophil count (ANC) <750 cells/µL haemoglobin <8.0 g/dL platelet count <50,000 cells/µL 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).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: No change<br>continue their current cART regimen | |
| Active Comparator: Replace N(t)RTI drugs with Maraviroc<br>Replace N(t)RTI drugs with MVC at a dose of 150mg bid (MVC 300mg bid can be used at the discretion of the Investigator if the PI/r is fosamprenavir/r) and continue the PI/r | Drug: Maraviroc<br>* 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.<br>|
| Active Comparator: Replace PI/r drugs with Maraviroc<br>Replace PI/r drugs with MVC at a dose of 300mg bid and continue 2N(t)RTI. | Drug: Maraviroc<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |