Trial of Maraviroc (UK-427,857) in Combination With Optimized Background Therapy Versus Optimized Background Therapy Alone for the Treatment of HIV-1 Infected Subjects
MOTIVATE 2
A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial of a Novel CCR5 Antagonist, UK-427,857, in Combination With Optimized Background Therapy Versus Optimized Background Therapy Alone for the Treatment of Antiretroviral-Experienced HIV-1 Infected Subjects
1 other identifier
interventional
474
13 countries
172
Brief Summary
Maraviroc (UK-427,857), a selective and reversible CCR5 coreceptor 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, maraviroc (UK-427,857) given as monotherapy for 10 days reduced HIV-1 viral load by up to 1.6 log, consistent with currently available agents. Safety and toleration have been studied in over 400 subjects for up to 28 days at 300 mg twice daily. No significant effects were seen on the QTc interval. The purpose of this study is to evaluate the antiretroviral activity of maraviroc (UK-427,857) in HIV infected, treatment experienced patients who are failing their current antiretroviral regimen and infected with R5-tropic virus exclusively. This study will involve more than 100 centers in Europe and Australia to achieve a total randomized subject population of 500 subjects. Patients will be randomly (2:2:1) 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. The study will enroll over approximately a 9 month period with 48 weeks of treatment. This may be extended for an additional year depending on the results at 48 weeks. 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2 hiv-infections
Started Dec 2004
Longer than P75 for phase_2 hiv-infections
172 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
December 1, 2004
CompletedFirst Submitted
Initial submission to the registry
December 7, 2004
CompletedFirst Posted
Study publicly available on registry
December 8, 2004
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 1, 2007
CompletedStudy Completion
Last participant's last visit for all outcomes
April 1, 2011
CompletedResults Posted
Study results publicly available
May 16, 2012
CompletedMay 16, 2012
April 1, 2012
2.3 years
December 7, 2004
April 16, 2012
April 16, 2012
Conditions
Outcome Measures
Primary Outcomes (3)
Log 10-transformed Human Immunodeficiency Virus Ribonucleic Acid (HIV-1 RNA) Levels at Baseline
Baseline value calculated as average of pre-dose measurements collected at screening, randomization, and immediately pre-dose.
Baseline
Change From Baseline in Log 10-transformed HIV-1 RNA Levels at Week 24
Change from baseline in log 10-transformed plasma viral load (HIV-1 RNA) levels (log10 copies/mL). Baseline value calculated as average of pre-dose measurements collected at screening, randomization, and immediately pre-dose.
Baseline and Week 24
Change From Baseline in Log 10-transformed HIV-1 RNA Levels at Week 48
Change from baseline in log 10-transformed plasma viral load (HIV-1 RNA) levels (log10 copies/mL). Baseline value calculated as average of pre-dose measurements collected at screening, randomization, and immediately pre-dose.
Baseline and Week 48
Secondary Outcomes (15)
Percentage of Participants With HIV-1 RNA Levels Less Than 400 Copies/mL
Week 24 and 48
Percentage of Participants With HIV-1 RNA Levels Less Than 400 Copies/ml or With at Least 0.5 log10 Decrease From Baseline
Week 24 and 48
Percentage of Participants With HIV-1 RNA Levels Less Than 400 Copies/ml or With at Least 1.0 log10 Decrease From Baseline
Week 24 and 48
Percentage of Participants With HIV-1 RNA Levels Less Than 50 Copies/mL
Week 24 and 48
Cluster of Differentiation 4 (CD4) and Cluster of Differentiation 8 (CD8) Cell Count at Baseline
Baseline
- +10 more secondary outcomes
Study Arms (3)
1
EXPERIMENTAL2
PLACEBO COMPARATOR3
EXPERIMENTALInterventions
maraviroc (UK-427,857) 150 mg taken once daily, OBT + maraviroc (UK-427,857) 150 mg taken twice daily, or OBT alone.
\[OBT (3-6 drugs based on treatment history and resistance testing)\]
Eligibility Criteria
You may qualify if:
- Men or women at least 16 yers 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 three of the four antiretroviral drug classes, OR, Antiretroviral-class experience greater than or equal to 6 months (sequential or cumulative) with at least three of the following: One nucleoside or nucleotide reverse transcriptase inhibitor, one non-nucleoside reverse transcriptase inhibitor, two protease inhibitors (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
- Initiating therapy with a potentially myelosuppressive, neurotoxic, hepatotoxic and/or cytotoxic agent within 60 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
- Certain medications
- Malignancy requiring parenteral chemotherapy that must be continued for the duration of the trial
- X4- or dual/mixed-tropic virus or repeated assay failure
- +1 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- ViiV Healthcarelead
- Pfizercollaborator
Study Sites (172)
Pfizer Investigational Site
Hobson City, Alabama, 36201, United States
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Garden Grove, California, 92845, United States
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Los Angeles, California, 90036, United States
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Oakland, California, 94609-3480, United States
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Palm Springs, California, 92262, United States
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Tarzana, California, 91356, United States
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Norwalk, Connecticut, 06851, United States
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Southport, Connecticut, 06490, United States
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Stratford, Connecticut, 06614, United States
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Washington D.C., District of Columbia, 20007, United States
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Washington D.C., District of Columbia, 20010-2976, United States
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Clearwater, Florida, 33765, United States
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Hollywood, Florida, 33021-6327, United States
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Miami, Florida, 33137, United States
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Miami, Florida, 33145, United States
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Miami, Florida, 33155, United States
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Miami Beach, Florida, 33139, United States
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Pensacola, Florida, 32504, United States
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Safety Harbor, Florida, 34695, United States
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St. Petersburg, Florida, 33713, United States
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Tampa, Florida, 33611, United States
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Tampa, Florida, 33614, United States
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Atlanta, Georgia, 30309, United States
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Atlanta, Georgia, 30318-2513, United States
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Atlanta, Georgia, 30339-3915, United States
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Jonesboro, Georgia, 30236, United States
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Chicago, Illinois, 60613, United States
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Chicago, Illinois, 60657, United States
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Springfield, Illinois, 62702, United States
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Metairie, Louisiana, 70006, United States
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Baltimore, Maryland, 21201, United States
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Silver Spring, Maryland, 20910, United States
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Ann Arbor, Michigan, 48109-0008, United States
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Ann Arbor, Michigan, 48109-0352, United States
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Detroit, Michigan, 48201, United States
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Detroit, Michigan, 48202, United States
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Kansas City, Missouri, 64106, United States
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St Louis, Missouri, 63139-2909, United States
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Buffalo, New York, 14215, United States
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East Meadow, New York, 11554, United States
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Elmira, New York, 14905, United States
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New York, New York, 10011, United States
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New York, New York, 10016, United States
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New York, New York, 10025, United States
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New York, New York, 10029, United States
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Greenville, North Carolina, 27834, United States
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Akron, Ohio, 44304, United States
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Cleveland, Ohio, 44109, United States
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Tulsa, Oklahoma, 74135, United States
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Portland, Oregon, 97210, United States
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Portland, Oregon, 97227, United States
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West Reading, Pennsylvania, 19611, United States
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Charleston, South Carolina, 29403, United States
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Charleston, South Carolina, 29425, United States
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Dallas, Texas, 75219, United States
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Fort Worth, Texas, 76104, United States
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Fort Worth, Texas, 76107, United States
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Pasadena, Texas, 77505-4245, United States
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Danville, Virginia, 24541, United States
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Hampton, Virginia, 23666, United States
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Lynchburg, Virginia, 24501, United States
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Richmond, Virginia, 23298, United States
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Burwood, New South Wales, 2134, Australia
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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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Sydney, New South Wales, 2010, Australia
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Wentworthville, New South Wales, 2145, Australia
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Herston, Queensland, 4029, Australia
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Miami, Queensland, 4220, Australia
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Fitzroy North, Victoria, 3068, Australia
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Melbourne, Victoria, 3004, Australia
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South Yarra, Victoria, 3141, Australia
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Darlinghurst, 2010, 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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Ghent, 9000, Belgium
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Liège, 4000, Belgium
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Montreal, Quebec, H2L 2W5, Canada
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Montreal, Quebec, H2L 4M1, Canada
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Toulon, Bp1412, 83056, France
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Lyon, Cedex 02, 69288, France
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Orléans, Cedex 02, 45067, France
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Marseille, Cedex 09, 13274, France
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Paris, Cedex 10, 75475, France
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Paris, Cedex 12, 75571, France
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Bobigny, Cedex, 93009, France
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Caen, Cedex, 14033, France
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Le Kremlin-BicĂªtre, 94270, France
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Montpellier, 34295, France
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Nantes, 44093, France
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Nice Cedex 3, 06, 06202, France
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Paris, 75015, France
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Paris, 75018, France
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Paris, 75020, France
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Aachen, 52062, Germany
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Berlin, 12157, Germany
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Bochum, 44791, Germany
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Bonn, 53105, Germany
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Cologne, 50924, Germany
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DĂ¼sseldorf, 40225, Germany
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Erlangen, 91054, Germany
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Essen, 45122, Germany
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Frankfurt, 60590, Germany
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Freiburg im Breisgau, 79098, Germany
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FĂ¼rth, 90762, Germany
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Hamburg, 20099, Germany
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Hamburg, 20246, Germany
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Hanover, 30625, Germany
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Mannheim, 68161, Germany
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MĂ¼nchen, 80336, Germany
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OsnabrĂ¼ck, 49090, Germany
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Stuttgart, 70197, Germany
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Ulm, 89081, Germany
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Antella (FI), 50011, Italy
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Brescia, 25123, Italy
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Florence, 50193, Italy
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Genova, 16132, Italy
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Milan, 20100, Italy
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Modena, 41100, Italy
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Monserrato, CA, 09042, Italy
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Roma, 00161, Italy
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Roma, 00184, Italy
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Roma, 00185, Italy
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Torino, 10149, Italy
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Venezia, 30170, Italy
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Amsterdam, 1081 HV, Netherlands
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Amsterdam, 1105 AZ, Netherlands
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Arnhem, 6815 AD, Netherlands
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Rotterdam, 3015 GD, Netherlands
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Utrecht, 3584 CX, Netherlands
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Bialystok, 15-540, Poland
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Bydgoszcz, 85-030, Poland
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ChorzĂ³w, 41-500, Poland
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Gdansk, 80-214, Poland
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Krakow, 31-531, Poland
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Szczecin, 71-455, Poland
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Warsaw, 01-201, Poland
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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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Barcelona, Barcelona, 08036, Spain
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CĂ³rdoba, Cordoba, 14004, Spain
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Madrid, Madrid, 28006, Spain
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Madrid, Madrid, 28029, Spain
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Madrid, Madrid, 28041, Spain
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Madrid, Madrid, 28046, Spain
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Seville, Sevilla, 41013, Spain
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Seville, Sevilla, 41014, Spain
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Donostia / San Sebastian, 20014, Spain
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Madrid, 28034, Spain
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Venhalsan, Stockholm County, 118 83, Sweden
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Gothenburg, 41685, Sweden
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Malmo, 214 01, Sweden
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Basel, 4031, Switzerland
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Geneva, Switzerland
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Lausanne, 1011, Switzerland
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Lugano, 6900, Switzerland
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Sankt Gallen, 9007, Switzerland
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Zurich, 8091, Switzerland
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Leicester, Leics, LE1 5WW, United Kingdom
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Edinburgh, Loth, ED4 2XU, United Kingdom
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Birmingham, B9 5SS, United Kingdom
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Brighton, BN2 1ES, United Kingdom
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Edinburgh, EH4 2XU, United Kingdom
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London, NW3 2QG, United Kingdom
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London, SE5 9RS, United Kingdom
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London, SW10 9TH, United Kingdom
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London, SW17 0QT, United Kingdom
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London, W2 1NY, United Kingdom
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Manchester, M8 5RB, United Kingdom
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Newcastle Upon Tyre, NE4 6BE, United Kingdom
Related Publications (5)
Lewis ME, Simpson P, Mori J, Jubb B, Sullivan J, McFadyen L, van der Ryst E, Craig C, Robertson DL, Westby M. V3-Loop genotypes do not predict maraviroc susceptibility of CCR5-tropic virus or clinical response through week 48 in HIV-1-infected, treatment-experienced persons receiving optimized background regimens. Antivir Chem Chemother. 2021 Jan-Dec;29:20402066211030380. doi: 10.1177/20402066211030380.
PMID: 34343443DERIVEDGulick RM, Fatkenheuer G, Burnside R, Hardy WD, Nelson MR, Goodrich J, Mukwaya G, Portsmouth S, Heera JR. Five-year safety evaluation of maraviroc in HIV-1-infected treatment-experienced patients. J Acquir Immune Defic Syndr. 2014 Jan 1;65(1):78-81. doi: 10.1097/QAI.0b013e3182a7a97a.
PMID: 24419064DERIVEDHardy WD, Gulick RM, Mayer H, Fatkenheuer G, Nelson M, Heera J, Rajicic N, Goodrich J. Two-year safety and virologic efficacy of maraviroc in treatment-experienced patients with CCR5-tropic HIV-1 infection: 96-week combined analysis of MOTIVATE 1 and 2. J Acquir Immune Defic Syndr. 2010 Dec 15;55(5):558-64. doi: 10.1097/QAI.0b013e3181ee3d82.
PMID: 20703158DERIVEDFatkenheuer G, Nelson M, Lazzarin A, Konourina I, Hoepelman AI, Lampiris H, Hirschel B, Tebas P, Raffi F, Trottier B, Bellos N, Saag M, Cooper DA, Westby M, Tawadrous M, Sullivan JF, Ridgway C, Dunne MW, Felstead S, Mayer H, van der Ryst E; MOTIVATE 1 and MOTIVATE 2 Study Teams. Subgroup analyses of maraviroc in previously treated R5 HIV-1 infection. N Engl J Med. 2008 Oct 2;359(14):1442-55. doi: 10.1056/NEJMoa0803154.
PMID: 18832245DERIVEDGulick RM, Lalezari J, Goodrich J, Clumeck N, DeJesus E, Horban A, Nadler J, Clotet B, Karlsson A, Wohlfeiler M, Montana JB, McHale M, Sullivan J, Ridgway C, Felstead S, Dunne MW, van der Ryst E, Mayer H; MOTIVATE Study Teams. Maraviroc for previously treated patients with R5 HIV-1 infection. N Engl J Med. 2008 Oct 2;359(14):1429-41. doi: 10.1056/NEJMoa0803152.
PMID: 18832244DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Pfizer ClinicalTrials.gov Call Center
- Organization
- Pfizer, Inc.
Study Officials
- STUDY DIRECTOR
Pfizer CT.gov Call Center
Pfizer
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 7, 2004
First Posted
December 8, 2004
Study Start
December 1, 2004
Primary Completion
April 1, 2007
Study Completion
April 1, 2011
Last Updated
May 16, 2012
Results First Posted
May 16, 2012
Record last verified: 2012-04