Back to resultsIntegrase Inhibitor (MK-0518) Viral Decay
Primary Purpose
HIV Infections
Status
Completed
Phase
Phase 2
Locations
Canada
Study Type
Interventional
Intervention
Raltegravir (MK0518)
Placebo
Leukopheresis
Sigmoid Biopsy
Sponsored by
About this trial
This is an interventional treatment trial for HIV Infections focused on measuring chronic HIV infection, Human Immunodeficiency Virus, Treatment Experienced
Eligibility Criteria
Inclusion Criteria:
- Participant must be HIV-1 infected
- Participant must be 18 years old
- Participant must be taking first standard cART with 2-3 NRTIs and 1-2 PIs or an NNRTI for at least four years (first cART regimen may include changes due to toxicity but not due to virologic failure).
- Participant must have a VL < 50 copies/ml (using the standard available methods of detection) during the entire time on standard cART except for initial fall of VL and a maximum of two non-consecutive blips of < 100 copies/ml that the study investigator deems to be not clinically significant
- Female participant must agree to use two methods of birth control or abstinence during the period of the study
- Participant has to have signed full informed consent
Exclusion Criteria:
- Participant who would have difficulty participating in a trial due to non-adherence or substance abuse
- Participant who has taken mono or dual antiretroviral therapy in the past
- Participant who has had a VL > 50 copies/ml on any antiretroviral regimen
Participant with any of the following abnormal laboratory test results in screening:
- Hemoglobin < 100 g/L
- Neutrophil count < 750 cells/L
- Platelet count < 50,000 cells/L
- AST or ALT > 5X the upper limit of normal
- Creatinine > 250 mol/L
- Participant with a malignancy
- Participant with other significant underlying disease (non-HIV) that might impinge upon disease progression or death
- Participant with an active AIDS-defining illness in the past six months
- Participant who is pregnant
Sites / Locations
- Maple Leaf Medical Clinic
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
MK0518 + cART
Placebo + cART
Arm Description
Raltegravir + standard of care combined antiretroviral therapy
Placebo + standard of care combined antiretroviral therapy
Outcomes
Primary Outcome Measures
change of proviral HIV-1 DNA in total CD4+ T cells from baseline to week 48
evaluate the change of proviral HIV-1 DNA in total CD4+ T cells from baseline to week 48 in participants randomized to the raltegravir arm (400mg raltegravir) for 48 weeks in addition to their current standard combination antiretroviral regimen versus the control arm, who remained on their current standard combination antiretroviral regimen.
Secondary Outcome Measures
evaluated the effect of raltegravir intensification on blood CD4+ T cell populations
evaluated the effect of raltegravir intensification on blood CD4+ T cell populations. In addition, after treatment-intensification in both groups at week 48, a post-hoc follow-up of all participants was conducted up to week 96 to examine if raltegravir intensification had any long-term effects on proviral HIV DNA and CD4+ T cell populations in the blood and gut.
Full Information
NCT ID
NCT00520897
First Posted
August 24, 2007
Last Updated
June 4, 2012
Sponsor
Canadian Immunodeficiency Research Collaborative
Collaborators
National Institutes of Health (NIH)
1. Study Identification
Unique Protocol Identification Number
NCT00520897
Brief Title
Integrase Inhibitor (MK-0518) Viral Decay
Official Title
Effect of Integrase Inhibitor (MK-0518) on Decay of Low Level Viral Replication in HIV Reservoirs in Infected Individuals Who Initiated Conventional Antiretroviral Therapy During the Chronic Phase of Infection
Study Type
Interventional
2. Study Status
Record Verification Date
June 2012
Overall Recruitment Status
Completed
Study Start Date
April 2007 (undefined)
Primary Completion Date
February 2009 (Actual)
Study Completion Date
November 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Canadian Immunodeficiency Research Collaborative
Collaborators
National Institutes of Health (NIH)
4. Oversight
5. Study Description
Brief Summary
The eradication of HIV by antiretroviral therapy has thus far been elusive. It has been consistently demonstrated that a pool of latently infected, resting CD4+ T cells persists in the majority of HIV-infected individuals receiving antiretroviral therapy in whom plasma viremia has been successfully suppressed for prolonged periods of time; this pool has emerged as the major obstacle in achieving the eradication of HIV. We believe that MK-0518 can further the decay and suppression of HIV-1 in patients who have been virologically suppressed for a prolonged period of time on effective cART (≥ 4 years).
Detailed Description
The trial is a prospective, double-blind, randomized, placebo-controlled study with two phases: phase I to 48 weeks and phase II to 96 weeks with the primary analysis at 48 weeks. HIV-infected individuals who are taking their first standard cART regimen for at least four years with complete viral suppression. Upon enrollment, he/she will be randomized to one of two arms: the MK-0518 arm or the control arm. As each participant reaches week 48, he/she will be unblinded and those in the MK-0518 arm will continue taking MK-0518. Based on the results of an interim analysis, the control arm will be rolled over to receive MK-0518 for 48 weeks. After the screening, baseline visits and week 4 safety visit, follow-up visits will occur every 8 weeks for both arms.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections
Keywords
chronic HIV infection, Human Immunodeficiency Virus, Treatment Experienced
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
24 (Actual)
8. Arms, Groups, and Interventions
Arm Title
MK0518 + cART
Arm Type
Experimental
Arm Description
Raltegravir + standard of care combined antiretroviral therapy
Arm Title
Placebo + cART
Arm Type
Placebo Comparator
Arm Description
Placebo + standard of care combined antiretroviral therapy
Intervention Type
Drug
Intervention Name(s)
Raltegravir (MK0518)
Intervention Description
400mg BID; 48 weeks
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
400mg QD
Intervention Type
Procedure
Intervention Name(s)
Leukopheresis
Intervention Description
pack of cells as per protocol
Intervention Type
Procedure
Intervention Name(s)
Sigmoid Biopsy
Intervention Description
gut samples as per protocol
Primary Outcome Measure Information:
Title
change of proviral HIV-1 DNA in total CD4+ T cells from baseline to week 48
Description
evaluate the change of proviral HIV-1 DNA in total CD4+ T cells from baseline to week 48 in participants randomized to the raltegravir arm (400mg raltegravir) for 48 weeks in addition to their current standard combination antiretroviral regimen versus the control arm, who remained on their current standard combination antiretroviral regimen.
Time Frame
48 weeks
Secondary Outcome Measure Information:
Title
evaluated the effect of raltegravir intensification on blood CD4+ T cell populations
Description
evaluated the effect of raltegravir intensification on blood CD4+ T cell populations. In addition, after treatment-intensification in both groups at week 48, a post-hoc follow-up of all participants was conducted up to week 96 to examine if raltegravir intensification had any long-term effects on proviral HIV DNA and CD4+ T cell populations in the blood and gut.
Time Frame
48 & 96 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Participant must be HIV-1 infected
Participant must be 18 years old
Participant must be taking first standard cART with 2-3 NRTIs and 1-2 PIs or an NNRTI for at least four years (first cART regimen may include changes due to toxicity but not due to virologic failure).
Participant must have a VL < 50 copies/ml (using the standard available methods of detection) during the entire time on standard cART except for initial fall of VL and a maximum of two non-consecutive blips of < 100 copies/ml that the study investigator deems to be not clinically significant
Female participant must agree to use two methods of birth control or abstinence during the period of the study
Participant has to have signed full informed consent
Exclusion Criteria:
Participant who would have difficulty participating in a trial due to non-adherence or substance abuse
Participant who has taken mono or dual antiretroviral therapy in the past
Participant who has had a VL > 50 copies/ml on any antiretroviral regimen
Participant with any of the following abnormal laboratory test results in screening:
Hemoglobin < 100 g/L
Neutrophil count < 750 cells/L
Platelet count < 50,000 cells/L
AST or ALT > 5X the upper limit of normal
Creatinine > 250 mol/L
Participant with a malignancy
Participant with other significant underlying disease (non-HIV) that might impinge upon disease progression or death
Participant with an active AIDS-defining illness in the past six months
Participant who is pregnant
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mona Loutfy, MD
Organizational Affiliation
Women's College Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Maple Leaf Medical Clinic
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5B 1L6
Country
Canada
12. IPD Sharing Statement
Learn more about this trial
Integrase Inhibitor (MK-0518) Viral Decay
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