A Study to Assess the Efficacy and Safety of Abatacept in Adults With Active Primary Sjögrens Syndrome

• Sponsor: Bristol-Myers Squibb (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02915159
• Collaborator: (none)
• Enrollment: 250
• Locations: 71
• Arms: 2
• Actual Duration (Months): 31.5
• Patients Per Site: 3.5
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy of abatacept compared to placebo in patients with Sjögren's Syndrome.

Condition or Disease	Intervention/Treatment	Phase
Sjogrens Disease	Biological: Abatacept; Other: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 250 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Subcutaneous Abatacept in Adults With Active Primary Sjögrens Syndrome
• Actual Study Start Date: Dec 6, 2016
• Actual Primary Completion Date: Aug 7, 2018
• Actual Study Completion Date: Jul 23, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Abatacept Abatacept for subcutaneous injection 125mg/mL in 1 mL pre-filled syringe for 6 months followed by Open-Label Abatacept for subcutaneous injection 125mg/mL in 1 mL pre-filled syringe for 6 months	Biological: Abatacept; Other Names: Orencia Bristol-Myers Squibb (BMS)-188667
Placebo Comparator: Placebo Placebo for Abatacept for subcutaneous injection 125mg/mL in 1 mL pre-filled syringe for 6 months followed by Open-Label Abatacept for subcutaneous injection 125mg/mL in 1 mL pre-filled syringe for 6 months	Biological: Abatacept; Other Names: Orencia Bristol-Myers Squibb (BMS)-188667 ; Other: Placebo

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in EULAR Sjogren's Syndrome Disease Activity Index (ESSDAI) [Day 169]

   The EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) total score is calculated as the sum of scores for activity level for each domain. The EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) Scoring Algorithm. Domain: (Score) Constitutional: (No=0, Low=3, Moderate=6) Lymphadenopathy: (No=0, Low=4, Moderate=8, High=12) Glandular: (No=0, Low=2, Moderate=4) Articular: (No=0, Low=2, Moderate=4, High=6) Cutaneous: (No=0, Low=3, Moderate=6, High=9) Pulmonary: (No=0, Low=5, Moderate=10, High=15) Renal: (No=0, Low=5, Moderate=10, High=15) Muscular: (No=0, Low=6, Moderate=12, High=18) Peripheral Nervous System (PNS): (No=0, Low=5, Moderate=10, High=15) Central Nervous System (CNS): (No=0, Moderate=10, High=15) Haematological: (No=0, Low=2, Moderate=4, High=6) Biological: (No=0, Low=1, Moderate=2) (No = No Disease Activity (DA), Low = Low DA, Moderate = Moderate DA, High = High DA) Overall score, which can range from 0 to 123, a higher score indicates more disease activity

Secondary Outcome Measures

1. Change From Baseline in EULAR Sjogren's Syndrome Patient Reported Inde (ESSPRI) [Day 169]

   The total score EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) is calculated as the mean of the 3 individual components. Total Score Range (0 = Best outcome and 10 = Worst Outcome) The scores for the ESSPRI individual components will be used as such reported by the participants and entered in the case report form (CRF), without any further calculations. It consists of 3 questions covering cardinal symptoms of Sjögren's syndrome: dryness, fatigue and pain. Each domain scored on scale of 0-10 (0 =no symptom at all and 10 = worst symptom imaginable), and overall score is calculated as the mean of 3 individual domains.

2. Change From Baseline in the Stimulated Whole Salivary Flow [Day 169]

   The mean change from baseline in the stimulated whole salivary flow at Day 169

3. Change From Baseline of DAS28-C-reactive Peptide (CRP): In The Full Population [Day 29, Day 57, Day 85, Day 113, Day 141, Day 169]

   The disease activity score DAS28-CRP is a continuous variable which is a composite of 4 variables: the 28 tender joint count (tender28), the 28 swollen joint count (swollen28), CRP and participant assessment of disease activity measure on a visual analogue scale (VAS) of 100mm. DAS28-CRP = 0.56 * sqrt(tender28) + 0.28 * sqrt(swollen28) + 0.36 * ln(hsCRP+1) + 0.014 * VAS + 0.96. (sqrt = Square root, ln = natural log) Positive Scores = Increased Disease Activity Negative Scores = Reduced Disease Activity

4. Change From Baseline of DAS28-CRP: Tender Swollen Joint Count of at Least 3 [Day 29, Day 57, Day 85, Day 113, Day 141, Day 169]

   The disease activity score DAS28-CRP is a continuous variable which is a composite of 4 variables: the 28 tender joint count (tender28), the 28 swollen joint count (swollen28), CRP and participant assessment of disease activity measure on a visual analogue scale (VAS) of 100mm. DAS28-CRP = 0.56 * sqrt(tender28) + 0.28 * sqrt(swollen28) + 0.36 * ln(hsCRP+1) + 0.014 * VAS + 0.96. (sqrt = Square root, ln = natural log) Positive Scores = Increased Disease Activity Negative Scores = Reduced Disease Activity

5. Change From Baseline of DAS28-CRP: Tender Swollen Joints Count Less Than 3 [Day 29, Day 57, Day 85, Day 113, Day 141, Day 169]

   The disease activity score DAS28-CRP is a continuous variable which is a composite of 4 variables: the 28 tender joint count (tender28), the 28 swollen joint count (swollen28), CRP and participant assessment of disease activity measure on a visual analogue scale (VAS) of 100mm. DAS28-CRP = 0.56 * sqrt(tender28) + 0.28 * sqrt(swollen28) + 0.36 * ln(hsCRP+1) + 0.014 * VAS + 0.96. (sqrt = Square root, ln = natural log) Positive Scores = Increased Disease Activity Negative Scores = Reduced Disease Activity

6. Change From Baseline in the Joint Component of DAS28-CRP: In the Full Population [Day 29, Day 57, Day 85, Day 113, Day 141, Day 169]

   The mean change from baseline at all measured time points up to Day 169 in the individual components of DAS28-CRP. Tender Joint: Count 1-28 Swollen Joint: Count 1-28 Negative Scores = Reduced number of joints impacted Positive Scores = Increased number of joints impacted

7. Change From Baseline in the CRP Component of DAS28-CRP: In the Full Population [Day 29, Day 57, Day 85, Day 113, Day 141, Day 169]

   The mean change from baseline at all measured time points up to Day 169 in the individual components of DAS28-CRP. CRP: measured lab value Positive Number = Increased level of CRP Negative Number = Reduced Level of CRP

8. Change From Baseline in the Assessment of Disease Activity Component of DAS28-CRP: In the Full Population [Day 29, Day 57, Day 85, Day 113, Day 141, Day 169]

   The mean change from baseline at all measured time points up to Day 169 in the individual components of DAS28-CRP. Assesment of Disease Activity: 0-100 scale [100=Most severe] Positive Numbers = Increased Disease Activity Negative Numbers = Decreased Diseased activity

9. Change From Baseline in the Joint Component of DAS28-CRP: Tender Swollen Joints of at Least 3 [Day 29, Day 57, Day 85, Day 113, Day 141, Day 169]

   The mean change from baseline at all measured time points up to Day 169 in the individual components of DAS28-CRP. Tender Joint: Count 1-28 Swollen Joint: Count 1-28 Negative Scores = Reduced number of joints impacted Positive Scores = Increased number of joints impacted

10. Change From Baseline in the CRP Component of DAS28-CRP: Tender Swollen Joints of at Least 3 [Day 29, Day 57, Day 85, Day 113, Day 141, Day 169]

    The mean change from baseline at all measured time points up to Day 169 in the individual components of DAS28-CRP. CRP: measured lab value Positive Number = Increased level of CRP Negative Number = Reduced Level of CRP

11. Change From Baseline in the Assessment of Disease Activity Component of DAS28-CRP: Tender Swollen Joints of at Least 3 [Day 29, Day 57, Day 85, Day 113, Day 141, Day 169]

    The mean change from baseline at all measured time points up to Day 169 in the individual components of DAS28-CRP. Assesment of Disease Activity: 0-100 scale [100=Most severe] Positive Numbers = Increased Disease Activity Negative Numbers = Decreased Diseased activity

12. Change From Baseline in the Joint Component of DAS28-CRP: Tender Swollen Joint Count Less Than 3 [Day 29, Day 57, Day 85, Day 113, Day 141, Day 169]

    The mean change from baseline at all measured time points up to Day 169 in the individual components of DAS28-CRP. Tender Joint: Count 1-28 Swollen Joint: Count 1-28 Negative Scores = Reduced number of joints impacted Positive Scores = Increased number of joints impacted

13. Change From Baseline in the CRP Component of DAS28-CRP: Tender Swollen Joint Count Less Than 3 [Day 29, Day 57, Day 85, Day 113, Day 141, Day 169]

    The mean change from baseline at all measured time points up to Day 169 in the individual components of DAS28-CRP. CRP: measured lab value Positive Number = Increased level of CRP Negative Number = Reduced Level of CRP

14. Change From Baseline in the Assessment of Disease Activity Component of DAS28-CRP: Tender Swollen Joint Count Less Than 3 [Day 29, Day 57, Day 85, Day 113, Day 141, Day 169]

    The mean change from baseline at all measured time points up to Day 169 in the individual components of DAS28-CRP. Assesment of Disease Activity: 0-100 scale [100=Most severe] Positive Numbers = Increased Disease Activity Negative Numbers = Decreased Diseased activity

15. Participants Who Achieve Minimally Clinically Important Change in ESSDAI in at Least 3 Points [Day 29, Day 57, Day 85, Day 113, Day 141, Day 169]

    Proportion of participants who achieve a minimally clinically important change (of at least 3 points) in the ESSDAI at all measured time points up to Day 169.

16. Participants Who Achieve Minimally Clinically Important Change in ESSDAI in at Least 5 Points [Day 29, Day 57, Day 85, Day 113, Day 141, Day 169]

    Proportion of participants who achieve a minimally clinically important change (of at least 5 points) in the ESSDAI at all measured time points up to Day 169.

17. Participants Who Achieve Minimally Clinically Important Change in ESSPRI in at Least 1 Point [Day 29, Day 57, Day 85, Day 113, Day 141, Day 169]

    Proportion of participants who achieve a minimally clinically important change (of at least 1 point) in the ESSPRI at all measured time points up to Day 169.

18. Change From Baseline at All Measured Time Points in the ESSDAI [Day 29, Day 57, Day 85, Day 113, Day 141, Day 169]

    The EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) total score is calculated as the sum of scores for activity level for each domain. The EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) Scoring Algorithm. Domain: (Score) Constitutional: (No=0, Low=3, Moderate=6) Lymphadenopathy: (No=0, Low=4, Moderate=8, High=12) Glandular: (No=0, Low=2, Moderate=4) Articular: (No=0, Low=2, Moderate=4, High=6) Cutaneous: (No=0, Low=3, Moderate=6, High=9) Pulmonary: (No=0, Low=5, Moderate=10, High=15) Renal: (No=0, Low=5, Moderate=10, High=15) Muscular: (No=0, Low=6, Moderate=12, High=18) Peripheral Nervous System (PNS): (No=0, Low=5, Moderate=10, High=15) Central Nervous System (CNS): (No=0, Moderate=10, High=15) Haematological: (No=0, Low=2, Moderate=4, High=6) Biological: (No=0, Low=1, Moderate=2) (No = No Disease Activity (DA), Low = Low DA, Moderate = Moderate DA, High = High DA) Overall score, which can range from 0 to 123, a higher score indicates more disease activity

19. Change From Baseline at All Measured Time Points in the ESSPRI [Day 29, Day 57, Day 85, Day 113, Day 141, Day 169]

    The total score EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) is calculated as the mean of the 3 individual components. Total Score Range (0 = Best outcome and 10 = Worst Outcome) The scores for the ESSPRI individual components will be used as such reported by the participants and entered in the case report form (CRF), without any further calculations. It consists of 3 questions covering cardinal symptoms of Sjögren's syndrome: dryness, fatigue and pain. Each domain scored on scale of 0-10 (0 =no symptom at all and 10 = worst symptom imaginable), and overall score is calculated as the mean of 3 individual domains.

20. Change From Baseline in Components of ESSDAI [Day 29, Day 57, Day 85, Day 113, Day 141 and Day 169]

    The EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) total score is calculated as the sum of scores for activity level for each domain. The EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) Scoring Algorithm. Domain: (Score for activity level) Constitutional: (No=0, Low=3, Moderate=6) Lymphadenopathy: (No=0, Low=4, Moderate=8, High=12) Glandular: (No=0, Low=2, Moderate=4) Articular: (No=0, Low=2, Moderate=4, High=6) Cutaneous: (No=0, Low=3, Moderate=6, High=9) Pulmonary: (No=0, Low=5, Moderate=10, High=15) Renal: (No=0, Low=5, Moderate=10, High=15) Muscular: (No=0, Low=6, Moderate=12, High=18) Peripheral Nervous System (PNS): (No=0, Low=5, Moderate=10, High=15) Central Nervous System (CNS): (No=0, Moderate=10, High=15) Haematological: (No=0, Low=2, Moderate=4, High=6) Biological: (No=0, Low=1, Moderate=2) (No = No Disease Activity, Low = Low Disease Activity, Moderate = Moderate Disease Activity, High = High Disease Activity)

21. Change From Baseline in ESSPRI Components [Day 29, Day 57, Day 85, Day 113, Day 141, Day 169]

    The total score EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) is calculated as the mean of the 3 individual components. Total Score Range (0 = Best outcome and 10 = Worst Outcome) The scores for the ESSPRI individual components will be used as such reported by the participants and entered in the case report form (CRF), without any further calculations. It consists of 3 questions covering cardinal symptoms of Sjögren's syndrome: dryness, fatigue and pain. Each domain scored on scale of 0-10 (0 =no symptom at all and 10 = worst symptom imaginable), and overall score is calculated as the mean of 3 individual domains.

22. Change From Baseline in Schirmer's Test [Day 85, Day 169]

    The Mean change from baseline in Schirmer's Test at all measured time points up to day 169 The length in millimeters that the strip wets during the 5 minute test period for each eye. Collection is done separately for each eye.

23. Change From Baseline in the Ocular Staining Score (OSS) [Day 85, Day 169]

    The Mean change from baseline in OSS at all measured time points up to day 169 Score of 0 = No Staining Score of 12 = diffuse staining The total score will be calculated as the sum of the score for these parameters for each eye. Medial Nasal Bulbar Conjunctiva (MNBC) [score scale: 0 - 3], Corneal (CORN) Staining of Punctate Epithelial Erosions (PEE) [score scale: 0 - 3], Lateral Temporal Bulbar Conjunctiva (LTBC) [score scale: 0 - 3], Patches of Confluent Staining (CONF) [score scale: 0 - 1], PEE observed in the pupil region, i.e. central 4mm diameter portion of the cornea (PUPL) [score scale: 0 - 1], one of more filaments seen anywhere on the cornea (FILA) [score scale: 0 - 1]

24. Change From Baseline in Tear Break-up Time [Day 85, Day 169]

    The Mean change from baseline in Tear Break-up Time at all measured time points up to day 169 The CRF collects the time in seconds to first appearance of a random dry spot on the corneal surface for 3 repetitions in each eye. The average time will calculated for each eye averaging the 3 measurements for each eye separately. In case only 2 measurements are available, the average of the 2 measurements will be calculated. In case there is only 1 measurement, that measurement will be used for the analysis.

25. Change From Baseline in Unstimulated Salivary Flow [Day 85, Day 169]

    The mean change from baseline in unstimulated whole salivary flow at all measured time points up to Day 169.

26. Change From Baseline in Stimulated Salivary Flow [Day 85, Day 169]

    The mean change from baseline in Stimulated whole salivary flow at all measured time points up to Day 169.

27. Change From Baseline in Numeric Rating Scale for Mouth Dryness [Day 1, 29, 57, 85, 113, 141, 169]

    The mean change from baseline in participant symptoms using the Numeric Rating Scale (NRS) for mouth dryness at all measured time points up to Day 169. The oral and ocular dryness are each assessed by the patients with numeric rating scales from 0 to 10 with 0 representing no dryness and 10 representing maximal dryness

28. Change From Baseline in Numeric Rating Scale for Eye Dryness [Day 1, 29, 57, 85, 113, 141, 169]

    The mean change from baseline in patient symptoms using the Numeric Rating Scale (NRS) for eye dryness at all measured time points up to Day 169. The oral and ocular dryness are each assessed by the patients with numeric rating scales from 0 to 10 with 0 representing no dryness and 10 representing maximal dryness

29. Change From Baseline in Participant Assessment of Disease Activity [Day 29, 57, 85, 113, 141, 169]

    The participant global assessment of disease activity are assessed with visual analog scales. The participant marks a vertical line through a horizontal line, where the beginning of the horizontal line represents the best situation, and the end of the horizontal line represents the very worst situation. The CRF collects the distance in millimeters from the start of the scale that is marked as well as the length of the scale in millimeters. In cases that the length of the scale is in less or more than 100 millimeters, then the participants measurement will be rescaled to the equivalent of 100 millimeters using the formula below: Rescale Measurement in mm = (measurement as reported on CRF in mm/length of the line on CRF in mm) * 100mm A negative score = participant assessment of disease activity has improved A positive score = participant assessment of disease activity has worsened

30. Change From Baseline in Physician Global Assessment of Disease Activity [Day 29, 57, 85, 113, 141, 169]

    The physician global assessment of disease activity are assessed with visual analog scales. The physician marks a vertical line through a horizontal line, where the beginning of the horizontal line represents the best situation, and the end of the horizontal line represents the very worst situation. The CRF collects the distance in millimeters from the start of the scale that is marked as well as the length of the scale in millimeters. In cases that the length of the scale is in less or more than 100 millimeters, then the participants measurement will be rescaled to the equivalent of 100 millimeters using the formula below: Rescale Measurement in mm = (measurement as reported on CRF in mm/length of the line on CRF in mm) * 100mm A negative score = physician assessment of disease activity has improved A positive score = physician assessment of disease activity has worsened

31. Change From Baseline in Patient Fatigue [Day 29, 57, 85, 113, 141, 169]

    The mean change from baseline in patient fatigue using Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue assessment of disease activity at all measured time points up to Day 169. PROMIS Fatigue instruments 10 Questions ranging from a score 0 to 40. Sum of the values gives you the raw sum. The raw is inputted into this formula to give you the raw score: Raw Score = (Raw sum*number of items on the short form)/(Number of items that were actually answered) Raw score is translated to a T-Score using a table. T-Score is used as the final score. The T-score rescales the raw score into a standardized score with a mean of 50 and a standard deviation (SD) of 10. The standardized T-score is reported as the final score for each participant. A negative T Score = Better Prognosis A positive T Score = Worse prognosis

32. Change From Baseline in Female Sexual Function Using the Female Sexual Function Index (FSFI) [Day 85, Day 169]

    For the FSFI, is a 19 item instrument used for assessing key dimensions of female sexual function over the past 4 weeks with 6 domains being analyzed. The specific domains (desire, arousal, lubrication, orgasm, satisfaction, and pain) analyzed in the FSFI are scored on a scale ranging from 0 to 5, with higher scores indicating better performance. Domain scores are calculated by summing the scores of the individual questions that make up the domain and multiplying the sum by the factor in the table below. The full scale score is the sum of the six domain scores. Full Scale Score range: 2.0(minimum score) - 36.0 (maximum score) Negative Score = Reduced functioning Positive Score = Improved functioning

33. Change From Baseline in 36-item Short Form Health Survey (SF-36) [Day 85, Day 169]

    The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Scores on each item are summed and averaged (range: 0=worst to 100=best). Increases from baseline indicate improvement

34. Geometric Mean of Trough Concentration (Cmin) of Abatacept [Day 29, 85, 113, 141, 169]

    Geometric mean of trough concentration (Cmin) of abatacept at all measured time points.

35. Percentage of Participants With a Positive Antibody Response [Day 85 db, day 169 db, post treatment day 85]

    Percentage of participants with at least one positive immunogenicity response up to Day 169 and during 3 months follow up (for participants who discontinue during the 6-months double-blind).

36. Summary of Adverse Events: Double Blind Period [Day 1 up to first dose of Open Label Treatment Period (OLTP) abatacept or up to 56 post last dose in double -blind for those not in OL.]

    Percentage of participants with adverse events, deaths, serious adverse events and adverse events leading to discontinuation

37. Laboratory Marked Abnormalities: Double Blind Period [Day 1 up to first dose of OL abatacept or up to 56 post last dose in double -blind for those not in OL.]

    Laboratory values meeting the marked abnormality criteria

38. Percentage of Participants With a Positive Antibody Response in the Cumulative Abatacept Period [Day 365, post open label treatment day 85]

    Percentage of participants with at least one positive immunogenicity response On Day 365 (end of Open label treatment period) and day 85 post open label follow up period.

39. Summary of Adverse Events: Cumulative Abatacept Period [Day 365 and 3 months of follow up approximately 450 Days]

    Percentage of participants with adverse events, deaths, serious adverse events and adverse events leading to discontinuation

40. Laboratory Marked Abnormalities: Cumulative Abatacept Period [Day 365 and 3 months of follow up approximately 450 Days]

    Laboratory values meeting the marked abnormality criteria

Eligibility Criteria

Criteria

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

For more information regarding Bristol-Myers Squibb Clinical Trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

• EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) score of at least 5

• Positive anti-SS-A/Ro antibody at screening

• meet the 2016 American College of Rheumatology (ACR) / European League Against Rheumatism Classification Criteria for Sjögren's Syndrome (EULAR SS)

Exclusion Criteria:

• Secondary Sjögrens syndrome

• Active life-threatening or organ-threatening complications of Sjögren's-syndrome

• Other medical condition associated with sicca syndrome

Other protocol defined inclusion/exclusion criteria could apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	St. Jude Hospital Yorba Linda	Fullerton	California	United States	92835
2	Riverside Medical Clinic	Riverside	California	United States	92506
3	Colorado Arthritis Associates	Lakewood	Colorado	United States	80228
4	North Georgia Rheumatology Group	Lawrenceville	Georgia	United States	30046
5	Intermountain Research Center Inc.	Boise	Idaho	United States	83702
6	Johns Hopkins University	Baltimore	Maryland	United States	21224
7	Clinical Pharmacology Study Group	Worcester	Massachusetts	United States	01605
8	St. Paul Rheumatology, P.A.	Eagan	Minnesota	United States	55121
9	Northwell Health	Great Neck	New York	United States	11021
10	Local Institution	Charlotte	North Carolina	United States	28203
11	Joint and Muscle Medical Care and Research Institute (JMMCRI)	Charlotte	North Carolina	United States	28204
12	Duke Clinical Research Unit, Duke Univ Med Ctr, Duke South	Durham	North Carolina	United States	27710
13	Health Research Of Oklahoma	Oklahoma City	Oklahoma	United States	73103
14	East Penn Rheumatology	Bethlehem	Pennsylvania	United States	18015
15	Altoona Center For Clinical Research	Duncansville	Pennsylvania	United States	16635-8406
16	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania	United States	15213
17	West Tennessee Research Institute	Jackson	Tennessee	United States	38305
18	Metroplex Clinical Research Center	Dallas	Texas	United States	75231
19	Scott Zashin Inc.	Dallas	Texas	United States	75231
20	Organizacion Medica De Investigacion S.A. (Omi)	Capital Federal	Buenos Aires	Argentina	1015
21	Local Institution	Ciudad Autonoma Beunos Aires	Buenos Aires	Argentina	1431
22	Instituto de Asistencia Reumatologica Integral	San Fernando	Buenos Aires	Argentina	1646
23	Local Institution	Buenos Aires		Argentina	1428
24	Consultorios Medicos Dr. Catalan Pellet	Caba		Argentina	1111
25	Instituto Reumatologico Strusberg	Cordoba		Argentina	5000
26	Local Institution	Maroochydore	Queensland	Australia	4558
27	Local Institution	Woodville	South Australia	Australia	5011
28	Local Institution	Camberwell	Victoria	Australia	3124
29	Local Institution	Nedlands	Western Australia	Australia	6009
30	Local Institution	Savaldor	Bahia	Brazil	40150-150
31	Local Institution	Vitoria	ES	Brazil	29055-450
32	Local Institution	Porto Alegre	RIO Grande DO SUL	Brazil	90480-000
33	Local Institution	Sao Paulo		Brazil	04032-060
34	Revmatologie s.r.o.	Brno		Czechia	638 00
35	Local Institution	Bordeaux		France	33075
36	Local Institution	Le Kremlin Bicetre Cedex		France	94275
37	Hopital Europeen	Marseille		France	13003
38	Local Institution	Marseille		France	13008
39	Hopital Lapeyronie	Montpellier Cedex 5		France	34295
40	Local Institution	Paris Cedex 10		France	75475
41	Local Institution	Strasbourg		France	67098
42	Medizinische Universitaetsklinik Freiburg	Freiburg		Germany	79106
43	Med Hochschule Hannover	Hannover		Germany	30625
44	Krankenhaus St. Josef	Wuppertal		Germany	42105
45	Local Institution	Milano		Italy	20122
46	Ospedale Santa Maria Della Misericordia	Udine		Italy	33100
47	Local Institution	Nagoya-shi	Aichi	Japan	4578511
48	Local Institution	Kitakyushu-shi	Fukuoka	Japan	8078555
49	Local Institution	Sapporo-shi	Hokkaido	Japan	0608648
50	Local Institution	Nishinomiya-shi	Hyogo	Japan	6638501
51	Local Institution	Tsukuba-shi	Ibaraki	Japan	3050005
52	Local Institution	Kamigyo-ku	Kyoto	Japan	602-8566
53	Local Institution	Sendai-shi	Miyagi	Japan	9808574
54	Local Institution	Nagasaki-shi	Nagasaki	Japan	8528501
55	Local Institution	Kurashiki-shi	Okayama	Japan	7108522
56	Local Institution	Hamamatsu-shi	Shizuoka	Japan	4313192
57	Local Institution	Chuo-ku	Tokyo	Japan	1048560
58	Local Institution	Itabashi-ku	Tokyo	Japan	1738610
59	Local Institution	Meguro-ku	Tokyo	Japan	1538515
60	Local Institution	Shinjuku-Ku	Tokyo	Japan	1608582
61	Local Institution	Daegu		Korea, Republic of	42472
62	Local Institution	Gwangju		Korea, Republic of	61469
63	Local Institution	Seoul		Korea, Republic of	06591
64	Consultorio Medico de Reumatologia Dr.Jesus Alberto Lopez Garcia	Leon	Guanajuato	Mexico	37000
65	Hospital Universitario Dr. Jose Eleuterio Gonzalez	Monterrey	Nuevo LEON	Mexico	64460
66	Local Institution	Distrito Federal		Mexico	14080
67	Centro de Alta Especialidad en Reumatologia e Investigacion del Potosi S.C.	San Luis Potosi		Mexico	78213
68	Local Institution	San Juan		Puerto Rico	00909
69	Local Institution	San Juan		Puerto Rico	00918
70	Local Institution	Solna		Sweden	171 64
71	Local Institution	Uppsala		Sweden	751 85

Sponsors and Collaborators

• Bristol-Myers Squibb

Investigators

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

Study Documents (Full-Text)

• Statistical Analysis Plan - Jun 17, 2019
• Study Protocol - Aug 25, 2016

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: NCT02915159
• Other Study ID Numbers: IM101-603; 2016-001948-19
• First Posted: Sep 26, 2016
• Last Update Posted: Aug 10, 2020
• Last Verified: Jul 1, 2020

• Additional relevant MeSH terms: Sjogren's Syndrome; Abatacept

Study Results

Participant Flow

Pre-assignment Detail	250 enrolled; 188 Randomized, 62 not Randomized:Reasons Not randomized: 6 withdrew consent, 1 lost to follow-up, 49 no longer meet study criteria, 6 screening failures

Arm/Group Title	Abatacept - Double Blind Treatment Period	Placebo - Double Blind Treatment Period
Arm/Group Description	Double Blind Treatment Period SC injection 125mg/mL in 1 mL pre-filled syringe	Double Blind Treatment Period SC injection in 1 mL pre-filled syringe
Period Title: Overall Study
STARTED	92	95
COMPLETED	81	87
NOT COMPLETED	11	8

Baseline Characteristics

Arm/Group Title	Abatacept - Double Blind Treatment Period	Placebo - Double Blind Treatment Period	Total
Arm/Group Description	Double Blind Treatment Period SC injection 125mg/mL in 1 mL pre-filled syringe	Double Blind Treatment Period SC injection in 1 mL pre-filled syringe	Total of all reporting groups
Overall Participants	92	95	187
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	51.2 (12.3)	52.9 (13.5)	52.0 (12.9)
Age, Customized (Count of Participants)
< 65 years	80 87%	73 76.8%	153 81.8%
≥ 65 years	12 13%	22 23.2%	34 18.2%
≤ 50 years	42 45.7%	42 44.2%	84 44.9%
> 50 years	50 54.3%	53 55.8%	103 55.1%
Sex: Female, Male (Count of Participants)
Female	85 92.4%	92 96.8%	177 94.7%
Male	7 7.6%	3 3.2%	10 5.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 2.2%	5 5.3%	7 3.7%
Not Hispanic or Latino	10 10.9%	13 13.7%	23 12.3%
Unknown or Not Reported	80 87%	77 81.1%	157 84%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	21 22.8%	23 24.2%	44 23.5%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	10 10.9%	9 9.5%	19 10.2%
White	60 65.2%	60 63.2%	120 64.2%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	1 1.1%	3 3.2%	4 2.1%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in EULAR Sjogren's Syndrome Disease Activity Index (ESSDAI)
Description	The EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) total score is calculated as the sum of scores for activity level for each domain. The EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) Scoring Algorithm. Domain: (Score) Constitutional: (No=0, Low=3, Moderate=6) Lymphadenopathy: (No=0, Low=4, Moderate=8, High=12) Glandular: (No=0, Low=2, Moderate=4) Articular: (No=0, Low=2, Moderate=4, High=6) Cutaneous: (No=0, Low=3, Moderate=6, High=9) Pulmonary: (No=0, Low=5, Moderate=10, High=15) Renal: (No=0, Low=5, Moderate=10, High=15) Muscular: (No=0, Low=6, Moderate=12, High=18) Peripheral Nervous System (PNS): (No=0, Low=5, Moderate=10, High=15) Central Nervous System (CNS): (No=0, Moderate=10, High=15) Haematological: (No=0, Low=2, Moderate=4, High=6) Biological: (No=0, Low=1, Moderate=2) (No = No Disease Activity (DA), Low = Low DA, Moderate = Moderate DA, High = High DA) Overall score, which can range from 0 to 123, a higher score indicates more disease activity
Time Frame	Day 169

Outcome Measure Data

Analysis Population Description

Modified Intent-to-treat (ITT) analysis population: all randomized participants who receive at least one dose of study medication.

Arm/Group Title	Abatacept - Double Blind Treatment Period	Placebo - Double Blind Treatment Period
Arm/Group Description	Double Blind Treatment Period SC injection 125mg/mL in 1 mL pre-filled syringe	Double Blind Treatment Period SC injection in 1 mL pre-filled syringe
Measure Participants	92	95
Mean (95% Confidence Interval) [Score on a Scale]	-3.2	-3.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Abatacept - Double Blind Treatment Period, Placebo - Double Blind Treatment Period
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4421
	Comments
	Method	longitudinal repeated measures analysis
	Comments

2. Secondary Outcome

Title	Change From Baseline in EULAR Sjogren's Syndrome Patient Reported Inde (ESSPRI)
Description	The total score EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) is calculated as the mean of the 3 individual components. Total Score Range (0 = Best outcome and 10 = Worst Outcome) The scores for the ESSPRI individual components will be used as such reported by the participants and entered in the case report form (CRF), without any further calculations. It consists of 3 questions covering cardinal symptoms of Sjögren's syndrome: dryness, fatigue and pain. Each domain scored on scale of 0-10 (0 =no symptom at all and 10 = worst symptom imaginable), and overall score is calculated as the mean of 3 individual domains.
Time Frame	Day 169

Outcome Measure Data

Analysis Population Description

Modified ITT Population

Arm/Group Title	Abatacept - Double Blind Treatment Period	Placebo - Double Blind Treatment Period
Arm/Group Description	Double Blind Treatment Period SC injection 125mg/mL in 1 mL pre-filled syringe	Double Blind Treatment Period SC injection in 1 mL pre-filled syringe
Measure Participants	92	95
Mean (95% Confidence Interval) [Score on a Scale]	-1.26	-1.52

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Abatacept - Double Blind Treatment Period, Placebo - Double Blind Treatment Period
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3367
	Comments
	Method	longitudinal repeated measures analysis
	Comments

3. Secondary Outcome

Title	Change From Baseline in the Stimulated Whole Salivary Flow
Description	The mean change from baseline in the stimulated whole salivary flow at Day 169
Time Frame	Day 169

Outcome Measure Data

Analysis Population Description

Modified ITT Population with Stimulated Whole Salivary Flow of at Least 0.1 mL/min at Both Screening and Baseline

Arm/Group Title	Abatacept - Double Blind Treatment Period	Placebo - Double Blind Treatment Period
Arm/Group Description	Double Blind Treatment Period SC injection 125mg/mL in 1 mL pre-filled syringe	Double Blind Treatment Period SC injection in 1 mL pre-filled syringe
Measure Participants	88	88
Mean (95% Confidence Interval) [mL/min]	0.057	0.108

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Abatacept - Double Blind Treatment Period, Placebo - Double Blind Treatment Period
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.5841
	Comments
	Method	longitudinal repeated measures analysis
	Comments

4. Secondary Outcome

Title	Change From Baseline of DAS28-C-reactive Peptide (CRP): In The Full Population
Description	The disease activity score DAS28-CRP is a continuous variable which is a composite of 4 variables: the 28 tender joint count (tender28), the 28 swollen joint count (swollen28), CRP and participant assessment of disease activity measure on a visual analogue scale (VAS) of 100mm. DAS28-CRP = 0.56 * sqrt(tender28) + 0.28 * sqrt(swollen28) + 0.36 * ln(hsCRP+1) + 0.014 * VAS + 0.96. (sqrt = Square root, ln = natural log) Positive Scores = Increased Disease Activity Negative Scores = Reduced Disease Activity
Time Frame	Day 29, Day 57, Day 85, Day 113, Day 141, Day 169

Outcome Measure Data

Analysis Population Description

Modified ITT Population

Arm/Group Title	Abatacept - Double Blind Treatment Period	Placebo - Double Blind Treatment Period
Arm/Group Description	Double Blind Treatment Period SC injection 125mg/mL in 1 mL pre-filled syringe	Double Blind Treatment Period SC injection in 1 mL pre-filled syringe
Measure Participants	92	95
Day 29	-0.4	-0.4
Day 57	-0.6	-0.7
Day 85	-0.8	-0.8
Day 113	-0.8	-1.0
Day 141	-0.8	-1.0
Day 169	-0.9	-1.1

5. Secondary Outcome

Title	Change From Baseline of DAS28-CRP: Tender Swollen Joint Count of at Least 3
Description	The disease activity score DAS28-CRP is a continuous variable which is a composite of 4 variables: the 28 tender joint count (tender28), the 28 swollen joint count (swollen28), CRP and participant assessment of disease activity measure on a visual analogue scale (VAS) of 100mm. DAS28-CRP = 0.56 * sqrt(tender28) + 0.28 * sqrt(swollen28) + 0.36 * ln(hsCRP+1) + 0.014 * VAS + 0.96. (sqrt = Square root, ln = natural log) Positive Scores = Increased Disease Activity Negative Scores = Reduced Disease Activity
Time Frame	Day 29, Day 57, Day 85, Day 113, Day 141, Day 169

Outcome Measure Data

Analysis Population Description

Modified ITT Population with Baseline Tender plus Swollen Joint Count of at Least 3

Arm/Group Title	Abatacept - Double Blind Treatment Period	Placebo - Double Blind Treatment Period
Arm/Group Description	Double Blind Treatment Period SC injection 125mg/mL in 1 mL pre-filled syringe	Double Blind Treatment Period SC injection in 1 mL pre-filled syringe
Measure Participants	57	63
Day 29	-0.5	-0.6
Day 57	-0.9	-1.0
Day 85	-1.1	-1.2
Day 113	-1.1	-1.4
Day 141	-1.2	-1.5
Day 169	-1.3	-1.5

6. Secondary Outcome

Title	Change From Baseline of DAS28-CRP: Tender Swollen Joints Count Less Than 3
Description	The disease activity score DAS28-CRP is a continuous variable which is a composite of 4 variables: the 28 tender joint count (tender28), the 28 swollen joint count (swollen28), CRP and participant assessment of disease activity measure on a visual analogue scale (VAS) of 100mm. DAS28-CRP = 0.56 * sqrt(tender28) + 0.28 * sqrt(swollen28) + 0.36 * ln(hsCRP+1) + 0.014 * VAS + 0.96. (sqrt = Square root, ln = natural log) Positive Scores = Increased Disease Activity Negative Scores = Reduced Disease Activity
Time Frame	Day 29, Day 57, Day 85, Day 113, Day 141, Day 169

Outcome Measure Data

Analysis Population Description

Modified ITT Population with Baseline Tender plus Swollen Joint Count of Less than 3

Arm/Group Title	Abatacept - Double Blind Treatment Period	Placebo - Double Blind Treatment Period
Arm/Group Description	Double Blind Treatment Period SC injection 125mg/mL in 1 mL pre-filled syringe	Double Blind Treatment Period SC injection in 1 mL pre-filled syringe
Measure Participants	35	31
Day 29	-0.3	-0.2
Day 57	-0.2	-0.2
Day 85	-0.4	-0.4
Day 113	-0.3	-0.3
Day 141	-0.2	-0.4
Day 169	-0.3	-0.5

7. Secondary Outcome

Title	Change From Baseline in the Joint Component of DAS28-CRP: In the Full Population
Description	The mean change from baseline at all measured time points up to Day 169 in the individual components of DAS28-CRP. Tender Joint: Count 1-28 Swollen Joint: Count 1-28 Negative Scores = Reduced number of joints impacted Positive Scores = Increased number of joints impacted
Time Frame	Day 29, Day 57, Day 85, Day 113, Day 141, Day 169

Outcome Measure Data

Analysis Population Description

Modified intent to treat (ITT)

Arm/Group Title	Abatacept - Double Blind Treatment Period	Placebo - Double Blind Treatment Period
Arm/Group Description	Double Blind Treatment Period SC injection 125mg/mL in 1 mL pre-filled syringe	Double Blind Treatment Period SC injection in 1 mL pre-filled syringe
Measure Participants	92	95
Day 29 - Tender Joint	-1.7	-1.9
Day 29 - Swollen Joint	-0.5	-0.6
Day 57 - Tender Joint	-2.6	-2.9
Day 57 - Swollen Joint	-1.0	-1.0
Day 85 - Tender Joint	-2.9	-3.4
Day 85 - Swollen Joint	-1.4	-1.4
Day 113 - Tender Joint	-3.1	-3.9
Day 113 - Swollen Joint	-1.5	-1.9
Day 141 - Tender Joint	-3.6	-4.1
Day 141 - Swollen Joint	-1.4	-1.8
Day 169 - Tender Joint	-2.9	-4.4
Day 169 - Swollen Joint	-1.4	-2.0

8. Secondary Outcome

Title	Change From Baseline in the CRP Component of DAS28-CRP: In the Full Population
Description	The mean change from baseline at all measured time points up to Day 169 in the individual components of DAS28-CRP. CRP: measured lab value Positive Number = Increased level of CRP Negative Number = Reduced Level of CRP
Time Frame	Day 29, Day 57, Day 85, Day 113, Day 141, Day 169

Outcome Measure Data

Analysis Population Description

Modified intent to treat (ITT)

Arm/Group Title	Abatacept - Double Blind Treatment Period	Placebo - Double Blind Treatment Period
Arm/Group Description	Double Blind Treatment Period SC injection 125mg/mL in 1 mL pre-filled syringe	Double Blind Treatment Period SC injection in 1 mL pre-filled syringe
Measure Participants	92	95
Day 29 - CRP	0.3	0.6
Day 57 - CRP	-0.1	1.8
Day 85 - CRP	-0.2	3.0
Day 113 - CRP	1.6	0.3
Day 141 - CRP	3.5	-0.2
Day 169 - CRP	-0.2	0.0

9. Secondary Outcome

Title	Change From Baseline in the Assessment of Disease Activity Component of DAS28-CRP: In the Full Population
Description	The mean change from baseline at all measured time points up to Day 169 in the individual components of DAS28-CRP. Assesment of Disease Activity: 0-100 scale [100=Most severe] Positive Numbers = Increased Disease Activity Negative Numbers = Decreased Diseased activity
Time Frame	Day 29, Day 57, Day 85, Day 113, Day 141, Day 169

Outcome Measure Data

Analysis Population Description

Modified intent to treat (ITT)

Arm/Group Title	Abatacept - Double Blind Treatment Period	Placebo - Double Blind Treatment Period
Arm/Group Description	Double Blind Treatment Period SC injection 125mg/mL in 1 mL pre-filled syringe	Double Blind Treatment Period SC injection in 1 mL pre-filled syringe
Measure Participants	92	95
Day 29 - Assessment of Disease Activity	-4.0	-7.1
Day 57 - Assessment of Disease Activity	-7.5	-6.3
Day 85 - Assessment of Disease Activity	-10.4	-10.2
Day 113 - Assessment of Disease Activity	-8.0	-9.7
Day 141 - Assessment of Disease Activity	-5.1	-11.0
Day 169 - Assessment of Disease Activity	-10.1	-9.0

10. Secondary Outcome

Title	Change From Baseline in the Joint Component of DAS28-CRP: Tender Swollen Joints of at Least 3
Description	The mean change from baseline at all measured time points up to Day 169 in the individual components of DAS28-CRP. Tender Joint: Count 1-28 Swollen Joint: Count 1-28 Negative Scores = Reduced number of joints impacted Positive Scores = Increased number of joints impacted
Time Frame	Day 29, Day 57, Day 85, Day 113, Day 141, Day 169

Outcome Measure Data

Analysis Population Description

Modified intent to treat (ITT) Population with Baseline Tender plus Swollen Joint Count of at least 3

Arm/Group Title	Abatacept - Double Blind Treatment Period	Placebo - Double Blind Treatment Period
Arm/Group Description	Double Blind Treatment Period SC injection 125mg/mL in 1 mL pre-filled syringe	Double Blind Treatment Period SC injection in 1 mL pre-filled syringe
Measure Participants	57	63
Day 29 - Tender Joint	-2.8	-3.0
Day 29 - Swollen Joint	-0.7	-0.9
Day 57 - Tender Joint	-4.1	-4.8
Day 57 - Swollen Joint	-1.5	-1.6
Day 85 - Tender Joint	-4.4	-5.4
Day 85 - Swollen Joint	-2.1	-2.2
Day 113 - Tender Joint	-4.8	-6.0
Day 113 - Swollen Joint	-2.3	-2.9
Day 141 - Tender Joint	-5.7	-6.4
Day 141 - Swollen Joint	-2.2	-3.0
Day 169 - Tender Joint	-4.6	-6.7
Day 169 - Swollen Joint	-2.2	-3.1

11. Secondary Outcome

Title	Change From Baseline in the CRP Component of DAS28-CRP: Tender Swollen Joints of at Least 3
Description	The mean change from baseline at all measured time points up to Day 169 in the individual components of DAS28-CRP. CRP: measured lab value Positive Number = Increased level of CRP Negative Number = Reduced Level of CRP
Time Frame	Day 29, Day 57, Day 85, Day 113, Day 141, Day 169

Outcome Measure Data

Analysis Population Description

Modified intent to treat (ITT) Population with Baseline Tender plus Swollen Joint Count of at least 3

Arm/Group Title	Abatacept - Double Blind Treatment Period	Placebo - Double Blind Treatment Period
Arm/Group Description	Double Blind Treatment Period SC injection 125mg/mL in 1 mL pre-filled syringe	Double Blind Treatment Period SC injection in 1 mL pre-filled syringe
Measure Participants	57	63
Day 29 - CRP	-1.5	-0.7
Day 57 - CRP	-1.3	1.3
Day 85 - CRP	-2.2	3.8
Day 113 - CRP	1.2	-0.4
Day 141 - CRP	4.5	-1.4
Day 169 - CRP	-1.4	-0.7

12. Secondary Outcome

Title	Change From Baseline in the Assessment of Disease Activity Component of DAS28-CRP: Tender Swollen Joints of at Least 3
Description	The mean change from baseline at all measured time points up to Day 169 in the individual components of DAS28-CRP. Assesment of Disease Activity: 0-100 scale [100=Most severe] Positive Numbers = Increased Disease Activity Negative Numbers = Decreased Diseased activity
Time Frame	Day 29, Day 57, Day 85, Day 113, Day 141, Day 169

Outcome Measure Data

Analysis Population Description

Modified intent to treat (ITT) Population with Baseline Tender plus Swollen Joint Count of at least 3

Arm/Group Title	Abatacept - Double Blind Treatment Period	Placebo - Double Blind Treatment Period
Arm/Group Description	Double Blind Treatment Period SC injection 125mg/mL in 1 mL pre-filled syringe	Double Blind Treatment Period SC injection in 1 mL pre-filled syringe
Measure Participants	57	63
Day 29 - Assessment of Disease Activity	0.6	-3.5
Day 57 - Assessment of Disease Activity	-3.5	-6.5
Day 85 - Assessment of Disease Activity	-7.5	-7.7
Day 113 - Assessment of Disease Activity	-6.6	-9.1
Day 141 - Assessment of Disease Activity	-1.2	-8.1
Day 169 - Assessment of Disease Activity	-6.7	-7.8

13. Secondary Outcome

Title	Change From Baseline in the Joint Component of DAS28-CRP: Tender Swollen Joint Count Less Than 3
Description	The mean change from baseline at all measured time points up to Day 169 in the individual components of DAS28-CRP. Tender Joint: Count 1-28 Swollen Joint: Count 1-28 Negative Scores = Reduced number of joints impacted Positive Scores = Increased number of joints impacted
Time Frame	Day 29, Day 57, Day 85, Day 113, Day 141, Day 169

Outcome Measure Data

Analysis Population Description

Modified intent to treat (ITT) Population with Baseline Tender plus Swollen Joint Count of Less than 3

Arm/Group Title	Abatacept - Double Blind Treatment Period	Placebo - Double Blind Treatment Period
Arm/Group Description	Double Blind Treatment Period SC injection 125mg/mL in 1 mL pre-filled syringe	Double Blind Treatment Period SC injection in 1 mL pre-filled syringe
Measure Participants	35	31
Day 29 - Tender Joint	-0.1	-0.2
Day 29 - Swollen Joint	0.1	0.1
Day 57 - Tender Joint	-0.2	0.1
Day 57 - Swollen Joint	0.2	0.0
Day 85 - Tender Joint	-0.5	0.1
Day 85 - Swollen Joint	-0.0	0.1
Day 113 - Tender Joint	-0.4	-0.5
Day 113 - Swollen Joint	0.0	0.1
Day 141 - Tender Joint	-0.2	-0.2
Day 141 - Swollen Joint	0.2	0.3
Day 169 - Tender Joint	-0.1	-0.7
Day 169 - Swollen Joint	0.2	-0.0

14. Secondary Outcome

Title	Change From Baseline in the CRP Component of DAS28-CRP: Tender Swollen Joint Count Less Than 3
Description	The mean change from baseline at all measured time points up to Day 169 in the individual components of DAS28-CRP. CRP: measured lab value Positive Number = Increased level of CRP Negative Number = Reduced Level of CRP
Time Frame	Day 29, Day 57, Day 85, Day 113, Day 141, Day 169

Outcome Measure Data

Analysis Population Description

Modified intent to treat (ITT) Population with Baseline Tender plus Swollen Joint Count of Less than 3

Arm/Group Title	Abatacept - Double Blind Treatment Period	Placebo - Double Blind Treatment Period
Arm/Group Description	Double Blind Treatment Period SC injection 125mg/mL in 1 mL pre-filled syringe	Double Blind Treatment Period SC injection in 1 mL pre-filled syringe
Measure Participants	35	31
Day 29 - CRP	2.1	1.8
Day 57 - CRP	0.5	1.0
Day 85 - CRP	1.4	0.1
Day 113 - CRP	1.3	0.1
Day 141 - CRP	0.7	0.8
Day 169 - CRP	0.2	0.2

15. Secondary Outcome

Title	Change From Baseline in the Assessment of Disease Activity Component of DAS28-CRP: Tender Swollen Joint Count Less Than 3
Description	The mean change from baseline at all measured time points up to Day 169 in the individual components of DAS28-CRP. Assesment of Disease Activity: 0-100 scale [100=Most severe] Positive Numbers = Increased Disease Activity Negative Numbers = Decreased Diseased activity
Time Frame	Day 29, Day 57, Day 85, Day 113, Day 141, Day 169

Outcome Measure Data

Analysis Population Description

Modified intent to treat (ITT) Population with Baseline Tender plus Swollen Joint Count of Less than 3

Arm/Group Title	Abatacept - Double Blind Treatment Period	Placebo - Double Blind Treatment Period
Arm/Group Description	Double Blind Treatment Period SC injection 125mg/mL in 1 mL pre-filled syringe	Double Blind Treatment Period SC injection in 1 mL pre-filled syringe
Measure Participants	35	31
Day 29 - Assessment of Disease Activity	-10.3	-11.8
Day 57 - Assessment of Disease Activity	-12.4	-4.8
Day 85 - Assessment of Disease Activity	-14.0	-13.5
Day 113 - Assessment of Disease Activity	-9.1	-11.1
Day 141 - Assessment of Disease Activity	-10.6	-15.3
Day 169 - Assessment of Disease Activity	-13.8	-10.9

16. Secondary Outcome

Title	Participants Who Achieve Minimally Clinically Important Change in ESSDAI in at Least 3 Points
Description	Proportion of participants who achieve a minimally clinically important change (of at least 3 points) in the ESSDAI at all measured time points up to Day 169.
Time Frame	Day 29, Day 57, Day 85, Day 113, Day 141, Day 169

Outcome Measure Data

Analysis Population Description

Modified intent to treat (ITT) Population

Arm/Group Title	Abatacept - Double Blind Treatment Period	Placebo - Double Blind Treatment Period
Arm/Group Description	Double Blind Treatment Period SC injection 125mg/mL in 1 mL pre-filled syringe	Double Blind Treatment Period SC injection in 1 mL pre-filled syringe
Measure Participants	92	95
Day 29	37	34.7
Day 57	37	44.2
Day 85	48.9	50.5
Day 113	55.4	50.5
Day 141	51.1	56.8
Day 169	55.4	57.9

17. Secondary Outcome

Title	Participants Who Achieve Minimally Clinically Important Change in ESSDAI in at Least 5 Points
Description	Proportion of participants who achieve a minimally clinically important change (of at least 5 points) in the ESSDAI at all measured time points up to Day 169.
Time Frame	Day 29, Day 57, Day 85, Day 113, Day 141, Day 169

Outcome Measure Data

Analysis Population Description

Modified intent to treat (ITT) Population

Arm/Group Title	Abatacept - Double Blind Treatment Period	Placebo - Double Blind Treatment Period
Arm/Group Description	Double Blind Treatment Period SC injection 125mg/mL in 1 mL pre-filled syringe	Double Blind Treatment Period SC injection in 1 mL pre-filled syringe
Measure Participants	92	95
Day 29	19.6	13.7
Day 57	26.1	24.2
Day 85	34.8	32.6
Day 113	37.0	36.8
Day 141	37.0	36.8
Day 169	35.9	46.3

18. Secondary Outcome

Title	Participants Who Achieve Minimally Clinically Important Change in ESSPRI in at Least 1 Point
Description	Proportion of participants who achieve a minimally clinically important change (of at least 1 point) in the ESSPRI at all measured time points up to Day 169.
Time Frame	Day 29, Day 57, Day 85, Day 113, Day 141, Day 169

Outcome Measure Data

Analysis Population Description

Modified intent to treat (ITT) Population

Arm/Group Title	Abatacept - Double Blind Treatment Period	Placebo - Double Blind Treatment Period
Arm/Group Description	Double Blind Treatment Period SC injection 125mg/mL in 1 mL pre-filled syringe	Double Blind Treatment Period SC injection in 1 mL pre-filled syringe
Measure Participants	92	95
Day 29	31.5	38.9
Day 57	42.4	47.4
Day 85	44.6	55.8
Day 113	42.4	52.6
Day 141	40.2	54.7
Day 169	41.3	52.6

19. Secondary Outcome

Title	Change From Baseline at All Measured Time Points in the ESSDAI
Description	The EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) total score is calculated as the sum of scores for activity level for each domain. The EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) Scoring Algorithm. Domain: (Score) Constitutional: (No=0, Low=3, Moderate=6) Lymphadenopathy: (No=0, Low=4, Moderate=8, High=12) Glandular: (No=0, Low=2, Moderate=4) Articular: (No=0, Low=2, Moderate=4, High=6) Cutaneous: (No=0, Low=3, Moderate=6, High=9) Pulmonary: (No=0, Low=5, Moderate=10, High=15) Renal: (No=0, Low=5, Moderate=10, High=15) Muscular: (No=0, Low=6, Moderate=12, High=18) Peripheral Nervous System (PNS): (No=0, Low=5, Moderate=10, High=15) Central Nervous System (CNS): (No=0, Moderate=10, High=15) Haematological: (No=0, Low=2, Moderate=4, High=6) Biological: (No=0, Low=1, Moderate=2) (No = No Disease Activity (DA), Low = Low DA, Moderate = Moderate DA, High = High DA) Overall score, which can range from 0 to 123, a higher score indicates more disease activity
Time Frame	Day 29, Day 57, Day 85, Day 113, Day 141, Day 169

Outcome Measure Data

Analysis Population Description

Modified intent to treat (ITT) Population

Arm/Group Title	Abatacept - Double Blind Treatment Period	Placebo - Double Blind Treatment Period
Arm/Group Description	Double Blind Treatment Period SC injection 125mg/mL in 1 mL pre-filled syringe	Double Blind Treatment Period SC injection in 1 mL pre-filled syringe
Measure Participants	92	95
Day 29	-10.9	-12.6
Day 57	-24.1	-18.9
Day 85	-26.0	-25.4
Day 113	-34.1	-32.1
Day 141	-29.7	-37.0
Day 169	-33.4	-37.6

20. Secondary Outcome

Title	Change From Baseline at All Measured Time Points in the ESSPRI
Description	The total score EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) is calculated as the mean of the 3 individual components. Total Score Range (0 = Best outcome and 10 = Worst Outcome) The scores for the ESSPRI individual components will be used as such reported by the participants and entered in the case report form (CRF), without any further calculations. It consists of 3 questions covering cardinal symptoms of Sjögren's syndrome: dryness, fatigue and pain. Each domain scored on scale of 0-10 (0 =no symptom at all and 10 = worst symptom imaginable), and overall score is calculated as the mean of 3 individual domains.
Time Frame	Day 29, Day 57, Day 85, Day 113, Day 141, Day 169

Outcome Measure Data

Analysis Population Description

Modified intent to treat (ITT) Population

Arm/Group Title	Abatacept - Double Blind Treatment Period	Placebo - Double Blind Treatment Period
Arm/Group Description	Double Blind Treatment Period SC injection 125mg/mL in 1 mL pre-filled syringe	Double Blind Treatment Period SC injection in 1 mL pre-filled syringe
Measure Participants	92	95
Day 29	-0.32	-0.54
Day 57	-0.81	-0.82
Day 85	-0.83	-1.20
Day 113	-0.79	-1.37
Day 141	-0.87	-1.32
Day 169	-1.03	-1.30

21. Secondary Outcome

Title	Change From Baseline in Components of ESSDAI
Description	The EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) total score is calculated as the sum of scores for activity level for each domain. The EULAR Sjögren's Syndrome Disease Activity Index (ESSDAI) Scoring Algorithm. Domain: (Score for activity level) Constitutional: (No=0, Low=3, Moderate=6) Lymphadenopathy: (No=0, Low=4, Moderate=8, High=12) Glandular: (No=0, Low=2, Moderate=4) Articular: (No=0, Low=2, Moderate=4, High=6) Cutaneous: (No=0, Low=3, Moderate=6, High=9) Pulmonary: (No=0, Low=5, Moderate=10, High=15) Renal: (No=0, Low=5, Moderate=10, High=15) Muscular: (No=0, Low=6, Moderate=12, High=18) Peripheral Nervous System (PNS): (No=0, Low=5, Moderate=10, High=15) Central Nervous System (CNS): (No=0, Moderate=10, High=15) Haematological: (No=0, Low=2, Moderate=4, High=6) Biological: (No=0, Low=1, Moderate=2) (No = No Disease Activity, Low = Low Disease Activity, Moderate = Moderate Disease Activity, High = High Disease Activity)
Time Frame	Day 29, Day 57, Day 85, Day 113, Day 141 and Day 169

Outcome Measure Data

Analysis Population Description

Modified ITT Population

Arm/Group Title	Abatacept - Double Blind Treatment Period	Placebo - Double Blind Treatment Period
Arm/Group Description	Double Blind Treatment Period SC injection 125mg/mL in 1 mL pre-filled syringe	Double Blind Treatment Period SC injection in 1 mL pre-filled syringe
Measure Participants	92	95
Day 29: Constitutional	-0.3	-0.4
Day 29: Lymphadenopathy	-0.6	-0.5
Day 29: Glandular	-0.2	-0.2
Day 29: Articular	-0.4	-0.3
Day 29: Cutaneous	-0.3	-0.2
Day 29: Pulmonary	0.0	0.1
Day 29: Renal	-0.0	-0.2
Day 29: Muscular	-0.0	-0.0
Day 29: Peripheral Nervous System	-0.0	0.0
Day 29: Haematogical	0.2	0.1
Day 29: Biological	0.1	0.1
Day 57: Constitutional	-0.2	-0.3
Day 57: Lymphadenopathy	-0.7	-0.6
Day 57: Glandular	-0.4	-0.4
Day 57: Articular	-0.7	-0.8
Day 57: Cutaneous	-0.3	-0.2
Day 57: Pulmonary	-0.0	0.2
Day 57: Renal	-0.0	-0.1
Day 57: Muscular	-0.0	-0.1
Day 57: Peripheral Nervous System	-0.0	0.0
Day 57: Haematological	0.1	0.2
Day 57: Biological	-0.1	0.0
Day 85: Constitutional	-0.3	-0.4
Day 85: Lymphadenopathy	-0.7	-0.8
Day 85: Glandular	-0.4	-0.5
Day 85: Articular	-1.0	-1.1
Day 85: Cutaneous	-0.4	-0.2
Day 85: Pulmonary	0.0	0.2
Day 85: Renal	-0.1	-0.1
Day 85: Muscular	-0.1	-0.0
Day 85: Peripheral Nervous System	-0.0	0.0
Day 85: Haematological	0.1	0.2
Day 85: Biological	0.0	0.2
Day 113: Constitutional	-0.3	-0.3
Day 113: Lymphadenopathy	-0.8	-0.9
Day 113: Glandular	-0.5	-0.5
Day 113: Articular	-1.3	-1.3
Day 113: Cutaneous	-0.4	-0.4
Day 113: Pulmonary	0.0	0.1
Day 113: Renal	-0.1	0.0
Day 113: Muscular	-0.0	-0.1
Day 113: Peripheral Nervous System	-0.0	-0.0
Day 113: Haematological	0.1	0.2
Day 113: Biological	-0.0	0.1
Day 141: Constitutional	-0.2	-0.4
Day 141: Lymphadenopathy	-0.6	-0.9
Day 141: Glandular	-0.5	-0.6
Day 141: Articular	-1.2	-1.4
Day 141: Cutaneous	-0.4	-0.5
Day 141: Pulmonary	-0.0	0.1
Day 141: Renal	-0.0	-0.1
Day 141: Muscular	-0.1	-0.1
Day 141: Peripheral Nervous System	-0.1	-0.0
Day 141: Haematological	0.1	0.1
Day 141: Biological	-0.0	0.1
Day 169: Constitutional	-0.3	-0.4
Day 169: Lymphadenopathy	-0.9	-1.1
Day 169: Glandular	-0.4	-0.5
Day 169: Articular	-1.4	-1.8
Day 169: Cutaneous	-0.3	-0.5
Day 169: Pulmonary	-0.0	0.1
Day 169: Renal	-0.0	0.0
Day 169: Muscular	-0.0	-0.1
Day 169: Peripheral Nervous	-0.1	-0.0
Day 169: Haematological	0.1	0.3
Day 169: Biological	0.0	0.2

22. Secondary Outcome

Title	Change From Baseline in ESSPRI Components
Description	The total score EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) is calculated as the mean of the 3 individual components. Total Score Range (0 = Best outcome and 10 = Worst Outcome) The scores for the ESSPRI individual components will be used as such reported by the participants and entered in the case report form (CRF), without any further calculations. It consists of 3 questions covering cardinal symptoms of Sjögren's syndrome: dryness, fatigue and pain. Each domain scored on scale of 0-10 (0 =no symptom at all and 10 = worst symptom imaginable), and overall score is calculated as the mean of 3 individual domains.
Time Frame	Day 29, Day 57, Day 85, Day 113, Day 141, Day 169

Outcome Measure Data

Analysis Population Description

Modified ITT Population

Arm/Group Title	Abatacept - Double Blind Treatment Period	Placebo - Double Blind Treatment Period
Arm/Group Description	Double Blind Treatment Period SC injection 125mg/mL in 1 mL pre-filled syringe	Double Blind Treatment Period SC injection in 1 mL pre-filled syringe
Measure Participants	92	95
Day 29: Dryness Score	-0.21	-0.26
Day 29: Fatigue Score	-0.57	-1.01
Day 29: Pain Score	-0.34	-0.53
Day 57: Dryness Score	-0.92	-0.52
Day 57: Fatigue Score	-1.09	-1.22
Day 57: Pain Score	-0.60	-0.90
Day 85: Dryness Score	-0.68	-0.91
Day 85: Fatigue Score	-1.27	-1.56
Day 85: Pain Score	-0.70	-1.31
Day 113: Dryness Score	-0.74	-1.19
Day 113: Fatigue Score	-1.02	-1.76
Day 113: Pain Score	-0.76	-1.37
Day 141: Dryness Score	-0.89	-1.05
Day 141: Fatigue Score	-1.18	-1.73
Day 141: Pain Score	-0.70	-1.39
Day 169: Dryness Score	-0.84	-1.04
Day 169: Fatigue Score	-1.28	-1.57
Day 169: Pain Score	-1.11	-1.45

23. Secondary Outcome

Title	Change From Baseline in Schirmer's Test
Description	The Mean change from baseline in Schirmer's Test at all measured time points up to day 169 The length in millimeters that the strip wets during the 5 minute test period for each eye. Collection is done separately for each eye.
Time Frame	Day 85, Day 169

Outcome Measure Data

Analysis Population Description

Modified ITT Population

Arm/Group Title	Abatacept - Double Blind Treatment Period	Placebo - Double Blind Treatment Period
Arm/Group Description	Double Blind Treatment Period SC injection 125mg/mL in 1 mL pre-filled syringe	Double Blind Treatment Period SC injection in 1 mL pre-filled syringe
Measure Participants	92	95
Day 85: Study Eye	1.9	1.5
Day 85: Non-Study Eye	0.1	0.8
Day 85: Average of Both Eyes	1.10	1.41
Day 169: Study Eye	1.7	1.0
Day 169: Non-Study Eye	0.6	0.2
Day 169: Average of Both Eyes	1.21	0.82

24. Secondary Outcome

Title	Change From Baseline in the Ocular Staining Score (OSS)
Description	The Mean change from baseline in OSS at all measured time points up to day 169 Score of 0 = No Staining Score of 12 = diffuse staining The total score will be calculated as the sum of the score for these parameters for each eye. Medial Nasal Bulbar Conjunctiva (MNBC) [score scale: 0 - 3], Corneal (CORN) Staining of Punctate Epithelial Erosions (PEE) [score scale: 0 - 3], Lateral Temporal Bulbar Conjunctiva (LTBC) [score scale: 0 - 3], Patches of Confluent Staining (CONF) [score scale: 0 - 1], PEE observed in the pupil region, i.e. central 4mm diameter portion of the cornea (PUPL) [score scale: 0 - 1], one of more filaments seen anywhere on the cornea (FILA) [score scale: 0 - 1]
Time Frame	Day 85, Day 169

Outcome Measure Data

Analysis Population Description

Modified ITT Population

Arm/Group Title	Abatacept - Double Blind Treatment Period	Placebo - Double Blind Treatment Period
Arm/Group Description	Double Blind Treatment Period SC injection 125mg/mL in 1 mL pre-filled syringe	Double Blind Treatment Period SC injection in 1 mL pre-filled syringe
Measure Participants	92	95
Day 85: Study Eye	-1.7	-0.5
Day 85: Non-Study Eye	-0.6	0.4
Day 85: Average of Both Eyes	-1.15	-0.06
Day 169: Study Eye	-1.5	-0.7
Day 169: Non-Study Eye	-0.5	0.3
Day 169: Average of Both Eyes	-0.99	-0.19

25. Secondary Outcome

Title	Change From Baseline in Tear Break-up Time
Description	The Mean change from baseline in Tear Break-up Time at all measured time points up to day 169 The CRF collects the time in seconds to first appearance of a random dry spot on the corneal surface for 3 repetitions in each eye. The average time will calculated for each eye averaging the 3 measurements for each eye separately. In case only 2 measurements are available, the average of the 2 measurements will be calculated. In case there is only 1 measurement, that measurement will be used for the analysis.
Time Frame	Day 85, Day 169

Outcome Measure Data

Analysis Population Description

Modified ITT Population

Arm/Group Title	Abatacept - Double Blind Treatment Period	Placebo - Double Blind Treatment Period
Arm/Group Description	Double Blind Treatment Period SC injection 125mg/mL in 1 mL pre-filled syringe	Double Blind Treatment Period SC injection in 1 mL pre-filled syringe
Measure Participants	92	95
Day 85: Study Eye	-0.13	0.18
Day 85: Non-Study Eye	-0.70	-0.12
Day 85: Average of Both Eyes	-0.41	0.09
Day 169: Study Eye	-0.23	-0.32
Day 169: Non-Study Eye	-0.79	-0.62
Day 169: Average of Both Eyes	-0.50	-0.43

26. Secondary Outcome

Title	Change From Baseline in Unstimulated Salivary Flow
Description	The mean change from baseline in unstimulated whole salivary flow at all measured time points up to Day 169.
Time Frame	Day 85, Day 169

Outcome Measure Data

Analysis Population Description

Modified ITT Population

Arm/Group Title	Abatacept - Double Blind Treatment Period	Placebo - Double Blind Treatment Period
Arm/Group Description	Double Blind Treatment Period SC injection 125mg/mL in 1 mL pre-filled syringe	Double Blind Treatment Period SC injection in 1 mL pre-filled syringe
Measure Participants	92	95
Day 85	0.106	0.158
Day 169	0.051	0.105

27. Secondary Outcome

Title	Change From Baseline in Stimulated Salivary Flow
Description	The mean change from baseline in Stimulated whole salivary flow at all measured time points up to Day 169.
Time Frame	Day 85, Day 169

Outcome Measure Data

Analysis Population Description

Modified ITT Population

Arm/Group Title	Abatacept - Double Blind Treatment Period	Placebo - Double Blind Treatment Period
Arm/Group Description	Double Blind Treatment Period SC injection 125mg/mL in 1 mL pre-filled syringe	Double Blind Treatment Period SC injection in 1 mL pre-filled syringe
Measure Participants	88	88
Day 85	0.11	0.169
Day 169	0.056	0.108

28. Secondary Outcome

Title	Change From Baseline in Numeric Rating Scale for Mouth Dryness
Description	The mean change from baseline in participant symptoms using the Numeric Rating Scale (NRS) for mouth dryness at all measured time points up to Day 169. The oral and ocular dryness are each assessed by the patients with numeric rating scales from 0 to 10 with 0 representing no dryness and 10 representing maximal dryness
Time Frame	Day 1, 29, 57, 85, 113, 141, 169

Outcome Measure Data

Analysis Population Description

Modified ITT Population

Arm/Group Title	Abatacept - Double Blind Treatment Period	Placebo - Double Blind Treatment Period
Arm/Group Description	Double Blind Treatment Period SC injection 125mg/mL in 1 mL pre-filled syringe	Double Blind Treatment Period SC injection in 1 mL pre-filled syringe
Measure Participants	92	95
Day 29	-0.8	-0.5
Day 57	-1.3	-0.9
Day 85	-1.3	-1.1
Day 113	-1.2	-1.3
Day 141	-1.3	-1.1
Day 169	-1.3	-1.2

29. Secondary Outcome

Title	Change From Baseline in Numeric Rating Scale for Eye Dryness
Description	The mean change from baseline in patient symptoms using the Numeric Rating Scale (NRS) for eye dryness at all measured time points up to Day 169. The oral and ocular dryness are each assessed by the patients with numeric rating scales from 0 to 10 with 0 representing no dryness and 10 representing maximal dryness
Time Frame	Day 1, 29, 57, 85, 113, 141, 169

Outcome Measure Data

Analysis Population Description

Modified ITT Population

Arm/Group Title	Abatacept - Double Blind Treatment Period	Placebo - Double Blind Treatment Period
Arm/Group Description	Double Blind Treatment Period SC injection 125mg/mL in 1 mL pre-filled syringe	Double Blind Treatment Period SC injection in 1 mL pre-filled syringe
Measure Participants	92	95
Day 29	-0.4	-0.3
Day 57	-0.9	-0.6
Day 85	-0.9	-0.8
Day 113	-1.0	-1.1
Day 141	-0.8	-1.0
Day 169	-0.9	-1.0

30. Secondary Outcome

Title	Change From Baseline in Participant Assessment of Disease Activity
Description	The participant global assessment of disease activity are assessed with visual analog scales. The participant marks a vertical line through a horizontal line, where the beginning of the horizontal line represents the best situation, and the end of the horizontal line represents the very worst situation. The CRF collects the distance in millimeters from the start of the scale that is marked as well as the length of the scale in millimeters. In cases that the length of the scale is in less or more than 100 millimeters, then the participants measurement will be rescaled to the equivalent of 100 millimeters using the formula below: Rescale Measurement in mm = (measurement as reported on CRF in mm/length of the line on CRF in mm) * 100mm A negative score = participant assessment of disease activity has improved A positive score = participant assessment of disease activity has worsened
Time Frame	Day 29, 57, 85, 113, 141, 169

Outcome Measure Data

Analysis Population Description

Modified ITT Population

Arm/Group Title	Abatacept - Double Blind Treatment Period	Placebo - Double Blind Treatment Period
Arm/Group Description	Double Blind Treatment Period SC injection 125mg/mL in 1 mL pre-filled syringe	Double Blind Treatment Period SC injection in 1 mL pre-filled syringe
Measure Participants	92	95
Day 29	-4.0	-7.1
Day 57	-7.5	-6.3
Day 85	-10.4	-10.2
Day 113	-8.0	-9.7
Day 141	-5.1	-11.0
Day 169	-10.1	-9.0

31. Secondary Outcome

Title	Change From Baseline in Physician Global Assessment of Disease Activity
Description	The physician global assessment of disease activity are assessed with visual analog scales. The physician marks a vertical line through a horizontal line, where the beginning of the horizontal line represents the best situation, and the end of the horizontal line represents the very worst situation. The CRF collects the distance in millimeters from the start of the scale that is marked as well as the length of the scale in millimeters. In cases that the length of the scale is in less or more than 100 millimeters, then the participants measurement will be rescaled to the equivalent of 100 millimeters using the formula below: Rescale Measurement in mm = (measurement as reported on CRF in mm/length of the line on CRF in mm) * 100mm A negative score = physician assessment of disease activity has improved A positive score = physician assessment of disease activity has worsened
Time Frame	Day 29, 57, 85, 113, 141, 169

Outcome Measure Data

Analysis Population Description

Modified ITT Population

Arm/Group Title	Abatacept - Double Blind Treatment Period	Placebo - Double Blind Treatment Period
Arm/Group Description	Double Blind Treatment Period SC injection 125mg/mL in 1 mL pre-filled syringe	Double Blind Treatment Period SC injection in 1 mL pre-filled syringe
Measure Participants	92	95
Day 29	-10.3	-10.5
Day 57	-16.2	-16.7
Day 85	-20.8	-19.4
Day 113	-22.8	-19.8
Day 141	-23.7	-21.7
Day 169	-23.0	-23.7

32. Secondary Outcome

Title	Change From Baseline in Patient Fatigue
Description	The mean change from baseline in patient fatigue using Patient Reported Outcomes Measurement Information System (PROMIS) Fatigue assessment of disease activity at all measured time points up to Day 169. PROMIS Fatigue instruments 10 Questions ranging from a score 0 to 40. Sum of the values gives you the raw sum. The raw is inputted into this formula to give you the raw score: Raw Score = (Raw sum*number of items on the short form)/(Number of items that were actually answered) Raw score is translated to a T-Score using a table. T-Score is used as the final score. The T-score rescales the raw score into a standardized score with a mean of 50 and a standard deviation (SD) of 10. The standardized T-score is reported as the final score for each participant. A negative T Score = Better Prognosis A positive T Score = Worse prognosis
Time Frame	Day 29, 57, 85, 113, 141, 169

Outcome Measure Data

Analysis Population Description

Modified ITT Population

Arm/Group Title	Abatacept - Double Blind Treatment Period	Placebo - Double Blind Treatment Period
Arm/Group Description	Double Blind Treatment Period SC injection 125mg/mL in 1 mL pre-filled syringe	Double Blind Treatment Period SC injection in 1 mL pre-filled syringe
Measure Participants	92	95
Day 29	-3.08	-3.99
Day 57	-4.12	-4.02
Day 85	-4.85	-5.48
Day 113	-4.17	-5.32
Day 141	-4.84	-5.68
Day 169	-5.56	-5.59

33. Secondary Outcome

Title	Change From Baseline in Female Sexual Function Using the Female Sexual Function Index (FSFI)
Description	For the FSFI, is a 19 item instrument used for assessing key dimensions of female sexual function over the past 4 weeks with 6 domains being analyzed. The specific domains (desire, arousal, lubrication, orgasm, satisfaction, and pain) analyzed in the FSFI are scored on a scale ranging from 0 to 5, with higher scores indicating better performance. Domain scores are calculated by summing the scores of the individual questions that make up the domain and multiplying the sum by the factor in the table below. The full scale score is the sum of the six domain scores. Full Scale Score range: 2.0(minimum score) - 36.0 (maximum score) Negative Score = Reduced functioning Positive Score = Improved functioning
Time Frame	Day 85, Day 169

Outcome Measure Data

Analysis Population Description

Modified ITT Population

Arm/Group Title	Abatacept - Double Blind Treatment Period	Placebo - Double Blind Treatment Period
Arm/Group Description	Double Blind Treatment Period SC injection 125mg/mL in 1 mL pre-filled syringe	Double Blind Treatment Period SC injection in 1 mL pre-filled syringe
Measure Participants	88	88
Day 85	-2.44	-1.56
Day 169	-2.32	-1.87

34. Secondary Outcome

Title	Change From Baseline in 36-item Short Form Health Survey (SF-36)
Description	The SF-36 determines participants' overall quality of life by assessing 1) limitations in physical functioning due to health problems; 2) limitations in usual role because of physical health problems; 3) bodily pain; 4) general health perceptions; 5) vitality; 6) limitations in social functioning because of physical or emotional problems; 7) limitations in usual role due to emotional problems; and 8) general mental health. Scores on each item are summed and averaged (range: 0=worst to 100=best). Increases from baseline indicate improvement
Time Frame	Day 85, Day 169

Outcome Measure Data

Analysis Population Description

Modified ITT Population

Arm/Group Title	Abatacept - Double Blind Treatment Period	Placebo - Double Blind Treatment Period
Arm/Group Description	Double Blind Treatment Period SC injection 125mg/mL in 1 mL pre-filled syringe	Double Blind Treatment Period SC injection in 1 mL pre-filled syringe
Measure Participants	92	95
Day 85: Physical Function	1.908	1.523
Day 85: Role Physical	5.248	4.416
Day 85: Bodily Pain	3.200	3.721
Day 85: General Health	4.042	3.409
Day 85: Vitality	3.827	3.859
Day 85: Social Functioning	3.020	4.771
Day 85: Role-Emotional	3.024	4.834
Day 85: Mental Health	2.942	2.287
Day 85: Physical component Summary	3.430	2.686
Day 85: Mental component Summary	2.693	3.672
Day 169: Physical Function	2.927	1.742
Day 169: Role-Physical	5.853	4.626
Day 169: Bodily Pain	3.842	3.458
Day 169: General Health	3.880	3.764
Day 169: Vitality	3.742	4.523
Day 169: Social functioning	4.125	4.471
Day 169: Role-Emotional	4.653	4.930
Day 169: Mental Health	2.375	2.972
Day 169: Physical Component Summary	3.998	2.650
Day 169: Mental Component Summary	2.940	4.112

35. Secondary Outcome

Title	Geometric Mean of Trough Concentration (Cmin) of Abatacept
Description	Geometric mean of trough concentration (Cmin) of abatacept at all measured time points.
Time Frame	Day 29, 85, 113, 141, 169

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) Evaluable Population

Arm/Group Title	Abatacept - Double Blind Treatment Period	Placebo - Double Blind Treatment Period
Arm/Group Description	Double Blind Treatment Period SC injection 125mg/mL in 1 mL pre-filled syringe	Double Blind Treatment Period SC injection in 1 mL pre-filled syringe
Measure Participants	92	0
Day 29	21.401 (36)
Day 85	27.543 (38.4)
Day 113	25.567 (42.1)
Day 141	25.870 (40.8)
Day 169	24.522 (42.7)

36. Secondary Outcome

Title	Percentage of Participants With a Positive Antibody Response
Description	Percentage of participants with at least one positive immunogenicity response up to Day 169 and during 3 months follow up (for participants who discontinue during the 6-months double-blind).
Time Frame	Day 85 db, day 169 db, post treatment day 85

Outcome Measure Data

Analysis Population Description

Immunogenicity Analysis Population

Arm/Group Title	Abatacept - Double Blind Treatment Period	Placebo - Double Blind Treatment Period
Arm/Group Description	Double Blind Treatment Period SC injection 125mg/mL in 1 mL pre-filled syringe	Double Blind Treatment Period SC injection in 1 mL pre-filled syringe
Measure Participants	90	43
Study Day 169	1.2
Post Treatment Day 85 (DB)	0
Post Treatment Day 169 (DB)	0

37. Secondary Outcome

Title	Summary of Adverse Events: Double Blind Period
Description	Percentage of participants with adverse events, deaths, serious adverse events and adverse events leading to discontinuation
Time Frame	Day 1 up to first dose of Open Label Treatment Period (OLTP) abatacept or up to 56 post last dose in double -blind for those not in OL.

Outcome Measure Data

Analysis Population Description

As-Treated Population

Arm/Group Title	Abatacept - Double Blind Treatment Period	Placebo - Double Blind Treatment Period
Arm/Group Description	Double Blind Treatment Period SC injection 125mg/mL in 1 mL pre-filled syringe	Double Blind Treatment Period SC injection in 1 mL pre-filled syringe
Measure Participants	92	95
Adverse Events (AEs)	85.9	71.6
Deaths	0	1.1
Serious Adverse Events	9.8	3.2
Discontinuation due to AEs	3.3	2.1

38. Secondary Outcome

Title	Laboratory Marked Abnormalities: Double Blind Period
Description	Laboratory values meeting the marked abnormality criteria
Time Frame	Day 1 up to first dose of OL abatacept or up to 56 post last dose in double -blind for those not in OL.

Outcome Measure Data

Analysis Population Description

As-Treated Analysis Population

Arm/Group Title	Abatacept - Double Blind Treatment Period	Placebo - Double Blind Treatment Period
Arm/Group Description	Double Blind Treatment Period SC injection 125mg/mL in 1 mL pre-filled syringe	Double Blind Treatment Period SC injection in 1 mL pre-filled syringe
Measure Participants	91	95
Hematocrit High	NA	NA
Hematocrit Low	0	0
Hemoglobin High	NA	NA
Hemoglobin Low	0	0
Platelet count High	0	0
Platelet count low	0	0
Leukocytes high	1.1	0
Leukocytes low	12.1	8.4
Basophils high	0	0
Basophils Low	NA	NA
Eosinophils High	4.4	1.1
Eosinophils Low	NA	NA
lymphocytes high	0	0
lymphocytes low	9.9	14.7
Monocytes high	0	0
Monocytes Low	NA	NA
Neutrophils+Bands High	NA	NA
Neutrophils+Bands Low	6.6	1.1
Alanine Aminotransferase High	1.1	2.1
Alkaline Phosphatase HIgh	0	0
Aspartate Aminotransferase High	1.1	3.2
Bilirubin, Total High	0	0
G-Glutamyl Transferase High	6.6	1.1
Blood Urea Nitrogen High	1.1	1.1
Creatinine High	0	0
Calcium High	0	0
Calcium Low	1.1	0
Chloride High	0	0
Chloride Low	1.1	0
Phosphorus High	0	0
Phosphorus Low	0	1.1
Potassium High	0	0
Potassium Low	1.1	0
Sodium High	0	1.1
Sodium Low	2.2	0
Glucose, Serum High	0	1.1
Glucose, Serum Low	2.2	5.3
Albumin High	NA	NA
Albumin Low	2.2	1.1
Protein, Total High	2.2	3.2
Protein, Total Low	1.1	0
Creatine Kinase High	0	4.2
Blood, Urine High	14.3	9.5
Blood, Urine Low	NA	NA
Glucose, Urine High	0	0
Glucose, Urine Low	NA	NA
Protein, Urine High	2.2	3.2

39. Secondary Outcome

Title	Percentage of Participants With a Positive Antibody Response in the Cumulative Abatacept Period
Description	Percentage of participants with at least one positive immunogenicity response On Day 365 (end of Open label treatment period) and day 85 post open label follow up period.
Time Frame	Day 365, post open label treatment day 85

Outcome Measure Data

Analysis Population Description

Immunogenicity Analysis Population

Arm/Group Title	Abatacept - Cumulative Open Label Treatment Period
Arm/Group Description	Cumulative Open Label Treatment Period SC injection 125mg/mL in 1 mL pre-filled syringe
Measure Participants	177
Study Day 365	2.1
Post Treatment Day 85 (OL)	43.2

40. Secondary Outcome

Title	Summary of Adverse Events: Cumulative Abatacept Period
Description	Percentage of participants with adverse events, deaths, serious adverse events and adverse events leading to discontinuation
Time Frame	Day 365 and 3 months of follow up approximately 450 Days

Outcome Measure Data

Analysis Population Description

Cumulative Abatacept Population

Arm/Group Title	Cumulative Treatment Period
Arm/Group Description	Cumulative Open Label Treatment Period SC injection 125mg/mL in 1 mL pre-filled syringe
Measure Participants	178
Adverse Events (AEs)	78.7
Deaths	0.6
Serious Adverse Events (SAEs)	14.6
Discontinuation due to AEs	5.6
Related Serious Adverse Events	3.4
Discontinued due to SAEs	3.4
Related AEs	40.4

41. Secondary Outcome

Title	Laboratory Marked Abnormalities: Cumulative Abatacept Period
Description	Laboratory values meeting the marked abnormality criteria
Time Frame	Day 365 and 3 months of follow up approximately 450 Days

Outcome Measure Data

Analysis Population Description

Cumulative Abatacept Population

Arm/Group Title	Cumulative Open Label Treatment Period
Arm/Group Description	Cumulative Open Label Treatment Period SC injection 125mg/mL in 1 mL pre-filled syringe
Measure Participants	177
Hematocrit High	NA
Hematocrit Low	0
Hemoglobin High	NA
Hemoglobin Low	0.6
Platelet count High	0
Platelet count low	0.6
Leukocytes high	0.6
Leukocytes low	18.6
Basophils high	0.6
Basophils Low	NA
Eosinophils High	5.6
Eosinophils Low	NA
lymphocytes high	0
lymphocytes low	12.4
Monocytes high	0
Monocytes Low	NA
Neutrophils+Bands High	NA
Neutrophils+Bands Low	7.3
Alanine Aminotransferase High	1.7
Alkaline Phosphatase HIgh	0.6
Aspartate Aminotransferase High	1.1
Bilirubin, Total High	0
G-Glutamyl Transferase High	5.6
Blood Urea Nitrogen High	1.7
Creatinine High	0.6
Calcium High	0
Calcium Low	1.1
Chloride High	0
Chloride Low	1.1
Phosphorus High	0.6
Phosphorus Low	1.1
Potassium High	0.6
Potassium Low	0.6
Sodium High	0.6
Sodium Low	1.7
Glucose, Serum High	0.6
Glucose, Serum Low	5.1
Albumin High	NA
Albumin Low	1.7
Protein, Total High	4.0
Protein, Total Low	0.6
Creatine Kinase High	2.3
Blood, Urine High	14.7
Blood, Urine Low	NA
Glucose, Urine High	0
Glucose, Urine Low	NA
Protein, Urine High	5.6
WBC, Urine High	100.0

Adverse Events

Time Frame	First dose to 169 days past open label period
Arm/Group Title	Abatacept - Double Blind Treatment Period		Placebo - Double Blind Treatment Period		Abatacept - Open Label Treatment Period
Arm/Group Description	Double Blind Treatment Period SC injection 125mg/mL in 1 mL pre-filled syringe		Double Blind Treatment Period SC injection in 1 mL pre-filled syringe		Open Label Treatment Period SC injection 125mg/mL in 1 mL pre-filled syringe
All Cause Mortality
	Abatacept - Double Blind Treatment Period		Placebo - Double Blind Treatment Period		Abatacept - Open Label Treatment Period
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/92 (0%)		1/95 (1.1%)		1/178 (0.6%)
Serious Adverse Events
	Abatacept - Double Blind Treatment Period		Placebo - Double Blind Treatment Period		Abatacept - Open Label Treatment Period
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/92 (9.8%)		3/95 (3.2%)		19/178 (10.7%)
Cardiac disorders
Acute myocardial infarction	0/92 (0%)		1/95 (1.1%)		0/165 (0%)
Angina pectoris	0/92 (0%)		0/95 (0%)		1/165 (0.6%)
Pericarditis	0/92 (0%)		0/95 (0%)		1/165 (0.6%)
Prinzmetal angina	1/92 (1.1%)		0/95 (0%)		0/165 (0%)
Gastrointestinal disorders
Colitis	0/92 (0%)		1/95 (1.1%)		0/165 (0%)
Intestinal obstruction	1/92 (1.1%)		0/95 (0%)		0/165 (0%)
General disorders
Pyrexia	0/92 (0%)		0/95 (0%)		1/165 (0.6%)
Sudden cardiac death	0/92 (0%)		0/95 (0%)		1/165 (0.6%)
Hepatobiliary disorders
Cholecystitis	0/92 (0%)		0/95 (0%)		1/165 (0.6%)
Cholelithiasis	0/92 (0%)		0/95 (0%)		1/165 (0.6%)
Hepatic cyst ruptured	1/92 (1.1%)		0/95 (0%)		0/165 (0%)
Immune system disorders
Anaphylactoid reaction	1/92 (1.1%)		0/95 (0%)		0/165 (0%)
Drug hypersensitivity	1/92 (1.1%)		0/95 (0%)		0/165 (0%)
Haemophagocytic lymphohistiocytosis	0/92 (0%)		0/95 (0%)		1/165 (0.6%)
Infections and infestations
Periorbital cellulitis	0/92 (0%)		0/95 (0%)		1/165 (0.6%)
Pneumonia bacterial	1/92 (1.1%)		0/95 (0%)		0/165 (0%)
Pyelonephritis acute	0/92 (0%)		0/95 (0%)		1/165 (0.6%)
Septic shock	0/92 (0%)		1/95 (1.1%)		0/165 (0%)
Injury, poisoning and procedural complications
Fall	0/92 (0%)		0/95 (0%)		1/165 (0.6%)
Musculoskeletal and connective tissue disorders
Arthropathy	1/92 (1.1%)		0/95 (0%)		0/165 (0%)
Hip deformity	0/92 (0%)		0/95 (0%)		1/165 (0.6%)
Intervertebral disc protrusion	1/92 (1.1%)		0/95 (0%)		0/165 (0%)
Periarthritis	0/92 (0%)		0/95 (0%)		1/165 (0.6%)
Rotator cuff syndrome	0/92 (0%)		0/95 (0%)		1/165 (0.6%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer	0/92 (0%)		0/95 (0%)		1/165 (0.6%)
Cervix carcinoma stage 0	0/92 (0%)		0/95 (0%)		1/165 (0.6%)
Plasma cell myeloma	1/92 (1.1%)		0/95 (0%)		0/165 (0%)
Uterine leiomyoma	0/92 (0%)		0/95 (0%)		1/165 (0.6%)
Nervous system disorders
Facial paralysis	0/92 (0%)		0/95 (0%)		1/165 (0.6%)
Migraine	0/92 (0%)		0/95 (0%)		1/165 (0.6%)
Syncope	0/92 (0%)		0/95 (0%)		1/165 (0.6%)
Product Issues
Device dislocation	0/92 (0%)		0/95 (0%)		2/165 (1.2%)
Psychiatric disorders
Depression	0/92 (0%)		0/95 (0%)		1/165 (0.6%)
Respiratory, thoracic and mediastinal disorders
Respiratory failure	0/92 (0%)		0/95 (0%)		1/165 (0.6%)
Other (Not Including Serious) Adverse Events
	Abatacept - Double Blind Treatment Period		Placebo - Double Blind Treatment Period		Abatacept - Open Label Treatment Period
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	47/92 (51.1%)		40/95 (42.1%)		61/165 (37%)
Gastrointestinal disorders
Abdominal pain upper	5/92 (5.4%)		0/95 (0%)		4/165 (2.4%)
Diarrhoea	11/92 (12%)		4/95 (4.2%)		9/165 (5.5%)
Nausea	9/92 (9.8%)		4/95 (4.2%)		1/165 (0.6%)
Infections and infestations
Nasopharyngitis	11/92 (12%)		18/95 (18.9%)		22/165 (13.3%)
Upper respiratory tract infection	9/92 (9.8%)		7/95 (7.4%)		15/165 (9.1%)
Urinary tract infection	6/92 (6.5%)		8/95 (8.4%)		12/165 (7.3%)
Musculoskeletal and connective tissue disorders
Myalgia	5/92 (5.4%)		2/95 (2.1%)		4/165 (2.4%)
Nervous system disorders
Headache	10/92 (10.9%)		9/95 (9.5%)		9/165 (5.5%)
Psychiatric disorders
Insomnia	5/92 (5.4%)		1/95 (1.1%)		2/165 (1.2%)
Respiratory, thoracic and mediastinal disorders
Cough	5/92 (5.4%)		4/95 (4.2%)		6/165 (3.6%)
Oropharyngeal pain	6/92 (6.5%)		1/95 (1.1%)		2/165 (1.2%)

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.