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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT00098293




Registration number
NCT00098293
Ethics application status
Date submitted
6/12/2004
Date registered
7/12/2004
Date last updated
9/10/2013

Titles & IDs
Public title
Trial of Maraviroc (UK-427,857) in Combination With Zidovudine/Lamivudine Versus Efavirenz in Combination With Zidovudine/Lamivudine
Scientific title
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
Secondary ID [1] 0 0
A4001026
Universal Trial Number (UTN)
Trial acronym
MERIT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
HIV-1 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Maraviroc + Zidovudine/Lamivudine
Treatment: Drugs - Efavirenz + Zidovudine/Lamivudine
Treatment: Drugs - Maraviroc (UK-427,857) + Zidovudine/Lamivudine

Experimental: 1 -

Active Comparator: 3 -

Experimental: 2 - Following 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


Treatment: Drugs: Maraviroc + Zidovudine/Lamivudine
maraviroc (UK-427,857) 300 mg once daily added to zidovudine/lamivudine (300 mg/150 mg twice daily)

Treatment: Drugs: Efavirenz + Zidovudine/Lamivudine
efavirenz (600 mg once daily) added to zidovudine/lamivudine (300 mg/150 mg twice daily)

Treatment: Drugs: Maraviroc (UK-427,857) + Zidovudine/Lamivudine
maraviroc (UK-427,857) 300 mg twice daily added to zidovudine/lamivudine (300 mg/150 mg twice daily)
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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
Timepoint [1] 0 0
Week 48
Primary outcome [2] 0 0
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
Timepoint [2] 0 0
Week 48
Secondary outcome [1] 0 0
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
Timepoint [1] 0 0
Week 48
Secondary outcome [2] 0 0
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
Timepoint [2] 0 0
Week 96
Secondary outcome [3] 0 0
Change From Baseline in Log 10-transformed Plasma Viral Load (HIV-1 RNA) Levels at Week 48 and 96
Timepoint [3] 0 0
Baseline, Week 48, Week 96
Secondary outcome [4] 0 0
Time-Averaged Difference (TAD) in log10-transformed HIV-1 RNA Levels
Timepoint [4] 0 0
Baseline up to Week 48 and Week 96
Secondary outcome [5] 0 0
Change From Baseline in Lymphocyte Cluster of Differentiation 4 (CD4) Count at Week 48 and 96
Timepoint [5] 0 0
Baseline, Week 48, Week 96
Secondary outcome [6] 0 0
Change From Baseline in Lymphocyte Cluster of Differentiation 8 (CD8) Count at Week 48 and 96
Timepoint [6] 0 0
Baseline, Week 48, Week 96
Secondary outcome [7] 0 0
Time to Virologic Failure
Timepoint [7] 0 0
Week 48, Week 96
Secondary outcome [8] 0 0
Number of Participants Per Tropism Status at Baseline and at the Time of Treatment Failure Through Week 48
Timepoint [8] 0 0
Baseline, time of failure through Week 48
Secondary outcome [9] 0 0
Number of Participants Per Tropism Status at Baseline and at the Time of Treatment Failure Through Week 96
Timepoint [9] 0 0
Baseline, time of failure through Week 96
Secondary outcome [10] 0 0
Number of Participants With Phenotypic Resistance at Time of Treatment Failure Through Week 48 and 96
Timepoint [10] 0 0
Screening, time of failure through Week 48, Week 96
Secondary outcome [11] 0 0
Number of Participants With NRTI Associated Mutations at Time of Treatment Failure Through Week 48 and 96
Timepoint [11] 0 0
Screening, time of failure through Week 48, Week 96
Secondary outcome [12] 0 0
Number of Participants With Efavirenz Associated Mutations at Time of Treatment Failure Through Week 48 and 96
Timepoint [12] 0 0
Screening, time of failure through Week 48, Week 96
Secondary outcome [13] 0 0
Percentage of Participants With HIV-1 RNA Levels Less Than 50 Copies/mL at Week 48 and Week 96 by Overall Susceptibility Score (OSS) at Screening
Timepoint [13] 0 0
Baseline, Week 48, Week 96

Eligibility
Key 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 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
Minimum age
16 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- 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

- Any other clinical condition that, in the Investigator's judgement, would potentially
compromise study compliance or the ability to evaluate safety/efficacy

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/11/2004
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/12/2012
Sample size
Target
Accrual to date
Final
916
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Pfizer Investigational Site - Burwood
Recruitment hospital [2] 0 0
Pfizer Investigational Site - Darlinghurst
Recruitment hospital [3] 0 0
Pfizer Investigational Site - Surrey Hills
Recruitment hospital [4] 0 0
Pfizer Investigational Site - Wentworthville
Recruitment hospital [5] 0 0
Pfizer Investigational Site - Herston
Recruitment hospital [6] 0 0
Pfizer Investigational Site - Miami
Recruitment hospital [7] 0 0
Pfizer Investigational Site - Melbourne
Recruitment hospital [8] 0 0
Pfizer Investigational Site - North Fitzroy
Recruitment hospital [9] 0 0
Pfizer Investigational Site - South Yarra
Recruitment postcode(s) [1] 0 0
2134 - Burwood
Recruitment postcode(s) [2] 0 0
2010 - Darlinghurst
Recruitment postcode(s) [3] 0 0
2010 - Surrey Hills
Recruitment postcode(s) [4] 0 0
2145 - Wentworthville
Recruitment postcode(s) [5] 0 0
4029 - Herston
Recruitment postcode(s) [6] 0 0
4220 - Miami
Recruitment postcode(s) [7] 0 0
3004 - Melbourne
Recruitment postcode(s) [8] 0 0
3068 - North Fitzroy
Recruitment postcode(s) [9] 0 0
3141 - South Yarra
Recruitment outside Australia
Country [1] 0 0
United States of America
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Alabama
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United States of America
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California
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Colorado
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United States of America
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Florida
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United States of America
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Georgia
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Illinois
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Indiana
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Maryland
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Massachusetts
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Nebraska
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New York
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North Carolina
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Ohio
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Oklahoma
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Pennsylvania
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South Carolina
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Texas
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Virginia
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Washington
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Argentina
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Provincia de Buenos Aires
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Argentina
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Provincia de Neuquen
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Argentina
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Buenos Aires
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Argentina
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Ciudad de Buenos Aires
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Argentina
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Ciudad de Buenos
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Argentina
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Provincia de Santa Fe
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Belgium
State/province [26] 0 0
Brussels
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Belgium
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Gent
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Belgium
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Leuven
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Brazil
State/province [29] 0 0
RJ
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Canada
State/province [30] 0 0
Alberta
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Canada
State/province [31] 0 0
British Columbia
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Canada
State/province [32] 0 0
Manitoba
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Canada
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Nova Scotia
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Canada
State/province [34] 0 0
Ontario
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Canada
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Quebec
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Italy
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Antella (FI)
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Italy
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Brescia
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Italy
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Milano
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Italy
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Modena
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Italy
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Roma
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Italy
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Torino
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Mexico
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Mexico City
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Mexico
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Mexico D.F.
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Netherlands
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Amsterdam
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Rotterdam
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Netherlands
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Utrecht
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Poland
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Bialystok
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Poland
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Bydgoszcz
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Chorzow
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Gdansk
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Krakow
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Szczecin
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Warszawa
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Puerto Rico
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Ponce
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Puerto Rico
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Rio Piedras
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Puerto Rico
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San Juan
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South Africa
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Eastern Cape
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South Africa
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Free State
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South Africa
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Gauteng
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South Africa
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KwaZulu Natal
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South Africa
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Bloomfontein
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South Africa
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Cape Town
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South Africa
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Johannesburg
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South Africa
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Pretoria North
Country [65] 0 0
South Africa
State/province [65] 0 0
Pretoria
Country [66] 0 0
South Africa
State/province [66] 0 0
Soweto, Johannesburg
Country [67] 0 0
Switzerland
State/province [67] 0 0
Basel
Country [68] 0 0
Switzerland
State/province [68] 0 0
Bern
Country [69] 0 0
Switzerland
State/province [69] 0 0
Genève
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Switzerland
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Lugano
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Switzerland
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St. Gallen
Country [72] 0 0
Switzerland
State/province [72] 0 0
Zürich
Country [73] 0 0
United Kingdom
State/province [73] 0 0
Loth
Country [74] 0 0
United Kingdom
State/province [74] 0 0
Birmingham
Country [75] 0 0
United Kingdom
State/province [75] 0 0
Brighton
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United Kingdom
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Edinburgh
Country [77] 0 0
United Kingdom
State/province [77] 0 0
London
Country [78] 0 0
United Kingdom
State/province [78] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
ViiV Healthcare
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Pfizer
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
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 website
https://clinicaltrials.gov/ct2/show/NCT00098293
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Pfizer CT.gov Call Center
Address 0 0
Pfizer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT00098293