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

History of Changes

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
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Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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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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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 ]

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2. Secondary:

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

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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 ]

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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 ]

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5. Secondary:

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

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6. Secondary:

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

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Measure Type	Secondary
Measure Title	Change From Baseline in CD4 Cell Count
Measure Description	Change from baseline in CD4 cell count (measured as cells per microliter [cells/µL]). Baseline value calculated as the average of pre-dose measurements collected at screening, randomization, and baseline visits.
Time Frame	Baseline to Week 24 and Week 48
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. Placebo N: 4 subjects did not have on-treatment information. Missing data imputed using 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	54
Change From Baseline in CD4 Cell Count [units: cells/µL] Mean ± Standard Error
Week 24	59.237 ± 8.9661	62.651 ± 10.0234	36.367 ± 8.4477
Week 48	65.86 ± 10.822	78.87 ± 11.566	51.29 ± 12.523

Statistical Analysis 1 for Change From Baseline in CD4 Cell Count

Groups ^[1]	Maraviroc QD vs. Placebo
Least squares mean ^[2]	23.927
Standard Error of the mean	± 12.8025
95% Confidence Interval	( -1.359 to 49.213 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	MVC QD vs PBO treatment difference at Week 24.
[2]	Other relevant estimation information:
	Negative values for change from baseline=benefit of TX; negative values for MVC vs PBO=advantage of MVC.

Statistical Analysis 2 for Change From Baseline in CD4 Cell Count

Groups ^[1]	Maraviroc BID vs. Placebo
Least squares mean ^[2]	26.679
Standard Error of the mean	± 13.0678
95% Confidence Interval	( 0.869 to 52.490 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	MVC BID vs PBO treatment difference at Week 24.
[2]	Other relevant estimation information:
	Negative values for change from baseline=benefit of TX; negative values for MVC vs PBO=advantage of MVC.

Statistical Analysis 3 for Change From Baseline in CD4 Cell Count

Groups ^[1]	Maraviroc QD vs. Placebo
Least squares mean ^[2]	14.61
Standard Error of the mean	± 16.412
95% Confidence Interval	( -17.80 to 47.03 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	MVC QD vs PBO treatment difference at Week 48.
[2]	Other relevant estimation information:
	Negative values for change from baseline=benefit of TX; negative values for MVC vs PBO=advantage of MVC.

Statistical Analysis 4 for Change From Baseline in CD4 Cell Count

Groups ^[1]	Maraviroc BID vs. Placebo
Least squares mean ^[2]	27.71
Standard Error of the mean	± 16.754
95% Confidence Interval	( -5.38 to 60.80 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	MVC BID vs PBO treatment difference at Week 48.
[2]	Other relevant estimation information:
	Negative values for change from baseline=benefit of TX; negative values for MVC vs PBO=advantage of MVC.

7. Secondary:

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

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8. Secondary:

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

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9. Secondary:

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

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10. Secondary:

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

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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 ]

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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 ]

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13. Secondary:

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

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14. Secondary:

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

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15. Secondary:

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

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16. Secondary:

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

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Serious Adverse Events

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Other Adverse Events

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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:

	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.
	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.
	Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed. Restriction Description: Pfizer has the right to review disclosures, requesting a delay of < 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), < 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.

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:

Saag M, Goodrich J, Fätkenheuer G, Clotet B, Clumeck N, Sullivan J, Westby M, van der Ryst E, Mayer H; A4001029 Study Group. A double-blind, placebo-controlled trial of maraviroc in treatment-experienced patients infected with non-R5 HIV-1. J Infect Dis. 2009 Jun 1;199(11):1638-47.

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

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