MTX-IR: Methotrexate - Inadequate Response Device Sub-Study

• Sponsor: Bristol-Myers Squibb (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01173120
• Collaborator: (none)
• Enrollment: 62
• Arm: 1
• Duration (Months): 8

Study Details

Study Description

Brief Summary

The purpose of this study is to determine the safety and acceptability of a device used in place of traditional syringes for abatacept self-injection.

Condition or Disease	Intervention/Treatment	Phase
Rheumatoid Arthritis (RA)	Device: Abatacept combination product (ACP)	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 62 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Sub-study-A Phase IIIB Multicenter, Randomized, Double-Blind, Double-Dummy Study to Compare the Efficacy and Safety of Abatacept Administered Subcutaneously and Intravenously in Subjects With Rheumatoid Arthritis, Receiving Background Methotrexate, and Experiencing an Inadequate Response to Methotrexate
• Study Start Date: Nov 1, 2009
• Actual Primary Completion Date: Feb 1, 2010
• Actual Study Completion Date: Jul 1, 2010

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Abatacept Combination Product (ACP) Participants from the long-term period of study NCT00559585 who enrolled in the ACP substudy switched to administration of subcutaneous (SC) abatacept via the ACP for the duration of the substudy. Abatacept was administered SC using the ACP by the participant or caregiver on Substudy Day 1 and at weekly intervals thereafter. The ACP was a pre-filled liquid product device delivering 125 mg abatacept/device (125 mg/mL).

Device: Abatacept combination product (ACP); Abatacept Solution, Subcutaneous, 125 mg/device, Weekly, 3 months; Other Names: Orencia BMS-188667

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Death, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Treatment-related AEs, and AEs Leading to Discontinuation [ACP substudy Day 1 to last substudy assessment occurring prior to the 1st dose of non-ACP subcutaneous (SC) abatacept, assessed up to 12 months]

   An AE is any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment. An SAE is any unfavorable medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency or abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=possibly, probably, or certainly related to and of unknown relationship to study treatment.

2. Number of Participants With AEs of Special Interest in the ACP Device Substudy [ACP substudy Day 1 to last substudy assessment occurring prior to 1st dose of non-ACP SC abatacept (administered once participants switched back to main study). For participants discontinuing both studies: Day 1 of ACP dosing to 56 days post last ACP dose]

   AE=any new untoward medical occurrence or worsening of a preexisting medical condition which does not necessarily have a causal relationship with this treatment. AEs of special interest are those AEs that may be associated with the use of immunomodulatory drugs including all infections, local injection reactions (prespecified), and systemic injection reactions (within 24 hours of dosing).

3. Number of Participants With Laboratory Test Results in Hematology Meeting the Criteria for Marked Abnormality in the ACP Device Substudy [ACP substudy Day 1 to last substudy assessment occurring prior to 1st dose of non-ACP SC abatacept (administered once participants switched back to main study). For participants discontinuing both studies: Day 1 of ACP dosing to 7 days post last ACP dose.]

   BL=baseline; LLN lower limit of normal; ULN=upper limit of normal. Marked abnormality criteria: Hemoglobin: >3 g/dL decrease from BL; Hematocrit: <0.75*BL; Erythrocytes: <0.75*BL; Platelets: <0.67*LLN/>1.5*ULN, or if BL <LLN, use 0.5*BL/<100,000 mm^3; Leukocytes: <0.75*LLN/ >1.25*ULN, or if BL<LLN, use <0.8*BL/>ULN, or if BL>ULN, use >1.2*BL/<LLN; neutrophils+bands: <1.0*10^3 c/uL; eosinophils: >0.750*10^3 c/uL; basophils: >400 mm^3; monocytes: >2000 mm^3; lymphocytes: <0.750*10^3 c/uL/ >7.50*10^3 c/uL.

4. Number of Participants With Liver Function Laboratories Meeting MA Criteria in the ACP Device Substudy [ACP substudy Day 1 to last substudy assessment occurring prior to 1st dose of non-ACP SC abatacept (administered once participants switched back to main study). For participants discontinuing both studies: Day 1 of ACP dosing to 7 days post last ACP dose.]

   Marked abnormality criteria: Alkaline phosphatase (ALP): >2* ULN, or if BL>ULN then use >3* BL; aspartate aminotransferase (AST): >3* ULN, or if BL>ULN then use >4* BL; alanine aminotransferase (ALT): >3* ULN, or if BL>ULN then use >4* BL; G-Glutamyl transferase (GGT): >2* ULN, or if BL>ULN then use >3* BL; Bilirubin: >2* ULN, or if BL>ULN then use >4* BL; blood urea nitrogen (BUN): >2* BL; creatinine: >1.5* BL

5. Number of Participants With Electrolyte Laboratories Meeting MA Criteria in the ACP Device Substudy [ACP substudy Day 1 to last substudy assessment occurring prior to 1st dose of non-ACP SC abatacept (administered once participants switched back to main study). For participants discontinuing both studies: Day 1 of ACP dosing to 7 days post last ACP dose.]

   Marked abnormality criteria: Sodium (Na): <0.95*LLN/ >1.05*ULN, or if BL<LLN then use <0.95* BL or >ULN, or if BL>ULN then use>1.05* BL or <LLN; potassium (K): <0.9* LLN/>1.1*ULN, or if BL<LLN then use <0.9* BL or >ULN, or if BL>ULN then use>1.1* BL or <LLN; (Cl): <0.9* LLN/>1.1* ULN, or if BL<LLN then use <0.9* BL or >ULN, or if BL>ULN then use>1.1* BL or <LLN; calcium (Ca): <0.8* LLN/>1.2* ULN, or if BL<LLN then use <0.75* BL or >ULN, or if BL>ULN then use>1.25* BL or <LLN; phosphorous (P): <0.75* LLN/ >1.25* ULN, or if BL<LLN then use 0.67* BL or >ULN, or if BL>ULN then use>1.33* BL or <LLN

6. Number of Participants With Other Chemistry and Urinalysis Laboratories Meeting MA Criteria in the ACP Device Substudy [ACP substudy Day 1 to last substudy assessment occurring prior to 1st dose of non-ACP SC abatacept (administered once participants switched back to main study). For participants discontinuing both studies: Day 1 of ACP dosing to 7 days post last ACP dose.]

   MA criteria: serum glucose (Glu): <65 mg/dL/>220 mg/dL;fasting serum Glu: <0.8* LLN/>1.5*ULN,or if BL<LLN then use 0.8*BL or >ULN,or if BL>ULN then use >2.0*BL or <LLN;total protein: <0.9*LLN/>1.1*ULN,or if BL<LLN then use <0.9*BL or >UNL,or if BL>UNL then use >1.1*BL or <LLN; albumin: <0.9*LLN,or if BL<LLN then use <0.75 BL;uric acid: >1.5*ULN,or if BL>ULN then use >2*BL. Urinalysis (Urine protein,urine Glu,urine blood,leukocyte esterase,Red Blood Cells [RBCs], White Blood Cells [WBCs]):Use ≥2 when BL value missing or when pre-dose=0 or 0.5; use ≥3 when pre-dose=1, use ≥4 when pre-dose=2 or 3

7. Mean Systolic Blood Pressure (SBP) Over Time in the ACP Device Substudy [ACP substudy Day 1 to last substudy assessment occurring prior to 1st dose of non-ACP SC abatacept (administered once participants switched back to main study). For participants discontinuing both studies: Day 1 of ACP dosing to 7 days post last ACP dose.]

8. Mean Diastolic Blood Pressure (DBP) Over Time in the ACP Device Substudy [ACP substudy Day 1 to last substudy assessment occurring prior to 1st dose of non-ACP SC abatacept (administered once participants switched back to main study). For participants discontinuing both studies: Day 1 of ACP dosing to 7 days post last ACP dose.]

9. Mean Heart Rate Over Time in the ACP Device Substudy [ACP substudy Day 1 to last substudy assessment occurring prior to 1st dose of non-ACP SC abatacept (administered once participants switched back to main study). For participants discontinuing both studies: Day 1 of ACP dosing to 7 days post last ACP dose.]

10. Mean Temperature Over Time in the ACP Device Substudy [ACP substudy Day 1 to last substudy assessment occurring prior to 1st dose of non-ACP SC abatacept (administered once participants switched back to main study). For participants discontinuing both studies: Day 1 of ACP dosing to 7 days post last ACP dose.]

Secondary Outcome Measures

1. Minimum Observed Serum Concentration (Cmin) of Abatacept Over Time in the ACP Device Substudy [Days 1, 29, 57, 85, 169, and 253 of ACP substudy]

   Trough levels of abatacept were evaluated based upon serum samples. Day 1 pharmacokinetics were based on exposure to the pre-filled syringes and did not reflect abatacept exposure via the ACP device.

2. Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Responses Over Time by Enzyme Linked Immunosorbant Assay (ELISA) in the ACP Device Substudy [ACP substudy Day 1 to last substudy assessment occurring prior to 1st dose of non-ACP SC abatacept (administered once participants switched back to main study). For participants discontinuing both studies: Day 1 of ACP dosing to 28 days post last ACP dose]

   Serum samples from all treated adult participants with active rheumatoid arthritis were screened for the presence of drug-specific antibodies using ELISA. Immunogenicity was defined as the presence of a positive anti-abatacept or anti-CTLA4 antibody.

3. Number of Participants With Positive Anti-abatacept Responses Over Time by Electrochemiluminescence Immunoassay in the ACP Device Substudy [ACP substudy Day 1 to last substudy assessment occurring prior to 1st dose of non-ACP SC abatacept (administered once participants switched back to main study). For participants discontinuing both studies: Day 1 of ACP dosing to 85 days post last ACP dose]

   An electrochemiluminescence immunoassay screened sera for drug-specific antibodies; immunocompetition was used to identify specific anti-Abatacept reactivity. CTLA4 and Possibly immunoglobulin (Ig) category=reactivity against extracellular domain of human CTLA4, constant regions of human IgG1, or both (CTLA4Ig; Abatacept molecule). Ig and/or Junction (JNCT)category=reactivity against constant regions and/or hinge region of human IgG1. Drug-induced seropositivity defined as a post-baseline titer higher than Baseline, or any post-baseline positivity if Baseline value was missing. TRT=treatment

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Men and women, ages ≥ 18

• Participants who are considered methotrexate inadequate responders (MTX-IR)

• 10 or more swollen joints (66 joint count) and 12 or more tender joints (68 joint count)

• Participants were to have been enrolled in the main MTX-IR study and been treated with open label abatacept for at least 3 months in the long term period

Exclusion Criteria:

• Participants who failed one or multiple anti-tumor necrosis factor (TNF) therapies

• Participants who meet diagnostic criteria for any other rheumatic disease (e.g., lupus erythematosus)

• Participants with active vasculitis of a major organ system (except for subcutaneous rheumatoid nodules)

• Participants with severe chronic or recurrent bacterial infections

• Participants who have received treatment with rituximab

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Bristol-Myers Squibb

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT01173120
• Other Study ID Numbers: IM101-174 (Sub study); 2007-005434-37
• First Posted: Jul 30, 2010
• Last Update Posted: Jan 12, 2012
• Last Verified: Jan 1, 2012

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

Study Results

Participant Flow

Arm/Group Title	Abatacept Combination Product (ACP)
Arm/Group Description	Participants from the long-term period of the IM101-174 main study who enrolled in the ACP substudy switched to administration of subcutaneous (SC) abatacept via the ACP for the duration of the substudy. Abatacept was administered SC using the ACP by the participant or caregiver on Substudy Day 1 and at weekly intervals thereafter. The ACP was a prefilled liquid product device delivering 125 mg abatacept/device (125 mg/mL).
Period Title: Overall Study
STARTED	62
Switched Back to Main Study	57
Discontinued ACP Substudy and Main Study	5
COMPLETED	0
NOT COMPLETED	62

Baseline Characteristics

Arm/Group Title	Abatacept Combination Product (ACP)
Arm/Group Description	Participants from the long-term period of the IM101-174 main study who enrolled in the ACP substudy switched to administration of subcutaneous (SC) abatacept via the ACP for the duration of the substudy. Abatacept was administered SC using the ACP by the participant or caregiver on Substudy Day 1 and at weekly intervals thereafter. The ACP was a prefilled liquid product device delivering 125 mg abatacept/device (125 mg/mL).
Overall Participants	62
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	54.2 (10.1)
Sex: Female, Male (Count of Participants)
Female	47 75.8%
Male	15 24.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	2 3.2%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	8 12.9%
White	51 82.3%
More than one race	0 0%
Unknown or Not Reported	1 1.6%
Region of Enrollment (participants) [Number]
North America	62 100%
Weight (kg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg]	86.3 (20.1)
Mean Duration of Disease (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	7.4 (10.1)
Duration of Disease-Categorical (participants) [Number]
≤ 2 years	28 45.2%
>2 - ≤5 years	10 16.1%
>5 - 10 years	7 11.3%
>10 years	17 27.4%
Number of Tender Joints (tender joints) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [tender joints]	31.6 (15.2)
Number of Swollen Joints (swollen joints) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [swollen joints]	20.8 (8.2)
Participant Pain Assessment (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	64.2 (21.5)
Physical Function (Health Assessment Questionnaire Disability Index [HAQ-DI]) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	1.5 (0.7)
Participant Global Assessment (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	61.6 (19.7)
Physician Global Assessment (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	62.0 (17.4)
High Sensitivity C-Reactive Protein (hs-CRP) Level (mg/dL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/dL]	1.7 (1.2)
Disease Activity Score (DAS 28) (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	6.0 (0.8)
Rheumatoid Factor (RF) Status (participants) [Number]
Positive	46 74.2%
Negative	16 25.8%
Baseline Methotrexate Dose (mg/wk) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mg/wk]	17.2 (3.8)

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Death, Serious Adverse Events (SAEs), Treatment-related SAEs, SAEs Leading to Discontinuation, Adverse Events (AEs), Treatment-related AEs, and AEs Leading to Discontinuation
Description	An AE is any new unfavorable symptom, sign, or disease or worsening of a preexisting condition that does not necessarily have a causal relationship with treatment. An SAE is any unfavorable medical event that at any dose results in death, persistent or significant disability/incapacity, or drug dependency or abuse; is life-threatening, an important medical event, or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=possibly, probably, or certainly related to and of unknown relationship to study treatment.
Time Frame	ACP substudy Day 1 to last substudy assessment occurring prior to the 1st dose of non-ACP subcutaneous (SC) abatacept, assessed up to 12 months

Outcome Measure Data

Analysis Population Description

As-Treated Population, defined as all participants enrolled in ACP substudy who received at least 1 dose of SC abatacept administered via the ACP.

Arm/Group Title	Abatacept Combination Product (ACP)
Arm/Group Description	Participants from the long-term period of the IM101-174 main study who enrolled in the ACP substudy switched to administration of SC abatacept via the ACP for the duration of the substudy. Abatacept was administered using the ACP by the participant or caregiver on Substudy SC on Day 1 and at weekly intervals thereafter. The ACP was a prefilled liquid product device delivering 125 mg abatacept/device (125 mg/mL).
Measure Participants	62
Deaths	0 0%
SAEs	2 3.2%
Treatment-related SAE	0 0%
SAEs Leading to Discontinuation	0 0%
AEs	36 58.1%
Treatment-related AEs	11 17.7%
AEs Leading to Discontinuation	0 0%

2. Secondary Outcome

Title	Minimum Observed Serum Concentration (Cmin) of Abatacept Over Time in the ACP Device Substudy
Description	Trough levels of abatacept were evaluated based upon serum samples. Day 1 pharmacokinetics were based on exposure to the pre-filled syringes and did not reflect abatacept exposure via the ACP device.
Time Frame	Days 1, 29, 57, 85, 169, and 253 of ACP substudy

Outcome Measure Data

Analysis Population Description

As-Treated Population, defined as all participants enrolled in ACP substudy who received at least 1 dose of SC abatacept administered via the ACP. Trough concentrations in participants who discontinued from the substudy were not summarized descriptively, but were included in the concentration listings.

Arm/Group Title	Abatacept Combination Product (ACP)
Arm/Group Description	Participants from the long-term period of the IM101-174 main study who enrolled in the ACP substudy switched to administration of subcutaneous (SC) abatacept via the ACP for the duration of the substudy. Abatacept was administered SC using the ACP by the participant or caregiver on Substudy Day 1 and at weekly intervals thereafter. The ACP was a prefilled liquid product device delivering 125 mg abatacept/device (125 mg/mL).
Measure Participants	62
Day 1 (prior to administration with ACP) (n =53)	24.34 (15.56)
Day 29 (n=52)	27.61 (14.12)
Day 57 (n=39)	31.52 (14.49)
Day 85 (n=47)	27.46 (17.43)
Day 169 (n=35)	26.85 (14.55)
Day 253 (n=5)	24.41 (14.19)

3. Primary Outcome

Title	Number of Participants With AEs of Special Interest in the ACP Device Substudy
Description	AE=any new untoward medical occurrence or worsening of a preexisting medical condition which does not necessarily have a causal relationship with this treatment. AEs of special interest are those AEs that may be associated with the use of immunomodulatory drugs including all infections, local injection reactions (prespecified), and systemic injection reactions (within 24 hours of dosing).
Time Frame	ACP substudy Day 1 to last substudy assessment occurring prior to 1st dose of non-ACP SC abatacept (administered once participants switched back to main study). For participants discontinuing both studies: Day 1 of ACP dosing to 56 days post last ACP dose

Outcome Measure Data

Analysis Population Description

As-Treated Population, defined as all participants enrolled in ACP substudy who received at least 1 dose of subcutaneous abatacept administered via the ACP.

Arm/Group Title	Abatacept Combination Product (ACP)
Arm/Group Description	Participants from the long-term period of the IM101-174 main study who enrolled in the ACP substudy switched to administration of subcutaneous abatacept via the ACP for the duration of the substudy. Abatacept was administered subcutaneously using the ACP by the participant or caregiver on Substudy Day 1 and at weekly intervals thereafter. The ACP was a pre-filled liquid product device delivering 125 mg abatacept/device (125 mg/mL).
Measure Participants	62
Infections	17 27.4%
Local injection reactions	5 8.1%
Systemic injection reactions	2 3.2%

4. Primary Outcome

Title	Number of Participants With Laboratory Test Results in Hematology Meeting the Criteria for Marked Abnormality in the ACP Device Substudy
Description	BL=baseline; LLN lower limit of normal; ULN=upper limit of normal. Marked abnormality criteria: Hemoglobin: >3 g/dL decrease from BL; Hematocrit: <0.75*BL; Erythrocytes: <0.75*BL; Platelets: <0.67*LLN/>1.5*ULN, or if BL <LLN, use 0.5*BL/<100,000 mm^3; Leukocytes: <0.75*LLN/ >1.25*ULN, or if BL<LLN, use <0.8*BL/>ULN, or if BL>ULN, use >1.2*BL/<LLN; neutrophils+bands: <1.0*10^3 c/uL; eosinophils: >0.750*10^3 c/uL; basophils: >400 mm^3; monocytes: >2000 mm^3; lymphocytes: <0.750*10^3 c/uL/ >7.50*10^3 c/uL.
Time Frame	ACP substudy Day 1 to last substudy assessment occurring prior to 1st dose of non-ACP SC abatacept (administered once participants switched back to main study). For participants discontinuing both studies: Day 1 of ACP dosing to 7 days post last ACP dose.

Outcome Measure Data

Analysis Population Description

As-Treated Population, defined as all participants enrolled in ACP substudy who received at least 1 dose of SC abatacept administered via the ACP.

Arm/Group Title	Abatacept Combination Product (ACP)
Arm/Group Description	Participants from the long-term period of the IM101-174 main study who enrolled in the ACP substudy switched to administration of subcutaneous (SC) abatacept via the ACP for the duration of the substudy. Abatacept was administered SC using the ACP by the participant or caregiver on Substudy Day 1 and at weekly intervals thereafter. The ACP was a prefilled liquid product device delivering 125 mg abatacept/device (125 mg/mL).
Measure Participants	50
Low hemoglobin (LLN=11.5 g/dL)	1 1.6%
Low hematocrit (LLN=34%)	1 1.6%
Low erythrocytes(LLN=3.8 x10*6c/uL)	1 1.6%
Low platelets (LLN=140*10^9 c/L)	0 0%
High platelets (ULN=450*10^9 c/L)	0 0%
Low leukocytes (LLN= 3.8*10^3 c/uL)	0 0%
High leukocytes (ULN = 10.6*10^3 c/uL)	1 1.6%
Low neutrophils+bands(LLN=1.8*10^3 c/uL)	0 0%
High eosinophils (ULN= 7*10^3 c/uL)	0 0%
High basophils (ULN= 0.2*10^3 c/uL)	0 0%
High monocytes (ULN=1*10^3 c/uL)	0 0%
Low lymphocytes (LLN= 0.7*10^3 c/uL)	3 4.8%
High lymphocytes(ULN=4.5*10^3 c/uL)	0 0%

5. Primary Outcome

Title	Number of Participants With Liver Function Laboratories Meeting MA Criteria in the ACP Device Substudy
Description	Marked abnormality criteria: Alkaline phosphatase (ALP): >2* ULN, or if BL>ULN then use >3* BL; aspartate aminotransferase (AST): >3* ULN, or if BL>ULN then use >4* BL; alanine aminotransferase (ALT): >3* ULN, or if BL>ULN then use >4* BL; G-Glutamyl transferase (GGT): >2* ULN, or if BL>ULN then use >3* BL; Bilirubin: >2* ULN, or if BL>ULN then use >4* BL; blood urea nitrogen (BUN): >2* BL; creatinine: >1.5* BL
Time Frame	ACP substudy Day 1 to last substudy assessment occurring prior to 1st dose of non-ACP SC abatacept (administered once participants switched back to main study). For participants discontinuing both studies: Day 1 of ACP dosing to 7 days post last ACP dose.

Outcome Measure Data

Analysis Population Description

As-Treated Population, defined as all participants enrolled in ACP substudy who received at least 1 dose of SC abatacept administered via the ACP.

Arm/Group Title	Abatacept Combination Product (ACP)
Arm/Group Description	Participants from the long-term period of the IM101-174 main study who enrolled in the ACP substudy switched to administration of subcutaneous (SC) abatacept via the ACP for the duration of the substudy. Abatacept was administered SC using the ACP by the participant or caregiver on Substudy Day 1 and at weekly intervals thereafter. The ACP was a prefilled liquid product device delivering 125 mg abatacept/device (125 mg/mL).
Measure Participants	50
High ALP (ULN=400 U/L)	0 0%
High AST (ULN=44 U/L)	1 1.6%
High ALT (ULN=55 U/L)	1 1.6%
High GGT (ULN=65 U/L)	2 3.2%
High bilirubin (ULN=1.2 mg/dL)	0 0%
High BUN (ULN=26 mg/dL)	1 1.6%
High creatinine (ULN=1.5 mg/dL)	1 1.6%

6. Primary Outcome

Title	Number of Participants With Electrolyte Laboratories Meeting MA Criteria in the ACP Device Substudy
Description	Marked abnormality criteria: Sodium (Na): <0.95*LLN/ >1.05*ULN, or if BL<LLN then use <0.95* BL or >ULN, or if BL>ULN then use>1.05* BL or <LLN; potassium (K): <0.9* LLN/>1.1*ULN, or if BL<LLN then use <0.9* BL or >ULN, or if BL>ULN then use>1.1* BL or <LLN; (Cl): <0.9* LLN/>1.1* ULN, or if BL<LLN then use <0.9* BL or >ULN, or if BL>ULN then use>1.1* BL or <LLN; calcium (Ca): <0.8* LLN/>1.2* ULN, or if BL<LLN then use <0.75* BL or >ULN, or if BL>ULN then use>1.25* BL or <LLN; phosphorous (P): <0.75* LLN/ >1.25* ULN, or if BL<LLN then use 0.67* BL or >ULN, or if BL>ULN then use>1.33* BL or <LLN
Time Frame	ACP substudy Day 1 to last substudy assessment occurring prior to 1st dose of non-ACP SC abatacept (administered once participants switched back to main study). For participants discontinuing both studies: Day 1 of ACP dosing to 7 days post last ACP dose.

Outcome Measure Data

Analysis Population Description

As-Treated Population, defined as all participants enrolled in ACP substudy who received at least 1 dose of SC abatacept administered via the ACP.

Arm/Group Title	Abatacept Combination Product (ACP)
Arm/Group Description	Participants from the long-term period of the IM101-174 main study who enrolled in the ACP substudy switched to administration of subcutaneous (SC) abatacept via the ACP for the duration of the substudy. Abatacept was administered SC using the ACP by the participant or caregiver on Substudy Day 1 and at weekly intervals thereafter. The ACP was a prefilled liquid product device delivering 125 mg abatacept/device (125 mg/mL).
Measure Participants	50
Low Na (LLN=135 mEq/L)	0 0%
High Na (ULN=148 mEq/L)	0 0%
Low K (LLN=3.5 mEq/L)	1 1.6%
High K (ULN=5.5 mEq/L)	1 1.6%
Low Cl (LLN= 96 mEq/L)	0 0%
High Cl (ULN=109 mEq/L)	0 0%
Low Ca (LLN=8.4 mg/dL)	0 0%
High Ca (ULN=10.6 mg/dL)	0 0%
Low P (LLN=0.8 mg/dL)	0 0%
High P (ULN 5.6 mg/dL)	0 0%

7. Primary Outcome

Title	Number of Participants With Other Chemistry and Urinalysis Laboratories Meeting MA Criteria in the ACP Device Substudy
Description	MA criteria: serum glucose (Glu): <65 mg/dL/>220 mg/dL;fasting serum Glu: <0.8* LLN/>1.5*ULN,or if BL<LLN then use 0.8*BL or >ULN,or if BL>ULN then use >2.0*BL or <LLN;total protein: <0.9*LLN/>1.1*ULN,or if BL<LLN then use <0.9*BL or >UNL,or if BL>UNL then use >1.1*BL or <LLN; albumin: <0.9*LLN,or if BL<LLN then use <0.75 BL;uric acid: >1.5*ULN,or if BL>ULN then use >2*BL. Urinalysis (Urine protein,urine Glu,urine blood,leukocyte esterase,Red Blood Cells [RBCs], White Blood Cells [WBCs]):Use ≥2 when BL value missing or when pre-dose=0 or 0.5; use ≥3 when pre-dose=1, use ≥4 when pre-dose=2 or 3
Time Frame	ACP substudy Day 1 to last substudy assessment occurring prior to 1st dose of non-ACP SC abatacept (administered once participants switched back to main study). For participants discontinuing both studies: Day 1 of ACP dosing to 7 days post last ACP dose.

Outcome Measure Data

Analysis Population Description

As-Treated Population, defined as all participants enrolled in ACP substudy who received at least 1 dose of SC abatacept administered via the ACP.

Arm/Group Title	Abatacept Combination Product (ACP)
Arm/Group Description	Participants from the long-term period of the IM101-174 main study who enrolled in the ACP substudy switched to administration of subcutaneous (SC) abatacept via the ACP for the duration of the substudy. Abatacept was administered SC using the ACP by the participant or caregiver on Substudy Day 1 and at weekly intervals thereafter. The ACP was a prefilled liquid product device delivering 125 mg abatacept/device (125 mg/mL).
Measure Participants	50
Low Glu (n=50)	2 3.2%
High Glu (n=50)	2 3.2%
Low fasting Glu (LLN=65 mg/dL) (n=12)	0 0%
High fasting Glu (ULN=115 mg/dL) (n=12)	0 0%
Low protein (LLN=6 g/dL) (n=50)	0 0%
High protein (ULN=8.5 g/dL) (n=50)	0 0%
Low albumin (LLN=3.5 g/dL) (n=50)	0 0%
High uric acid (ULN=8.7 mg/dL) (n=50)	0 0%
High urine protein (normal=trace) (n=50)	0 0%
High urine glucose (normal=negative) (n=50)	2 3.2%
High urine blood (normal=negative) (n=50)	2 3.2%
High leukocyte esterase (n=19)	1 1.6%
High urine WBC (n=25)	10 16.1%
High urine RBC (n=18)	3 4.8%

8. Primary Outcome

Title	Mean Systolic Blood Pressure (SBP) Over Time in the ACP Device Substudy
Time Frame	ACP substudy Day 1 to last substudy assessment occurring prior to 1st dose of non-ACP SC abatacept (administered once participants switched back to main study). For participants discontinuing both studies: Day 1 of ACP dosing to 7 days post last ACP dose.

Outcome Measure Data

Analysis Population Description

As-Treated Population, defined as all participants enrolled in ACP substudy who received at least 1 dose of SC abatacept administered via the ACP.

Arm/Group Title	Abatacept Combination Product (ACP)
Arm/Group Description	Participants from the long-term period of the IM101-174 main study who enrolled in the ACP substudy switched to administration of subcutaneous (SC) abatacept via the ACP for the duration of the substudy. Abatacept was administered SC using the ACP by the participant or caregiver on Substudy Day 1 and at weekly intervals thereafter. The ACP was a prefilled liquid product device delivering 125 mg abatacept/device (125 mg/mL).
Measure Participants	62
Day 1 before injection (n=62)	128.1 (14.96)
Day 85 (n=50)	130.7 (17.08)
Day 169 before injection (n=42)	128.0 (13.61)
Day 253 before injection (n=15)	127.3 (16.63)
Day 365 (n=4)	135.3 (7.80)

9. Primary Outcome

Title	Mean Diastolic Blood Pressure (DBP) Over Time in the ACP Device Substudy
Time Frame	ACP substudy Day 1 to last substudy assessment occurring prior to 1st dose of non-ACP SC abatacept (administered once participants switched back to main study). For participants discontinuing both studies: Day 1 of ACP dosing to 7 days post last ACP dose.

Outcome Measure Data

Analysis Population Description

As-Treated Population, defined as all participants enrolled in ACP substudy who received at least 1 dose of SC abatacept administered via the ACP.

Arm/Group Title	Abatacept Combination Product (ACP)
Arm/Group Description	Participants from the long-term period of the IM101-174 main study who enrolled in the ACP substudy switched to administration of subcutaneous (SC) abatacept via the ACP for the duration of the substudy. Abatacept was administered SC using the ACP by the participant or caregiver on Substudy Day 1 and at weekly intervals thereafter. The ACP was a prefilled liquid product device delivering 125 mg abatacept/device (125 mg/mL).
Measure Participants	62
Day 1 before injection (n=62)	76.4 (8.08)
Day 85 (n=50)	78.7 (9.99)
Day 169 before injection (n=42)	75.7 (9.31)
Day 253 before injection (n=15)	78.1 (8.29)
Day 365 (n=4)	77.5 (14.73)

10. Primary Outcome

Title	Mean Heart Rate Over Time in the ACP Device Substudy
Time Frame	ACP substudy Day 1 to last substudy assessment occurring prior to 1st dose of non-ACP SC abatacept (administered once participants switched back to main study). For participants discontinuing both studies: Day 1 of ACP dosing to 7 days post last ACP dose.

Outcome Measure Data

Analysis Population Description

As-Treated Population, defined as all participants enrolled in ACP substudy who received at least 1 dose of SC abatacept administered via the ACP.

Arm/Group Title	Abatacept Combination Product (ACP)
Arm/Group Description	Participants from the long-term period of the IM101-174 main study who enrolled in the ACP substudy switched to administration of subcutaneous (SC) abatacept via the ACP for the duration of the substudy. Abatacept was administered SC using the ACP by the participant or caregiver on Substudy Day 1 and at weekly intervals thereafter. The ACP was a prefilled liquid product device delivering 125 mg abatacept/device (125 mg/mL).
Measure Participants	62
Day 1 before injection (n=62)	73.4 (10.18)
Day 85 (n=50)	74.0 (9.53)
Day 169 before injection (n=42)	73.4 (9.22)
Day 253 before injection (n=15)	76.9 (12.73)
Day 365 (n=4)	84.3 (4.79)

11. Primary Outcome

Title	Mean Temperature Over Time in the ACP Device Substudy
Time Frame	ACP substudy Day 1 to last substudy assessment occurring prior to 1st dose of non-ACP SC abatacept (administered once participants switched back to main study). For participants discontinuing both studies: Day 1 of ACP dosing to 7 days post last ACP dose.

Outcome Measure Data

Analysis Population Description

As-Treated Population, defined as all participants enrolled in ACP substudy who received at least 1 dose of SC abatacept administered via the ACP.

Arm/Group Title	Abatacept Combination Product (ACP)
Arm/Group Description	Participants from the long-term period of the IM101-174 main study who enrolled in the ACP substudy switched to administration of subcutaneous (SC) abatacept via the ACP for the duration of the substudy. Abatacept was administered SC using the ACP by the participant or caregiver on Substudy Day 1 and at weekly intervals thereafter. The ACP was a prefilled liquid product device delivering 125 mg abatacept/device (125 mg/mL).
Measure Participants	62
Day 1 before injection (n=62)	36.6 (0.39)
Day 85 (n=50)	36.6 (0.36)
Day 169 before injection (n=42)	36.6 (0.39)
Day 253 before injection (n=15)	36.6 (0.27)
Day 365 (n=4)	36.4 (0.38)

12. Secondary Outcome

Title	Number of Participants With Positive Anti-abatacept or Anti-Cytotoxic T Lymphocyte Antigen 4-T Cell (CTLA4-T) Responses Over Time by Enzyme Linked Immunosorbant Assay (ELISA) in the ACP Device Substudy
Description	Serum samples from all treated adult participants with active rheumatoid arthritis were screened for the presence of drug-specific antibodies using ELISA. Immunogenicity was defined as the presence of a positive anti-abatacept or anti-CTLA4 antibody.
Time Frame	ACP substudy Day 1 to last substudy assessment occurring prior to 1st dose of non-ACP SC abatacept (administered once participants switched back to main study). For participants discontinuing both studies: Day 1 of ACP dosing to 28 days post last ACP dose

Outcome Measure Data

Analysis Population Description

Immunogenicity Population, defined as all participants who received at least 1 dose of abatacept administered with the ACP who had at least one post Substudy Day 1 immunogenicity result available.

Arm/Group Title	Abatacept Combination Product (ACP)
Arm/Group Description	Participants from the long-term period of the IM101-174 main study who enrolled in the ACP substudy switched to administration of subcutaneous (SC) abatacept via the ACP for the duration of the substudy. Abatacept was administered SC using the ACP by the participant or caregiver on Substudy Day 1 and at weekly intervals thereafter. The ACP was a prefilled liquid product device delivering 125 mg abatacept/device (125 mg/mL).
Measure Participants	53
Day 29 anti-ABA (n=50)	0 0%
Day 29 anti-CTLA4 (n=51)	0 0%
Day 29 total (n=51)	0 0%
Day 57 anti-ABA (n=43)	0 0%
Day 57 anti-CTLA4 (n=43)	1 1.6%
Day 57 total (n=43)	1 1.6%
Day 85 anti-ABA (n=42)	0 0%
Day 85 anti-CTLA4 (n=42)	0 0%
Day 85 total (n=42)	0 0%
Overall on-treatment visits anti-ABA (n=53)	0 0%
Overall on-treatment visits anti-CTLA4 (n=53)	1 1.6%
Overall total on-treatment visits (n=53)	1 1.6%
28 days post last dose anti-ABA (n=1)	0 0%
28 days post last dose anti-CTLA4 (n=1)	0 0%
28 days post last dose total (n=1)	0 0%
Overall post visits anti-ABA (n=1)	0 0%
Overall post visits anti-CTLA4 (n=1)	0 0%
Overall post visits total (n=1)	0 0%
Overall anti-ABA (n=53)	0 0%
Overall anti-CTLA4 (n=53)	1 1.6%
Overall total (n=53)	1 1.6%

13. Secondary Outcome

Title	Number of Participants With Positive Anti-abatacept Responses Over Time by Electrochemiluminescence Immunoassay in the ACP Device Substudy
Description	An electrochemiluminescence immunoassay screened sera for drug-specific antibodies; immunocompetition was used to identify specific anti-Abatacept reactivity. CTLA4 and Possibly immunoglobulin (Ig) category=reactivity against extracellular domain of human CTLA4, constant regions of human IgG1, or both (CTLA4Ig; Abatacept molecule). Ig and/or Junction (JNCT)category=reactivity against constant regions and/or hinge region of human IgG1. Drug-induced seropositivity defined as a post-baseline titer higher than Baseline, or any post-baseline positivity if Baseline value was missing. TRT=treatment
Time Frame	ACP substudy Day 1 to last substudy assessment occurring prior to 1st dose of non-ACP SC abatacept (administered once participants switched back to main study). For participants discontinuing both studies: Day 1 of ACP dosing to 85 days post last ACP dose

Outcome Measure Data

Analysis Population Description

Immunogenicity Population, defined as all participants who received at least 1 dose of abatacept administered with the ACP who had at least one post Substudy Day 1 immunogenicity result available.

Arm/Group Title	Abatacept Combination Product (ACP)
Arm/Group Description	Participants from the long-term period of the IM101-174 main study who enrolled in the ACP substudy switched to administration of subcutaneous (SC) abatacept via the ACP for the duration of the substudy. Abatacept was administered SC using the ACP by the participant or caregiver on Substudy Day 1 and at weekly intervals thereafter. The ACP was a prefilled liquid product device delivering 125 mg abatacept/device (125 mg/mL).
Measure Participants	60
Day 29 CTLA4 + possibly Ig (n=57)	0 0%
Day 29 Ig and/or JNCT (n=57)	1 1.6%
Day 29 total (n=57)	1 1.6%
Day 57 CTLA4 + possibly Ig (n=47)	0 0%
Day 57 Ig and/or JNCT (n=47)	1 1.6%
Day 57 total (n=47)	1 1.6%
Day 85 CTLA4 + possibly Ig (n=49)	0 0%
Day 85 Ig and/or JNCT (n=49)	0 0%
Day 85 total (n=49)	0 0%
Day 169 CTLA4 + possibly Ig (n=43)	0 0%
Day 169 Ig and/or JNCT (n=43)	0 0%
Day 169 total (n=43)	0 0%
Day 253 CTLA4 + possibly Ig (n=2)	0 0%
Day 253 Ig and/or JNCT (n=2)	0 0%
Day 253 total (n=2)	0 0%
Overall on-TRT visits CTLA4 + possibly Ig (n=60)	0 0%
Overall on-TRT visits Ig and/or JNCT (n=60)	1 1.6%
Overall total on-TRT visits (n=60)	1 1.6%
28 days post last dose CTLA4 + possibly Ig (n=1)	0 0%
28 days post last dose Ig and/or JNCT (n=1)	0 0%
28 days post last dose total (n=1)	0 0%
56 days post last dose CTLA4 + possibly Ig (n=1)	0 0%
56 days post last dose Ig and/or JNCT (n=1)	0 0%
56 days post last dose total (n=1)	0 0%
85 days post last dose CTLA4 + possibly Ig (n=1)	0 0%
85 days post last dose Ig and/or JNCT (n=1)	0 0%
85 days post last dose total (n=1)	0 0%
Overall post visits CTLA4 + possibly Ig (n=1)	0 0%
Overall post visits Ig and/or JNCT (n=1)	0 0%
Overall post visits total (n=1)	0 0%
Overall CTLA4 + possibly Ig (n=60)	0 0%
Overall Ig and/or JNCT (n=60)	1 1.6%
Overall total (n=60)	1 1.6%

Adverse Events

Arm/Group Title	Abatacept Combination Product (ACP)
Arm/Group Description	Participants from the long-term period of the IM101-174 main study who enrolled in the ACP substudy switched to administration of subcutaneous (SC) abatacept via the ACP for the duration of the substudy. Abatacept was administered SC using the ACP by the participant or caregiver on Substudy Day 1 and at weekly intervals thereafter. The ACP was a prefilled liquid product device delivering 125 mg abatacept/device (125 mg/mL).
All Cause Mortality
	Abatacept Combination Product (ACP)
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Abatacept Combination Product (ACP)
	Affected / at Risk (%)	# Events
Total	2/62 (3.2%)
General disorders
Chest Pain	1/62 (1.6%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal Cell Carcinoma	1/62 (1.6%)	1
Other (Not Including Serious) Adverse Events
	Abatacept Combination Product (ACP)
	Affected / at Risk (%)	# Events
Total	4/62 (6.5%)
Infections and infestations
Bronchitis	4/62 (6.5%)	4
Upper Respiratory Tract Infection	4/62 (6.5%)	4

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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.