A Study of the Safety, Tolerability, and Antiretroviral Activity of Raltegravir (MK-0518) in Combination With Other Antiretroviral Therapies in Russian Children and Adolescents Infected With Human Immunodeficiency Virus (HIV-1) (MK-0518-248)

A Phase II, Multicenter, Open-Label, Noncomparative Study of Raltegravir (MK-0518) in Two Oral Formulations in Combination With Other Antiretroviral Agents to Evaluate the Safety, Tolerability, and Antiretroviral Activity in HIV-1 Infected Russian Children and Adolescents

This multicenter, open-label, noncomparative study evaluates two oral formulations of raltegravir (MK-0518, film-coated tablet and chewable tablet) in combination with other antiretroviral agents for safety, tolerability, and antiretroviral activity in treatment-naive or treatment-experienced Russian children and adolescents infected with human immunodeficiency virus-1 (HIV-1).

As raltegravir is indicated in combination with other antiretroviral therapies (ARTs) for the treatment of HIV-1 infection in pediatric patients in the United States (US), this study is designed to gain local treatment experience on the use

of raltegravir in the pediatric HIV-infected population in Russia.

Study Overview

• Status: Completed
• Conditions: HIV Infection
• Intervention / Treatment: Drug: Raltegravir Film-coated Tablet; Drug: Other Anti-Retroviral Therapy; Drug: Raltegravir Chewable Tablet

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• HIV positive
• Weight of at least 7 kg
• HIV RNA ≥1000 copies/mL within 45 days before study treatment
• Participants of reproductive potential and sexually active agree to remain

abstinent or use (or have their partner use) an acceptable method of birth control throughout the study.

Exclusion Criteria:

• Females pregnant or breast-feeding, or expecting to conceive or donate eggs

during the study; males planning to impregnate or provide sperm donation

during the study

• Use of any non-antiretroviral (ART) investigational agents within one month before study treatment
• Current (active) diagnosis of acute hepatitis or chronic hepatitis other than stable chronic Hepatitis B and/or C
• Prior or current use of raltegravir
• Use of another experimental HIV-integrase inhibitor
• History or current evidence of any condition, therapy, laboratory

abnormality, or other circumstance that might confound the results of the study, or interfere with participation for the full duration of the study

• Requires or is anticipated to require any prohibited medications
• Use of immunosuppressive therapy within 30 days before beginning

raltegravir study treatment; short courses of corticosteroids are permitted.

• History of malignancy
• Current treatment for active tuberculosis infection
• Use of recreational or illicit drugs or a recent history (within the

last year) of drug or alcohol abuse or dependence

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Raltegravir Film-coated Tablet; Raltegravir film-coated tablet 400 mg administered orally twice-daily, in combination with other anti-retroviral therapy for 24 weeks	Drug: Raltegravir Film-coated Tablet; Other Names: MK-0518; ISENTRESS®; Drug: Other Anti-Retroviral Therapy; At baseline, the investigator selected the other anti-retroviral therapies to be used in combination with raltegravir based on current treatment guidelines, the participant's treatment history, and prior anti-retroviral resistance testing
Experimental: Raltegravir Chewable Tablet; Raltegravir chewable tablet weight-based dose up to 300 mg administered orally twice-daily, in combination with other anti-retroviral therapy for 24 weeks	Drug: Other Anti-Retroviral Therapy; At baseline, the investigator selected the other anti-retroviral therapies to be used in combination with raltegravir based on current treatment guidelines, the participant's treatment history, and prior anti-retroviral resistance testing; Drug: Raltegravir Chewable Tablet; Other Names: MK-0518; ISENTRESS®

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With at Least One Clinical Adverse Experience	A clinical adverse experience is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the study drug is also an adverse experience.	Up to Week 26
Percentage of Participants Who Discontinued Study Treatment Due to a Clinical Adverse Experience	A clinical adverse experience is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the study drug is also an adverse experience.	Up to Week 24
Percentage of Participants With at Least One Laboratory Adverse Experience	A laboratory adverse experience is defined as any unfavorable and unintended change in the chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the study drug is also an adverse experience.	Up to Week 26
Percentage of Participants Who Discontinued Study Treatment Due to a Laboratory Adverse Experience	A laboratory adverse experience is defined as any unfavorable and unintended change in the chemistry of the body temporally associated with the use of the study drug, whether or not considered related to the use of the product. Any worsening of a preexisting condition which is temporally associated with the use of the study drug is also an adverse experience.	Up to Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in Cluster of Differentiation 4 (CD4) Cell Count	This outcome is a measure of immunological response to treatment	Baseline and Week 24
Change From Baseline in CD4 Cell Percentage	This outcome is a measure of immunological response to treatment	Baseline and Week 24
Percentage of Participants Achieving >=1 log10 Reduction From Baseline in Human Immunodeficiency Virus (HIV) Ribonucleic Acid (RNA) or Had an HIV RNA Assessment of <200 Copies/mL	This outcome is a measure of virological (anti-retroviral) response to treatment. Plasma HIV RNA was measured using the Abbott RealTime HIV-1 assay, which has a linear range of 40 HIV RNA copies/mL to 10 million HIV RNA copies/mL	Week 24
Percentage of Participants Achieving HIV RNA <40 Copies/mL	This outcome is a measure of virological (anti-retroviral) response to treatment. Plasma HIV RNA was measured using the Abbott RealTime HIV-1 assay, which has a linear range of 40 HIV RNA copies/mL to 10 million HIV RNA copies/mL	Week 24
Percentage of Participants Achieving HIV RNA <200 Copies/mL	This outcome is a measure of virological (anti-retroviral) response to treatment. Plasma HIV RNA was measured using the Abbott RealTime HIV-1 assay, which has a linear range of 40 HIV RNA copies/mL to 10 million HIV RNA copies/mL	Week 24

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Collaborators: Covance

Study record dates

Study Major Dates

• Study Start (Actual): November 16, 2012
• Primary Completion (Actual): December 11, 2013
• Study Completion (Actual): December 11, 2013

Study Registration Dates

• First Submitted: October 26, 2012
• First Submitted That Met QC Criteria: October 26, 2012
• First Posted (Estimate): October 30, 2012

Study Record Updates

• Last Update Posted (Actual): August 21, 2018
• Last Update Submitted That Met QC Criteria: July 23, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• 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; HIV Integrase Inhibitors; Integrase Inhibitors; Raltegravir Potassium; Anti-Retroviral Agents
• Other Study ID Numbers: 0518-248

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf

Study Data/Documents

1. CSR Synopsis