MedDataX Logo

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

NCT ID: NCT00098748

Last Updated: 2010-12-07

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE2/PHASE3

Total Enrollment

190 participants

Study Classification

INTERVENTIONAL

Study Start Date

2004-11-30

Study Completion Date

2009-04-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

(i) Subjects remained on their assigned therapy for 48 weeks, unless the subject was discontinued early for protocol-defined treatment failure or other reasons such as adverse event, loss to follow-up, withdrawal of consent, or death.

(ii) If a subject met the criteria for treatment failure or discontinued for another reason (eg, pregnancy, adverse event) and required an alternative regimen, the subject was followed until the Week 48 visit according to protocol guidelines. The new regimen, selected by the Investigator based on the results of resistance testing at the time of failure, had to be recorded in the CRF.

(iii) Open-label maraviroc (UK-427,857) was provided by the sponsor, until it was commercially available, to subjects who completed 48 weeks of therapy and for whom it was medically appropriate to continue therapy with maraviroc (UK-427,857).

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

HIV Infections

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

1

Group Type EXPERIMENTAL

Optimized Background Therapy (OBT)

Intervention Type DRUG

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

maraviroc (UK-427,857)

Intervention Type DRUG

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

2

Group Type EXPERIMENTAL

Optimized Background Therapy (OBT)

Intervention Type DRUG

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

maraviroc (UK-427,857)

Intervention Type DRUG

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

3

Group Type EXPERIMENTAL

Optimized Background Therapy (OBT)

Intervention Type DRUG

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

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Optimized Background Therapy (OBT)

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

Intervention Type DRUG

maraviroc (UK-427,857)

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

Intervention Type DRUG

Optimized Background Therapy (OBT)

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

Intervention Type DRUG

maraviroc (UK-427,857)

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

Intervention Type DRUG

Optimized Background Therapy (OBT)

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

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

Selzentry, Celsentri Selzentry, Celsentri

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Men or women at least 16 years of age (or minimum age as determined by local regulatory authorities)
* HIV-1 RNA viral load of greater than or equal to 5,000 copies/mL
* Stable pre-study antiretroviral regimen, or on no antiretroviral agents, for at least 4 weeks
* Documented genotypic or phenotypic resistance to two of the four antiretroviral drug classes, OR, Antiretroviral-class experience greater than or equal to 3 months (sequential or cumulative) with at least three of the following: One nucleoside or nucleotide reverse transcriptase inhibitor (excluding low-dose ritonavir) and/or enfuvirtide
* Be willing to remain on randomized treatment without any changes or additions to the OBT regimen, except for toxicity management or upon meeting criteria for treatment failure
* A negative urine pregnancy test at the baseline visit for Women of Child Bearing Potential (WOCBP)
* Effective barrier contraception for WOCBP and males

Exclusion Criteria

* Patients requiring treatment with more than 6 antiretroviral agents (excluding low-dose ritonavir)
* Prior treatment with maraviroc (UK-427,857) or another experimental HIV entry inhibitor for more than 14 days
* Suspected or documented active, untreated HIV-1 related opportunistic infection (OI) or other condition requiring acute therapy
* Treatment for an active opportunistic infection, or unexplained temperature \>38.5 degrees Celsius for 7 consecutive days
* Active alcohol or substance abuse sufficient, in the Investigator's judgment, to prevent adherence to study medication and/or follow up
* Lactating women, or planned pregnancy during the trial period
* Significant renal insufficiency
* Previous therapy with a potentially myelosuppressive, neurotoxic, hepatotoxic and/or cytotoxic agent within 30 days prior to randomization or the expected need for such therapy during the study period
* Documented or suspected acute hepatitis or pancreatitis within 30 days prior to randomization
* Significantly elevated liver enzymes or cirrhosis
* Significant neutropenia, anemia or thrombocytopenia
* Malabsorption or an inability to tolerate oral medications
* Symptomatic postural hypotension or severe cardiovascular or cerebrovascular disease
* Certain medications
* Malignancy requiring parenteral chemotherapy that must be continued for the duration of the trial
* R5 virus phenotype only
* No option to use at least one non-nucleoside reverse transcriptase inhibitor or protease inhibitor, or enfuvirtide, based on resistance testing
* Any other clinical condition that, in the Investigator's judgment, would potentially compromise study compliance or the ability to evaluate safety/efficacy
Minimum Eligible Age

16 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Pfizer

INDUSTRY

Sponsor Role collaborator

ViiV Healthcare

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Pfizer, Inc.

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Pfizer CT.gov Call Center

Role: STUDY_DIRECTOR

Pfizer

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Pfizer Investigational Site

Birmingham, Alabama, United States

Site Status

Pfizer Investigational Site

Phoenix, Arizona, United States

Site Status

Pfizer Investigational Site

Beverly Hills, California, United States

Site Status

Pfizer Investigational Site

Fountain Valley, California, United States

Site Status

Pfizer Investigational Site

Hayward, California, United States

Site Status

Pfizer Investigational Site

Los Angeles, California, United States

Site Status

Pfizer Investigational Site

Los Angeles, California, United States

Site Status

Pfizer Investigational Site

Los Angeles, California, United States

Site Status

Pfizer Investigational Site

Newport Beach, California, United States

Site Status

Pfizer Investigational Site

Oakland, California, United States

Site Status

Pfizer Investigational Site

San Francisco, California, United States

Site Status

Pfizer Investigational Site

San Francisco, California, United States

Site Status

Pfizer Investigational Site

San Francisco, California, United States

Site Status

Pfizer Investigational Site

Union City, California, United States

Site Status

Pfizer Investigational Site

Washington D.C., District of Columbia, United States

Site Status

Pfizer Investigational Site

Washington D.C., District of Columbia, United States

Site Status

Pfizer Investigational Site

Miami, Florida, United States

Site Status

Pfizer Investigational Site

North Miami Beach, Florida, United States

Site Status

Pfizer Investigational Site

Orlando, Florida, United States

Site Status

Pfizer Investigational Site

Orlando, Florida, United States

Site Status

Pfizer Investigational Site

Sarasota, Florida, United States

Site Status

Pfizer Investigational Site

Tampa, Florida, United States

Site Status

Pfizer Investigational Site

Vero Beach, Florida, United States

Site Status

Pfizer Investigational Site

Atlanta, Georgia, United States

Site Status

Pfizer Investigational Site

Springfield, Massachusetts, United States

Site Status

Pfizer Investigational Site

Santa Fe, New Mexico, United States

Site Status

Pfizer Investigational Site

Albany, New York, United States

Site Status

Pfizer Investigational Site

Brooklyn, New York, United States

Site Status

Pfizer Investigational Site

Manhasset, New York, United States

Site Status

Pfizer Investigational Site

New York, New York, United States

Site Status

Pfizer Investigational Site

Stony Brook, New York, United States

Site Status

Pfizer Investigational Site

Stony Brook, New York, United States

Site Status

Pfizer Investigational Site

The Bronx, New York, United States

Site Status

Pfizer Investigational Site

The Bronx, New York, United States

Site Status

Pfizer Investigational Site

Huntersville, North Carolina, United States

Site Status

Pfizer Investigational Site

Philadelphia, Pennsylvania, United States

Site Status

Pfizer Investigational Site

Philadelphia, Pennsylvania, United States

Site Status

Pfizer Investigational Site

Columbia, South Carolina, United States

Site Status

Pfizer Investigational Site

Dallas, Texas, United States

Site Status

Pfizer Investigational Site

Dallas, Texas, United States

Site Status

Pfizer Investigational Site

Annandale, Virginia, United States

Site Status

Pfizer Investigational Site

Puyallup, Washington, United States

Site Status

Pfizer Investigational Site

Tacoma, Washington, United States

Site Status

Pfizer Investigational Site

Vancouver, Washington, United States

Site Status

Pfizer Investigational Site

Darlinghurst, New South Wales, Australia

Site Status

Pfizer Investigational Site

Surry Hills, New South Wales, Australia

Site Status

Pfizer Investigational Site

Herston, Queensland, Australia

Site Status

Pfizer Investigational Site

Carlton, Victoria, Australia

Site Status

Pfizer Investigational Site

Melbourne, Victoria, Australia

Site Status

Pfizer Investigational Site

Brussels, , Belgium

Site Status

Pfizer Investigational Site

Brussels, , Belgium

Site Status

Pfizer Investigational Site

Brussels, , Belgium

Site Status

Pfizer Investigational Site

Liège, , Belgium

Site Status

Pfizer Investigational Site

Winnipeg, Manitoba, Canada

Site Status

Pfizer Investigational Site

Toronto, Ontario, Canada

Site Status

Pfizer Investigational Site

Toronto, Ontario, Canada

Site Status

Pfizer Investigational Site

Montreal, Quebec, Canada

Site Status

Pfizer Investigational Site

Montreal, Quebec, Canada

Site Status

Pfizer Investigational Site

Montreal, Quebec, Canada

Site Status

Pfizer Investigational Site

Montreal, Quebec, Canada

Site Status

Pfizer Investigational Site

Berlin, , Germany

Site Status

Pfizer Investigational Site

Cologne, , Germany

Site Status

Pfizer Investigational Site

Hamburg, , Germany

Site Status

Pfizer Investigational Site

Hamburg, , Germany

Site Status

Pfizer Investigational Site

Hamburg, , Germany

Site Status

Pfizer Investigational Site

Utrecht, , Netherlands

Site Status

Pfizer Investigational Site

Elche, Alicante, Spain

Site Status

Pfizer Investigational Site

Badalona, Barcelona, Spain

Site Status

Pfizer Investigational Site

Barcelona, Barcelona, Spain

Site Status

Pfizer Investigational Site

Córdoba, Cordoba, Spain

Site Status

Pfizer Investigational Site

Madrid, Madrid, Spain

Site Status

Pfizer Investigational Site

Madrid, Madrid, Spain

Site Status

Pfizer Investigational Site

Zurich, , Switzerland

Site Status

Pfizer Investigational Site

Brighton, , United Kingdom

Site Status

Pfizer Investigational Site

Edinburgh, , United Kingdom

Site Status

Pfizer Investigational Site

London, , United Kingdom

Site Status

Pfizer Investigational Site

London, , United Kingdom

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States Australia Belgium Canada Germany Netherlands Spain Switzerland United Kingdom

References

Explore related publications, articles, or registry entries linked to this study.

Saag M, Goodrich J, Fatkenheuer G, Clotet B, Clumeck N, Sullivan J, Westby M, van der Ryst E, Mayer H; A4001029 Study Group. A double-blind, placebo-controlled trial of maraviroc in treatment-experienced patients infected with non-R5 HIV-1. J Infect Dis. 2009 Jun 1;199(11):1638-47. doi: 10.1086/598965.

Reference Type DERIVED
PMID: 19432546 (View on PubMed)

Related Links

Access external resources that provide additional context or updates about the study.

https://trialinfoemail.pfizer.com/pages/landing.aspx?StudyID=A4001029&StudyName=Trial%20of%20Maraviroc%20%28UK-427%2C857%29%20in%20Combination%20with%20Optimized%20Background%20Therapy%20Versus%20Optimized%20Background%20Therapy%20Alone%20for%20the%20Tre

To obtain contact information for a study center near you, click here.

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

A4001029

Identifier Type: -

Identifier Source: org_study_id