Maraviroc Immune Recovery Study (MIRS)

This study has been completed.
Sponsor:
Collaborators:
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Erasmus Medical Center
Leiden University Medical Center
Onze Lieve Vrouwe Gasthuis
Slotervaart Hospital
Rijnstate Hospital
Pfizer
Information provided by (Responsible Party):
S.F.L. van Lelyveld, UMC Utrecht
ClinicalTrials.gov Identifier:
NCT00875368
First received: April 2, 2009
Last updated: September 6, 2013
Last verified: September 2013
  Purpose

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).

Condition Intervention Phase
HIV Infections
Drug: maraviroc
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Maraviroc Immune Recovery Study, A Multicenter, Randomized, Placebo-controlled, Exploratory Mechanistic Study Into the Role of Maraviroc on Immune Recovery

Resource links provided by NLM:


Further study details as provided by UMC Utrecht:

Primary Outcome Measures:
  • 30% increase in CD4+ cell count after 48 weeks [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]

Enrollment: 85
Study Start Date: February 2009
Study Completion Date: August 2012
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Maraviroc Drug: maraviroc
maraviroc dose dependent on co-medication
Other Names:
  • Celsentri
  • Celsentry
Placebo Comparator: Placebo
Placebo drug
Drug: Placebo
Placebo drug

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00875368

Locations
Netherlands
Onze Lieve Vrouwe Gasthuis
Amsterdam, Netherlands, 1091 AC
Slotervaartziekenhuis
Amsterdam, Netherlands
Academisch Medisch Centrum (AMC)
Amsterdam, Netherlands, 1105AZ
Rijnstate Hospital
Arnhem, Netherlands
Kennemer Gasthuis
Haarlem, Netherlands
Leids Universitair Medisch Centrum (LUMC)
Leiden, Netherlands
Maasstad Ziekenhuis
Rotterdam, Netherlands
Erasmus MC
Rotterdam, Netherlands, 3015GJ
Sint Elisabeth Ziekenhuis
Tilburg, Netherlands
Ùniversity Medical Center Utrecht
Utrecht, Netherlands, 3584CX
Sponsors and Collaborators
S.F.L. van Lelyveld
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Erasmus Medical Center
Leiden University Medical Center
Onze Lieve Vrouwe Gasthuis
Slotervaart Hospital
Rijnstate Hospital
Pfizer
Investigators
Principal Investigator: Andy IM Hoepelman, MD, PhD UMC Utrecht
  More Information

No publications provided

Responsible Party: S.F.L. van Lelyveld, Coordinating investigator, UMC Utrecht
ClinicalTrials.gov Identifier: NCT00875368     History of Changes
Other Study ID Numbers: 08-283
Study First Received: April 2, 2009
Last Updated: September 6, 2013
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by UMC Utrecht:
HIV-1
HAART
CD4 cell
Immunologic non-responders
Immunology
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

ClinicalTrials.gov processed this record on September 14, 2014