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

NCT00098748 | Completed Phase 2 Results DMC

• 1 other identifier: A4001029
• Study Type: interventional
• Target: 190
• Locations: 9 countries
• Sites: 77

Brief 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

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in Human Immunodeficiency Virus (HIV-1) Viral Load (Ribonucleic Acid [RNA])

  Change from baseline in log 10-transformed plasma viral load (HIV-1 RNA) levels (log 10 copies per milliliter \[log10 copies/mL\]). Baseline value calculated as average of pre-dose measurements collected at screening, randomization, and baseline visits.

  Baseline to Week 24 and Week 48

Secondary Outcomes (15)

• Number of Subjects With HIV-1 RNA Levels < 400 Copies/mL

  Week 24, Week 48

• Number of Subjects With HIV-1 RNA Levels < 400 Copies/mL or at Least 0.5 Log 10-transformed Decrease From Baseline in HIV-1 RNA Levels

  Baseline, Week 24, Week 48

• Number of Subjects With HIV-1 RNA Levels < 400 Copies/mL or at Least 1.0 Log 10-transformed Decrease From Baseline in HIV-1 RNA Levels

  Baseline, Week 24, Week 48

• Number of Subjects With HIV-1 RNA Levels < 50 Copies/mL

  Baseline, Week 24, Week 48

• Change From Baseline in CD4 Cell Count

  Baseline to Week 24 and Week 48

Study Arms (3)

1

EXPERIMENTAL

Drug: Optimized Background Therapy (OBT); Drug: maraviroc (UK-427,857)

2

EXPERIMENTAL

Drug: Optimized Background Therapy (OBT); Drug: maraviroc (UK-427,857)

3

EXPERIMENTAL

Drug: Optimized Background Therapy (OBT)

Interventions

Optimized Background Therapy (OBT) DRUG

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

1

maraviroc (UK-427,857) DRUG

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

Also known as: Selzentry, Celsentri

1

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• ViiV Healthcare: lead
• Pfizer: collaborator

Study Sites (77)

Pfizer Investigational Site

Birmingham, Alabama, 35294, United States

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Pfizer Investigational Site

Phoenix, Arizona, 85006, United States

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Beverly Hills, California, 90211, United States

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Fountain Valley, California, 92708, United States

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Hayward, California, 94545, United States

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Los Angeles, California, 90027, United States

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Los Angeles, California, 90028, United States

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Los Angeles, California, 90069, United States

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Newport Beach, California, 92663, United States

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Oakland, California, 94602, United States

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San Francisco, California, 94102, United States

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San Francisco, California, 94115-1931, United States

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San Francisco, California, 94118, United States

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Union City, California, 94587, United States

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Washington D.C., District of Columbia, 20009, United States

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Washington D.C., District of Columbia, 20036, United States

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Miami, Florida, 33133, United States

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North Miami Beach, Florida, 33169, United States

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Orlando, Florida, 32803, United States

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Orlando, Florida, 32806, United States

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Sarasota, Florida, 34243, United States

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Tampa, Florida, 33614, United States

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Vero Beach, Florida, 32960, United States

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Atlanta, Georgia, 30308, United States

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Springfield, Massachusetts, 01107, United States

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Santa Fe, New Mexico, 87505, United States

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Albany, New York, 12208, United States

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Brooklyn, New York, 11203, United States

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Manhasset, New York, 11030, United States

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New York, New York, 10018, United States

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Stony Brook, New York, 11794-7310, United States

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Stony Brook, New York, 11794, United States

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The Bronx, New York, 10461, United States

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The Bronx, New York, 10467, United States

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Huntersville, North Carolina, 28078, United States

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Philadelphia, Pennsylvania, 19106, United States

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Philadelphia, Pennsylvania, 19130, United States

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Columbia, South Carolina, 29206, United States

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Dallas, Texas, 75204, United States

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Dallas, Texas, 75246, United States

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Annandale, Virginia, 22003, United States

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Puyallup, Washington, 98372, United States

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Tacoma, Washington, 98405, United States

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Vancouver, Washington, 98664, United States

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Darlinghurst, New South Wales, 2010, Australia

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Surry Hills, New South Wales, 2010, Australia

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Herston, Queensland, 4029, Australia

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Carlton, Victoria, 3053, Australia

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Melbourne, Victoria, 3004, Australia

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Brussels, 1000, Belgium

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Brussels, 1070, Belgium

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Brussels, 1200, Belgium

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Liège, 4000, Belgium

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Winnipeg, Manitoba, R3A 1R9, Canada

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Toronto, Ontario, M5B 1W8, Canada

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Toronto, Ontario, M5G 2N2, Canada

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Montreal, Quebec, H2L 4P9, Canada

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Montreal, Quebec, H2L 5B1, Canada

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Montreal, Quebec, H2X 2P4, Canada

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Montreal, Quebec, H3G 1A4, Canada

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Berlin, 12157, Germany

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Cologne, 50924, Germany

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Hamburg, 20099, Germany

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Hamburg, 20146, Germany

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Hamburg, 20246, Germany

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Utrecht, 3584 CX, Netherlands

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Elche, Alicante, 03202, Spain

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Badalona, Barcelona, 08916, Spain

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Barcelona, Barcelona, 08025, Spain

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Córdoba, Cordoba, 14004, Spain

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Madrid, Madrid, 28006, Spain

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Pfizer Investigational Site

Madrid, Madrid, 28046, Spain

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Pfizer Investigational Site

Zurich, 8091, Switzerland

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Brighton, BN2 1ES, United Kingdom

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Pfizer Investigational Site

Edinburgh, EH4 2XU, United Kingdom

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Pfizer Investigational Site

London, SE5 9RS, United Kingdom

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Pfizer Investigational Site

London, SW10 9TH, United Kingdom

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Related Publications (1)

• 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.

  PMID: 19432546 DERIVED

Related Links

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

MeSH Terms

Conditions

HIV Infections

Interventions

Maraviroc

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)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.govCallCenter@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: December 7, 2004
• First Posted: December 8, 2004
• Study Start: November 1, 2004
• Primary Completion: December 1, 2005
• Study Completion: April 1, 2009
• Last Updated: December 7, 2010
• Results First Posted: October 21, 2010

Record last verified: 2010-11

Locations

GB (4); NL (1); CH (1); AU (5); CA (7); DE (5); BE (4); US (44); ES (6)