Trial of Maraviroc (UK-427,857) in Combination With Zidovudine/Lamivudine Versus Efavirenz in Combination With Zidovudine/Lamivudine
MERIT
A Multicenter, Randomized, Double-Blind, Comparative Trial Of A Novel CCR5 Antagonist, UK-427,857, In Combination With Zidovudine/Lamivudine Versus Efavirenz In Combination With Zidovudine/Lamivudine For The Treatment Of Antiretroviral-Naive HIV-1 Infected Subjects
1 other identifier
interventional
916
14 countries
144
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 goal of this study is to compare the safety and efficacy of maraviroc (UK-427,857) versus efavirenz, when each are combined with two other antiretroviral agents, in patients who are previously naive to antiretroviral therapy. This study will involve approximately 200 centers from around the world to achieve a total randomized subject population of 1071 subjects. Patients will be randomly assigned to one of three groups: maraviroc (UK-427,857) 300 mg once daily added to zidovudine/lamivudine (300 mg/150 mg twice daily), Maraviroc (UK-427,857) 300 mg twice daily added to zidovudine/lamivudine (300 mg/150 mg twice daily) or efavirenz (600 mg once daily) added to zidovudine/lamivudine (300 mg/150 mg twice daily). The study will enroll over approximately an 18 month period (5 months Phase 2b run-in, 13 months Phase 3) with 96 weeks of treatment. This may be extended for an additional 3 years depending on the results at 96 weeks. Physical examinations will be performed at study entry, weeks 4, 8, 12, 16, 20, 24, 32, 40, 48, 60, 72, 84 and 96. Blood samples will also be taken at study entry, weeks 2, 4, 8, 12, 16, 20, 24, 32, 40, 48, 60, 72, 84 and 96. Additionally, blood samples will be drawn twice, at least 30 minutes apart, at weeks 2 and 48 for maraviroc (UK-427,857) pharmacokinetic analysis. As part of this clinical study a blood sample will be taken for non-anonymized pharmacogenetic analysis. Patients will undergo a 12-lead electrocardiogram at study entry, weeks 24, 48 and 96. A computerized tomography (CT) scan will also be performed, at selected centers, at study entry and week 96. Patients will be asked to complete a symptom distress questionnaire at study entry, weeks 12, 24, 48 and 96.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Nov 2004
Longer than P75 for phase_3
144 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
November 1, 2004
CompletedFirst Submitted
Initial submission to the registry
December 6, 2004
CompletedFirst Posted
Study publicly available on registry
December 7, 2004
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 1, 2007
CompletedResults Posted
Study results publicly available
October 5, 2012
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2012
CompletedOctober 9, 2013
August 1, 2013
2.4 years
December 6, 2004
July 9, 2012
August 7, 2013
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Percentage of Participants With Viral Load of Less Than 400 Copies/Milliliter [Copies/mL] and Less Than 50 Copies/mL of Human Immunodeficiency Virus (HIV)-1 Ribonucleic Acid (RNA) at Week 48 for Full Analysis Set (FAS) Population
Week 48
Percentage of Participants With Viral Load of Less Than 400 Copies/mL and Less Than 50 Copies/mL of HIV-1 RNA at Week 48 for Per Protocol (PP) Population
Percentage of participants with viral load of less than 400 copies/mL and less than 50 copies/mL of HIV-1 RNA were not analyzed for participants originally randomized to maraviroc once daily arm since after termination, focus was shifted from efficacy and safety to only safety as reflected in the abbreviated set of efficacy measures noted in the amended planned analysis.
Week 48
Secondary Outcomes (13)
Percentage of Participants With HIV-1 RNA Levels of Less Than 400 Copies/mL and Less Than 50 Copies/mL at Week 48 Analyzed Using Logistic Regression
Week 48
Percentage of Participants With HIV-1 RNA Levels of Less Than 400 Copies/mL and Less Than 50 Copies/mL at Week 96 Analyzed Using Logistic Regression
Week 96
Change From Baseline in Log 10-transformed Plasma Viral Load (HIV-1 RNA) Levels at Week 48 and 96
Baseline, Week 48, Week 96
Time-Averaged Difference (TAD) in log10-transformed HIV-1 RNA Levels
Baseline up to Week 48 and Week 96
Change From Baseline in Lymphocyte Cluster of Differentiation 4 (CD4) Count at Week 48 and 96
Baseline, Week 48, Week 96
- +8 more secondary outcomes
Other Outcomes (1)
Percentage of Participants With Viral Load of Less Than 400 Copies/mL and Less Than 50 Copies/mL of HIV-1 RNA at Week 96
Week 96
Study Arms (3)
1
EXPERIMENTAL3
ACTIVE COMPARATOR2
EXPERIMENTALFollowing a review of the interim analysis data, the DSMB recommended to terminate the UK-427,857 300 mg QD arm based on pre-specified protocol non-inferiority criteria not being met for the QD arm versus efavirenz
Interventions
maraviroc (UK-427,857) 300 mg once daily added to zidovudine/lamivudine (300 mg/150 mg twice daily)
efavirenz (600 mg once daily) added to zidovudine/lamivudine (300 mg/150 mg twice daily)
maraviroc (UK-427,857) 300 mg twice daily added to zidovudine/lamivudine (300 mg/150 mg twice daily)
Eligibility Criteria
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 2, 000 copies/mL
- 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:
- 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
- Prior treatment with efavirenz, zidovudine or lamivudine or with any other antiretroviral therapy for more than 14 days at any time
- 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
- Suspected primary (acute) HIV-1 infection
- 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
- Genotypic or phenotypic resistance to efavirenz, zidovudine or lamivudine
- 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 (144)
Pfizer Investigational Site
Birmingham, Alabama, 35233, United States
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Birmingham, Alabama, 35294-2050, United States
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Beverly Hills, California, 90211, United States
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Los Angeles, California, 90022, United States
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Los Angeles, California, 90048, 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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Sacramento, California, 95825, United States
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San Francisco, California, 94115-3029, United States
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San Francisco, California, 94115, United States
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Aurora, Colorado, 80045, United States
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Jacksonville, Florida, 32209, United States
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Miami, Florida, 33133, United States
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Miami, Florida, 33136, United States
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Miami Beach, Florida, 33139, United States
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Orlando, Florida, 32803, United States
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Sarasota, Florida, 34243, United States
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Tampa, Florida, 33614, United States
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Atlanta, Georgia, 30308, United States
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Chicago, Illinois, 60611, United States
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Indianapolis, Indiana, 46202, United States
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Baltimore, Maryland, 21201, United States
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Boston, Massachusetts, 02111, United States
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Boston, Massachusetts, 02118-2393, United States
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Boston, Massachusetts, 02215, United States
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Springfield, Massachusetts, 01107, United States
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Omaha, Nebraska, 68106, 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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Flushing, New York, 11355, United States
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Manhasset, New York, 11030, United States
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New York, New York, 10016, United States
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Huntersville, North Carolina, 28078, United States
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Cincinnati, Ohio, 45267-0405, United States
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Oklahoma City, Oklahoma, 73104-5068, United States
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Oklahoma City, Oklahoma, 73104, United States
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Philadelphia, Pennsylvania, 19104, United States
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Columbia, South Carolina, 29206, United States
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Dallas, Texas, 75208, United States
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Dallas, Texas, 75246, United States
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Houston, Texas, 77006, United States
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Houston, Texas, 77098, 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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El Palomar, Buenos Aires, 1684, Argentina
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Neuquén, Neuquén Province, Q8300PMB, Argentina
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Buenos Aires, Argentina
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Ciudad de Buenos Aires, C1202ABB, Argentina
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Ciudad de Buenos Aires, C1406FWY, Argentina
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Ciudad de Buenos, C1282AEN, Argentina
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Provincia de Buenos Aires, Argentina
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Provincia de Santa Fe, Argentina
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Burwood, New South Wales, 2134, Australia
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Darlinghurst, New South Wales, 2010, Australia
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Surrey Hills, 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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Brussels, 1000, Belgium
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Brussels, 1200, Belgium
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Ghent, 9000, Belgium
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Leuven, B-3000 Leuven, Belgium
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Rio de Janeiro, Rio de Janeiro, 20210-030, Brazil
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Calgary, Alberta, T2R0X7, Canada
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Edmonton, Alberta, T6G 2B7, Canada
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Edmonton, Alberta, T6G 2C8, Canada
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Vancouver, British Columbia, V6B 1R3, Canada
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Vancouver, British Columbia, V6Z 1Y6, Canada
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Vancouver, British Columbia, V6Z 2C7, Canada
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Vancouver, British Columbia, V6Z 2T1, Canada
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Winnipeg, Manitoba, R3A 1R9, Canada
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Halifax, Nova Scotia, B3H 1V7, Canada
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Hamilton, Ontario, L8N 3Z5, Canada
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Ottawa, Ontario, K1H 8L6, Canada
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Toronto, Ontario, M4N 3M5, 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 4M1, 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, H2W 1T8, Canada
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Montreal, Quebec, H2X 2P4, Canada
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Montreal, Quebec, H3G 1A4, Canada
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Sainte-Foy, Quebec, G1V 4G2, Canada
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Antella (FI), 50011, Italy
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Brescia, 25123, Italy
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Milan, 20127, Italy
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Modena, 41100, Italy
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Roma, 00161, Italy
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Roma, 00185, Italy
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Torino, 10149, Italy
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Del. Tlalpan C.P., Mexico City, 14050, Mexico
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Del. Tlalpan, C.P., Mexico City, 14000, Mexico
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Del. Tlalpan, C.P., Mexico City, 14080, Mexico
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Delegacion Tlalpan C. P, Mexico City, 14080, Mexico
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Amsterdam, 1091 AC, 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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Chorzów, 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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Ponce, 00731, Puerto Rico
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Rio Piedras, 00935, Puerto Rico
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San Juan, 00909, Puerto Rico
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San Juan, 00935, Puerto Rico
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Port Elizabeth, Eastern Cape, 6065, South Africa
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Bloemfontein, Free State, 9300, South Africa
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Johannesburg, Gauteng, 2092, South Africa
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Pretoria, Gauteng, 0083, South Africa
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Dundee, KwaZulu-Natal, 3000, South Africa
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Bloomfontein, South Africa
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Cape Town, 7405, South Africa
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Cape Town, 7550, South Africa
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Cape Town, 7705, South Africa
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Cape Town, 7780, South Africa
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Johannesburg, 2047, South Africa
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Pretoria, 0132, South Africa
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Pretoria North, 0182, South Africa
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Soweto, Johannesburg, 2013, South Africa
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Basel, 4031, Switzerland
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Bern, 3010, Switzerland
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Geneva, 1211, Switzerland
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Lugano, 6900, Switzerland
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Sankt Gallen, 9007, Switzerland
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Zurich, 8038, Switzerland
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Zurich, 8091, Switzerland
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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 9NH, United Kingdom
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London, W2 1NY, United Kingdom
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Manchester, M8 5RB, United Kingdom
Related Publications (4)
Vourvahis M, McFadyen L, Nepal S, Valluri SR, Fang A, Fate GD, Wood LS, Marshall JC, Chan PLS, Nedderman A, Haynes J, Savage ME, Clark A, Smith KY, Heera J. No Clinical Impact of CYP3A5 Gene Polymorphisms on the Pharmacokinetics and/or Efficacy of Maraviroc in Healthy Volunteers and HIV-1-Infected Subjects. J Clin Pharmacol. 2019 Jan;59(1):139-152. doi: 10.1002/jcph.1306. Epub 2018 Sep 7.
PMID: 30192390DERIVEDMacInnes A, Lazzarin A, Di Perri G, Sierra-Madero JG, Aberg J, Heera J, Rajicic N, Goodrich J, Mayer H, Valdez H. Maraviroc can improve lipid profiles in dyslipidemic patients with HIV: results from the MERIT trial. HIV Clin Trials. 2011 Jan-Feb;12(1):24-36. doi: 10.1310/hct1201-24.
PMID: 21388938DERIVEDFunderburg N, Kalinowska M, Eason J, Goodrich J, Heera J, Mayer H, Rajicic N, Valdez H, Lederman MM. Effects of maraviroc and efavirenz on markers of immune activation and inflammation and associations with CD4+ cell rises in HIV-infected patients. PLoS One. 2010 Oct 6;5(10):e13188. doi: 10.1371/journal.pone.0013188.
PMID: 20949133DERIVEDCooper DA, Heera J, Goodrich J, Tawadrous M, Saag M, Dejesus E, Clumeck N, Walmsley S, Ting N, Coakley E, Reeves JD, Reyes-Teran G, Westby M, Van Der Ryst E, Ive P, Mohapi L, Mingrone H, Horban A, Hackman F, Sullivan J, Mayer H. Maraviroc versus efavirenz, both in combination with zidovudine-lamivudine, for the treatment of antiretroviral-naive subjects with CCR5-tropic HIV-1 infection. J Infect Dis. 2010 Mar 15;201(6):803-13. doi: 10.1086/650697.
PMID: 20151839DERIVED
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
Following DSMB decision to discontinue maraviroc 300 mg once daily, inferential statistical analyses was performed between maraviroc 300 mg twice daily and efavirenz 600 mg once daily only. Data at Week 24 was not analyzed as planned in protocol.
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 3
- 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 6, 2004
First Posted
December 7, 2004
Study Start
November 1, 2004
Primary Completion
April 1, 2007
Study Completion
December 1, 2012
Last Updated
October 9, 2013
Results First Posted
October 5, 2012
Record last verified: 2013-08