A Study to Evaluate the Safety and Efficacy of Raltegravir (MK0518) in HIV-Infected Patients Failing Current Antiretroviral Therapies (0518-019)

A Multicenter, Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Safety and Antiretroviral Activity of MK-0518 in Combination With an Optimized Background Therapy (OBT), Versus Optimized Background Therapy Alone, in HIV-Infected Patients With Documented Resistance to at Least 1 Drug in Each of the 3 Classes of Licensed Oral Antiretroviral Therapies

This study will investigate the safety and efficacy of raltegravir as a therapy for Human Immunodeficiency Virus (HIV)-infected patients failing current therapy with 3-class antiviral resistance.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: raltegravir potassium; Drug: Comparator: placebo

Detailed Description

The primary double-blind study of raltegravir versus placebo was extended to 156 weeks and was followed by an open-label raltegravir phase in which continuing participants from both the raltegravir and placebo groups received open-label raltegravir for an additional 84 weeks for a maximum duration of up to 240 weeks. Participants who had viral failure after Week 16 may have received open-label raltegravir until Week 240.

• Study Type: Interventional
• Enrollment (Actual): 351
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patient must be HIV positive with HIV RNA values that are within ranges required by the study
• Patient must have documented failure of certain antiretroviral therapy
• Patient must be on the same antiretroviral therapy for at least the past two months

Exclusion Criteria:

• Patient less than 16 years old
• Additional study criteria will be discussed and identified by the study doctor

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: 2; Placebo	Drug: Comparator: placebo; Placebo p.o. b.i.d. with optimized background therapy. Treatment period of 48 weeks.
Experimental: 1; raltegravir potassium	Drug: raltegravir potassium; Raltegravir 400 mg twice daily (b.i.d.) by mouth (p.o.) with optimized background therapy. Treatment period of 48 weeks.; Other Names: ISENTRESS™

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving HIV RNA <400 Copies/mL at Week 16	Percentage of participants who achieved HIV RNA <400 copies/mL at Week 16	16 Weeks
Percentage of Participants Achieving HIV RNA <400 Copies/mL at Week 48	Percentage of participants who achieved HIV RNA <400 copies/mL at Week 48	48 Weeks
Double-Blind Extension - Week 156: Percentage of Participants Achieving HIV RNA <400 Copies/mL	Percentage of participants who achieved HIV RNA <400 copies/mL at Week 156	156 Weeks
Open-Label Extension - Week 240: Percentage of Participants Achieving HIV RNA <400 Copies/mL	Percentage of participants who achieved HIV RNA <400 Copies/mL at Week 240	240 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving HIV RNA <50 Copies/mL at Week 16	Percentage of participants who achieved HIV RNA <50 copies/mL at Week 16	16 Weeks
Percentage of Participants Achieving HIV RNA <50 Copies/mL at Week 48	Percentage of participants who achieved HIV RNA <50 copies/mL at Week 48	48 Weeks
Change From Baseline in HIV RNA (log10 Copies/mL) at Week 48	Mean change from baseline at Week 48 in HIV RNA (log10 copies/mL)	Baseline and Week 48
Double-Blind Extension - Week 156: Change From Baseline in HIV RNA (log10 Copies/mL)	Mean change from baseline at Week 156 in HIV RNA (log10 copies/mL)	Baseline and Week 156
Open-Label Extension - Week 240: Change From Baseline in HIV RNA (log10 Copies/mL)	Mean change from baseline at Week 240 in HIV RNA (log10 copies/mL)	Baseline and Week 240
Double-Blind Extension - Week 156: Percentage of Participants Achieving HIV RNA <50 Copies/mL	Percentage of participants who achieved HIV RNA <50 copies/mL at Week 156	156 Weeks
Open-Label Extension - Week 240: Percentage of Participants Achieving HIV RNA <50 Copies/mL	Percentage of participants who achieved HIV RNA <50 copies/mL at Week 240	240 Weeks
Double-Blind Extension - Week 156: Percentage of Participants Without Loss of Virologic Response	For participants with confirmed HIV RNA levels <50 copies/mL on 2 consecutive visits, loss of virologic response is the occurrence of the first value >50 copies/mL or loss to follow-up; participants who never achieved HIV RNA <50 copies/mL on 2 consecutive visits are also considered as having loss of virologic response. Events are the numbers of participants with loss of virologic response versus the numbers of participants with no loss of virologic response (event-free).	156 Weeks
Change From Baseline in HIV RNA (Log 10 Copies/mL) at Week 16	Mean change from baseline at Week 16 in HIV RNA (log 10 copies/mL)	Baseline and Week 16
Change From Baseline in CD4 Cell Count (Cells/mm^3) at Week 16	Mean change from baseline at Week 16 in CD4 cell count (cells/mm^3)	Baseline and Week 16
Change From Baseline in CD4 Cell Count (Cells/mm^3) at Week 48	Mean change from baseline at Week 48 in CD4 cell count (cells/mm^3)	Baseline and Week 48
Double-Blind Extension - Week 156: Change From Baseline in CD4 Cell Count(Cells/mm^3)	Mean change from baseline at Week 156 in CD4 cell count (cells/mm^3)	Baseline and Week 156
Open-Label Extension - Week 240: Change From Baseline in CD4 Cell Count (Cells/mm^3)	Mean change from baseline at Week 240 in CD4 cell count (cells/mm^3)	Baseline and Week 240

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Steigbigel RT, Cooper DA, Kumar PN, Eron JE, Schechter M, Markowitz M, Loutfy MR, Lennox JL, Gatell JM, Rockstroh JK, Katlama C, Yeni P, Lazzarin A, Clotet B, Zhao J, Chen J, Ryan DM, Rhodes RR, Killar JA, Gilde LR, Strohmaier KM, Meibohm AR, Miller MD, Hazuda DJ, Nessly ML, DiNubile MJ, Isaacs RD, Nguyen BY, Teppler H; BENCHMRK Study Teams. Raltegravir with optimized background therapy for resistant HIV-1 infection. N Engl J Med. 2008 Jul 24;359(4):339-54. doi: 10.1056/NEJMoa0708975.
• Cooper DA, Steigbigel RT, Gatell JM, Rockstroh JK, Katlama C, Yeni P, Lazzarin A, Clotet B, Kumar PN, Eron JE, Schechter M, Markowitz M, Loutfy MR, Lennox JL, Zhao J, Chen J, Ryan DM, Rhodes RR, Killar JA, Gilde LR, Strohmaier KM, Meibohm AR, Miller MD, Hazuda DJ, Nessly ML, DiNubile MJ, Isaacs RD, Teppler H, Nguyen BY; BENCHMRK Study Teams. Subgroup and resistance analyses of raltegravir for resistant HIV-1 infection. N Engl J Med. 2008 Jul 24;359(4):355-65. doi: 10.1056/NEJMoa0708978.
• Steigbigel RT, Cooper DA, Teppler H, Eron JJ, Gatell JM, Kumar PN, Rockstroh JK, Schechter M, Katlama C, Markowitz M, Yeni P, Loutfy MR, Lazzarin A, Lennox JL, Clotet B, Zhao J, Wan H, Rhodes RR, Strohmaier KM, Barnard RJ, Isaacs RD, Nguyen BY; BENCHMRK Study Teamsa. Long-term efficacy and safety of Raltegravir combined with optimized background therapy in treatment-experienced patients with drug-resistant HIV infection: week 96 results of the BENCHMRK 1 and 2 Phase III trials. Clin Infect Dis. 2010 Feb 15;50(4):605-12. doi: 10.1086/650002.

Study record dates

Study Major Dates

• Study Start: February 1, 2006
• Primary Completion (Actual): October 1, 2007
• Study Completion (Actual): May 1, 2011

Study Registration Dates

• First Submitted: February 15, 2006
• First Submitted That Met QC Criteria: February 15, 2006
• First Posted (Estimate): February 17, 2006

Study Record Updates

• Last Update Posted (Actual): March 21, 2017
• Last Update Submitted That Met QC Criteria: February 14, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: Treatment Experienced
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; HIV Integrase Inhibitors; Integrase Inhibitors; Raltegravir Potassium
• Other Study ID Numbers: 0518-019; 2005_097

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

http://www.merck.com/clinical-trials/pdf/Merck%20Procedure%20on%20Clinical%20Trial%20Data%20Access%20Final_Updated%20July_9_2014.pdf

http://engagezone.msd.com/ds_documentation.php