Study to Assess Changes in the Immune Profile in Adults With Early Rheumatoid Arthritis

• Sponsor: Bristol-Myers Squibb (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02557100
• Collaborator: (none)
• Enrollment: 80
• Locations: 28
• Arms: 3
• Actual Duration (Months): 40.2
• Patients Per Site: 2.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to examine changes in immune cells and proteins in response to treatment with two approved therapies for Rheumatoid arthritis (RA), abatacept versus adalimumab, both given in combination with methotrexate.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis	Drug: Abatacept; Drug: Adalimumab; Drug: Methotrexate	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 80 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Basic Science
• Official Title: A Randomized, Head-to-Head, Single-Blinded Study to Assess Changes in the Immune Profile in Response to Treatment With Subcutaneous Abatacept in Combination With Methotrexate Versus Subcutaneous Adalimumab in Combination With Methotrexate in Adults With Early Rheumatoid Arthritis Who Are Naive to Biologic Disease-Modifying Antirheumatic Drugs
• Actual Study Start Date: Nov 19, 2015
• Actual Primary Completion Date: Mar 28, 2019
• Actual Study Completion Date: Mar 28, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment A Abatacept Single Blind Treatment Period	Drug: Abatacept; Other Names: Orencia ; Drug: Methotrexate
Active Comparator: Treatment B Adalimumab Single Blind Treatment Period	Drug: Abatacept; Other Names: Orencia ; Drug: Adalimumab; Other Names: Humira ; Drug: Methotrexate
Active Comparator: Treatment C Abatacept Cumulative Treatment Period	Drug: Abatacept; Other Names: Orencia

Outcome Measures

Primary Outcome Measures

1. Percentage of Adverse Events (AEs) [up to 85 days post last dose, approximately 40 weeks]

   Percentage of participants who experienced an AE

2. Percentage of Participants With an Serious Adverse Events (SAEs) [up to 85 days post last dose, approximately 40 weeks]

   Percentage of participants who experienced an SAEs

3. Percentage of Participants With Adverse Events Leading to Discontinuation (AEsDc) [up to 85 days post last dose, approximately 40 weeks]

   Percentage of participants who experienced an (AEsDc)

4. Percentage of Serious Adverse Events Leading to Discontinuation (SAEsDc) [up to 85 days post last dose, approximately 40 weeks]

   Percentage of participants who experienced an (SAEsDc)

5. Percentage of Drug Related Adverse Events (DRAEs) [up to 85 days post last dose, approximately 40 weeks]

   Percentage of participants who experienced an DRAEs

6. Percentage of Drug Related Serious Adverse Events (DRSAEs) [up to 85 days post last dose, approximately 40 weeks]

   Percentage of participants who experienced an DRSAEs

7. Number of Deaths [up to 85 days post last dose, approximately 40 weeks]

   Number of participants who experienced Death

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

• Symptoms of RA for no more than 12 months prior to enrollment

• Meet American College of Rheumatology/European League against Rheumatism (ACR/EULAR) 2010 criteria for classification of RA

• Treated with Methotrexate (MTX) for at least 12 weeks prior to randomization with a stable oral dose for at least 4 weeks, Subjects must randomize on the maximum tolerated dose of oral methotrexate (minimum of 15 mg and maximum of 25 mg per week), dose of MTX < 15 mg/week but ≥ 7.5 mg/week is permitted if subjects are intolerant to higher doses

• At least 3 tender & 3 swollen joints

• Anti-cyclic citrullinated peptide (CCP) > 3X the upper limit of normal and positive rheumatoid factor

Exclusion Criteria:

• History of other autoimmune diseases (eg, psoriasis, systemic lupus, erythematosus, etc)

• Prior use of non-biologic therapy other than methotrexate

• Prior use of biologic and targeted synthetic disease-modifying anti-rheumatic drugs (DMARD) therapy

• Subjects with chronic or recent acute serious infection

Other protocol defined inclusion/exclusion criteria could apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University Of Alabama At Birmingham	Birmingham	Alabama	United States	35294-7201
2	Rheumatology Associates Of North Alabama, P.C.	Huntsville	Alabama	United States	35801
3	Clinical And Translational Research Center Of Alabama, Pc	Tuscaloosa	Alabama	United States	35406
4	Arizona Arthritis & Rheumatology Research PLLC	Glendale	Arizona	United States	85306
5	Arizona Arthritis & Rheumatology Research PLLC	Phoenix	Arizona	United States	85037
6	St. Joseph Heritage Medical Group	Fullerton	California	United States	92835
7	Desert Medical Advances	Palm Desert	California	United States	92260
8	University Of Colorado Health Sciences Center	Aurora	Colorado	United States	80045
9	Medical Faculty Associates,Inc.	Washington	District of Columbia	United States	20037
10	Howard University Hospital	Washington	District of Columbia	United States	20060
11	Integral Rheumatology & Immunology Specialists	Plantation	Florida	United States	33324
12	Marietta Rheumatology	Marietta	Georgia	United States	30060
13	The Center For Rheumatology And Bone Research	Wheaton	Maryland	United States	20902
14	Clinical Pharmacology Study Group	Worcester	Massachusetts	United States	01605
15	Aa Mrc Llc	Grand Blanc	Michigan	United States	48439
16	Dartmouth-Hitchcock Medical Center	Lebanon	New Hampshire	United States	03756
17	Oregon Health & Science University (Ohsu)	Portland	Oregon	United States	97239
18	Altoona Center For Clinical Research	Duncansville	Pennsylvania	United States	16635-8406
19	Carolina Health Specialists	Myrtle Beach	South Carolina	United States	29572
20	West Tennessee Research Institute	Jackson	Tennessee	United States	38305
21	Arthritis Clinic Of Northern Virginia, P.C.	Arlington	Virginia	United States	22205
22	Dr. Anil K Gupta Med Prof Corp	Toronto	Ontario	Canada	M9V 4B4
23	Essex County Medical Society	Windsor	Ontario	Canada	N8X 5A6
24	Institut De Rhumatologie De Montreal	Montreal	Quebec	Canada	H2L 1S6
25	Centre De Recherche Musculo-Squelettique	Trois-rivieres	Quebec	Canada	G8Z 1Y2
26	CINTRE - Centro de investigacion y tratamiento reumatologico, S.C.	Mexico City	Distrito Federal	Mexico	11850
27	Clinica de Investigacion en Reumatologia y Obesidad S.C.	Guadalajara	Jalisco	Mexico	44650
28	Clinica Integral en Osteoporosis y Artritis CLINOSAR Mexico S.A. de C.V.	Mexico D.F.		Mexico	06760

Sponsors and Collaborators

• Bristol-Myers Squibb

Investigators

• Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Study Documents (Full-Text)

• Study Protocol - Jul 27, 2015
• Statistical Analysis Plan - Jul 11, 2019

More Information

Additional Information:

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting
• FDA Safety Alerts and Recalls

Publications

None provided.

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT02557100
• Other Study ID Numbers: IM101-567
• First Posted: Sep 23, 2015
• Last Update Posted: Sep 3, 2020
• Last Verified: Aug 1, 2020

• Additional relevant MeSH terms: Arthritis; Arthritis, Rheumatoid; Adalimumab; Methotrexate; Abatacept

Study Results

Participant Flow

Pre-assignment Detail	80 participants randomized and treated.

Arm/Group Title	Treatment A	Treatment B	Treatment C
Arm/Group Description	Abatacept Single Blind Treatment Period	Adalimumab Single Blind Treatment Period	Cumulative Abatacept Period
Period Title: Single Blind Treatment Period
STARTED	40	40	0
COMPLETED	40	36	0
NOT COMPLETED	0	4	0
Period Title: Single Blind Treatment Period
STARTED	40	36	0
COMPLETED	0	0	0
NOT COMPLETED	40	36	0
Period Title: Single Blind Treatment Period
STARTED	0	0	76
COMPLETED	0	0	72
NOT COMPLETED	0	0	4

Baseline Characteristics

Arm/Group Title	Treatment A	Treatment B	Treatment C	Total
Arm/Group Description	Abatacept Single Blind Treatment Period	Adalimumab Single Blind Treatment Period	Cumulative Abatacept Period	Total of all reporting groups
Overall Participants	40	40	0	80
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	47.2 (12.16)	44.7 (16.30)	46.0 (14.35)
Sex: Female, Male (Count of Participants)
Female	29 72.5%	31 77.5%	60 Infinity
Male	11 27.5%	9 22.5%	20 Infinity
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	4 10%	6 15%	10 Infinity
Not Hispanic or Latino	16 40%	14 35%	30 Infinity
Unknown or Not Reported	20 50%	20 50%	40 Infinity
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 NaN
Asian	0 0%	2 5%	2 Infinity
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 NaN
Black or African American	4 10%	1 2.5%	5 Infinity
White	36 90%	36 90%	72 Infinity
More than one race	0 0%	0 0%	0 NaN
Unknown or Not Reported	0 0%	1 2.5%	1 Infinity

Outcome Measures

1. Primary Outcome

Title	Percentage of Adverse Events (AEs)
Description	Percentage of participants who experienced an AE
Time Frame	up to 85 days post last dose, approximately 40 weeks

Outcome Measure Data

Analysis Population Description

All Treated Participants

Arm/Group Title	Treatment A	Treatment B	Treatment C
Arm/Group Description	Abatacept Single Blind Treatment Period	Adalimumab Single Blind Treatment Period	Cumulative Abatacept Period
Measure Participants	40	40	76
Number [Percentage of participant with AEs]	55.0	70.0	57.9

2. Primary Outcome

Title	Percentage of Participants With an Serious Adverse Events (SAEs)
Description	Percentage of participants who experienced an SAEs
Time Frame	up to 85 days post last dose, approximately 40 weeks

Outcome Measure Data

Analysis Population Description

All treated participants

Arm/Group Title	Treatment A	Treatment B	Treatment C
Arm/Group Description	Abatacept Single Blind Treatment Period	Adalimumab Single Blind Treatment Period	Cumulative Abatacept Period
Measure Participants	40	40	76
Number [Percentage of participants with SAEs]	2.5 6.3%	5.0 12.5%	5.3 Infinity

3. Primary Outcome

Title	Percentage of Participants With Adverse Events Leading to Discontinuation (AEsDc)
Description	Percentage of participants who experienced an (AEsDc)
Time Frame	up to 85 days post last dose, approximately 40 weeks

Outcome Measure Data

Analysis Population Description

All Treated Participants

Arm/Group Title	Treatment A	Treatment B	Treatment C
Arm/Group Description	Abatacept Single Blind Treatment Period	Adalimumab Single Blind Treatment Period	Cumulative Abatacept Period
Measure Participants	40	40	76
Number [Percentage of participants with AEsDC]	0 0%	2.5 6.3%	0 NaN

4. Primary Outcome

Title	Percentage of Serious Adverse Events Leading to Discontinuation (SAEsDc)
Description	Percentage of participants who experienced an (SAEsDc)
Time Frame	up to 85 days post last dose, approximately 40 weeks

Outcome Measure Data

Analysis Population Description

All Treated Participants

Arm/Group Title	Treatment A	Treatment B	Treatment C
Arm/Group Description	Abatacept Single Blind Treatment Period	Adalimumab Single Blind Treatment Period	Cumulative Abatacept Period
Measure Participants	40	40	76
Number [Percentage of participants with SAEsDc]	0 0%	2.5 6.3%	0 NaN

5. Primary Outcome

Title	Percentage of Drug Related Adverse Events (DRAEs)
Description	Percentage of participants who experienced an DRAEs
Time Frame	up to 85 days post last dose, approximately 40 weeks

Outcome Measure Data

Analysis Population Description

All Treated Participants

Arm/Group Title	Treatment A	Treatment B	Treatment C
Arm/Group Description	Abatacept Single Blind Treatment Period	Adalimumab Single Blind Treatment Period	Cumulative Abatacept Period
Measure Participants	40	40	76
Number [Percentage of participants with DRAEs]	30.0 75%	27.5 68.8%	22.4 Infinity

6. Primary Outcome

Title	Percentage of Drug Related Serious Adverse Events (DRSAEs)
Description	Percentage of participants who experienced an DRSAEs
Time Frame	up to 85 days post last dose, approximately 40 weeks

Outcome Measure Data

Analysis Population Description

All Treated Participants

Arm/Group Title	Treatment A	Treatment B	Treatment C
Arm/Group Description	Abatacept Single Blind Treatment Period	Adalimumab Single Blind Treatment Period	Cumulative Abatacept Period
Measure Participants	40	40	76
Number [Percentage of Participants with DRSAEs]	0 0%	2.5 6.3%	0 NaN

7. Primary Outcome

Title	Number of Deaths
Description	Number of participants who experienced Death
Time Frame	up to 85 days post last dose, approximately 40 weeks

Outcome Measure Data

Analysis Population Description

All Treated Participants

Arm/Group Title	Treatment A	Treatment B	Treatment C
Arm/Group Description	Abatacept Single Blind Treatment Period	Adalimumab Single Blind Treatment Period	Cumulative Abatacept Period
Measure Participants	40	40	76
Number [Number of Deaths]	0	1	0

Adverse Events

Time Frame	up to 85 days post last dose, approximately 40 weeks
Arm/Group Title	Treatment A		Treatment B		Treatment C
Arm/Group Description	Abatacept Single Blind Treatment Period		Adalimumab Single Blind Treatment Period		Cumulative Abatacept Period
All Cause Mortality
	Treatment A		Treatment B		Treatment C
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/40 (0%)		1/40 (2.5%)		0/76 (0%)
Serious Adverse Events
	Treatment A		Treatment B		Treatment C
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/40 (2.5%)		2/40 (5%)		4/76 (5.3%)
Cardiac disorders
Myocardial Infarction	0/40 (0%)		0/40 (0%)		1/76 (1.3%)
Congenital, familial and genetic disorders
Atrial Septal Defect	1/40 (2.5%)		0/40 (0%)		1/76 (1.3%)
General disorders
Sudden Death	0/40 (0%)		1/40 (2.5%)		0/76 (0%)
Infections and infestations
Varicella	0/40 (0%)		1/40 (2.5%)		0/76 (0%)
Injury, poisoning and procedural complications
Incision site complication	0/40 (0%)		0/40 (0%)		1/76 (1.3%)
Patella fracture	0/40 (0%)		0/40 (0%)		1/76 (1.3%)
Nervous system disorders
Cerebral Infarction	1/40 (2.5%)		0/40 (0%)		1/76 (1.3%)
Other (Not Including Serious) Adverse Events
	Treatment A		Treatment B		Treatment C
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/40 (52.5%)		28/40 (70%)		19/76 (25%)
Blood and lymphatic system disorders
Leukopenia	0/40 (0%)		2/40 (5%)		0/76 (0%)
Neutropenia	0/40 (0%)		2/40 (5%)		0/76 (0%)
Infections and infestations
Upper respiratory tract infection	3/40 (7.5%)		14/40 (35%)		10/76 (13.2%)
Nasopharyngitis	4/40 (10%)		2/40 (5%)		5/76 (6.6%)
Urinary Tract Infection	4/40 (10%)		0/40 (0%)		5/76 (6.6%)
Investigations
Alanine Aminotransferase Increased	3/40 (7.5%)		6/40 (15%)		9/76 (11.8%)
Aspartate Aminotransferase Increased	2/40 (5%)		5/40 (12.5%)		7/76 (9.2%)
Gamma-glutamyltransferase increased	2/40 (5%)		0/40 (0%)		2/76 (2.6%)
Nervous system disorders
Headache	2/40 (5%)		2/40 (5%)		0/76 (0%)
Skin and subcutaneous tissue disorders
Alopecia	1/40 (2.5%)		3/40 (7.5%)		0/76 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

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.