Maraviroc Immune Recovery Study

HIV Infections Clinical Trial

— MIRS  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00875368
• Other study ID #: 08-283
• Status: Completed
• Phase: Phase 4
• First received: April 2, 2009
• Last updated: September 6, 2013
• Start date: February 2009
• Est. completion date: August 2012

Study information

• Verified date: September 2013
• Source: UMC Utrecht
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 85
• Est. completion date: August 2012
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

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

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• maraviroc
maraviroc dose dependent on co-medication
• Placebo
Placebo drug

Locations

Country	Name	City	State
Netherlands	Academisch Medisch Centrum (AMC)	Amsterdam
Netherlands	Onze Lieve Vrouwe Gasthuis	Amsterdam
Netherlands	Slotervaartziekenhuis	Amsterdam
Netherlands	Rijnstate Hospital	Arnhem
Netherlands	Kennemer Gasthuis	Haarlem
Netherlands	Leids Universitair Medisch Centrum (LUMC)	Leiden
Netherlands	Erasmus MC	Rotterdam
Netherlands	Maasstad Ziekenhuis	Rotterdam
Netherlands	Sint Elisabeth Ziekenhuis	Tilburg
Netherlands	Ùniversity Medical Center Utrecht	Utrecht

Sponsors (8)

Lead Sponsor	Collaborator
S.F.L. van Lelyveld	Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), Erasmus Medical Center, Leiden University Medical Center, Onze Lieve Vrouwe Gasthuis, Pfizer, Rijnstate Hospital, Slotervaart Hospital

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	30% increase in CD4+ cell count after 48 weeks		48 weeks	No