Maraviroc Immune Recovery Study (MIRS)

Maraviroc Immune Recovery Study, A Multicenter, Randomized, Placebo-controlled, Exploratory Mechanistic Study Into the Role of Maraviroc on Immune Recovery

Rationale: Improving cellular immunity by means of increasing CD4 cells is one of the goals of antiretroviral therapy in HIV, which is achieved by means of virological suppression. A certain group of patients, the so called "immunologic non responders", fail to reach an acceptable CD4 cell increase despite an adequate virologic response on antiretroviral treatment. Recently a new antiretroviral agent, maraviroc (Celsentry®), is registered for the treatment of patients infected with CCR5 tropic HIV-1 virus. However, data is available suggesting that treatment with maraviroc leads to immune recovery (increase in CD4 cells) in patients who are infected with dual/mixed tropic HIV-1 virus, in the absence of a virologic response. This suggests an alternative mechanism for immune recovery, which could be especially beneficial for this group of patients.

Hypothesis: Maraviroc, by a yet unknown mechanism, stimulates immune recovery by increasing CD4+ cell count.

Objective: The primary objective is to confirm the hypothesis that maraviroc stimulates immune recovery; the secondary objective is to explore, by virologic and immunologic investigations, the underlying mechanisms of this hypothesis.

Study design: multicentre, randomized, placebo-controlled, double blind, exploratory mechanistic study.

Study population: HIV-1 infected patients 18 years or older, who meet the inclusion criteria.

Intervention: One group receives maraviroc (dose dependent on co-medication), the other group placebo.

Main study parameters/endpoints: A 30% increase in CD4 cell rise in the treatment group (compared with placebo).

Nature and extent of the burden and risks associated with participation, benefit and group relatedness:

1. In the treatment group subjects will start with a registered antiretroviral agent (maraviroc).
2. During the treatment year patients will perform several study visits, probably three more compared with regular visits on the outpatient clinic.
3. Each visit, blood will be drawn by venepuncture for immunologic and virologic investigations (see flow chart).

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Placebo; Drug: maraviroc

• Study Type: Interventional
• Enrollment (Actual): 85
• Phase: Phase 4

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands, 1091 AC
    • Onze Lieve Vrouwe Gasthuis
  • Amsterdam, Netherlands
    • Slotervaartziekenhuis
  • Amsterdam, Netherlands, 1105AZ
    • Academisch Medisch Centrum (AMC)
  • Arnhem, Netherlands
    • Rijnstate Hospital
  • Haarlem, Netherlands
    • Kennemer Gasthuis
  • Leiden, Netherlands
    • Leids Universitair Medisch Centrum (LUMC)
  • Rotterdam, Netherlands
    • Maasstad Ziekenhuis
  • Rotterdam, Netherlands, 3015GJ
    • Erasmus MC
  • Tilburg, Netherlands
    • Sint Elisabeth Ziekenhuis
  • Utrecht, Netherlands, 3584CX
    • University Medical Center Utrecht

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 18 years or older
• HAART with a maximal treatment interruption of two weeks
• viral suppression (< 50 copies/ml) for 6 months

• And either:

  • CD4+ count < 200 cells/microliter after minimal one year of treatment with HAART (study group one) OR
  • a CD4+ cell count between 200 and 350 cells/microliter after minimal two years of treatment with HAART (study group two)

Exclusion Criteria:

• HAART consisting of a combination of tenofovir and didanosine
• Active infection for which antimicrobial treatment
• Acute hepatitis B or C
• Chronic hepatitis B or C for which treatment with (peg)interferon and/or ribavirin (Note: patients with untreated chronic hepatitis B or C can be included)
• Immunosuppressive medication
• Radiotherapy or chemotherapy in the past 2 years
• Pregnancy or breastfeeding an infant

• Subjects with known hypersensitivity to maraviroc or to peanuts, or any of its excipients or dyes as follows:

  • Excipients from tablet: microcrystalline cellulose, dibasic calcium phosphate (anhydrous), sodium starch glycolate, magnesium stearate.
  • Film-coat: [Opadry II Blue (85G20583) contains FD&C blue #2 aluminium lake, soya lecithin, polyethylene glycol (macrogol 3350), polyvinyl alcohol, talc and titanium dioxide.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Maraviroc	Drug: maraviroc; maraviroc dose dependent on co-medication; Other Names: Celsentri; Celsentry
Placebo Comparator: Placebo; Placebo drug	Drug: Placebo; Placebo drug

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
30% increase in CD4+ cell count after 48 weeks	48 weeks

Collaborators and Investigators

• Sponsor: S.F.L. van Lelyveld
• Collaborators: Pfizer; Erasmus Medical Center; Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA); Leiden University Medical Center; Rijnstate Hospital; Onze Lieve Vrouwe Gasthuis; Slotervaart Hospital
• Investigators: Principal Investigator: Andy IM Hoepelman, MD, PhD, UMC Utrecht

Publications and helpful links

General Publications

• van Lelyveld SF, Drylewicz J, Krikke M, Veel EM, Otto SA, Richter C, Soetekouw R, Prins JM, Brinkman K, Mulder JW, Kroon F, Middel A, Symons J, Wensing AM, Nijhuis M, Borghans JA, Tesselaar K, Hoepelman AI; MIRS study group. Maraviroc Intensification of cART in Patients with Suboptimal Immunological Recovery: A 48-Week, Placebo-Controlled Randomized Trial. PLoS One. 2015 Jul 24;10(7):e0132430. doi: 10.1371/journal.pone.0132430. eCollection 2015.

Study record dates

Study Major Dates

• Study Start: February 1, 2009
• Primary Completion (Actual): December 1, 2011
• Study Completion (Actual): August 1, 2012

Study Registration Dates

• First Submitted: April 2, 2009
• First Submitted That Met QC Criteria: April 2, 2009
• First Posted (Estimate): April 3, 2009

Study Record Updates

• Last Update Posted (Estimate): September 10, 2013
• Last Update Submitted That Met QC Criteria: September 6, 2013
• Last Verified: September 1, 2013

More Information

Terms related to this study

• Keywords: Immunology; HIV-1; treatment experienced; HAART; CD4 cell; Immunologic non-responders
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Anti-HIV Agents; Anti-Retroviral Agents; HIV Fusion Inhibitors; Viral Fusion Protein Inhibitors; CCR5 Receptor Antagonists; Maraviroc
• Other Study ID Numbers: 08-283