Maraviroc in Rheumatoid Arthritis

This study has been terminated.

(See Detailed Description.)

Sponsor:

Collaborator:

Pfizer

Information provided by:

ViiV Healthcare

ClinicalTrials.gov Identifier:

NCT00427934

First received: January 25, 2007

Last updated: November 10, 2010

Last verified: November 2010

History of Changes

Results First Received: October 6, 2009

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:	Arthritis, Rheumatoid
Interventions:	Drug: Maraviroc Drug: Maraviroc Placebo

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 150 mg BID (Pharmacokinetic [PK])	150 mg tablet was administered by mouth twice a day (BID) for 4 weeks with stable weekly doses of methotrexate (MTX).
Maraviroc 300 mg BID (PK)	300 mg (Two 150 mg tablets) were administered by mouth BID for 4 weeks with stable weekly doses of MTX.
Maraviroc 300 mg BID (Proof-of-Concept [POC])	300 mg (Two 150 mg tablets) were administered by mouth BID for 12 weeks with stable weekly doses of MTX.
Placebo (POC)	Placebo tablets to match active drug. Two tablets were administered by mouth BID for 12 weeks with stable weekly doses of MTX.

Participant Flow: Overall Study

	Maraviroc 150 mg BID (Pharmacokinetic [PK])	Maraviroc 300 mg BID (PK)	Maraviroc 300 mg BID (Proof-of-Concept [POC])	Placebo (POC)
STARTED	8	8	78	34
Treated	8	8	77	33
COMPLETED	7	8	55	19
NOT COMPLETED	1	0	23	15
Adverse Event	1	0	5	4
Lack of Efficacy	0	0	5	2
Randomized But Did Not Receive Treatment	0	0	1	1
Unknown	0	0	11	5
Withdrawal by Subject	0	0	1	3

Baseline Characteristics

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Reporting Groups

	Description
Maraviroc 150 mg BID (PK)	150 mg tablet was administered by mouth BID for 4 weeks with stable weekly doses of MTX.
Maraviroc 300 mg BID (PK)	300 mg (Two 150 mg tablets) were administered by mouth BID for 4 weeks with stable weekly doses of MTX.
Maraviroc 300 mg BID (POC)	300 mg (Two 150 mg tablets) were administered by mouth BID for 12 weeks with stable weekly doses of MTX.
Placebo (POC)	Placebo tablets to match active drug. Two tablets were administered by mouth BID for 12 weeks with stable weekly doses of MTX.
Total	Total of all reporting groups

Baseline Measures

	Maraviroc 150 mg BID (PK)	Maraviroc 300 mg BID (PK)	Maraviroc 300 mg BID (POC)	Placebo (POC)	Total
Number of Participants [units: participants]	8	8	77	33	126
Age, Customized [units: Participants]
< 18 years	0	0	0	0	0
18 to 44 years	1	0	15	6	22
45 to 64 years	4	8	48	21	81
> = 65 years	3	0	14	6	23
Gender [units: Participants]
Female	4	5	71	22	102
Male	4	3	6	11	24

Outcome Measures

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1. Primary:

American College of Rheumatology (ACR) 20% Responders at Week 12 [ Time Frame: Week 12 ]

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2. Secondary:

ACR 20% Responders at Weeks 1, 2, 4, and 8 [ Time Frame: Weeks 1, 2, 4, and 8 ]

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3. Secondary:

ACR 50% Responders at Weeks 1, 2, 4, 8, and 12 [ Time Frame: Weeks 1, 2, 4, 8, and 12 ]

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4. Secondary:

ACR 70% Responders at Weeks 1, 2, 4, 8, and 12 [ Time Frame: Weeks 1, 2, 4, 8, and 12 ]

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Measure Type	Secondary
Measure Title	ACR 70% Responders at Weeks 1, 2, 4, 8, and 12
Measure Description	A subject was an ACR 70 responder if: the counts for both tender and swollen joints had reduced by 70% or more from baseline; and 3 out of the following 5 assessments showed reduction of 70% or more from baseline assessment: Patient’s Assessment of Arthritis Pain, Patient’s Global Assessment of Arthritis, Physician’s Global Assessment of Arthritis, HAQ-DI, and CRP. The Week 16 visit (follow-up) was designed for safety rather than efficacy, thus Week 16 ACR 70% data were collected, but not analyzed.
Time Frame	Weeks 1, 2, 4, 8, and 12
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. Missing values were imputed by the method of LOCF.

Reporting Groups

	Description
Maraviroc 300 mg BID (POC)	300 mg (Two 150 mg tablets) were administered by mouth BID for 12 weeks with stable weekly doses of MTX.
Placebo (POC)	Placebo tablets to match active drug. Two tablets were administered by mouth BID for 12 weeks with stable weekly doses of MTX.

Measured Values

	Maraviroc 300 mg BID (POC)	Placebo (POC)
Number of Participants Analyzed [units: participants]	77	33
ACR 70% Responders at Weeks 1, 2, 4, 8, and 12 [units: Participants]
Week 1	0	0
Week 2	0	0
Week 4	0	1
Week 8	2	0
Week 12	0	1

Statistical Analysis 1 for ACR 70% Responders at Weeks 1, 2, 4, 8, and 12

Groups ^[1]	All groups
Method ^[2]	Barnard/Pearson chi-square test
P Value ^[3]	1.000
Percentage Difference ^[4]	-3.03
90% Confidence Interval	( -13.59 to 1.28 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Week 4
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[4]	Other relevant estimation information:
	Percentage Difference = maraviroc responders divided by the number of maraviroc participants analyzed minus placebo responders divided by the number of placebo participants analyzed.

Statistical Analysis 2 for ACR 70% Responders at Weeks 1, 2, 4, 8, and 12

Groups ^[1]	All groups
Method ^[2]	Barnard/Pearson chi-square test
P Value ^[3]	0.258
Percentage Difference ^[4]	2.60
90% Confidence Interval	( -5.08 to 7.95 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Week 8
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[4]	Other relevant estimation information:
	Percentage Difference = maraviroc responders divided by the number of maraviroc participants analyzed minus placebo responders divided by the number of placebo participants analyzed.

Statistical Analysis 3 for ACR 70% Responders at Weeks 1, 2, 4, 8, and 12

Groups ^[1]	All groups
Method ^[2]	Barnard/Pearson chi-square test
P Value ^[3]	1.000
Percentage Difference ^[4]	-3.03
90% Confidence Interval	( -13.59 to 1.28 )

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	Week 12
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[4]	Other relevant estimation information:
	Percentage Difference = maraviroc responders divided by the number of maraviroc participants analyzed minus placebo responders divided by the number of placebo participants analyzed.

5. Secondary:

Change From Baseline in Tender/Painful Joint Count at Weeks 1, 2, 4, 8, and 12 [ Time Frame: Baseline, Weeks 1, 2, 4, 8, and 12 ]

Show Outcome Measure 5

6. Secondary:

Change From Baseline in Swollen Joint Count at Weeks 1, 2, 4, 8, and 12 [ Time Frame: Baseline, Weeks 1, 2, 4, 8, and 12 ]

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7. Secondary:

Change From Baseline in Patient's Assessment of Arthritis Pain at Weeks 1, 2, 4, 8, and 12 [ Time Frame: Baseline, Weeks 1, 2, 4, 8, and 12 ]

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8. Secondary:

Change From Baseline in Patient's Global Assessment of Arthritis Pain at Weeks 1, 2, 4, 8, and 12 [ Time Frame: Baseline, Weeks 1, 2, 4, 8, and 12 ]

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9. Secondary:

Change From Baseline in Physician's Global Assessment of Arthritis Pain at Weeks 1, 2, 4, 8, and 12 [ Time Frame: Baseline, Weeks 1, 2, 4, 8, and 12 ]

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10. Secondary:

Change From Baseline in HAQ-DI at Weeks 1, 2, 4, 8, and 12 [ Time Frame: Baseline, Weeks 1, 2, 4, 8, and 12 ]

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11. Secondary:

Change From Baseline in CRP at Weeks 1, 2, 4, 8, and 12 [ Time Frame: Baseline, Weeks 1, 2, 4, 8, and 12 ]

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12. Secondary:

Change From Baseline in Disease Activity Score Using CRP (DAS28-4[CRP]) at Weeks 1, 2, 4, 8, and 12 [ Time Frame: Baseline, Weeks 1, 2, 4, 8, and 12 ]

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13. Secondary:

Change From Baseline in Mean Orthostatic Blood Pressure (BP) [ Time Frame: Baseline, 16 weeks ]

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14. Secondary:

Change From Baseline in Mean Heart Rate [ Time Frame: Baseline, 16 weeks ]

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15. Secondary:

Number of Subjects With Categorical Absolute Vital Signs and Vital Sign Changes Compared to Baseline [ Time Frame: Baseline, 16 weeks ]

Show Outcome Measure 15

16. Secondary:

Change From Baseline in 12-Lead Electrocardiogram (ECG) Parameters (RR Interval, PR Interval, QRS Complex, QT Interval, Corrected QT [QTc] Interval, QTcB Interval [Bazett's Correction], QTcF Interval [Fridericia's Correction]). [ Time Frame: Baseline, 16 weeks ]

Show Outcome Measure 16

17. Secondary:

Change From Baseline in 12-Lead Electrocardiogram (ECG) Parameters (Heart Rate). [ Time Frame: Baseline, 16 weeks ]

Show Outcome Measure 17

18. Secondary:

Number of Subjects With Categorical Absolute ECG Parameters and ECG Changes Compared to Baseline [ Time Frame: Baseline, 16 weeks ]

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19. Secondary:

Change From Baseline in Short Form-36 (SF-36) Physical Component Summary at Weeks 4 and 12 [ Time Frame: Baseline, Weeks 4 and 12 ]

Show Outcome Measure 19

20. Secondary:

Change From Baseline in SF-36 Mental Component Summary at Weeks 4 and 12 [ Time Frame: Baseline, Weeks 4 and 12 ]

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21. Secondary:

Number of Subjects With Withdrawal From Study Due to Lack of Efficacy [ Time Frame: 16 weeks ]

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22. Secondary:

Survival Analysis of Time to Withdrawal: Proportion of Subjects Who Did Not Withdraw From the Study Due to Lack of Efficacy. [ Time Frame: Weeks 1 to 12 ]

Show Outcome Measure 22

23. Secondary:

Area Under the Plasma Concentration-Time Profile From Time Zero to Four Hours Postdose (AUC 0-4) for MTX at Screening and Week 1 and Maraviroc at Week 1 [ Time Frame: Screening (1, 2, 3, and 4 hours post-dose), Week 1 (0.5, 1, 2, 3, and 4 hours post-dose) ]

Show Outcome Measure 23

24. Secondary:

Maximum Observed Concentration (Cmax) During the Dosing Interval for MTX at Screening and Week 1 and Maraviroc at Week 1 [ Time Frame: Screening (1, 2, 3, and 4 hours post-dose), Week 1 (0.5, 1, 2, 3, and 4 hours post-dose) ]

Show Outcome Measure 24

25. Secondary:

Time for Cmax (Tmax) for MTX at Screening and Week 1 and Maraviroc at Week 1 [ Time Frame: Screening (1, 2, 3, and 4 hours post-dose), Week 1 (0.5, 1, 2, 3, and 4 hours post-dose) ]

Show Outcome Measure 25

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:

Fleishaker DL, Garcia Meijide JA, Petrov A, Kohen MD, Wang X, Menon S, Stock TC, Mebus CA, Goodrich JM, Mayer HB, Zeiher BG. Maraviroc, a chemokine receptor-5 antagonist, fails to demonstrate efficacy in the treatment of patients with rheumatoid arthritis in a randomized, double-blind placebo-controlled trial. Arthritis Res Ther. 2012 Jan 17;14(1):R11.

Responsible Party:	Director, Clinical Trial Disclosure Group, Pfizer
ClinicalTrials.gov Identifier:	NCT00427934 History of Changes
Other Study ID Numbers:	A4001056
Study First Received:	January 25, 2007
Results First Received:	October 6, 2009
Last Updated:	November 10, 2010
Health Authority:	United States: Food and Drug Administration

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