Trial of Maraviroc (UK-427,857) in Combination With Optimized Background Therapy Versus Optimized Background Therapy Alone for the Treatment of Antiretroviral-Experienced NonCCR5-Tropic HIV-1 Infected Subjects

Summary

Maraviroc (UK-427,857), a selective and reversible CCR5 co-receptor antagonist, has been shown to be active in vitro against a wide range of clinical isolates (including those resistant to existing classes). In HIV-1 infected patients in the United States, maraviroc (UK-427,857) is approved for use as part of combination antiretroviral treatment in treatment-experienced and treatment-naive adult subjects. At least 50% of treatment-experienced patients are infected with R5-tropic HIV-1 exclusively. However, even in patients infected with a dual tropic (R5 + X4) phenotype, a large proportion of the virus population still uses CCR5 exclusively. Thus, the purpose of this study is to evaluate the antiretroviral activity, and safety, of maraviroc (UK-427,857) (in combination with other agents) in HIV infected, treatment experienced patients who are failing their current antiretroviral regimen and not infected with R5-tropic virus exclusively. This study will involve more than 200 centers globally to achieve a total randomized subject population of 192 subjects. Patients will be randomly (1:1:1) assigned to one of three groups: Optimized Background Therapy \[OBT (3-6 drugs based on treatment history and resistance testing)\] + maraviroc (UK-427,857) 150 mg taken once daily, OBT + maraviroc (UK-427,857) 150 mg taken twice daily, or OBT alone. Randomization was stratified by Enfuvirtide use in OBT (yes/no) and Screening HIV-1 RNA level (viral load) (\<100,000/≥ 100, 000 copies per milliliter \[copies per mL\]). The study will enroll over approximately a 9 month period with 48 weeks of treatment. Physical examinations will be performed at study entry, weeks 4, 8, 12, 16, 20, 24, 32, 40 and 48. Blood samples will also be taken at study entry, weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, and 48. Additionally, blood samples will be drawn twice, at least 30 minutes apart, at weeks 2 and 24 for maraviroc (UK-427,857) pharmacokinetic analysis. As part of this clinical study a blood sample will also be taken for non-anonymized pharmacogenetic analysis. Patients will undergo a 12-lead electrocardiogram at study entry, weeks 24 and 48.

Conditions

• HIV Infections

Interventions

DRUG

Optimized Background Therapy (OBT)

OBT (3-6 drugs based on treatment history and resistance testing)

DRUG

maraviroc (UK-427,857)

maraviroc (UK-427,857) 150 mg taken once daily

DRUG

Optimized Background Therapy (OBT)

OBT (3-6 drugs based on treatment history and resistance testing)

DRUG

maraviroc (UK-427,857)

maraviroc (UK-427,857) 150 mg taken twice daily

DRUG

Optimized Background Therapy (OBT)

OBT (3-6 drugs based on treatment history and resistance testing)

Sponsors & Collaborators

• Pfizer

  collaborator INDUSTRY

• ViiV Healthcare

  lead INDUSTRY

Principal Investigators

• Pfizer CT.gov Call Center · Pfizer

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

16 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2004-11-30

Primary Completion

2005-12-31

Completion

2009-04-30

Countries

• United States
• Australia
• Belgium
• Canada
• Germany
• Netherlands
• Spain
• Switzerland
• United Kingdom

Study Locations