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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00098722




Registration number
NCT00098722
Ethics application status
Date submitted
7/12/2004
Date registered
8/12/2004
Date last updated
16/05/2012

Titles & IDs
Public title
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
Scientific title
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
Secondary ID [1] 0 0
A4001028
Universal Trial Number (UTN)
Trial acronym
MOTIVATE 2
Linked study record

Health condition
Health condition(s) or problem(s) studied:
HIV Infections 0 0
Condition category
Condition code
Infection 0 0 0 0
Acquired immune deficiency syndrome (AIDS / HIV)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Maraviroc (UK-427,857)
Treatment: Drugs - optimized background therapy
Treatment: Drugs - Maraviroc (UK-427,857)
Treatment: Drugs - optimized background therapy
Treatment: Drugs - optimized background therapy

Experimental: 1 -

Placebo comparator: 2 -

Experimental: 3 -


Treatment: Drugs: Maraviroc (UK-427,857)
maraviroc (UK-427,857) 150 mg taken once daily, OBT + maraviroc (UK-427,857) 150 mg taken twice daily, or OBT alone.

Treatment: Drugs: optimized background therapy
\[OBT (3-6 drugs based on treatment history and resistance testing)\]

Treatment: Drugs: Maraviroc (UK-427,857)
maraviroc (UK-427,857) 150 mg taken twice daily

Treatment: Drugs: optimized background therapy
\[OBT (3-6 drugs based on treatment history and resistance testing)\]

Treatment: Drugs: optimized background therapy
\[OBT (3-6 drugs based on treatment history and resistance testing)\]
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Log 10-transformed Human Immunodeficiency Virus Ribonucleic Acid (HIV-1 RNA) Levels at Baseline
Timepoint [1] 0 0
Baseline
Primary outcome [2] 0 0
Change From Baseline in Log 10-transformed HIV-1 RNA Levels at Week 24
Timepoint [2] 0 0
Baseline and Week 24
Primary outcome [3] 0 0
Change From Baseline in Log 10-transformed HIV-1 RNA Levels at Week 48
Timepoint [3] 0 0
Baseline and Week 48
Secondary outcome [1] 0 0
Percentage of Participants With HIV-1 RNA Levels Less Than 400 Copies/mL
Timepoint [1] 0 0
Week 24 and 48
Secondary outcome [2] 0 0
Percentage of Participants With HIV-1 RNA Levels Less Than 400 Copies/ml or With at Least 0.5 log10 Decrease From Baseline
Timepoint [2] 0 0
Week 24 and 48
Secondary outcome [3] 0 0
Percentage of Participants With HIV-1 RNA Levels Less Than 400 Copies/ml or With at Least 1.0 log10 Decrease From Baseline
Timepoint [3] 0 0
Week 24 and 48
Secondary outcome [4] 0 0
Percentage of Participants With HIV-1 RNA Levels Less Than 50 Copies/mL
Timepoint [4] 0 0
Week 24 and 48
Secondary outcome [5] 0 0
Cluster of Differentiation 4 (CD4) and Cluster of Differentiation 8 (CD8) Cell Count at Baseline
Timepoint [5] 0 0
Baseline
Secondary outcome [6] 0 0
Change From Baseline in CD4 Cell Count at Week 24 and 48
Timepoint [6] 0 0
Week 24 and 48
Secondary outcome [7] 0 0
Change From Baseline in CD8 Cell Count at Week 24 and 48
Timepoint [7] 0 0
Week 24 and 48
Secondary outcome [8] 0 0
Time to Virological Failure
Timepoint [8] 0 0
Week 48
Secondary outcome [9] 0 0
Time-Averaged Difference (TAD) From Baseline in log10 Transformed HIV-1 RNA Levels
Timepoint [9] 0 0
Baseline to Week 24 and Week 48
Secondary outcome [10] 0 0
Number of Participants With Genotypic Susceptibility Score (GSS) and Phenotypic Susceptibility Score (PSS) at Screening
Timepoint [10] 0 0
Screening
Secondary outcome [11] 0 0
Number of Participants With Change in GSS and PSS From Screening at the Time of Treatment Failure Through Week 24
Timepoint [11] 0 0
Screening and time of failure through Week 24
Secondary outcome [12] 0 0
Number of Participants With Change in GSS and PSS From Screening at the Time of Treatment Failure Through Week 48
Timepoint [12] 0 0
Screening and time of failure through Week 48
Secondary outcome [13] 0 0
Number of Participants Per Tropism Status at Baseline and at the Time of Treatment Failure Through Week 24
Timepoint [13] 0 0
Baseline and time of failure through Week 24
Secondary outcome [14] 0 0
Number of Participants Per Tropism Status at Baseline and at the Time of Treatment Failure Through Week 48
Timepoint [14] 0 0
Baseline and time of failure through Week 48
Secondary outcome [15] 0 0
Change From Baseline in Viral Load at Week 24 and Week 48 by Overall Susceptibility Score (OSS) at Screening
Timepoint [15] 0 0
Baseline, Week 24 and Week 48

Eligibility
Key inclusion criteria
* 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
Minimum age
16 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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
* 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
* 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 2
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
1/12/2004
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/04/2011
Sample size
Target
Accrual to date
Final
474
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 - Surry Hills
Recruitment hospital [4] 0 0
Pfizer Investigational Site - Sydney
Recruitment hospital [5] 0 0
Pfizer Investigational Site - Wentworthville
Recruitment hospital [6] 0 0
Pfizer Investigational Site - Herston
Recruitment hospital [7] 0 0
Pfizer Investigational Site - Miami
Recruitment hospital [8] 0 0
Pfizer Investigational Site - Melbourne
Recruitment hospital [9] 0 0
Pfizer Investigational Site - North Fitzroy
Recruitment hospital [10] 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 - Surry Hills
Recruitment postcode(s) [4] 0 0
2010 - Sydney
Recruitment postcode(s) [5] 0 0
2145 - Wentworthville
Recruitment postcode(s) [6] 0 0
4029 - Herston
Recruitment postcode(s) [7] 0 0
4220 - Miami
Recruitment postcode(s) [8] 0 0
3004 - Melbourne
Recruitment postcode(s) [9] 0 0
3068 - North Fitzroy
Recruitment postcode(s) [10] 0 0
3141 - South Yarra
Recruitment outside Australia
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United States of America
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Alabama
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California
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Connecticut
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Florida
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Georgia
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Cedex
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Nice Cedex 3, 06
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Stockholm
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Malmö
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Switzerland
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Basel
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Switzerland
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Genève
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Switzerland
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Lausanne
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Switzerland
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Lugano
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St. Gallen
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Switzerland
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Zürich
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United Kingdom
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Leics
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United Kingdom
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Loth
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United Kingdom
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Birmingham
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United Kingdom
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Brighton
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United Kingdom
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Edinburgh
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United Kingdom
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London
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United Kingdom
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Manchester
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United Kingdom
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Newcastle Upon Tyre

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 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 website
https://clinicaltrials.gov/study/NCT00098722
Trial related presentations / publications
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.
Gulick 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.
Hardy 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.
Fatkenheuer 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.
Gulick 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.
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/study/NCT00098722