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Pilot Study of Adding Raltegravir (MK-0518) to Antiretroviral Therapy in Patients With Low Level Viremia

This study has been completed.
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Frank Maldarelli, National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00618371
First received: September 29, 2007
Last updated: October 11, 2016
Last verified: October 2016
  Purpose
The medicines used to treat HIV can suppress but cannot kill all the virus in the body. A small amount of virus remains at low levels in the part of the blood called the plasma. It is of crucial importance to identify the source of the residual virus in patients receiving antiretroviral therapy. The purpose of this study is to investigate whether the source of low level plasma virus is from latent (old) infection or ongoing (new) infection. MK-0518 is a investigational drug, which means that is not yet FDA approved, that works in a different way to other anti-HIV medicines to help kill the virus. We hypothesize that addition of MK-0518 to a stable anti-HIV regimen will reduce the viral load further in patients with undetectable plasma virus.

Condition Intervention
HIV Infection
Drug: Raltegravir (MK-0518)

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: Investigating the Source of HIV-1 Viremia in Patients on Antiretroviral Therapy Through Intensification With MK-0518

Resource links provided by NLM:


Further study details as provided by University of Pittsburgh:

Primary Outcome Measures:
  • Number of Participants With HIV-1 RNA Response: ≥ 1 Log Decrease in Viral Load [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    HIV RNA levels were determined with a non-commercial, sensitive single copy assay for HIV. The primary outcome measure was to determine the number of individuals with ≥10fold decrease in HIV RNA


Secondary Outcome Measures:
  • Proviral DNA Response, HIV-1 Sequence Variation Levels of Cell Associated HIV DNA and Genetic Variation in HIV During Raltegravir Addition in Individuals Who Have Declines in HIV [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
    We planned to compare HIV DNA levels and HIV genetic variation in individuals with and without ≥10 fold decreases in HIV RNA. As none of the patients had a decline in viral RNA, this analysis could not be readily analyzed


Enrollment: 10
Study Start Date: October 2007
Study Completion Date: March 2009
Primary Completion Date: March 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Raltegravir intensification
Patients will be administered raltegravir 400 mg orally twice daily in addition to antiretroviral therapy
Drug: Raltegravir (MK-0518)
Antiretroviral drug intensification with Raltegravir (MK0518) 400mg orally every 12 hours for 28 days in addition to the prescribed antiretroviral therapy
Other Name: MK-0518

Detailed Description:
This is a non-randomized, non-comparative, single center trial of antiretroviral therapy intensification using the investigational integrase inhibitor MK-0518 and an investigational viral load assay to measure response to additional antiviral therapy. Eighteen patients will receive open-label MK-0518 400 mg P.O. every 12 hours for 28 days in addition to their prescribed antiretroviral therapy. Patients will take their doses of MK-0518 without regard to food. The study will enroll patients on antiretroviral therapy regimens with Cluster of Differentiation 4 (CD4) counts greater than 200 cells/ul, HIV-1 RNA levels <50 copies RNA/ml plasma using a commercial assay(conventional Amplicor) and with detectable plasma virus (viral loads ≥ 1 copies RNA/ml plasma, Single copy assay, "SCA"). Acceptable antiretroviral regimens will include those on Nucleoside reverse transcriptase inhibitors ("NRTIs") + protease inhibitor (PI)I, NRTIs + non-nucleoside reverse transcriptase inhibitors (NNRTIs), + PI, or NRTIs + NNRTI-containing regimens. Patients cannot have prior evidence of resistance to antiretroviral drugs. Patients will be screened for intensification by history, physical exam, and laboratory evaluations (see below). Patients who are eligible and who agree to participate will intensify their antiretroviral therapy for 28 days with MK-0518 400 mg by mouth twice a day. During the 28- day drug addition, patients will have samples drawn for SCA assay at entry and on days 7, 14, 21, and 28 (+/- 1 d), with the last day of intensification as day 28. Patients will have additional phlebotomy after intensification on days 29, 30, 35, 42, 49 and 58 (+/- 1 day). The intensification period is followed by a post- intensification period to determine whether removal of the drug resulted in viral RNA changes.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • HIV-1 infection documented by positive HIV-1 ELISA and positive
  • Male or female at least 18 years of age, and able to provide written, informed consent
  • Current antiretroviral therapy with Department of Health and Human Services (DHHS)-recommended regimen: NRTIs + PI, NRTIs + NNRTI + PI, or NRTIs + NNRTI
  • Screening CD4 > 200 cells/ µl and CD4%> 14%; does not require prophylaxis for opportunistic infections
  • Receiving a stable antiretroviral regimen for 4 months prior to screening
  • HIV-1 RNA level below the limit of detection by commercial HIV-1 RNA determination assays for at least 12 months prior to screening.
  • HIV RNA ≥ 0.6 copy RNA/ml plasma by SCA(single copy assay)
  • Hgb ≥ 9.0 mg/dl, absolute neutrophil count > 1000/mm3, platelet count > 100,000/mm3
  • Alkaline phosphatase, Aspartate transaminase (AST) and Alanine aminotransferase (ALT) < 2.0 x upper limit of normal
  • Willing to take MK-0518 for 28 days in addition to ongoing antiretroviral therapy
  • Be considered clinically stable, in the opinion of the investigator, at the time of entry into the study; i.e., clinical status and all chronic medications should be unchanged for at least two weeks prior to entry.

Exclusion Criteria:

  • Prior participation in an MK-0518 or other integrase inhibitor trial
  • Requires prohibited medications noted in the protocol
  • Requires cytotoxic agents including hydroxyurea or vaccinations during the study period
  • Received immunosuppressive therapy including steroids within one month prior to treatment in this study
  • Used any investigational agents within a month prior to treatment in this study
  • Documented resistance to any drug in each of the 4 classes of licensed antiretroviral agents by genotype or phenotype
  • Any febrile illness (T>38oC) in the 3 weeks prior to enrollment
  • Any vaccination in the 6 weeks prior to enrollment
  • Diagnosis of acute hepatitis due to any cause
  • Positive Hepatitis B surface antigen
  • Severe renal insufficiency defined as a calculated creatinine clearance at time of screening as < 30 ml/min, based on the Cockcroft-Gault equation.
  • Condition (including but not limited to alcohol or other substance use) which in the opinion of the investigator would interfere with patient compliance or safety
  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: NCT00618371

Locations
United States, Pennsylvania
University of Pittsburgh
Pittsburgh, Pennsylvania, United States, 15213
Sponsors and Collaborators
University of Pittsburgh
National Cancer Institute (NCI)
Investigators
Principal Investigator: Deborah McMahon, MD University of Pittsburgh
  More Information

Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Frank Maldarelli, Principal Investigator, National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00618371     History of Changes
Other Study ID Numbers: 27XS050  HHSN261200800001E  ZIABC011464 
Study First Received: September 29, 2007
Results First Received: September 12, 2011
Last Updated: October 11, 2016
Health Authority: United States: Food and Drug Administration
Individual Participant Data  
Plan to Share IPD: No
Plan Description: Data were analyzed and there is no plan to make individual participant data available

Keywords provided by University of Pittsburgh:
Intensification
HIV viremia
Human Immunodeficiency Virus

Additional relevant MeSH terms:
HIV Infections
Viremia
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Sepsis
Systemic Inflammatory Response Syndrome
Inflammation
Pathologic Processes
Raltegravir Potassium
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
HIV Integrase Inhibitors
Integrase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on December 09, 2016