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

This study has been completed.
Sponsor:
Collaborator:
Pfizer
Information provided by:
ViiV Healthcare
ClinicalTrials.gov Identifier:
NCT00098748
First received: December 7, 2004
Last updated: November 19, 2010
Last verified: November 2010
Results First Received: March 25, 2010  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Investigator);   Primary Purpose: Treatment
Condition: HIV Infections
Interventions: Drug: Optimized Background Therapy (OBT)
Drug: maraviroc (UK-427,857)

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Maraviroc QD Maraviroc 150 mg by mouth (PO) once daily (QD) in combination with optimized background therapy (OBT) (3 to 6 drugs based on treatment history and resistance testing). The 150 mg QD arm = placebo drug in the morning and active drug in the evening.
Maraviroc BID Maraviroc 150 mg PO twice a day (BID) in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The 150 mg BID arm = active drug in the morning and evening.
Placebo Placebo BID in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The placebo arm = placebo drug in the morning and evening.

Participant Flow for 3 periods

Period 1:   Assigned to Study Treatment
    Maraviroc QD     Maraviroc BID     Placebo  
STARTED     63     63     64  
COMPLETED     63     61     62  
NOT COMPLETED     0     2     2  
Randomized, but not treated                 0                 2                 2  

Period 2:   Received Study Treatment
    Maraviroc QD     Maraviroc BID     Placebo  
STARTED     63     61 [1]   62 [2]
Dual-tropic Subjects by Phenotype Assay     57 [3]   52     58  
COMPLETED     15     25     18  
NOT COMPLETED     48     36     44  
Death                 2                 1                 2  
Adverse Event                 1                 2                 5  
Lack of Efficacy                 40                 27                 27  
Unspecified                 2                 2                 6  
Subject defaulted                 3                 4                 4  
[1] Due to 1 placebo subject switched to maraviroc BID, BID = 62 subjects in Adverse event tables.
[2] Due to 1 placebo subject switched to maraviroc BID, Placebo = 61 subjects in Adverse event tables.
[3] Dual-tropic: Virus capable of using both CCR5 and CXCR4 coreceptors for cell entry.

Period 3:   Continued on Open-Label Treatment
    Maraviroc QD     Maraviroc BID     Placebo  
STARTED     15     25     0 [1]
COMPLETED     7     10     0  
NOT COMPLETED     8     15     0  
Adverse Event                 0                 1                 0  
Lack of Efficacy                 1                 2                 0  
Other reason includes protocol violation                 6                 7                 0  
Lost to Follow-up                 1                 1                 0  
Withdrawal by Subject                 0                 4                 0  
[1] Placebo group not offered open-label maraviroc due to study not reaching primary endpoint at Week 24



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Maraviroc QD Maraviroc 150 mg by mouth (PO) once daily (QD) in combination with optimized background therapy (OBT) (3 to 6 drugs based on treatment history and resistance testing). The 150 mg QD arm = placebo drug in the morning and active drug in the evening.
Maraviroc BID Maraviroc 150 mg PO twice a day (BID) in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The 150 mg BID arm = active drug in the morning and evening.
Placebo Placebo BID in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The placebo arm = placebo drug in the morning and evening.
Total Total of all reporting groups

Baseline Measures
    Maraviroc QD     Maraviroc BID     Placebo     Total  
Number of Participants  
[units: participants]
  63     61     62     186  
Age, Customized  
[units: participants]
       
<18 years     2     2     0     4  
Between 18 and 24 years     1     1     1     3  
Between 25 and 34 years     2     3     2     7  
Between 35 and 44 years     30     31     31     92  
Between 45 and 54 years     25     21     20     66  
Between 55 and 64 years     3     3     7     13  
≥65 years     0     0     1     1  
Age  
[units: years]
Mean ( Full Range )
  42.7  
  ( 16 to 59 )  
  42.5  
  ( 16 to 62 )  
  44.6  
  ( 23 to 65 )  
  43.3  
  ( 16 to 65 )  
Gender  
[units: participants]
       
Female     10     6     9     25  
Male     53     55     53     161  



  Outcome Measures
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1.  Primary:   Change From Baseline in Human Immunodeficiency Virus (HIV-1) Viral Load (Ribonucleic Acid [RNA])   [ Time Frame: Baseline to Week 24 and Week 48 ]

2.  Secondary:   Number of Subjects With HIV-1 RNA Levels < 400 Copies/mL   [ Time Frame: Week 24, Week 48 ]

3.  Secondary:   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   [ Time Frame: Baseline, Week 24, Week 48 ]

4.  Secondary:   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   [ Time Frame: Baseline, Week 24, Week 48 ]

5.  Secondary:   Number of Subjects With HIV-1 RNA Levels < 50 Copies/mL   [ Time Frame: Baseline, Week 24, Week 48 ]

6.  Secondary:   Change From Baseline in CD4 Cell Count   [ Time Frame: Baseline to Week 24 and Week 48 ]

7.  Secondary:   Change From Baseline in CD8 Cell Count   [ Time Frame: Baseline to Week 24 and Week 48 ]

8.  Secondary:   Time (50% Quartile Point Estimate) to Virologic Failure   [ Time Frame: Day 1 through Week 24 and through Week 48 ]

9.  Secondary:   Change From Baseline in Time Averaged Difference (TAD) in log10 HIV-1 RNA   [ Time Frame: Baseline to Week 24 and Week 48 ]

10.  Secondary:   Number of Subjects Per Genotype and Phenotype at Baseline and at Time of Failure   [ Time Frame: Baseline through Week 48 ]

11.  Secondary:   Number of Subjects Per Tropism Status at Screening and at the Time of Treatment Failure (Analysis at Week 24)   [ Time Frame: Screening through Week 24 ]

12.  Secondary:   Number of Subjects Per Tropism Status at Screening and Time of Treatment Failure (Analysis at Week 48)   [ Time Frame: Screening through Week 48 ]

13.  Secondary:   Number of Subjects With Treatment Failure at Week 24 by Overall Susceptibility Score (OSS) at Screening   [ Time Frame: Screening, Week 24 ]

14.  Secondary:   Number of Subjects With Treatment Failure at Week 48 by Overall Susceptibility Score (OSS) at Screening   [ Time Frame: Screening, Week48 ]
  Hide Outcome Measure 14

Measure Type Secondary
Measure Title Number of Subjects With Treatment Failure at Week 48 by Overall Susceptibility Score (OSS) at Screening
Measure Description Number of subjects for association between screening resistance and virologic response as determined by treatment failure and OSS at screening. OSS categorized as 0, 1, 2, or ≥3 (maximum value of 6) and calculated as the sum of the net assessment of in vitro phenotypic and genotypic susceptibility using a binary scoring system (0= reduced susceptibility, 1=susceptible) for each antiretroviral agent in OBT. Higher scores indicate greater susceptibility.
Time Frame Screening, Week48  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
FAS - as treated dual-tropic subjects. Missing values imputed as LOCF.

Reporting Groups
  Description
Maraviroc QD Maraviroc 150 mg by mouth (PO) once daily (QD) in combination with optimized background therapy (OBT) (3 to 6 drugs based on treatment history and resistance testing). The 150 mg QD arm = placebo drug in the morning and active drug in the evening.
Maraviroc BID Maraviroc 150 mg PO twice a day (BID) in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The 150 mg BID arm = active drug in the morning and evening.
Placebo Placebo BID in combination with OBT (3 to 6 drugs based on treatment history and resistance testing). The placebo arm = placebo drug in the morning and evening.

Measured Values
    Maraviroc QD     Maraviroc BID     Placebo  
Number of Participants Analyzed  
[units: participants]
  57     52     58  
Number of Subjects With Treatment Failure at Week 48 by Overall Susceptibility Score (OSS) at Screening  
[units: particpants]
     
Scr score: 0     1     2     2  
Scr score: 1     19     11     15  
Scr score: 2     21     14     13  
Scr score: ≥3     15     24     27  
Scr score: missing     1     1     1  

No statistical analysis provided for Number of Subjects With Treatment Failure at Week 48 by Overall Susceptibility Score (OSS) at Screening



15.  Secondary:   Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 24)   [ Time Frame: Baseline through Week 24 ]

16.  Secondary:   Number of Subjects With Acquired Immunodeficiency Syndrome (AIDS)-Defining Opportunistic Illnesses (Analysis at Week 48)   [ Time Frame: Baseline through Week 48 ]


  Serious Adverse Events


  Other Adverse Events


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.  


Results Point of Contact:  
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
phone: 1-800-718-1021
e-mail: ClinicalTrials.govCallCenter@pfizer.com


No publications provided by ViiV Healthcare

Publications automatically indexed to this study:

Responsible Party: Director, Clinical Trial Disclosure Group, Pfizer, Inc.
ClinicalTrials.gov Identifier: NCT00098748     History of Changes
Other Study ID Numbers: A4001029
Study First Received: December 7, 2004
Results First Received: March 25, 2010
Last Updated: November 19, 2010
Health Authority: United States: Food and Drug Administration