Effect of Addition of Raltegravir (MK-0518) to PI- or NNRTI-Based ART Regimens in HIV Infected Subjects With Undetectable Viral Load

NCT00515827 | Completed Phase 2 Results

• 3 other identifiers: A524410440ACTG A5244
• Study Type: interventional
• Target: 53
• Locations: 1 country
• Sites: 20

Brief Summary

Raltegravir (MK-0518) is an HIV-1 integrase inhibitor with potent in vitro activity against HIV-1 strains including those resistant to currently available antiretroviral drugs. The purpose of this study is to assess the effectiveness of raltegravir in further reducing viral load in HIV infected patients that have already achieved viral suppression below the level of detection of standard viral load assays when added to antiretroviral therapy (ART).

Conditions

HIV Infections

Keywords

Treatment Experienced

Outcome Measures

Primary Outcomes (1)

• HIV-1 RNA Level

  HIV-1 RNA level, as measured by single copy assay (units are copies/ml), averaged at weeks 10 and 12. The quantification limit of single copy assay was determined by the volume of plasma tested. When averaging the week 10 and 12 measurements, if one of both measurements were below the single copy assay lower limits, the lower limit of quantification was used to compute the average and the result was treated as below the averaged value.

  At Weeks 10 and 12

Secondary Outcomes (8)

• Change in HIV-1 RNA Level

  At pre-entry, entry, weeks 10 and 12

• Change in Total CD4 Cell Count

  At pre-entry, entry, and week 12

• Change in Total CD8 Cell Count

  At pre-entry, entry, and week 12

• Change in CD4+/CD38+/HLA-DR+ Percent

  At pre-entry, entry, and week 12

• Change in CD8+/CD38+/HLA-DR+ Percent

  At pre-entry, entry, and week 12

Study Arms (2)

Raltegravir then Placebo (Arm A)

EXPERIMENTAL

400 mg raltegravir (MK-0518) administered twice daily in addition to optimized background regimen (OBR) from entry to Week 12; halt raltegravir at Week 12 and add placebo twice daily for 12 weeks

Drug: Raltegravir (MK-0518); Drug: Placebo

Placebo then Raltegravir (Arm B)

EXPERIMENTAL

Placebo administered twice daily in addition to OBR from entry until Week 12; halt placebo at Week 12 and add 400 mg raltegravir tablet twice daily for 12 weeks

Drug: Raltegravir (MK-0518); Drug: Placebo

Interventions

Raltegravir (MK-0518) DRUG

400 mg tablet taken orally twice daily

Placebo then Raltegravir (Arm B); Raltegravir then Placebo (Arm A)

Placebo DRUG

400 mg placebo tablet taken orally twice daily

Placebo then Raltegravir (Arm B); Raltegravir then Placebo (Arm A)

Eligibility Criteria

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

You may qualify if:

• HIV-1 Infection
• ART for at least 12 months prior to study entry that includes at least two NRTIs and either an NNRTI or a ritonavir-boosted PI
• No change in ART regimen for at least 3 months prior to study entry
• CD4 count of 200 or more at screening
• Viral load below the limit of quantification of an ultrasensitive assay for at least 6 months prior to study entry
• Viral load less than 50 copies/ml using Roche Amplicor HIV-1 RNA Ultrasensitive assay within 60 days of study entry
• All viral load assays obtained within 6 months prior to study entry lower than limits of quantification on all tests
• Pre-ART viral load level greater than 100,000 copies/ml
• Detectable viral load of 1 copy or more on the screening SCA
• Available pre-study entry plasma sample for SCA viral load determination
• Absolute neutrophil count of 750/mm3 or more
• Hemoglobin of 9 g/dL or more for female subjects and 10 g/dL or more for male subjects
• Platelet count of 50,000/mm3 or more
• Calculated creatinine clearance of 30 ml/min or more
• AST, ALT, and alkaline phosphate less than or equal to 5 x ULN

You may not qualify if:

• Previous documented virologic failure on an antiretroviral regimen
• Unstable clinical condition that would preclude the subject from undergoing study procedures
• Use of immunosuppressive medications within 60 days prior to study entry. Participants using inhaled or nasal steroids are not excluded.
• Opportunistic infection within 60 days prior to study entry
• Allergy or sensitivity to components of study drug
• Active drug or alcohol abuse
• Serious illness requiring systemic treatment within 60 days prior to study entry
• Receipt of non-HIV vaccination within 30 days prior to study entry
• Receipt of any HIV vaccines
• Plan to change background ART within 24 weeks after study entry
• Pregnant or breastfeeding

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (20)

Alabama Therapeutics CRS

Birmingham, Alabama, 35294-2050, United States

Location

Stanford CRS

Palo Alto, California, 94304-5350, United States

Location

Ucsf Aids Crs

San Francisco, California, 94110, United States

Location

Harbor-UCLA Med. Ctr. CRS

Torrance, California, 90502, United States

Location

University of Colorado Hospital CRS

Aurora, Colorado, 80045, United States

Location

Northwestern University CRS

Chicago, Illinois, 60611, United States

Location

Massachusetts General Hospital ACTG CRS

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Med. Ctr., ACTG CRS

Boston, Massachusetts, 02215, United States

Location

Washington U CRS

St Louis, Missouri, 63110, United States

Location

Cornell CRS

New York, New York, 10011, United States

Location

NY Univ. HIV/AIDS CRS

New York, New York, 10016, United States

Location

Columbia P&S CRS

New York, New York, 10032-3732, United States

Location

Harlem ACTG CRS

New York, New York, 10037, United States

Location

Univ. of Rochester ACTG CRS

Rochester, New York, 14642, United States

Location

Unc Aids Crs

Chapel Hill, North Carolina, 27514, United States

Location

Duke Univ. Med. Ctr. Adult CRS

Durham, North Carolina, 27710, United States

Location

MetroHealth CRS

Cleveland, Ohio, 44109, United States

Location

Hosp. of the Univ. of Pennsylvania CRS

Philadelphia, Pennsylvania, 19104, United States

Location

Pitt CRS

Pittsburgh, Pennsylvania, 15213-2582, United States

Location

University of Washington AIDS CRS

Seattle, Washington, 98104, United States

Location

Related Publications (5)

• Grinsztejn B, Nguyen BY, Katlama C, Gatell JM, Lazzarin A, Vittecoq D, Gonzalez CJ, Chen J, Harvey CM, Isaacs RD; Protocol 005 Team. Safety and efficacy of the HIV-1 integrase inhibitor raltegravir (MK-0518) in treatment-experienced patients with multidrug-resistant virus: a phase II randomised controlled trial. Lancet. 2007 Apr 14;369(9569):1261-1269. doi: 10.1016/S0140-6736(07)60597-2.

  PMID: 17434401 BACKGROUND

• Kassahun K, McIntosh I, Cui D, Hreniuk D, Merschman S, Lasseter K, Azrolan N, Iwamoto M, Wagner JA, Wenning LA. Metabolism and disposition in humans of raltegravir (MK-0518), an anti-AIDS drug targeting the human immunodeficiency virus 1 integrase enzyme. Drug Metab Dispos. 2007 Sep;35(9):1657-63. doi: 10.1124/dmd.107.016196. Epub 2007 Jun 25.

  PMID: 17591678 BACKGROUND

• Markowitz M, Morales-Ramirez JO, Nguyen BY, Kovacs CM, Steigbigel RT, Cooper DA, Liporace R, Schwartz R, Isaacs R, Gilde LR, Wenning L, Zhao J, Teppler H. Antiretroviral activity, pharmacokinetics, and tolerability of MK-0518, a novel inhibitor of HIV-1 integrase, dosed as monotherapy for 10 days in treatment-naive HIV-1-infected individuals. J Acquir Immune Defic Syndr. 2006 Dec 15;43(5):509-15. doi: 10.1097/QAI.0b013e31802b4956.

  PMID: 17133211 BACKGROUND

• Gandhi RT, Zheng L, Bosch RJ, Chan ES, Margolis DM, Read S, Kallungal B, Palmer S, Medvik K, Lederman MM, Alatrakchi N, Jacobson JM, Wiegand A, Kearney M, Coffin JM, Mellors JW, Eron JJ; AIDS Clinical Trials Group A5244 team. The effect of raltegravir intensification on low-level residual viremia in HIV-infected patients on antiretroviral therapy: a randomized controlled trial. PLoS Med. 2010 Aug 10;7(8):e1000321. doi: 10.1371/journal.pmed.1000321.

  PMID: 20711481 RESULT

• Gandhi RT, Coombs RW, Chan ES, Bosch RJ, Zheng L, Margolis DM, Read S, Kallungal B, Chang M, Goecker EA, Wiegand A, Kearney M, Jacobson JM, D'Aquila R, Lederman MM, Mellors JW, Eron JJ; AIDS Clinical Trials Group (ACTG) A5244 Team. No effect of raltegravir intensification on viral replication markers in the blood of HIV-1-infected patients receiving antiretroviral therapy. J Acquir Immune Defic Syndr. 2012 Mar 1;59(3):229-35. doi: 10.1097/QAI.0b013e31823fd1f2.

  PMID: 22083073 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

Raltegravir Potassium

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

Intervention Hierarchy (Ancestors)

Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: ACTG ClinicalTrials.gov Coordinator
• Organization: ACTG Network Coordinating Center, Social and Scientific Systems, Inc.

ACTGCT.Gov@s-3.com

(301) 628-3313

Study Officials

• Rajesh T Gandhi, MD

  Massachusetts General Hospital

  STUDY CHAIR

• Joseph J Eron Jr., MD

  University of North Carolina, Chapel Hill

  STUDY CHAIR

• John W Mellors, MD

  University of Pittsburgh Medical Center

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: August 10, 2007
• First Posted: August 14, 2007
• Study Start: November 1, 2007
• Primary Completion: September 1, 2008
• Study Completion: November 1, 2008
• Last Updated: November 4, 2021
• Results First Posted: June 23, 2011

Record last verified: 2019-01

Locations

US (20)