A Phase III Study of BMS-188667 in Subjects With Active Rheumatoid Arthritis

This study has been completed.

Sponsor:

Information provided by (Responsible Party):

Bristol-Myers Squibb

ClinicalTrials.gov Identifier:

NCT00048932

First received: November 11, 2002

Last updated: November 15, 2011

Last verified: November 2011

History of Changes

Results First Received: April 1, 2011

Study Type:	Interventional
Study Design:	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double Blind (Subject, Investigator); Primary Purpose: Treatment
Condition:	Rheumatoid Arthritis
Interventions:	Drug: Double-blind Abatacept Drug: Double-blind Placebo Drug: Open-label Abatacept

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
1795 enrolled in study and 339 were not randomized due to no longer meeting study criteria (n=214), withdraw of consent (n=83), other reasons (n=32), participant was lost to follow-up (n=5), administrative reason by sponsor (n=2), adverse event (n=2), and poor/non-compliance (n=1). Of 1456 randomized, 15 were not treated.

Reporting Groups

	Description
Abatacept (ABA)	Participants received a fixed dose of abatacept approximating 10 mg/kg (500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 g for participants > 100 kg). Abatacept was administered intravenously (IV) on Days 1, 15, 29, and every 28 days thereafter, for a total of 14 doses. Participants also received background therapy(ies) for rheumatoid arthritis (RA) (non-biologic or biologic disease-modifying drugs [DMARDs], or combination) throughout the double-blind treatment period.
Placebo (PLA)	Participants received Placebo (dextrose 5% water [D5W] for injection U.S.P or normal saline [NS]) for IV infusion administered on Days 1, 15, 29, and every 28 days thereafter, for a total of 14 doses. Participants also received background therapy(ies) for rheumatoid arthritis (RA) (non-biologic or biologic disease-modifying drugs [DMARDs], or combination) throughout the double-blind treatment period.
Open Label (OL) Abatacept	Participants received abatacept (weight-tiered 10 mg/kg dose) IV every 28 days during the open-label period.

Participant Flow for 2 periods

Period 1: Double Blind Period (DB)

	Abatacept (ABA)	Placebo (PLA)
STARTED	959 ^[1]	482 ^[1]
COMPLETED	836	395
NOT COMPLETED	123	87
Administrative Reason By Sponsor	1	0
Adverse Event	51	19
Death	5	3
Lack of Efficacy	26	44
Lost to Follow-up	3	4
Relocation	1	0
Uncontrolled hypertension	0	1
Missed 2 doses while undergoing work-up	1	0
Pregnancy	1	0
No Longer Meets Study Criteria	8	2
Withdrawal by Subject	24	10
Poor/Non-Compliance	2	4

[1]	Number Treated

Period 2: Open Label Period (OL)

	Abatacept (ABA)	Placebo (PLA)	Open Label (OL) Abatacept
STARTED	0	0	1184 ^[1]
COMPLETED	0	0	743
NOT COMPLETED	0	0	441
Death	0	0	25
Adverse Event	0	0	103
Lack of Efficacy	0	0	81
Lost to Follow-up	0	0	27
Withdrawal by Subject	0	0	117
No Longer Meets Study Criteria	0	0	5
Poor/Non-Compliance	0	0	13
Pregnancy	0	0	6
Administrative Reason By Sponsor	0	0	20
Investigator Retiring	0	0	2
Participant Transportation Issues	0	0	1
Participant Relocated	0	0	6
Investigator Dosing the Trial	0	0	1
Site Closure	0	0	3
Trial Terminated	0	0	1
Difficult IV Access with Participant	0	0	1
Patient Decision	0	0	4
Participant Received Wrong Medication	0	0	1
Participant Desires Pregnancy	0	0	2
Participant Missed Consecutive Doses	0	0	5
Medication Lost Efficacy	0	0	1
Investigator Decision	0	0	4
Site Staff Issues	0	0	2
Site Not Participating in Open Label	0	0	9
Participant Surgery	0	0	1

[1]	47 participants who completed the double-blind did not enter the open-label

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.
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Reporting Groups

	Description
Abatacept (ABA)	Participants received a fixed dose of abatacept approximating 10 mg/kg (500 mg for participants < 60 kg, 750 mg for participants 60 to 100 kg and 1 g for participants > 100 kg). Abatacept was administered intravenously (IV) on Days 1, 15, 29, and every 28 days thereafter, for a total of 14 doses. Participants also received background therapy(ies) for rheumatoid arthritis (RA) (non-biologic or biologic disease-modifying drugs [DMARDs], or combination) throughout the double-blind treatment period.
Placebo (PLA)	Participants received Placebo (dextrose 5% water [D5W] for injection U.S.P or normal saline [NS]) for IV infusion administered on Days 1, 15, 29, and every 28 days thereafter, for a total of 14 doses. Participants also received background therapy(ies) for rheumatoid arthritis (RA) (non-biologic or biologic disease-modifying drugs [DMARDs], or combination) throughout the double-blind treatment period.
Total	Total of all reporting groups

Baseline Measures

	Abatacept (ABA)	Placebo (PLA)	Total
Number of Participants [units: participants]	959	482	1441
Age [units: years] Mean (Standard Deviation)	52.4 (11.7)	52.1 (12.0)	52.3 (11.8)
Gender [units: participants]
Female	789	398	1187
Male	170	84	254

Outcome Measures

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1. Primary:

Double Blind Period (DB); Number of Participants With Death, Serious Adverse Events (SAEs), Related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Related AEs, or AEs Leading to Discontinuation [ Time Frame: Day 1 to Day 365, and including data up to 56 days post last dose of double-blind medication ]

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2. Primary:

DB; Number of Participants With AEs of Special Interest [ Time Frame: Day 1 to Day 365, and including data up to 56 days post last dose of double-blind medication ]

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3. Primary:

DB; Number of Participants With Hematology Laboratories Meeting Marked Abnormality Criteria [ Time Frame: Day 1 to Day 365, and including data up to 56 days post last dose of double-blind medication ]

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4. Primary:

DB; Number of Participants With Blood Chemistry Laboratories Meeting Marked Abnormality (MA) Criteria [ Time Frame: Day 1 to Day 365, and including data up to 56 days post last dose of double-blind medication ]

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5. Primary:

DB; Number of Participants With Clinically Significant Physical Examination or Vital Signs Abnormalities [ Time Frame: Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337. Vital signs were measured at these visits before and after study medication infusion. ]

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6. Primary:

Open Label Period (OL); Number of Participants With Death, Serious Adverse Events (SAEs), Related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Related AEs, or AEs Leading to Discontinuation [ Time Frame: Day 365 to Day 1,821 ]

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7. Primary:

OL; Number of Participants With AEs of Special Interest [ Time Frame: Day 365 to Day 1821 ]

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8. Primary:

OL; Number of Participants With Hematology Laboratories Meeting Marked Abnormality Criteria [ Time Frame: Day 365 to Day 1821, and including data up to 56 days post last dose of double-blind medication ]

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9. Primary:

OL; Number of Participants With Liver Function Laboratories Meeting Marked Abnormality Criteria [ Time Frame: Day 365 to Day 1821, and including data up to 56 days post last dose of double-blind medication ]

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10. Primary:

OL; Number of Participants With Electrolyte Laboratories Meeting Marked Abnormality Criteria [ Time Frame: Day 365 to Day 1821, and including data up to 56 days post last dose of double-blind medication ]

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11. Primary:

OL; Number of Participants With Other Chemistry and Urinalysis Laboratories Meeting Marked Abnormality Criteria [ Time Frame: Day 365 to Day 1821, and including data up to 56 days post last dose of double-blind medication ]

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12. Primary:

OL; Number of Participants With Clinically Significant Physical Examination or Vital Signs Abnormalities [ Time Frame: Days 365 to Day 1821 ]

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13. Secondary:

DB; Number of Participants With Positive Anti-Abatacept or Anti-Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) Responses by Enzyme-Linked Immunosorbant Assay (ELISA) [ Time Frame: Days 1, 29, 57, 85, 113,169, 281, 365 ]

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14. Secondary:

DB; Number of Participants With Positive Anti-Abatacept or Anti-Cytotoxic T-Lymphocyte Antigen 4 (CTLA4) Responses by ELISA [ Time Frame: Days 1, 15, 29, 57, 85, 113, 141, 169, 197, 225, 253, 281, 309, 337 ]

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Serious Adverse Events

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Other Adverse Events

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Limitations and Caveats

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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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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: Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.

Results Point of Contact:

Name/Title: BMS Study Director
Organization: Bristol-Myers Squibb
e-mail: Clinical.Trials@bms.com

Responsible Party:	Bristol-Myers Squibb
ClinicalTrials.gov Identifier:	NCT00048932 History of Changes
Other Study ID Numbers:	IM101-031
Study First Received:	November 11, 2002
Results First Received:	April 1, 2011
Last Updated:	November 15, 2011
Health Authority:	United States: Food and Drug Administration

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