Integrase Inhibitor (MK-0518) Viral Decay

NCT00520897 | Completed Phase 2

• 1 other identifier: 038-00
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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).

Conditions

HIV Infections

Keywords

chronic HIV infection; Human Immunodeficiency Virus; Treatment Experienced

Outcome Measures

Primary Outcomes (1)

• 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.

  48 weeks

Secondary Outcomes (1)

• evaluated the effect of raltegravir intensification on blood CD4+ T cell populations

  48 & 96 weeks

Study Arms (2)

MK0518 + cART

EXPERIMENTAL

Raltegravir + standard of care combined antiretroviral therapy

Drug: Raltegravir (MK0518); Procedure: Leukopheresis; Procedure: Sigmoid Biopsy

Placebo + cART

PLACEBO COMPARATOR

Placebo + standard of care combined antiretroviral therapy

Drug: Placebo; Procedure: Leukopheresis; Procedure: Sigmoid Biopsy

Interventions

Raltegravir (MK0518) DRUG

400mg BID; 48 weeks

MK0518 + cART

Placebo DRUG

400mg QD

Placebo + cART

Leukopheresis PROCEDURE

pack of cells as per protocol

MK0518 + cART; Placebo + cART

Sigmoid Biopsy PROCEDURE

gut samples as per protocol

MK0518 + cART; Placebo + cART

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Canadian Immunodeficiency Research Collaborative: lead
• National Institutes of Health (NIH): collaborator

Study Sites (1)

Maple Leaf Medical Clinic

Toronto, Ontario, M5B 1L6, Canada

Location

MeSH Terms

Conditions

HIV Infections; Acquired Immunodeficiency Syndrome

Interventions

Raltegravir Potassium; Leukapheresis

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases

Intervention Hierarchy (Ancestors)

Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Cytapheresis; Biological Therapy; Therapeutics; Blood Component Removal; Leukocyte Reduction Procedures; Cell Separation; Cytological Techniques; Clinical Laboratory Techniques; Investigative Techniques

Study Officials

• Mona Loutfy, MD

  Women's College Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 24, 2007
• First Posted: August 27, 2007
• Study Start: April 1, 2007
• Primary Completion: February 1, 2009
• Study Completion: November 1, 2011
• Last Updated: June 5, 2012

Record last verified: 2012-06

Locations

CA (1)