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 - Study Results

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Safety/Efficacy Study; Intervention Model: Parallel Assignment; Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor); Primary Purpose: Treatment
Condition:	HIV Infections
Interventions:	Drug: Maraviroc (UK-427,857) Drug: optimized background therapy

Participant Flow

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, Double Blind	Maraviroc 150 or 300 milligrams (mg) tablet orally once daily (QD) in the evening, dose adjusted according to the other prescribed drugs taken by participants as part of optimized background therapy (OBT) selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally in the morning.
Maraviroc BID, Double Blind	Maraviroc 150 or 300 mg tablet orally twice daily (BID) in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
Placebo, Double Blind	Placebo matched to maraviroc tablet orally BID in the morning and evening, in combination with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
Maraviroc BID, Open Label	Participants from maraviroc QD, maraviroc BID and Placebo (double blind phase) who received maraviroc 150 or 300 mg BID in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations) during open label phase.
In Study-off Drug (ISOD), Open Label	Participants from maraviroc QD, maraviroc BID and Placebo (double blind phase) who received no study treatment along with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations) during open label phase.
Maraviroc BID, Observation Phase	Participants continuing from open label phase, who received maraviroc 150 or 300 mg BID in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations) during observational phase.
In Study-off Drug (ISOD), Observation Phase	Participants continuing from open label phase, who received no study treatment along with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations) during observational phase.

Participant Flow for 3 periods

Period 1: Double Blind Phase

	Maraviroc QD, Double Blind	Maraviroc BID, Double Blind	Placebo, Double Blind
STARTED	186	194	94
Treated	182	191	91
COMPLETED	0	0	0
NOT COMPLETED	186	194	94
Adverse Event	7	7	3
Death	2	5	0
Lack of Efficacy	21	23	15
Participant defaulted	16	11	9
Pregnancy	1	0	0
Randomized, not treated	4	3	3
Ongoing at cut-off date	128	137	57
Unspecified	7	8	7

Period 2: Open Label Phase

	Maraviroc BID, Open Label	In Study-off Drug (ISOD), Open Label
STARTED	272	50
COMPLETED	0	0
NOT COMPLETED	272	50
Adverse Event	5	0
Death	2	0
Lack of Efficacy	8	0
Pregnancy	1	0
Participant defaulted	18	0
Ongoing at cut-off date	220	50
Unspecified	18	0

Period 3: Observation Phase

	Maraviroc BID, Observation Phase	In Study-off Drug (ISOD), Observation Phase
STARTED	205	65
COMPLETED	160	48
NOT COMPLETED	45	17
Death	5	3
Lack of Efficacy	2	0
Participant defaulted	17	4
Unspecified	21	10

Baseline Characteristics

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Reporting Groups

	Description
Maraviroc QD	Maraviroc 150 or 300 milligrams (mg) tablet orally once daily (QD) in the evening, dose adjusted according to the other prescribed drugs taken by participants as part of optimized background therapy (OBT) selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations). Placebo matched to maraviroc tablet orally in the morning.
Maraviroc BID	Maraviroc 150 or 300 mg tablet orally twice daily (BID) in the morning and evening, dose adjusted according to the other prescribed drugs taken by participants as part of OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
Placebo	Placebo matched to maraviroc tablet orally BID in the morning and evening, in combination with OBT selected according to local standard of care (3 to 6 drugs based on resistance testing, treatment history and safety considerations).
Total	Total of all reporting groups

Baseline Measures

	Maraviroc QD	Maraviroc BID	Placebo	Total
Number of Participants [units: participants]	182	191	91	464
Age, Customized ^[1] [units: participants]
Less than 18 years	1	0	0	1
18 to 24 years	1	1	0	2
25 to 34 years	8	9	6	23
35 to 44 years	85	71	40	196
45 to 54 years	63	70	32	165
55 to 64 years	19	37	11	67
Greater than or equal to 65 years	5	3	2	10
Gender ^[2] [units: participants]
Female	29	21	12	62
Male	153	170	79	402

[1]	Out of a total of 474 participants, data for baseline measure (age) was available for 464 participants who were treated.
[2]	Out of a total of 474 participants, data for baseline measure (gender) was available for 464 participants who were treated.

Outcome Measures

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1. Primary:

Log 10-transformed Human Immunodeficiency Virus Ribonucleic Acid (HIV-1 RNA) Levels at Baseline [ Time Frame: Baseline ]

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2. Primary:

Change From Baseline in Log 10-transformed HIV-1 RNA Levels at Week 24 [ Time Frame: Baseline and Week 24 ]

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3. Primary:

Change From Baseline in Log 10-transformed HIV-1 RNA Levels at Week 48 [ Time Frame: Baseline and Week 48 ]

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4. Secondary:

Percentage of Participants With HIV-1 RNA Levels Less Than 400 Copies/mL [ Time Frame: Week 24 and 48 ]

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5. Secondary:

Percentage of Participants With HIV-1 RNA Levels Less Than 400 Copies/ml or With at Least 0.5 log10 Decrease From Baseline [ Time Frame: Week 24 and 48 ]

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6. Secondary:

Percentage of Participants With HIV-1 RNA Levels Less Than 400 Copies/ml or With at Least 1.0 log10 Decrease From Baseline [ Time Frame: Week 24 and 48 ]

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7. Secondary:

Percentage of Participants With HIV-1 RNA Levels Less Than 50 Copies/mL [ Time Frame: Week 24 and 48 ]

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8. Secondary:

Cluster of Differentiation 4 (CD4) and Cluster of Differentiation 8 (CD8) Cell Count at Baseline [ Time Frame: Baseline ]

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9. Secondary:

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

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10. Secondary:

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

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11. Secondary:

Time to Virological Failure [ Time Frame: Week 48 ]

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12. Secondary:

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

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13. Secondary:

Number of Participants With Genotypic Susceptibility Score (GSS) and Phenotypic Susceptibility Score (PSS) at Screening [ Time Frame: Screening ]

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14. Secondary:

Number of Participants With Change in GSS and PSS From Screening at the Time of Treatment Failure Through Week 24 [ Time Frame: Screening and time of failure through Week 24 ]

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15. Secondary:

Number of Participants With Change in GSS and PSS From Screening at the Time of Treatment Failure Through Week 48 [ Time Frame: Screening and time of failure through Week 48 ]

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16. Secondary:

Number of Participants Per Tropism Status at Baseline and at the Time of Treatment Failure Through Week 24 [ Time Frame: Baseline and time of failure through Week 24 ]

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17. Secondary:

Number of Participants Per Tropism Status at Baseline and at the Time of Treatment Failure Through Week 48 [ Time Frame: Baseline and time of failure through Week 48 ]

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18. Secondary:

Change From Baseline in Viral Load at Week 24 and Week 48 by Overall Susceptibility Score (OSS) at Screening [ Time Frame: Baseline, Week 24 and 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 less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 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
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Results Point of Contact:

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

No publications provided by ViiV Healthcare

Publications automatically indexed to this study:

Hardy WD, Gulick RM, Mayer H, Fätkenheuer 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.

Fätkenheuer 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.

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.

Responsible Party:	ViiV Healthcare
ClinicalTrials.gov Identifier:	NCT00098722 History of Changes
Other Study ID Numbers:	A4001028
Study First Received:	December 7, 2004
Results First Received:	April 16, 2012
Last Updated:	April 16, 2012
Health Authority:	United States: Food and Drug Administration

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 (MOTIVATE 2)