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A Study of Abatacept in Patients With Active Ulcerative Colitis

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ClinicalTrials.gov Identifier: NCT00410410
Recruitment Status : Completed
First Posted : December 12, 2006
Results First Posted : December 2, 2010
Last Update Posted : March 24, 2015
Sponsor:
Information provided by (Responsible Party):
Bristol-Myers Squibb

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Ulcerative Colitis
Interventions Drug: abatacept (ABA)
Drug: placebo
Drug: abatacept
Enrollment 591
Recruitment Details In this study, a first cohort (Induction Period First Cohort, IP1C) of 490 participants was randomized and used for analysis of the primary endpoint. Following randomization of IP1C, a second cohort (IP2C) of 146 participants was randomized to provide a sufficient number of participants for the Maintenance Period.
Pre-assignment Details  
Arm/Group Title Induction Period Cohort 1 (IP1C)-Abatacept (ABA) 30/~10 mg/kg IP1C-ABA ~10 mg/kg IP1C-ABA 3 mg/kg IP1C-Placebo IP Cohort 2 (IP2C)-ABA 30/~10 mg/kg IP2C-ABA ~10 mg/kg ABA ~10 mg/kg, Maintenance Period (MP) Placebo, MP ABA ~10 mg/kg, Open-Label Period (OL)
Hide Arm/Group Description During IP, abatacept was administered intravenously (IV) on Days IP-1 and IP-15 at a dose of 30 mg/kg (fixed dose). Following this, on Days IP-29 and IP-57 abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered). During IP, abatacept was administered IV on Days IP-1,IP-15, IP-29, and IP-57 at a dose of ~10 mg/kg (weight-tiered). During IP, abatacept was administered IV on Days IP-1, IP-15, IP-29, and IP-57 at a dose of 3 mg/kg (fixed dose). During the IP, placebo was administered IV on Days IP-1, IP-15, IP-29, and IP-57. During IP, abatacept was administered intravenously (IV) on Days IP-1 and IP-15 at a dose of 30 mg/kg (fixed dose). Following this, on Days IP-29 and IP-57 abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered). During IP, abatacept was administered IV on Days IP-1,IP-15, IP-29, and IP-57 at a dose of ~10 mg/kg (weight-tiered). During MP, abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered) every 28 days beginning Day MP-1. During the MP, placebo was administered IV every 28 days beginning Day MP-1 through Day MP-337. During OL, abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered) every 28 days beginning Day OL-1.
Period Title: Induction Period (IP)
Started 141 139 70 140 51 50 0 0 0
Completed 106 104 53 120 19 21 0 0 0
Not Completed 35 35 17 20 32 29 0 0 0
Reason Not Completed
Death             1             0             0             0             0             0             0             0             0
Adverse Event             3             4             2             4             1             0             0             0             0
Lack of Efficacy             26             24             8             8             7             7             0             0             0
Lost to Follow-up             2             2             2             3             0             1             0             0             0
Withdrawal by Subject             3             5             3             5             2             0             0             0             0
Subject No Longer Meets Study Criteria             0             0             1             0             0             0             0             0             0
Administrative Reason By Sponsor             0             0             0             0             22             21             0             0             0
not specified             0             0             1             0             0             0             0             0             0
Period Title: Maintenance Period (MP)
Started 0 0 0 0 0 0 65 [1] 66 [2] 0
Completed 0 0 0 0 0 0 15 11 0
Not Completed 0 0 0 0 0 0 50 55 0
Reason Not Completed
Death             0             0             0             0             0             0             1             0             0
Adverse Event             0             0             0             0             0             0             1             3             0
Lack of Efficacy             0             0             0             0             0             0             25             24             0
Lost to Follow-up             0             0             0             0             0             0             1             2             0
Withdrawal by Subject             0             0             0             0             0             0             1             1             0
Administrative Reason By Sponsor             0             0             0             0             0             0             21             25             0
[1]
At end of IP, 65 participants met response criteria and were randomly assigned to abatacept in MP.
[2]
At end of IP, 66 participants met response criteria and were randomly assigned to placebo in MP.
Period Title: Open-Label Period (OL)
Started 0 0 0 0 0 0 0 0 349 [1]
Completed 0 0 0 0 0 0 0 0 0
Not Completed 0 0 0 0 0 0 0 0 349
Reason Not Completed
Death             0             0             0             0             0             0             0             0             1
Adverse Event             0             0             0             0             0             0             0             0             10
Lack of Efficacy             0             0             0             0             0             0             0             0             161
Lost to Follow-up             0             0             0             0             0             0             0             0             4
Withdrawal by Subject             0             0             0             0             0             0             0             0             20
Pregnancy             0             0             0             0             0             0             0             0             1
Administrative Reason By Sponsor             0             0             0             0             0             0             0             0             145
not specified             0             0             0             0             0             0             0             0             7
[1]
349 entered OL (those who completed IP but failed response criteria, or completed/relapsed on MP).
Arm/Group Title Induction Period Cohort 1 (IP1C)-ABA 30/~10 mg/kg IP1C-ABA ~10 mg/kg IP1C-ABA 3 mg/kg IP1C-Placebo IP Cohort 2 (IP2C)-ABA 30/~10 mg/kg IP2C-ABA ~10 mg/kg Total
Hide Arm/Group Description During IP, abatacept was administered intravenously (IV) on Days IP-1 and IP-15 at a dose of 30 mg/kg (fixed dose). Following this, on Days IP-29 and IP-57 abatacept was administered IV at a dose of ~10 mg/kg. During IP, abatacept was administered IV on Days IP-1,IP-15, IP-29,and IP-57 at a dose of ~10 mg/kg (weight-tiered). During IP, abatacept was administered IV on Days IP-1, IP-15, IP-29, and IP-57 at a dose of 3 mg/kg (fixed dose). During the IP, placebo was administered IV on Days IP-1, IP-15, IP-29, and IP-57. During IP, abatacept was administered intravenously (IV) on Days IP-1 and IP-15 at a dose of 30 mg/kg (fixed dose). Following this, on Days IP-29 and IP-57 abatacept was administered IV at a dose of ~10 mg/kg. During IP, abatacept was administered IV on Days IP-1,IP-15, IP-29,and IP-57 at a dose of ~10 mg/kg (weight-tiered). Total of all reporting groups
Overall Number of Baseline Participants 141 139 70 140 51 50 591
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 141 participants 139 participants 70 participants 140 participants 51 participants 50 participants 591 participants
<30 years 26 23 18 34 12 4 117
30-50 years 70 84 35 73 30 32 324
>50 years 45 32 17 33 9 14 150
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 141 participants 139 participants 70 participants 140 participants 51 participants 50 participants 591 participants
Female
57
  40.4%
52
  37.4%
26
  37.1%
66
  47.1%
21
  41.2%
26
  52.0%
248
  42.0%
Male
84
  59.6%
87
  62.6%
44
  62.9%
74
  52.9%
30
  58.8%
24
  48.0%
343
  58.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 141 participants 139 participants 70 participants 140 participants 51 participants 50 participants 591 participants
United States 43 42 22 55 20 13 195
Ireland 1 0 0 1 0 1 3
Italy 7 6 2 3 2 1 21
Switzerland 1 1 1 2 1 0 6
United Kingdom 0 0 0 3 2 4 9
India 12 12 10 10 5 2 51
France 7 12 6 6 1 5 37
Czech Republic 0 1 0 0 0 0 1
Mexico 20 14 10 8 7 9 68
Puerto Rico 0 1 0 1 0 0 2
Canada 9 12 2 13 1 3 40
Brazil 10 5 5 11 4 6 41
Poland 2 2 0 1 1 0 6
Belgium 4 6 1 5 0 1 17
Australia 8 7 4 13 1 1 34
South Africa 9 8 5 3 2 0 27
Germany 2 2 0 1 2 2 9
Netherlands 2 5 1 2 2 1 13
Korea, Republic of 4 3 1 2 0 1 11
Participants with Inadequate Response/Intolerance to Prior Anti-Tumor (TNF) Therapy (Infliximab)   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 141 participants 139 participants 70 participants 140 participants 51 participants 50 participants 591 participants
Inadequate Response/Intolerant to prior Infliximab 45 46 24 45 21 21 202
No Inadequate Response/Intolerance to Infliximab 96 93 46 95 30 29 389
[1]
Measure Description: Prior to this study, participants had an inadequate response and/or intolerance to an approved anti-TNF agent at an approved labeled dose for at least 8 weeks. Inadequate response was assessed by the treating physician and was primarily due to lack of efficacy. Because the treating physician determined prior inadequate response, there was no standard definition for this and criteria for determination may have varied between institutions. Intolerance was defined a an inability to achieve doses or treatment durations because of dose limiting side effects.
1.Primary Outcome
Title Induction Period (IP); Number of Participants With Clinical Response (Per Mayo Score) at Week 12: IP Cohort 1 (IP1C)
Hide Description The Mayo Scoring system ranges from 0 - 12 points and is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician’s Global Assessment). Higher Mayo scores indicate greater severity of disease. A clinical response is defined as a reduction from baseline in the Mayo score of ≥ 3 points and ≥ 30%, with an accompanying decrease in the rectal bleeding subscore of ≥ 1 point or absolute rectal bleeding subscore of ≤ 1 point.
Time Frame Week 12 (Day IP-85)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who were randomized and received at least one infusion of study medication (Intent To Treat Population, ITT) were included in the efficacy analyses. Participants with missing Mayo score were defined as not having achieved clinical response, remission, or mucosal healing.
Arm/Group Title Induction Period Cohort 1 (IP1C)-ABA 30/~10 mg/kg IP1C-ABA ~10 mg/kg IP1C-ABA 3 mg/kg IP1C-Placebo
Hide Arm/Group Description:
During IP, abatacept was administered intravenously (IV) on Days IP-1 and IP-15 at a dose of 30 mg/kg (fixed dose). Following this, on Days IP-29 and IP-57 abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered).
During IP, abatacept was administered IV on Days IP-1,IP-15, IP-29,and IP-57 at a dose of ~10 mg/kg (weight-tiered).
During IP, abatacept was administered IV on Days IP-1, IP-15, IP-29, and IP-57 at a dose of 3 mg/kg (fixed dose).
During the IP, placebo was administered IV on Days IP-1, IP-15, IP-29, and IP-57.
Overall Number of Participants Analyzed 140 137 69 139
Measure Type: Number
Unit of Measure: participants
30 26 14 41
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Induction Period Cohort 1 (IP1C)-ABA 30/~10 mg/kg, IP1C-Placebo
Comments Null hypothesis=no treatment difference between ABA arm and placebo (PLA) arm. ABA 30/~10 mg/kg vs PLA: power=98%, sample size=140 per arm,expected PLA response rate=40%, ABA 30/~10 mg/kg=65%. ABA ~10 mg/kg vs. PLA: power=90%, sample size=140 per arm, 5% significance; expected PLA response rate= 40%, ABA ~10=60%.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.124
Comments Cochran-Mantel-Haenszel Chi square p-value and RR along with 95% confidence interval provided, adjusting for randomization strata (whether a participant had an inadequate response and/or intolerance to anti-TNF therapy).
Method Cochran-Mantel-Haenszel
Comments Conditional on ABA 30/~10 mg/kg vs PLA comparison being statistically significant at 5% level, ABA ~10 vs PLA to be tested at 5% significance level.
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.73
Confidence Interval (2-Sided) 95%
0.48 to 1.09
Estimation Comments [Not Specified]
2.Primary Outcome
Title Maintenance Period (MP); Number of Participants With Clinical Response (Per Mayo Score) at Month 12
Hide Description The Mayo Scoring system ranges from 0 - 12 points and is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Higher Mayo scores indicate greater severity of disease. A clinical response is defined as a reduction from baseline in the Mayo score of ≥ 3 points and ≥ 30%, with an accompanying decrease in the rectal bleeding subscore of ≥ 1 point or absolute rectal bleeding subscore of ≤ 1 point.
Time Frame Month 12 (Day MP-365)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants in the ITT Population were included in the efficacy analyses. Participants with missing Mayo score were defined as not having achieved clinical response, remission, or mucosal healing.
Arm/Group Title ABA ~10 mg/kg, MP Placebo, MP
Hide Arm/Group Description:
During MP, abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered) every 28 days beginning Day MP-1.
During the MP, placebo was administered IV every 28 days beginning Day MP-1 through Day MP-337.
Overall Number of Participants Analyzed 64 64
Measure Type: Number
Unit of Measure: participants
11 11
3.Primary Outcome
Title Open-Label Extension Period (OL); Number of Participants With Adverse Events (AEs), Related AEs, Deaths, Serious AEs (SAEs), Related SAEs, and AEs Leading to Discontinuation
Hide Description AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. Related AE=relationship of certain, probable, possible, or missing. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event.
Time Frame Day OL-1 through the end of the OL
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 infusion of open-label study medication at any time were included in the safety analyses of the Open-Label Extension phase.
Arm/Group Title ABA ~10 mg/kg, OL
Hide Arm/Group Description:
During OL, abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered) every 28 days beginning Day OL-1.
Overall Number of Participants Analyzed 349
Measure Type: Number
Unit of Measure: participants
AEs 241
Related AEs 100
Deaths 1
SAEs 66
Related SAEs 9
AEs Leading to Discontinuation 7
SAEs Leading to Discontinuation 4
4.Primary Outcome
Title OL; Number of Participants With AEs of Special Interest
Hide Description AE=any new untoward medical occurrence or worsening of a pre-existing 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, serious infections, and opportunistic infections; autoimmune disorders; neoplasms; acute infusional AEs (pre-specified AEs occurring within 1 hour of start of infusion) and peri-infusional AEs (pre-specified AEs occurring within 24 hours of the start of infusion).
Time Frame Day OL-1 through Day OL-729
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 infusion of open-label study medication at any time were included in the safety analyses of the Open-Label Extension phase.
Arm/Group Title ABA ~10 mg/kg, OL
Hide Arm/Group Description:
During OL, abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered) every 28 days beginning Day OL-1.
Overall Number of Participants Analyzed 349
Measure Type: Number
Unit of Measure: participants
Infections and Infestations 127
Serious Infections 9
Opportunistic Infections-Total 2
Opportunistic Infections-cytomegalovirus 1
Opportunistic Infections-listeriosis 1
Malignancies-Total 5
Malignancies-Basal Cell Carcinoma 2
Malignancies-Bowen's Disease 1
Malignancies-Chronic Myeloid Leukemia 1
Malignancies-Squamous Cell Carcinoma 1
Autoimmune Disorders-Total 5
Autoimmune Disorders-episcleritis 2
Autoimmune Disorders-scleritis 1
Autoimmune Disorders-anemia hemolytic autoimmune 1
Autoimmune Disorders-psoriasis 1
Acute Infusional AEs 12
Peri-infusional AEs 25
5.Primary Outcome
Title OL; Number of Participants With Physical Examination Findings
Hide Description Complete physical examination was obtained at the Screening Visit, Day MP-365, and OL Final Visit/Early Termination visits. Interim physical examinations were performed at other study visits. Interim physical exam were not as comprehensive as the initial full examination but did note any changes in the participant's condition since the last assessment and did not preclude examination of any of the body systems as clinically indicated. Participants were observed for AEs and vital signs (blood pressure, heart rate, and temperature).
Time Frame Day OL-1 through Day OL-729
Hide Outcome Measure Data
Hide Analysis Population Description
As the results of this study were presented in a synoptic report, physical examination evaluations were not summarized. Laboratory abnormalities and vital signs were collected and summarized.
Arm/Group Title ABA ~10 mg/kg, MP Placebo, MP
Hide Arm/Group Description:
During MP, abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered) every 28 days beginning Day MP-1.
During the MP, placebo was administered IV every 28 days beginning Day MP-1 through Day MP-337.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
6.Primary Outcome
Title OL; Number of Participants With Marked Hematology Laboratory Abnormalities
Hide Description High=greater than Upper Normal Limit (ULN), Low=lower than Lower Normal Limit (LLN). LLN/ULN= Hemoglobin (HGB): >3 g/dL decrease from Baseline (BL); Hematocrit: <0.75 x BL; Erythrocytes: <0.75 x BL; Platelets (PLT): <0.67 x LLN/>1.5 x ULN; Leukocytes: <0.75 x LLN/ >1.25 x ULN; neutrophils+bands: <1.0 x 10^3 c/uL; eosinophils: >0.750 x 10^3 c/uL; monocytes: >2000 mm3; lymphocytes: <0.750 x 10^3 c/uL/ >7.50 x 10^3 c/uL.
Time Frame Day OL-1 through Day OL-729
Hide Outcome Measure Data
Hide Analysis Population Description
The As Treated analysis population was used for all safety summaries and was defined to include all participants who received at least one infusion of study medication.
Arm/Group Title ABA ~10 mg/kg, OL
Hide Arm/Group Description:
During IP, abatacept was administered IV on Days IP-1 and IP-15 at a dose of ~10 mg/kg (weight-tiered). On Days IP-29 and IP-57, abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered).
Overall Number of Participants Analyzed 349
Measure Type: Number
Unit of Measure: participants
Low HGB; n=326 20
Low hematocrit; n=322 17
Low erythrocytes; n=326 6
High PLT; n=323 3
Low leukocytes; n=326 3
High leukocytes; n=326 18
Low neutrophils + bands; n=324 1
High eosinophils; n=324 17
High monocytes; n=324 2
Low lymphocytes; n=324 43
7.Primary Outcome
Title OL; Number of Participants With Liver and Kidney Function and Electrolyte Laboratory Abnormalities
Hide Description Low=lower than LLN, High=greater than ULN. LLN/ULN= Alkaline phosphatase (ALP): >2 x ULN; aspartate aminotransferase (AST): >3 x ULN; alanine aminotransferase (ALT): >3 x ULN; G-Glutamyl transferase (GGT): >2 x ULN; Bilirubin: >2 x ULN; blood urea nitrogen (BUN): >2 x BL; creatinine: >4 x BL; potassium (K): <0.9 x LLN/ >1.1 x ULN; calcium (Ca): <0.8 x LLN/>1.2 x ULN; phosphorous (P): <0.75 x LLN/ >1.2 5 x ULN
Time Frame Day OL-1 through Day OL-729
Hide Outcome Measure Data
Hide Analysis Population Description
The As Treated analysis population was used for all safety summaries and was defined to include all participants who received at least one infusion of study medication.
Arm/Group Title ABA ~10 mg/kg, OL
Hide Arm/Group Description:
During IP, abatacept was administered IV on Days IP-1 and IP-15 at a dose of ~10 mg/kg (weight-tiered). On Days IP-29 and IP-57, abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered).
Overall Number of Participants Analyzed 349
Measure Type: Number
Unit of Measure: participants
High ALP, n=331 4
High AST, n=331 3
High ALT; n=331 3
High GGT; n=332 17
High bilirubin, n=331 1
High BUN; n=310 10
High creatinine; n=330 5
Low K; n=331 7
Low Ca; n=330 2
Low P; n=330 4
High P, n=330 1
8.Primary Outcome
Title OL; Number of Participants With Chemistry and Urinalysis Laboratory Abnormalities
Hide Description Low=lower than LLN, High=greater than ULN. LLN/ULN= serum glucose (Glu): <65 mg/dL/ >220 mg/dL; fasting serum Glu: <0.8 x LLN/ >1.5 x ULN; total protein: < 0.9 x LLN/ >1.1 x ULN; albumin:<0.9 x LLN; uric acid: >1.5 x ULN. For Urinalysis (Urine protein, urine Glu, urine blood, leukocyte esterase, Red Blood Cells [RBCs], White Blood Cells [WBCs]): Use ≥2 when BL value missing or value ≥4, or when pre-dose=0 or 0.5. Use ≥3 when pre-dose=1. Use ≥4 when pre-dose=2 or 3
Time Frame Day OL-1 through Day OL-729
Hide Outcome Measure Data
Hide Analysis Population Description
The As Treated analysis population was used for all safety summaries and was defined to include all participants who received at least one infusion of study medication.
Arm/Group Title ABA ~10 mg/kg, OL
Hide Arm/Group Description:
During IP, abatacept was administered IV on Days IP-1 and IP-15 at a dose of ~10 mg/kg (weight-tiered). On Days IP-29 and IP-57, abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered).
Overall Number of Participants Analyzed 349
Measure Type: Number
Unit of Measure: participants
Low Glu; n=245 4
High Glu; n=245 6
Low protein; n=331 3
Low albumin; n=331 12
High urine protein; n=312 11
High urine Glu; n=312 4
High urine blood; n=312 27
High leukocyte esterase; n=122 10
High urine RBC; n=115 22
High urine WBC; n=150 45
9.Secondary Outcome
Title IP; Baseline Mayo Score: IP1C
Hide Description The Mayo Scoring system ranges from 0 - 12 points and is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Higher Mayo scores indicate greater severity of disease. A clinical response is defined as a reduction from baseline in the Mayo score of ≥ 3 points and ≥ 30%, with an accompanying decrease in the rectal bleeding subscore of ≥ 1 point or absolute rectal bleeding subscore of ≤ 1 point.
Time Frame Baseline
Hide Outcome Measure Data
Hide Analysis Population Description
The As Treated analysis population was used for all safety summaries and was defined to include all participants who received at least one infusion of study medication.
Arm/Group Title IP1C-ABA 30/~10 mg/kg IP1C-ABA ~10 mg/kg IP1C-ABA 3 mg/kg, IP1C-Placebo
Hide Arm/Group Description:
During IP, abatacept was administered intravenously (IV) on Days IP-1 and IP-15 at a dose of 30 mg/kg (fixed dose). Following this, on Days IP-29 and IP-57 abatacept was administered IV at a dose of ~10 mg/kg.
During IP, abatacept was administered IV on Days IP-1 and IP-15 at a dose of ~10 mg/kg (weight-tiered). On Days IP-29 and IP-57, abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered).
During IP, abatacept was administered IV on Days IP-1 and IP-15 at a dose of 3 mg/kg (fixed dose). On Days IP-29 and IP-57, abatacept was administered IV at a dose of 3 mg/kg.
During the IP, placebo was administered IV on Days IP-1, IP-15, IP-29, and IP-57.
Overall Number of Participants Analyzed 141 139 70 140
Mean (Standard Deviation)
Unit of Measure: units on a scale
8.9  (1.74) 8.8  (1.73) 8.6  (1.82) 8.8  (1.59)
10.Secondary Outcome
Title IP; Number of Participants in Clinical Remission (Per Mayo Score) at Week 12: IP1C
Hide Description The Mayo Scoring system ranges from 0 - 12 points and is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician’s Global Assessment). Higher Mayo scores indicate greater severity of disease. Clinical remission is defined as a Mayo score of ≤ 2 points with no individual subscore exceeding 1 point.
Time Frame Week 12 (Day IP-85)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants in the ITT Population were included in the efficacy analyses. Participants with missing Mayo score were defined as not having achieved clinical response, remission, or mucosal healing.
Arm/Group Title Induction Period Cohort 1 (IP1C)-ABA 30/~10 mg/kg IP1C-ABA ~10 mg/kg IP1C-ABA 3 mg/kg IP1C-Placebo
Hide Arm/Group Description:
During IP, abatacept was administered intravenously (IV) on Days IP-1 and IP-15 at a dose of 30 mg/kg (fixed dose). Following this, on Days IP-29 and IP-57 abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered).
During IP, abatacept was administered IV on Days IP-1,IP-15, IP-29,and IP-57 at a dose of ~10 mg/kg (weight-tiered).
During IP, abatacept was administered IV on Days IP-1, IP-15, IP-29, and IP-57 at a dose of 3 mg/kg (fixed dose).
During the IP, placebo was administered IV on Days IP-1, IP-15, IP-29, and IP-57.
Overall Number of Participants Analyzed 140 137 69 139
Measure Type: Number
Unit of Measure: participants
3 6 4 15
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Induction Period Cohort 1 (IP1C)-ABA 30/~10 mg/kg, IP1C-Placebo
Comments Null hypothesis=no treatment difference between each of the ABA and placebo (PLA). At 5% significance level, Aba 30/~10 vs. PLA: power=96%, sample size=140 per arm, expected PLA rate=15%. ABA 30/~10 =35%; Aba ~10 vs. PLA: power=82%, sample size=140 per arm, expected PLA response rate= 15%, ABA/~10 mg/kg=30%
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments Cochran-Mantel-Haenszel Chi square p-value and RR along with 95% confidence interval provided, adjusting for randomization strata.
Method Cochran-Mantel-Haenszel
Comments Conditional on ABA 30/~10 vs PLA comparison for clinical response being significant at 5% level, this comparison for remission will be tested at 5%.
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.2
Confidence Interval (2-Sided) 95%
.06 to 0.67
Estimation Comments Conditional on both the remission comparison for ABA 30/~10 vs PLA, and the clinical response comparison for ABA~10 vs PLA being significant at 5%, the secondary remission comparison for ABA ~10 vs PLA will be tested at 5%.
11.Secondary Outcome
Title IP; Number of Participants in Mucosal Healing (Per Mayo Score) at Week 12: IP1C
Hide Description The Mayo Scoring system ranges from 0 - 12 points and is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician’s Global Assessment). Higher Mayo scores indicate greater severity of disease. Mucosal healing was defined as endoscopic subscore ≤ 1 point
Time Frame Week 12 (Day IP-85)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants in the ITT Population were included in the efficacy analyses. Participants with missing Mayo score were defined as not having achieved clinical response, remission, or mucosal healing.
Arm/Group Title Induction Period Cohort 1 (IP1C)-ABA 30/~10 mg/kg IP1C-ABA ~10 mg/kg IP1C-ABA 3 mg/kg IP1C-Placebo
Hide Arm/Group Description:
During IP, abatacept was administered intravenously (IV) on Days IP-1 and IP-15 at a dose of 30 mg/kg (fixed dose). Following this, on Days IP-29 and IP-57 abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered).
During IP, abatacept was administered IV on Days IP-1,IP-15, IP-29,and IP-57 at a dose of ~10 mg/kg (weight-tiered).
During IP, abatacept was administered IV on Days IP-1, IP-15, IP-29, and IP-57 at a dose of 3 mg/kg (fixed dose).
During the IP, placebo was administered IV on Days IP-1, IP-15, IP-29, and IP-57.
Overall Number of Participants Analyzed 140 137 69 139
Measure Type: Number
Unit of Measure: participants
24 20 11 36
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Induction Period Cohort 1 (IP1C)-ABA 30/~10 mg/kg, IP1C-Placebo
Comments Null hypothesis=no treatment difference (relative risk [RR] of ABA over placebo=1) for mucosal healing. ABA 30/~10 vs. placebo: power=99%, sample size=140 per arm, expected PLA response rate=30%, ABA 30/~10 mg/kg=60%. ABA ~10 vs. placebo: power=98%, sample size=140 per arm, 5% significance; expected PLA response rate= 30%, ABA ~10 mg/kg=55%
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value [Not Specified]
Comments Cochran-Mantel-Haenszel Chi square p-value and RR along with 95% confidence interval provided, adjusting for randomization strata.
Method Cochran-Mantel-Haenszel
Comments If ABA 30/~10 vs PLA remission comparison is significant at 5% level, the mucosal healing comparison for the same treatment group will be tested at 5%
Method of Estimation Estimation Parameter Risk Ratio (RR)
Estimated Value 0.66
Confidence Interval (2-Sided) 95%
0.42 to 1.05
Estimation Comments Conditional on both the comparison for mucosal healing for ABA 30/~10 vs PLA and the comparison for remission for ABA ~10 vs. PLA being significant, the comparison for mucosal healing for ABA ~10 vs PLA will be tested at 5%.
12.Secondary Outcome
Title IP; Number of Participants With Clinical Response (Per Mayo Score) at Week 12 Analyzed by Cochran-Armitage Trend Test for Dose-Response Relationship: IP1C
Hide Description The Mayo Scoring system ranges from 0 - 12 points and is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Higher Mayo scores indicate greater severity of disease. A clinical response is defined as a reduction from baseline in the Mayo score of ≥ 3 points and ≥ 30%, with an accompanying decrease in the rectal bleeding subscore of ≥ 1 point or absolute rectal bleeding subscore of ≤ 1 point.
Time Frame Week 12 (Day IP-85)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants in the ITT Population were included in the efficacy analyses. Participants with missing Mayo score were defined as not having achieved clinical response, remission, or mucosal healing.
Arm/Group Title IP1C-Placebo IP1C-ABA 3 mg/kg IP1C-ABA ~10 mg/kg IP1C-ABA 30/~10 mg/kg
Hide Arm/Group Description:
During the IP, placebo was administered IV on Days IP-1, IP-15, IP-29, and IP-57.
During IP, abatacept was administered IV on Days IP-1 and IP-15 at a dose of 3 mg/kg (fixed dose). On Days IP-29 and IP-57, abatacept was administered IV at a dose of 3 mg/kg.
During IP, abatacept was administered IV on Days IP-1 and IP-15 at a dose of ~10 mg/kg (weight-tiered). On Days IP-29 and IP-57, abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered).
During IP, abatacept was administered intravenously (IV) on Days IP-1 and IP-15 at a dose of 30 mg/kg (fixed dose). Following this, on Days IP-29 and IP-57 abatacept was administered IV at a dose of ~10 mg/kg.
Overall Number of Participants Analyzed 139 69 137 140
Measure Type: Number
Unit of Measure: participants
41 14 26 30
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection IP1C-Placebo, IP1C-ABA 3 mg/kg, IP1C-ABA ~10 mg/kg, IP1C-ABA 30/~10 mg/kg
Comments The Cochran-Armitage trend test was performed to evaluate whether a relationship existed between the response and dose regimen by comparing the proportion of participants in response across all four treatment arms.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.044
Comments All statistical testing was performed at a pre-specified alpha-level of 5%.
Method Cochran-Armitage Trend Test
Comments [Not Specified]
13.Secondary Outcome
Title IP; Baseline Inflammatory Bowel Disease Questionnaire (IBDQ) Score: IP1C
Hide Description The Inflammatory Bowel Disease Questionnaire (IBDQ) was used to measure disease specific quality of life. The IBDQ consists of a self-administered 32-item questionnaire that evaluates quality of life across 4 dimensional scores: Bowel, Systemic, Social and Emotional. The response to each question can range from 1 to 7, with 1 indicating severe problem and 7 indicating normal health. The total IBDQ is computed as the sum of the responses to the individual IBDQ questions. The total score can range between 32 to 224 with higher scores indicating a better quality of life.
Time Frame Baseline
Hide Outcome Measure Data
Hide Analysis Population Description
The As Treated analysis population was used for all safety summaries and was defined to include all participants who received at least one infusion of study medication.
Arm/Group Title IP1C-ABA 30/~10 mg/kg IP1C-ABA ~10 mg/kg IP1C-ABA 3 mg/kg, IP1C-Placebo
Hide Arm/Group Description:
During IP, abatacept was administered intravenously (IV) on Days IP-1 and IP-15 at a dose of 30 mg/kg (fixed dose). Following this, on Days IP-29 and IP-57 abatacept was administered IV at a dose of ~10 mg/kg.
During IP, abatacept was administered IV on Days IP-1 and IP-15 at a dose of ~10 mg/kg (weight-tiered). On Days IP-29 and IP-57, abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered).
During IP, abatacept was administered IV on Days IP-1 and IP-15 at a dose of 3 mg/kg (fixed dose). On Days IP-29 and IP-57, abatacept was administered IV at a dose of 3 mg/kg.
During the IP, placebo was administered IV on Days IP-1, IP-15, IP-29, and IP-57.
Overall Number of Participants Analyzed 141 139 70 140
Mean (Standard Deviation)
Unit of Measure: units on a scale
120.0  (35.43) 121.5  (36.42) 126.9  (35.93) 124.3  (33.43)
14.Secondary Outcome
Title IP; Mean Change From Baseline To Week 12 in Inflammatory Bowel Disease Questionnaire (IBDQ): IP1C
Hide Description The Inflammatory Bowel Disease Questionnaire (IBDQ) was used to measure disease specific quality of life. The IBDQ consists of a self-administered 32-item questionnaire that evaluates quality of life across 4 dimensional scores: Bowel, Systemic, Social and Emotional. The response to each question can range from 1 to 7, with 1 indicating severe problem and 7 indicating normal health. The total IBDQ is computed as the sum of the responses to the individual IBDQ questions. The total score can range between 32 to 224 with higher scores indicating a better quality of life.
Time Frame Baseline (Day IP-1), Day IP-85 (Week 12)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants in the ITT Population were included in the efficacy analyses. Participants with missing Mayo score were defined as not having achieved clinical response, remission, or mucosal healing.
Arm/Group Title Induction Period Cohort 1 (IP1C)-ABA 30/~10 mg/kg IP1C-ABA ~10 mg/kg IP1C-ABA 3 mg/kg IP1C-Placebo
Hide Arm/Group Description:
During IP, abatacept was administered intravenously (IV) on Days IP-1 and IP-15 at a dose of 30 mg/kg (fixed dose). Following this, on Days IP-29 and IP-57 abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered).
During IP, abatacept was administered IV on Days IP-1,IP-15, IP-29,and IP-57 at a dose of ~10 mg/kg (weight-tiered).
During IP, abatacept was administered IV on Days IP-1, IP-15, IP-29, and IP-57 at a dose of 3 mg/kg (fixed dose).
During the IP, placebo was administered IV on Days IP-1, IP-15, IP-29, and IP-57.
Overall Number of Participants Analyzed 97 99 46 112
Mean (Standard Error)
Unit of Measure: units on a scale
9.45  (3.514) 13.36  (3.476) 9.87  (5.108) 23.68  (3.268)
15.Secondary Outcome
Title IP; Number of Participants With Mayo Rectal Bleeding Subscores Indicating Mild Disease (≤1 Point) at Week 12: IP1C
Hide Description The Mayo Scoring system ranges from 0 - 12 points and is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician’s Global Assessment). Higher Mayo scores indicate greater severity of disease. An absolute rectal bleeding subscore of ≤1 point was indicative of mild disease.
Time Frame Day IP-85 (Week 12)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants in the ITT Population were included in the efficacy analyses. Participants with missing Mayo score were defined as not having achieved clinical response, remission, or mucosal healing.
Arm/Group Title Induction Period Cohort 1 (IP1C)-ABA 30/~10 mg/kg IP1C-ABA ~10 mg/kg IP1C-ABA 3 mg/kg IP1C-Placebo
Hide Arm/Group Description:
During IP, abatacept was administered intravenously (IV) on Days IP-1 and IP-15 at a dose of 30 mg/kg (fixed dose). Following this, on Days IP-29 and IP-57 abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered).
During IP, abatacept was administered IV on Days IP-1,IP-15, IP-29,and IP-57 at a dose of ~10 mg/kg (weight-tiered).
During IP, abatacept was administered IV on Days IP-1, IP-15, IP-29, and IP-57 at a dose of 3 mg/kg (fixed dose).
During the IP, placebo was administered IV on Days IP-1, IP-15, IP-29, and IP-57.
Overall Number of Participants Analyzed 104 106 53 118
Measure Type: Number
Unit of Measure: participants
Rectal Subscore=0 28 36 16 47
Rectal Subscore=1 31 30 13 27
16.Secondary Outcome
Title IP; Number of Participants With Mayo Stool Frequency Subscores Indicating Mild Disease (≤1 Point) at Week 12: IP1C
Hide Description The Mayo Scoring system ranges from 0 - 12 points and is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician’s Global Assessment). Higher Mayo scores indicate greater severity of disease. An absolute stool frequency subscore of ≤1 point was indicative of mild disease.
Time Frame Day IP-85 (Week 12)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants in the ITT Population were included in the efficacy analyses. Participants with missing Mayo score were defined as not having achieved clinical response, remission, or mucosal healing.
Arm/Group Title Induction Period Cohort 1 (IP1C)-ABA 30/~10 mg/kg IP1C-ABA ~10 mg/kg IP1C-ABA 3 mg/kg IP1C-Placebo
Hide Arm/Group Description:
During IP, abatacept was administered intravenously (IV) on Days IP-1 and IP-15 at a dose of 30 mg/kg (fixed dose). Following this, on Days IP-29 and IP-57 abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered).
During IP, abatacept was administered IV on Days IP-1,IP-15, IP-29,and IP-57 at a dose of ~10 mg/kg (weight-tiered).
During IP, abatacept was administered IV on Days IP-1, IP-15, IP-29, and IP-57 at a dose of 3 mg/kg (fixed dose).
During the IP, placebo was administered IV on Days IP-1, IP-15, IP-29, and IP-57.
Overall Number of Participants Analyzed 104 106 53 118
Measure Type: Number
Unit of Measure: participants
Stool Frequency Subscore=0 13 8 4 14
Stool Frequency Subscore=1 14 21 10 32
17.Secondary Outcome
Title IP; Number of Participants With Mayo Physician Global Assessment (PGA) Subscores Indicating Mild Disease (≤1 Point) at Week 12: IP1C
Hide Description The Mayo Scoring system ranges from 0 - 12 points and is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician’s Global Assessment). Higher Mayo scores indicate greater severity of disease. An absolute PGA subscore of ≤1 point was indicative of mild disease.
Time Frame Day IP-85 (Week 12)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants in the ITT Population were included in the efficacy analyses. Participants with missing Mayo score were defined as not having achieved clinical response, remission, or mucosal healing.
Arm/Group Title Induction Period Cohort 1 (IP1C)-ABA 30/~10 mg/kg IP1C-ABA ~10 mg/kg IP1C-ABA 3 mg/kg IP1C-Placebo
Hide Arm/Group Description:
During IP, abatacept was administered intravenously (IV) on Days IP-1 and IP-15 at a dose of 30 mg/kg (fixed dose). Following this, on Days IP-29 and IP-57 abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered).
During IP, abatacept was administered IV on Days IP-1,IP-15, IP-29,and IP-57 at a dose of ~10 mg/kg (weight-tiered).
During IP, abatacept was administered IV on Days IP-1, IP-15, IP-29, and IP-57 at a dose of 3 mg/kg (fixed dose).
During the IP, placebo was administered IV on Days IP-1, IP-15, IP-29, and IP-57.
Overall Number of Participants Analyzed 104 106 53 118
Measure Type: Number
Unit of Measure: participants
PGA Subscore=0 2 4 3 11
PGA Subscore=1 22 25 15 34
18.Secondary Outcome
Title IP; Number of Participants Who Are Anti-TNF-Inadequate Responders/Anti-TNF Intolerant With Clinical Response At Week 12 Analyzed by Cochran-Armitage Trend Test for Dose-Response Relationship: IP1C
Hide Description The Mayo Scoring system (range 0-12 points, high scores=greater severity of disease) is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Clinical response=reduction from baseline in the Mayo score of ≥ 3 points and ≥ 30%, with accompanying decrease in the rectal bleeding subscore of ≥ 1 point or absolute rectal bleeding subscore of ≤ 1 point. Inadequate response/intolerance=inadequate response/intolerance to an approved anti-TNF agent prior to this study at an approved labeled dose for ≥8 weeks.
Time Frame Week 12 (Day IP-85)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants in ITT Population were included in the efficacy analyses. Participants with missing Mayo score were defined as not having achieved clinical response, remission, or mucosal healing. Prior inadequate response/intolerance was to an approved anti-TNF agent at an approved labeled dose for ≥8 weeks.
Arm/Group Title IP1C-Placebo IP1C-ABA 3 mg/kg IP1C-ABA ~10 mg/kg IP1C-ABA 30/~10 mg/kg
Hide Arm/Group Description:
During the IP, placebo was administered IV on Days IP-1, IP-15, IP-29, and IP-57.
During IP, abatacept was administered IV on Days IP-1 and IP-15 at a dose of 3 mg/kg (fixed dose). On Days IP-29 and IP-57, abatacept was administered IV at a dose of 3 mg/kg.
During IP, abatacept was administered IV on Days IP-1 and IP-15 at a dose of ~10 mg/kg (weight-tiered). On Days IP-29 and IP-57, abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered).
During IP, abatacept was administered intravenously (IV) on Days IP-1 and IP-15 at a dose of 30 mg/kg (fixed dose). Following this, on Days IP-29 and IP-57 abatacept was administered IV at a dose of ~10 mg/kg.
Overall Number of Participants Analyzed 45 24 46 45
Measure Type: Number
Unit of Measure: participants
12 4 7 8
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection IP1C-Placebo, IP1C-ABA 3 mg/kg, IP1C-ABA ~10 mg/kg, IP1C-ABA 30/~10 mg/kg
Comments The Cochran-Armitage trend test was performed to evaluate whether a relationship existed between the response and dose regimen by comparing the proportion of participants in response across all four treatment arms. Normal approximation was used if the number of responses in a treatment group is at least 5. Otherwise an exact method was used.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.149
Comments All statistical testing was performed at a pre-specified alpha-level of 5%
Method Cochran-Armitage Trend Test
Comments [Not Specified]
19.Secondary Outcome
Title IP; Number of Participants With Clinical Response At Week 12 Among Participants With Anti-TNF (Infliximab) Failure/Intolerance: IP1C
Hide Description The Mayo Scoring system (range 0-12 points, high scores=greater severity of disease) is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Clinical response=reduction from baseline in the Mayo score of ≥ 3 points and ≥ 30%, with accompanying decrease in the rectal bleeding subscore of ≥ 1 point or absolute rectal bleeding subscore of ≤ 1 point. Inadequate response/intolerance=inadequate response/intolerance to an approved anti-TNF agent prior to this study at an approved labeled dose for ≥8 weeks.
Time Frame Week 12 (Day IP-85)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants in ITT Population were included in the efficacy analyses. Participants with missing Mayo score were defined as not having achieved clinical response, remission, or mucosal healing. Prior inadequate response/intolerance was to an approved anti-TNF agent at an approved labeled dose for ≥8 weeks.
Arm/Group Title Induction Period Cohort 1 (IP1C)-ABA 30/~10 mg/kg IP1C-ABA ~10 mg/kg IP1C-ABA 3 mg/kg IP1C-Placebo
Hide Arm/Group Description:
During IP, abatacept was administered intravenously (IV) on Days IP-1 and IP-15 at a dose of 30 mg/kg (fixed dose). Following this, on Days IP-29 and IP-57 abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered).
During IP, abatacept was administered IV on Days IP-1,IP-15, IP-29,and IP-57 at a dose of ~10 mg/kg (weight-tiered).
During IP, abatacept was administered IV on Days IP-1, IP-15, IP-29, and IP-57 at a dose of 3 mg/kg (fixed dose).
During the IP, placebo was administered IV on Days IP-1, IP-15, IP-29, and IP-57.
Overall Number of Participants Analyzed 45 46 24 45
Measure Type: Number
Unit of Measure: participants
8 7 4 12
20.Secondary Outcome
Title IP; Number of Participants in Clinical Remission at Week 12 Among Participants With Anti-TNF (Infliximab) Failure/Intolerance: IP1C
Hide Description

The Mayo Scoring system (range 0-12 points, high scores=greater severity of disease) is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Clinical remission is defined as a Mayo score of ≤ 2 points with no individual subscore exceeding 1 point. Inadequate response/intolerance

=inadequate response/intolerance to an approved anti-TNF agent prior to this study at an approved labeled dose for ≥8 weeks.

Time Frame Week 12 (Day IP-85)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants in ITT Population were included in the efficacy analyses. Participants with missing Mayo score were defined as not having achieved clinical response, remission, or mucosal healing. Prior inadequate response/intolerance was to an approved anti-TNF agent at an approved labeled dose for ≥8 weeks.
Arm/Group Title Induction Period Cohort 1 (IP1C)-ABA 30/~10 mg/kg IP1C-ABA ~10 mg/kg IP1C-ABA 3 mg/kg IP1C-Placebo
Hide Arm/Group Description:
During IP, abatacept was administered intravenously (IV) on Days IP-1 and IP-15 at a dose of 30 mg/kg (fixed dose). Following this, on Days IP-29 and IP-57 abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered).
During IP, abatacept was administered IV on Days IP-1,IP-15, IP-29,and IP-57 at a dose of ~10 mg/kg (weight-tiered).
During IP, abatacept was administered IV on Days IP-1, IP-15, IP-29, and IP-57 at a dose of 3 mg/kg (fixed dose).
During the IP, placebo was administered IV on Days IP-1, IP-15, IP-29, and IP-57.
Overall Number of Participants Analyzed 45 46 24 45
Measure Type: Number
Unit of Measure: participants
2 0 0 4
21.Secondary Outcome
Title IP; Number of Participants in Mucosal Healing at Week 12 Among Participants With Anti-TNF (Infliximab) Failure/Intolerance: IP1C
Hide Description The Mayo Scoring system ranges from 0 - 12 points and is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician’s Global Assessment). Higher Mayo scores indicate greater severity of disease. Mucosal healing was defined as endoscopic subscore ≤ 1 point. Inadequate response/intolerance = inadequate response/intolerance to an approved anti-TNF agent prior to this study at an approved labeled dose for ≥8 weeks.
Time Frame Week 12 (Day IP-85)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants in ITT Population were included in the efficacy analyses. Participants with missing Mayo score were defined as not having achieved clinical response, remission, or mucosal healing. Prior inadequate response/intolerance was to an approved anti-TNF agent at an approved labeled dose for ≥8 weeks.
Arm/Group Title Induction Period Cohort 1 (IP1C)-ABA 30/~10 mg/kg IP1C-ABA ~10 mg/kg IP1C-ABA 3 mg/kg IP1C-Placebo
Hide Arm/Group Description:
During IP, abatacept was administered intravenously (IV) on Days IP-1 and IP-15 at a dose of 30 mg/kg (fixed dose). Following this, on Days IP-29 and IP-57 abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered).
During IP, abatacept was administered IV on Days IP-1,IP-15, IP-29,and IP-57 at a dose of ~10 mg/kg (weight-tiered).
During IP, abatacept was administered IV on Days IP-1, IP-15, IP-29, and IP-57 at a dose of 3 mg/kg (fixed dose).
During the IP, placebo was administered IV on Days IP-1, IP-15, IP-29, and IP-57.
Overall Number of Participants Analyzed 45 46 24 45
Measure Type: Number
Unit of Measure: participants
4 4 1 13
22.Secondary Outcome
Title IP; Number of Participants With Adverse Events (AEs), Related AEs, Deaths, Serious AEs (SAEs), Related SAEs, and AEs Leading to Discontinuation: IP1C + IP2C
Hide Description AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. Related AE=relationship of certain, probable, possible, or missing. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event.
Time Frame Day IP-1 through Day IP-85
Hide Outcome Measure Data
Hide Analysis Population Description
The As Treated analysis population was used for all safety summaries and was defined to include all participants who received at least one infusion of study medication.
Arm/Group Title IP1C-ABA 30/~10 mg/kg IP1C-ABA ~10 mg/kg IP1C-ABA 3 mg/kg, IP1C-Placebo IP Cohort 2 (IP2C)-ABA 30/~10 mg/kg IP2C-ABA ~10 mg/kg
Hide Arm/Group Description:
During IP, abatacept was administered intravenously (IV) on Days IP-1 and IP-15 at a dose of 30 mg/kg (fixed dose). Following this, on Days IP-29 and IP-57 abatacept was administered IV at a dose of ~10 mg/kg.
During IP, abatacept was administered IV on Days IP-1 and IP-15 at a dose of ~10 mg/kg (weight-tiered). On Days IP-29 and IP-57, abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered).
During IP, abatacept was administered IV on Days IP-1 and IP-15 at a dose of 3 mg/kg (fixed dose). On Days IP-29 and IP-57, abatacept was administered IV at a dose of 3 mg/kg.
During the IP, placebo was administered IV on Days IP-1, IP-15, IP-29, and IP-57.
During IP, abatacept was administered intravenously (IV) on Days IP-1 and IP-15 at a dose of 30 mg/kg (fixed dose). Following this, on Days IP-29 and IP-57 abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered).
During IP, abatacept was administered IV on Days IP-1 and IP-15 at a dose of ~10 mg/kg (weight-tiered). On Days IP-29 and IP-57, abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered).
Overall Number of Participants Analyzed 141 139 70 140 51 50
Measure Type: Number
Unit of Measure: participants
AEs 85 92 39 86 26 27
Related AEs 48 46 23 37 10 11
Deaths 1 0 0 0 0 0
SAEs 22 20 8 7 6 4
Related SAEs 4 1 1 3 1 0
AEs Leading to Discontinuation 4 6 2 5 1 0
SAEs Leading to Discontinuation 1 2 1 3 1 0
23.Secondary Outcome
Title IP; Number of Participants With AEs Of Special Interest: IP1C + IP2C
Hide Description AE=any new untoward medical occurrence or worsening of a pre-existing 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, serious infections, and opportunistic infections; autoimmune disorders; neoplasms; acute infusional AEs (pre-specified AEs occurring within 1 hour of start of infusion) and peri-infusional AEs (pre-specified AEs occurring within 24 hours of the start of infusion).
Time Frame Day IP-1 through Day IP-85
Hide Outcome Measure Data
Hide Analysis Population Description
The As Treated analysis population was used for all safety summaries and was defined to include all participants who received at least one infusion of study medication.
Arm/Group Title IP1C-ABA 30/~10 mg/kg IP1C-ABA ~10 mg/kg IP1C-ABA 3 mg/kg, IP1C-Placebo IP Cohort 2 (IP2C)-ABA 30/~10 mg/kg IP2C-ABA ~10 mg/kg
Hide Arm/Group Description:
During IP, abatacept was administered intravenously (IV) on Days IP-1 and IP-15 at a dose of 30 mg/kg (fixed dose). Following this, on Days IP-29 and IP-57 abatacept was administered IV at a dose of ~10 mg/kg.
During IP, abatacept was administered IV on Days IP-1 and IP-15 at a dose of ~10 mg/kg (weight-tiered). On Days IP-29 and IP-57, abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered).
During IP, abatacept was administered IV on Days IP-1 and IP-15 at a dose of 3 mg/kg (fixed dose). On Days IP-29 and IP-57, abatacept was administered IV at a dose of 3 mg/kg.
During the IP, placebo was administered IV on Days IP-1, IP-15, IP-29, and IP-57.
During IP, abatacept was administered intravenously (IV) on Days IP-1 and IP-15 at a dose of 30 mg/kg (fixed dose). Following this, on Days IP-29 and IP-57 abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered).
During IP, abatacept was administered IV on Days IP-1 and IP-15 at a dose of ~10 mg/kg (weight-tiered). On Days IP-29 and IP-57, abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered).
Overall Number of Participants Analyzed 141 139 70 140 51 50
Measure Type: Number
Unit of Measure: participants
Infections and Infestations 23 29 8 25 12 7
Serious Infections 5 0 1 0 0 0
Opportunistic Infections-Total 0 1 1 0 0 0
Opportunistic Infections-candidiasis 0 0 1 0 0 0
Opportunistic Infections-esophageal candidiasis 0 1 0 0 0 0
Malignancies-Total 1 0 0 1 0 0
Malignancies-basal cell carcinoma 1 0 0 0 0 0
Malignancies-malignant melanoma 0 0 0 1 0 0
Autoimmune Disorders-Total 2 1 0 4 0 0
Autoimmune Disorders-uveitis 1 1 0 1 0 0
Autoimmune Disorders-episcleritis 0 0 0 1 0 0
Autoimmune Disorders-scleritis 0 0 0 1 0 0
Autoimmune Disorders-rheumatoid arthritis 0 0 0 1 0 0
Autoimmune Disorders-psoriasis 1 0 0 0 0 0
Acute Infusional AEs 4 4 0 2 0 0
Peri Infusional AEs 17 20 5 14 2 4
24.Secondary Outcome
Title IP; Number of Participants With Physical Examination Findings: IP1C + IP2C
Hide Description Complete physical examination was obtained at the Screening Visit, Day MP-365, and OL Final Visit/Early Termination visits. Interim physical examinations were performed at other study visits. Interim physical exam were not as comprehensive as the initial full examination but did note any changes in the participant's condition since the last assessment and did not preclude examination of any of the body systems as clinically indicated. Participants were observed for AEs and vital signs (blood pressure, heart rate, and temperature).
Time Frame Day IP-1 through Day IP-85
Hide Outcome Measure Data
Hide Analysis Population Description
As the results of this study were presented in a synoptic report, physical examination evaluations were not summarized. Laboratory abnormalities and vital signs were collected and summarized.
Arm/Group Title IP1C-ABA 30/~10 mg/kg IP1C-ABA ~10 mg/kg IP1C-ABA 3 mg/kg, IP1C-Placebo IP Cohort 2 (IP2C)-ABA 30/~10 mg/kg IP2C-ABA ~10 mg/kg
Hide Arm/Group Description:
During IP, abatacept was administered intravenously (IV) on Days IP-1 and IP-15 at a dose of 30 mg/kg (fixed dose). Following this, on Days IP-29 and IP-57 abatacept was administered IV at a dose of ~10 mg/kg.
During IP, abatacept was administered IV on Days IP-1 and IP-15 at a dose of ~10 mg/kg (weight-tiered). On Days IP-29 and IP-57, abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered).
During IP, abatacept was administered IV on Days IP-1 and IP-15 at a dose of 3 mg/kg (fixed dose). On Days IP-29 and IP-57, abatacept was administered IV at a dose of 3 mg/kg.
During the IP, placebo was administered IV on Days IP-1, IP-15, IP-29, and IP-57.
During IP, abatacept was administered intravenously (IV) on Days IP-1 and IP-15 at a dose of 30 mg/kg (fixed dose). Following this, on Days IP-29 and IP-57 abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered).
During IP, abatacept was administered IV on Days IP-1 and IP-15 at a dose of ~10 mg/kg (weight-tiered). On Days IP-29 and IP-57, abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered).
Overall Number of Participants Analyzed 0 0 0 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
25.Secondary Outcome
Title IP; Number of Participants With Marked Hematology Laboratory Abnormalities: IP1C
Hide Description High=greater than Upper Normal Limit (ULN), Low=lower than Lower Normal Limit (LLN). LLN/ULN= Hemoglobin (HGB): >3 g/dL decrease from Baseline (BL); Hematocrit: <0.75 x BL; Erythrocytes: <0.75 x BL; Platelets (PLT): <0.67 x LLN/>1.5 x ULN; Leukocytes: <0.75 x LLN/ >1.25 x ULN; neutrophils+bands: <1.0 x 10^3 c/uL; eosinophils: >0.750 x 10^3 c/uL; monocytes: >2000 mm3; lymphocytes: <0.750 x 10^3 c/uL/ >7.50 x 10^3 c/uL.
Time Frame Day IP-1 through Day IP-85
Hide Outcome Measure Data
Hide Analysis Population Description
The As Treated analysis population was used for all safety summaries and was defined to include all participants who received at least one infusion of study medication.
Arm/Group Title IP1C-ABA 30/~10 mg/kg IP1C-ABA ~10 mg/kg IP1C-ABA 3 mg/kg, IP1C-Placebo
Hide Arm/Group Description:
During IP, abatacept was administered intravenously (IV) on Days IP-1 and IP-15 at a dose of 30 mg/kg (fixed dose). Following this, on Days IP-29 and IP-57 abatacept was administered IV at a dose of ~10 mg/kg.
During IP, abatacept was administered IV on Days IP-1 and IP-15 at a dose of ~10 mg/kg (weight-tiered). On Days IP-29 and IP-57, abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered).
During IP, abatacept was administered IV on Days IP-1 and IP-15 at a dose of 3 mg/kg (fixed dose). On Days IP-29 and IP-57, abatacept was administered IV at a dose of 3 mg/kg.
During the IP, placebo was administered IV on Days IP-1, IP-15, IP-29, and IP-57.
Overall Number of Participants Analyzed 141 139 70 140
Measure Type: Number
Unit of Measure: participants
Low HGB; n=136, n=134, n=67, n=133 3 2 6 1
Low hematocrit; n=134, n=133, n=67, n=131 1 2 4 1
Low erythrocytes; n=136, n=134, n=67, n=133 2 2 4 1
Low PLT; n=136, n=133, n=66, n=133 1 0 1 0
High PLT; n=136, n=133, n=66, n=133 0 2 0 0
Low leukocytes; n=136, n=134, n=67, n=133 1 0 4 1
High leukocytes; n=136, n=134, n=67, n=133 10 6 3 5
Low neutrophils + bands; n=136, n=134, n=67, n=131 0 0 1 0
High eosinophils; n=136, n=134, n=67, n=131 6 4 3 4
High monocytes; n=136, n=134, n=67, n=131 0 0 1 0
Low lymphocytes; n=136, n=134, n=67, n=131 23 13 11 26
26.Secondary Outcome
Title IP; Number of Participants With Marked Liver and Kidney Function and Electrolyte Laboratory Abnormalities: IP1C
Hide Description Low=lower than LLN, High=greater than ULN. LLN/ULN= Alkaline phosphatase (ALP): >2 x ULN; aspartate aminotransferase (AST): >3 x ULN; alanine aminotransferase (ALT): >3 x ULN; G-Glutamyl transferase (GGT): >2 x ULN; Bilirubin: >2 x ULN; blood urea nitrogen (BUN): >2 x BL; creatinine: >4 x BL; Sodium (Na): <0.95 x LLN/ >1.05 x ULN; potassium (K): <0.9 x LLN/ >1.1 x ULN; calcium (Ca): <0.8 x LLN/>1.2 x ULN; phosphorous (P): <0.75 x LLN/ >1.2 5 x ULN
Time Frame Day IP-1 through Day IP-85
Hide Outcome Measure Data
Hide Analysis Population Description
The As Treated analysis population was used for all safety summaries and was defined to include all participants who received at least one infusion of study medication.
Arm/Group Title IP1C-ABA 30/~10 mg/kg IP1C-ABA ~10 mg/kg IP1C-ABA 3 mg/kg, IP1C-Placebo
Hide Arm/Group Description:
During IP, abatacept was administered intravenously (IV) on Days IP-1 and IP-15 at a dose of 30 mg/kg (fixed dose). Following this, on Days IP-29 and IP-57 abatacept was administered IV at a dose of ~10 mg/kg.
During IP, abatacept was administered IV on Days IP-1 and IP-15 at a dose of ~10 mg/kg (weight-tiered). On Days IP-29 and IP-57, abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered).
During IP, abatacept was administered IV on Days IP-1 and IP-15 at a dose of 3 mg/kg (fixed dose). On Days IP-29 and IP-57, abatacept was administered IV at a dose of 3 mg/kg.
During the IP, placebo was administered IV on Days IP-1, IP-15, IP-29, and IP-57.
Overall Number of Participants Analyzed 141 139 70 140
Measure Type: Number
Unit of Measure: participants
High ALP, n=137, n=135, n=66, n=135 1 0 0 0
High ALT; n=137, n=135, n=66, n=135 0 1 0 0
High GGT; n=137, n=135, n=66, n=135 6 2 0 2
High BUN; n=127, n=130, n=62, n=124 0 2 2 3
High creatinine; n=137, n=135, n=66, n=135 0 0 0 1
Low Na; n=138, n=135, n=66, n=135 0 0 2 0
Low K; n=138, n=135, n=66, n=135 1 2 2 0
High K; n=138, n=135, n=66, n=135 0 1 0 1
Low Ca; n=137, n=135, n=66, n=135 0 1 2 0
Low P; n=137, 135, n=66, n=135 0 1 0 3
27.Secondary Outcome
Title IP; Number of Participants With Marked Chemistry and Urinalysis Laboratory Abnormalities: IP1C
Hide Description Low=lower than LLN, High=greater than ULN. LLN/ULN= serum glucose (Glu): <65 mg/dL/ >220 mg/dL; total protein: < 0.9 x LLN/ >1.1 x ULN; albumin:<0.9 x LLN; uric acid: >1.5 x ULN. For Urinalysis (Urine protein, urine Glu, urine blood, leukocyte esterase, Red Blood Cells [RBCs], White Blood Cells [WBCs]): Use ≥2 when BL value missing or value ≥4, or when pre-dose=0 or 0.5. Use ≥3 when pre-dose=1. Use ≥4 when pre-dose=2 or 3
Time Frame Day IP-1 through Day IP-85
Hide Outcome Measure Data
Hide Analysis Population Description
The As Treated analysis population was used for all safety summaries and was defined to include all participants who received at least one infusion of study medication.
Arm/Group Title IP1C-ABA 30/~10 mg/kg IP1C-ABA ~10 mg/kg IP1C-ABA 3 mg/kg, IP1C-Placebo
Hide Arm/Group Description:
During IP, abatacept was administered intravenously (IV) on Days IP-1 and IP-15 at a dose of 30 mg/kg (fixed dose). Following this, on Days IP-29 and IP-57 abatacept was administered IV at a dose of ~10 mg/kg.
During IP, abatacept was administered IV on Days IP-1 and IP-15 at a dose of ~10 mg/kg (weight-tiered). On Days IP-29 and IP-57, abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered).
During IP, abatacept was administered IV on Days IP-1 and IP-15 at a dose of 3 mg/kg (fixed dose). On Days IP-29 and IP-57, abatacept was administered IV at a dose of 3 mg/kg.
During the IP, placebo was administered IV on Days IP-1, IP-15, IP-29, and IP-57.
Overall Number of Participants Analyzed 141 139 70 140
Measure Type: Number
Unit of Measure: participants
Low Glu; n=88, n=91, n=41, n=105 1 6 2 0
High Glu; n=88, n=91, n=41, n=105 0 0 1 0
Low protein; n=137, n=135, n=66, n=135 5 3 3 0
High protein; n=137, n=135, n=66, n=135 0 1 0 0
Low albumin; n=137, n=135, n=66, n=135 7 5 3 0
High urine protein; n=132, n=129, n=66, n=128 5 3 2 4
High urine Glu; n=132, n=129, n=66, n=128 4 1 2 4
High urine blood; n=132, n=129, n=66, n=128 6 7 4 11
High leukocyte esterase; n=54, n=51, n=27, n=52 1 5 2 2
High urine RBC; n=47, n=42, n=17, n=52 9 8 4 12
High urine WBC; n=64, n=56, n=27, n=58 14 21 3 14
28.Secondary Outcome
Title IP; Number of Participants With Marked Hematology, Liver and Kidney Function, and Electrolyte Laboratory Abnormalities: IP2C
Hide Description High=greater than Upper Normal Limit (ULN), Low=lower than Lower Normal Limit (LLN). LLN/ULN= Hemoglobin (HGB): >3 g/dL decrease from Baseline (BL); Hematocrit: <0.75 x BL; Erythrocytes: <0.75 x BL; Platelets (PLT): <0.67 x LLN/>1.5 x ULN; Leukocytes: <0.75 x LLN/ >1.25 x ULN; eosinophils: >0.750 x 10^3 c/uL; monocytes: >2000 mm3; lymphocytes: <0.750 x 10^3 c/uL/ >7.50 x 10^3 c/uL; blood urea nitrogen (BUN): >2 x BL; creatinine: >4 x BL; Sodium (Na): <0.95 x LLN/ >1.05 x ULN; potassium (K): <0.9 x LLN/ >1.1 x ULN; phosphorous (P): <0.75 x LLN/ >1.2 5 x ULN;
Time Frame Day IP-1 through Day IP-85
Hide Outcome Measure Data
Hide Analysis Population Description
The As Treated analysis population was used for all safety summaries and was defined to include all participants who received at least one infusion of study medication.
Arm/Group Title IP2C-ABA 30/~10 mg/kg IP2C-ABA ~10 mg/kg
Hide Arm/Group Description:
During IP, abatacept was administered intravenously (IV) on Days IP-1 and IP-15 at a dose of 30 mg/kg (fixed dose). Following this, on Days IP-29 and IP-57 abatacept was administered IV at a dose of ~10 mg/kg.
During IP, abatacept was administered IV on Days IP-1 and IP-15 at a dose of ~10 mg/kg (weight-tiered). On Days IP-29 and IP-57, abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered).
Overall Number of Participants Analyzed 51 50
Measure Type: Number
Unit of Measure: participants
Low HGB; n=50, n=49 2 2
Low hematocrit; n=50, n=49 1 0
Low erythrocytes; n=50, n=49 1 0
High PLT; n=50, n=49 0 1
Low leukocytes; n=50, n=49 0 1
High leukocytes; n=50, n=49 3 4
High eosinophils; n=49, n=49 3 1
High monocytes; n=49, n=49 0 1
Low lymphocytes; n=49, n=49 5 3
High BUN; n=46, n=44 3 1
High creatinine; n=50, n=50 1 0
Low Na; n=50, n=50 1 0
Low K; n=50, n=50 2 1
Low P; n=50, n=50 1 0
Low Glu; n=37, n=28 0 2
High Glu; n=37, n=28 0 2
Low protein; n=50, n=50 2 0
Low albumin; n=50, n=50 2 0
High urine protein; n=50, n=48 0 4
High urine Glu; n=50, n=48 0 2
High urine blood; n=50, n=48 2 3
High leukocyte esterase; n=21, n=16 4 2
High urine RBC; n=15, n=20 0 4
High urine WBC; n=24, n=23 7 6
29.Secondary Outcome
Title IP; Number of Participants With Marked Chemistry and Urinalysis Laboratory Abnormalities: IP2C
Hide Description Low=lower than LLN, High=greater than ULN. LLN/ULN= serum glucose (Glu): <65 mg/dL/ >220 mg/dL; total protein: < 0.9 x LLN/ >1.1 x ULN; albumin:<0.9 x LLN. For Urinalysis (Urine protein, urine Glu, urine blood, leukocyte esterase, Red Blood Cells [RBCs], White Blood Cells [WBCs]): Use ≥2 when BL value missing or value ≥4, or when pre-dose=0 or 0.5. Use ≥3 when pre-dose=1. Use ≥4 when pre-dose=2 or 3
Time Frame Day IP-1 through Day IP-85
Hide Outcome Measure Data
Hide Analysis Population Description
The As Treated analysis population was used for all safety summaries and was defined to include all participants who received at least one infusion of study medication.
Arm/Group Title IP2C-ABA 30/~10 mg/kg IP2C-ABA ~10 mg/kg
Hide Arm/Group Description:
During IP, abatacept was administered intravenously (IV) on Days IP-1 and IP-15 at a dose of 30 mg/kg (fixed dose). Following this, on Days IP-29 and IP-57 abatacept was administered IV at a dose of ~10 mg/kg.
During IP, abatacept was administered IV on Days IP-1 and IP-15 at a dose of ~10 mg/kg (weight-tiered). On Days IP-29 and IP-57, abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered).
Overall Number of Participants Analyzed 51 50
Measure Type: Number
Unit of Measure: participants
Low Glu; n=37, n=28 0 2
High Glu; n=37, n=28 0 2
Low protein; n=50, n=50 2 0
Low albumin; n=50, n=50 2 0
High urine protein; n=50, n=48 0 4
High urine Glu; n=50, n=48 0 2
High urine blood; n=50, n=48 2 3
High leukocyte esterase; n=21, n=16 4 2
High urine RBC; n=15, n=20 0 4
High urine WBC; n=24, n=23 7 6
30.Secondary Outcome
Title IP; Number of Participants With Abatacept-Induced Antibodies: IP1C + IP2C
Hide Description A electrochemiluminescent immunoassay screened sera for drug-specific antibodies, immunocompetition was used to identify specific anti-Abatacept reactivity. CTLA4 and Possibly Ig category=reactivity against extracellular domain of human CTLA4, constant regions of human IgG1, or both (CTLA4Ig; Abatacept molecule). Ig and/or Junction category=reactivity against constant regions and/or hinge region of human IgG1. Drug-induced seropositivity was defined as a post-baseline titer higher than Baseline, or any post-baseline positivity if Baseline value was missing.
Time Frame For participants treated in MP: Day IP-1 (Baseline) to Day MP-1 (Day IP-85). For participants treated in OL directly after IP: Day IP-1 to Day OL-1. For participants treated only in IP: All measurements after Day IP-1 (including follow-up visits)
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects with at least one post-baseline immunogenicity measurement during the study period were included in the immunogenicity data set. "Positive" was defined as "positive post-baseline IP-1" and with a titer value greater than the baseline titer value. Participants with missing baseline titer were assumed "negative" at baseline.
Arm/Group Title IP1C+IP2C: ABA 30/~10 mg/kg IP1C+IP2C: ABA ~10 mg/kg IP1C-ABA 3 mg/kg
Hide Arm/Group Description:
During IP, abatacept was administered intravenously (IV) on Days IP-1 and IP-15 at a dose of 30 mg/kg (fixed dose). Following this, on Days IP-29 and IP-57 abatacept was administered IV at a dose of ~10 mg/kg.
During IP, abatacept was administered IV on Days IP-1 and IP-15 at a dose of ~10 mg/kg (weight-tiered). On Days IP-29 and IP-57, abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered).
During IP, abatacept was administered IV on Days IP-1 and IP-15 at a dose of 3 mg/kg (fixed dose). On Days IP-29 and IP-57, abatacept was administered IV at a dose of 3 mg/kg.
Overall Number of Participants Analyzed 189 185 66
Measure Type: Number
Unit of Measure: participants
Total 6 19 4
CTLA4/Possibly Ig 2 17 4
Ig and/or Ig Junction 4 3 0
31.Secondary Outcome
Title MP; Number of Participants in Clinical Remission at Month 12
Hide Description The Mayo Scoring system ranges from 0 - 12 points and is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Higher Mayo scores indicate greater severity of disease. Clinical remission is defined as a Mayo score of ≤ 2 points with no individual subscore exceeding 1 point.
Time Frame Month 12 (Day MP-365)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants in the ITT Population were included in the efficacy analyses. Participants with missing Mayo score were defined as not having achieved clinical response, remission, or mucosal healing.
Arm/Group Title ABA ~10 mg/kg, MP Placebo, MP
Hide Arm/Group Description:
During MP, abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered) every 28 days beginning Day MP-1.
During the MP, placebo was administered IV every 28 days beginning Day MP-1 through Day MP-337.
Overall Number of Participants Analyzed 64 64
Measure Type: Number
Unit of Measure: participants
8 9
32.Secondary Outcome
Title MP; Number of Participants With Mayo Endoscopic Subscores Indicating Mucosal Healing (≤1 Point) at Month 12
Hide Description The Mayo Scoring system ranges from 0 - 12 points and is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician’s Global Assessment). Higher Mayo scores indicate greater severity of disease. Mucosal healing was defined as endoscopic subscore ≤ 1 point
Time Frame Month 12 (Day MP-365)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants in the ITT Population were included in the efficacy analyses. Participants with missing Mayo score were defined as not having achieved clinical response, remission, or mucosal healing.
Arm/Group Title ABA ~10 mg/kg, MP Placebo, MP
Hide Arm/Group Description:
During MP, abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered) every 28 days beginning Day MP-1.
During the MP, placebo was administered IV every 28 days beginning Day MP-1 through Day MP-337.
Overall Number of Participants Analyzed 17 12
Measure Type: Number
Unit of Measure: participants
11 10
33.Secondary Outcome
Title MP; Number of Participants in Clinical Remission at Both Month 6 and Month 12
Hide Description The Mayo Scoring system ranges from 0 - 12 points and is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Higher Mayo scores indicate greater severity of disease. Clinical remission is defined as a Mayo score of ≤ 2 points with no individual subscore exceeding 1 point.
Time Frame Month 6 (Day MP-169), Month 12 (Day MP-365)
Hide Outcome Measure Data
Hide Analysis Population Description
Due to the early termination of the study after preliminary IP1C results were reviewed and the primary efficacy endpoint was not achieved, the secondary endpoint analysis to determine the percentage of participants in clinical remission at both Month 6 and Month 12 was not conducted for the MP as planned.
Arm/Group Title ABA ~10 mg/kg, MP Placebo, MP
Hide Arm/Group Description:
During MP, abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered) every 28 days beginning Day MP-1.
During the MP, placebo was administered IV every 28 days beginning Day MP-1 through Day MP-337.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
34.Secondary Outcome
Title MP; Number of Participants With Baseline Oral Corticosteroid Use Who Have Discontinued Corticosteroids and Achieved Clinical Remission by Month 12
Hide Description Baseline corticosteroids equivalent of ≤30 mg prednisone daily. The Mayo Scoring system ranges from 0 - 12 points and is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician’s Global Assessment). Higher Mayo scores indicate greater frequency or severity. Clinical remission is defined as a Mayo score of ≤ 2 points with no individual subscore exceeding 1 point.
Time Frame Day MP-365 (Month 12)
Hide Outcome Measure Data
Hide Analysis Population Description
Due to the early termination of the study after preliminary IP1C results were reviewed and the primary efficacy endpoint was not achieved, the secondary endpoint analyses for corticosteroid sparing were not conducted for the MP as planned.
Arm/Group Title ABA ~10 mg/kg, MP Placebo, MP
Hide Arm/Group Description:
During MP, abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered) every 28 days beginning Day MP-1.
During the MP, placebo was administered IV every 28 days beginning Day MP-1 through Day MP-337.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
35.Secondary Outcome
Title MP; Mean Change From Baseline to Month 12 in IBDQ
Hide Description The Inflammatory Bowel Disease Questionnaire (IBDQ) was used to measure disease specific quality of life. The IBDQ consists of a self-administered 32-item questionnaire that evaluates quality of life across 4 dimensional scores: Bowel, Systemic, Social and Emotional. The response to each question can range from 1 to 7, with 1 indicating severe problem and 7 indicating normal health. The total IBDQ is computed as the sum of the responses to the individual IBDQ questions. The total score can range between 32 to 224 with higher scores indicating a better quality of life.
Time Frame Day MP-365
Hide Outcome Measure Data
Hide Analysis Population Description
Due to the early termination of the study after preliminary IP1C results were reviewed and the primary efficacy endpoint was not achieved, the secondary endpoint analysis for changes from baseline in IBDQ responses were not conducted for the MP as planned.
Arm/Group Title ABA ~10 mg/kg, MP Placebo, MP
Hide Arm/Group Description:
During MP, abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered) every 28 days beginning Day MP-1.
During the MP, placebo was administered IV every 28 days beginning Day MP-1 through Day MP-337.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
36.Secondary Outcome
Title MP; Mean Change From Baseline to Month 12 in Short Form-36 (SF-36)
Hide Description The SF-36 is a validated instrument to measure health-related quality of life across multiple disease states. Individual subscale scores and 2 summary scores are calculated: (1) physical component summary (PCS) which includes physical functioning, role-physical, bodily pain, and general health; (2) mental component summary (MCS) which includes vitality, social functioning, role-emotional, and mental health. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight, with values ranging from worse health (0) to best health (100).
Time Frame Day MP-365
Hide Outcome Measure Data
Hide Analysis Population Description
Due to the early termination of the study after preliminary IP1C results were reviewed and the primary efficacy endpoint was not achieved, the secondary endpoint analysis for changes from baseline in SF-36 responses were not conducted for the MP as planned.
Arm/Group Title ABA ~10 mg/kg, MP Placebo, MP
Hide Arm/Group Description:
During MP, abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered) every 28 days beginning Day MP-1.
During the MP, placebo was administered IV every 28 days beginning Day MP-1 through Day MP-337.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
37.Secondary Outcome
Title MP; Number of Participants With Baseline Oral Corticosteroid Use Who Have Discontinued Corticosteroids for 90 Consecutive Days and Achieved Clinical Remission by Month 12
Hide Description Baseline corticosteroids equivalent of ≤30 mg prednisone daily. The Mayo Scoring system ranges from 0 - 12 points and is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Higher Mayo scores indicate greater frequency or severity. Clinical remission is defined as a Mayo score of ≤ 2 points with no individual subscore exceeding 1 point.
Time Frame Day MP-365 (Month 12)
Hide Outcome Measure Data
Hide Analysis Population Description
Due to the early termination of the study after preliminary IP1C results were reviewed and the primary efficacy endpoint was not achieved, the secondary endpoint analyses for corticosteroid sparing were not conducted for the MP as planned.
Arm/Group Title ABA ~10 mg/kg, MP Placebo, MP
Hide Arm/Group Description:
During MP, abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered) every 28 days beginning Day MP-1.
During the MP, placebo was administered IV every 28 days beginning Day MP-1 through Day MP-337.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
38.Secondary Outcome
Title MP; Number of Participants With Mayo Rectal Bleeding Subscores Indicating Mild Disease (≤1 Point) at Month 12
Hide Description The Mayo Scoring system ranges from 0 - 12 points and is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Higher Mayo scores indicate greater severity of disease. An absolute rectal bleeding subscore of ≤1 point was indicative of mild disease.
Time Frame Day MP-365 (Month 12)
Hide Outcome Measure Data
Hide Analysis Population Description
Due to the early termination of the study after preliminary IP1C results were reviewed and the primary efficacy endpoint was not achieved, the secondary endpoint analysis to determine the percentage of participants with rectal subscores indicating mild disease (≤1) was not conducted for the MP as planned.
Arm/Group Title ABA ~10 mg/kg, MP Placebo, MP
Hide Arm/Group Description:
During MP, abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered) every 28 days beginning Day MP-1.
During the MP, placebo was administered IV every 28 days beginning Day MP-1 through Day MP-337.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
39.Secondary Outcome
Title MP; Number of Participants With Mayo Stool Frequency Subscores Indicating Mild Disease (≤1 Point) at Month 12
Hide Description The Mayo Scoring system ranges from 0 - 12 points and is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Higher Mayo scores indicate greater severity of disease. An absolute stool frequency subscore of ≤1 point was indicative of mild disease.
Time Frame Day MP-365 (Month 12)
Hide Outcome Measure Data
Hide Analysis Population Description
Due to the early termination of the study after preliminary IP1C results were reviewed and the primary efficacy endpoint was not achieved, the secondary endpoint analysis to determine the percentage of participants with stool frequency subscores indicating mild disease (≤1) was not conducted for the MP as planned.
Arm/Group Title ABA ~10 mg/kg, MP Placebo, MP
Hide Arm/Group Description:
During MP, abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered) every 28 days beginning Day MP-1.
During the MP, placebo was administered IV every 28 days beginning Day MP-1 through Day MP-337.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
40.Secondary Outcome
Title MP; Number of Participants With Mayo PGA Subscores Indicating Mild Disease (≤1 Point) at Month 12
Hide Description The Mayo Scoring system ranges from 0 - 12 points and is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Higher Mayo scores indicate greater severity of disease. An absolute PGA subscore of ≤1 point was indicative of mild disease.
Time Frame Day MP-365 (Month 12)
Hide Outcome Measure Data
Hide Analysis Population Description
Due to the early termination of the study after preliminary IP1C results were reviewed and the primary efficacy endpoint was not achieved, the secondary endpoint analysis to determine the percentage of participants with PGA subscores indicating mild disease (≤1) was not conducted for the MP as planned.
Arm/Group Title ABA ~10 mg/kg, MP Placebo, MP
Hide Arm/Group Description:
During MP, abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered) every 28 days beginning Day MP-1.
During the MP, placebo was administered IV every 28 days beginning Day MP-1 through Day MP-337.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
41.Secondary Outcome
Title MP; Number of Participants With Clinical Response at Month 12 Among Participants With Inadequate Response/Intolerance to Prior Anti-TNF Therapy (Infliximab)
Hide Description The Mayo Scoring system (range 0-12 points, high scores=greater severity of disease) is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Clinical response=reduction from baseline in the Mayo score of ≥ 3 points and ≥ 30%, with accompanying decrease in the rectal bleeding subscore of ≥ 1 point or absolute rectal bleeding subscore of ≤ 1 point. Inadequate response/intolerance=inadequate response/intolerance to an approved anti-TNF agent prior to this study at an approved labeled dose for ≥8 weeks.
Time Frame Month 12 (Day MP-365)
Hide Outcome Measure Data
Hide Analysis Population Description
Due to the early termination of the study after preliminary IP1C results were reviewed and the primary efficacy endpoint was not achieved, the secondary subgroup analyses of clinical response in subjects who have had an inadequate response and/or intolerance to anti-TNF therapy was not conducted for the MP as planned.
Arm/Group Title ABA ~10 mg/kg, MP Placebo, MP
Hide Arm/Group Description:
During MP, abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered) every 28 days beginning Day MP-1.
During the MP, placebo was administered IV every 28 days beginning Day MP-1 through Day MP-337.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
42.Secondary Outcome
Title MP; Number of Participants With Clinical Remission at Month 12 Among Participants With Inadequate Response/Intolerance to Prior Anti-TNF Therapy (Infliximab)
Hide Description The Mayo Scoring system (range 0-12 points, high scores=greater severity of disease) is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Clinical remission is defined as a Mayo score of ≤ 2 points with no individual subscore exceeding 1 point. Inadequate response/intolerance =inadequate response/intolerance to an approved anti-TNF agent prior to this study at an approved labeled dose for ≥8 weeks.
Time Frame Month 12 (Day MP-365)
Hide Outcome Measure Data
Hide Analysis Population Description
Due to the early termination of the study after preliminary IP1C results were reviewed and the primary efficacy endpoint was not achieved, the secondary subgroup analyses of clinical remission in subjects who have had an inadequate response and/or intolerance to anti-TNF therapy was not conducted for the MP as planned.
Arm/Group Title ABA ~10 mg/kg, MP Placebo, MP
Hide Arm/Group Description:
During MP, abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered) every 28 days beginning Day MP-1.
During the MP, placebo was administered IV every 28 days beginning Day MP-1 through Day MP-337.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
43.Secondary Outcome
Title MP; Number of Participants With Clinical Mucosal Healing at Month 12 Among Participants With Inadequate Response/Intolerance to Prior Anti-TNF Therapy (Infliximab)
Hide Description The Mayo Scoring system ranges from 0 - 12 points and is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician’s Global Assessment). Higher Mayo scores indicate greater severity of disease. Mucosal healing was defined as endoscopic subscore ≤1 point. Inadequate response/intolerance = inadequate response/intolerance to an approved anti-TNF agent prior to this study at an approved labeled dose for ≥8 weeks.
Time Frame Month 12 (Day MP-365)
Hide Outcome Measure Data
Hide Analysis Population Description
Due to the early termination of the study after preliminary IP1C results were reviewed and the primary efficacy endpoint was not achieved, the secondary subgroup analyses of mucosal healing in subjects who have had an inadequate response and/or intolerance to anti-TNF therapy was not conducted for the MP as planned.
Arm/Group Title ABA ~10 mg/kg, MP Placebo, MP
Hide Arm/Group Description:
During MP, abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered) every 28 days beginning Day MP-1.
During the MP, placebo was administered IV every 28 days beginning Day MP-1 through Day MP-337.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
44.Secondary Outcome
Title MP; Number of Participants With Abatacept-Induced Antibodies
Hide Description A electrochemiluminescent immunoassay screened sera for drug-specific antibodies, immunocompetition was used to identify specific anti-Abatacept reactivity. CTLA4 and Possibly Ig category=reactivity against extracellular domain of human CTLA4, constant regions of human IgG1, or both (CTLA4Ig; Abatacept molecule). Ig and/or Junction category=reactivity against constant regions and/or hinge region of human IgG1. Drug-induced seropositivity was defined as a post-baseline titer higher than Baseline, or any post-baseline positivity if Baseline value was missing.
Time Frame For participants not entering OL: All measurements starting after Day MP-1 (including follow-up visits). For participants entering OL: From first measurement after Day MP-1 to Day MP-365 (Day OL-1).
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects with at least one post-baseline immunogenicity measurement during the study period were included in the immunogenicity data set. "Positive" was defined as "positive post-baseline IP-1" and with a titer value greater than the baseline titer value. Participants with missing baseline titer were assumed "negative" at baseline.
Arm/Group Title ABA ~10 mg/kg, MP Placebo, MP
Hide Arm/Group Description:
During MP, abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered) every 28 days beginning Day MP-1.
During the MP, placebo was administered IV every 28 days beginning Day MP-1 through Day MP-337.
Overall Number of Participants Analyzed 62 47
Measure Type: Number
Unit of Measure: participants
Total 8 20
CTLA4/Possibly Ig 8 17
Ig and/or Ig Junction 0 3
45.Secondary Outcome
Title MP; Number of Participants With Adverse Events (AEs), Related AEs, Deaths, Serious AEs (SAEs), Related SAEs, and AEs Leading to Discontinuation
Hide Description AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. Related AE=relationship of certain, probable, possible, or missing. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, results in development of drug dependency or drug abuse, is an important medical event.
Time Frame Day MP-1 through Day MP-365
Hide Outcome Measure Data
Hide Analysis Population Description
The As Treated analysis population was used for all safety summaries and was defined to include all participants who received at least one infusion of study medication.
Arm/Group Title ABA ~10 mg/kg, MP Placebo, MP
Hide Arm/Group Description:
During MP, abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered) every 28 days beginning Day MP-1.
During the MP, placebo was administered IV every 28 days beginning Day MP-1 through Day MP-337.
Overall Number of Participants Analyzed 65 66
Measure Type: Number
Unit of Measure: participants
AEs 39 36
Related AEs 12 13
Deaths 1 0
SAEs 7 4
Related SAEs 2 2
AEs Leading to Discontinuation 1 3
SAEs Leading to Discontinuation 1 1
46.Secondary Outcome
Title MP; Number of Participants With AEs of Special Interest
Hide Description AE=any new untoward medical occurrence or worsening of a pre-existing 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, serious infections, and opportunistic infections; autoimmune disorders; neoplasms; acute infusional AEs (pre-specified AEs occurring within 1 hour of start of infusion) and peri-infusional AEs (pre-specified AEs occurring within 24 hours of the start of infusion).
Time Frame Day MP-1 through Day MP-365
Hide Outcome Measure Data
Hide Analysis Population Description
The As Treated analysis population was used for all safety summaries and was defined to include all participants who received at least one infusion of study medication.
Arm/Group Title ABA ~10 mg/kg, MP Placebo, MP
Hide Arm/Group Description:
During MP, abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered) every 28 days beginning Day MP-1.
During the MP, placebo was administered IV every 28 days beginning Day MP-1 through Day MP-337.
Overall Number of Participants Analyzed 65 66
Measure Type: Number
Unit of Measure: participants
Infections and Infestations 39 36
Serious Infections 5 2
Opportunistic Infections-Total 1 0
Opportunistic Infections-pneumonia herpes viral 1 0
Malignancies-Total 0 1
Malignancies-breast cancer 0 1
Autoimmune Disorders-Total 2 0
Autoimmune Disorders-erythema nodosum 1 0
Autoimmune Disorders-pemphigoid 1 0
Acute Infusional AEs 2 1
Peri-infusional AEs 3 2
47.Secondary Outcome
Title MP; Number of Participants With Physical Examination Findings
Hide Description Complete physical examination was obtained at the Screening Visit, Day MP-365, and OL Final Visit/Early Termination visits. Interim physical examinations were performed at other study visits. Interim physical exam were not as comprehensive as the initial full examination but did note any changes in the participant's condition since the last assessment and did not preclude examination of any of the body systems as clinically indicated. Participants were observed for AEs and vital signs (blood pressure, heart rate, and temperature).
Time Frame Day IP-85 through Day MP-365
Hide Outcome Measure Data
Hide Analysis Population Description
As the results of this study were presented in a synoptic report, physical examination evaluations were not summarized. Laboratory abnormalities and vital signs were collected and summarized.
Arm/Group Title ABA ~10 mg/kg, MP Placebo, MP
Hide Arm/Group Description:
During MP, abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered) every 28 days beginning Day MP-1.
During the MP, placebo was administered IV every 28 days beginning Day MP-1 through Day MP-337.
Overall Number of Participants Analyzed 0 0
No data displayed because Outcome Measure has zero total analyzed.
48.Secondary Outcome
Title MP; Number of Participants With Marked Hematology Laboratory Abnormalities
Hide Description High=greater than ULN, Low=lower than LLN. LLN/ULN= HGB: >3 g/dL decrease from Baseline (BL); Hematocrit: <0.75 x BL; Erythrocytes: <0.75 x BL; PLT: <0.67 x LLN/>1.5 x ULN; Leukocytes: <0.75 x LLN/ >1.25 x ULN; neutrophils+bands: <1.0 x 10^3 c/uL; eosinophils: >0.750 x 10^3 c/uL; monocytes: >2000 mm3; lymphocytes: <0.750 x 10^3 c/uL/ >7.50 x 10^3 c/uL; GGT: >2 x ULN; Bilirubin: >2 x ULN; BUN: >2 x BL; Na: <0.95 x LLN/ >1.05 x ULN; K: <0.9 x LLN/ >1.1 x ULN; Ca: <0.8 x LLN/>1.2 x ULN
Time Frame Day IP-85 through Day MP-365
Hide Outcome Measure Data
Hide Analysis Population Description
The As Treated analysis population was used for all safety summaries and was defined to include all participants who received at least one infusion of study medication.
Arm/Group Title ABA 30/~10 mg/kg, MP ABA ~10 mg/kg, MP
Hide Arm/Group Description:
During IP, abatacept was administered intravenously (IV) on Days IP-1 and IP-15 at a dose of 30 mg/kg (fixed dose). Following this, on Days IP-29 and IP-57 abatacept was administered IV at a dose of ~10 mg/kg.
During IP, abatacept was administered IV on Days IP-1 and IP-15 at a dose of ~10 mg/kg (weight-tiered). On Days IP-29 and IP-57, abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered).
Overall Number of Participants Analyzed 65 66
Measure Type: Number
Unit of Measure: participants
Low HGB; n=64, n=61 1 2
Low hematocrit; n=64, n=60 3 2
Low erythrocytes; n=64, n=61 1 2
High PLT; n= 64, n=61 0 1
Low leukocytes; n=64, n=60 2 0
High leukocytes; n=64, n=60 2 0
Low neutrophils + bands; n=64, n=60 1 0
High eosinophils; n=64, n=60 2 3
High monocytes; n=64, n=60 1 0
Low lymphocytes; n=64, n=60 7 6
High lymphocytes; n=64, n=60 1 0
High GGT; n=64, n=62 3 2
High bilirubin, n=64, n=61 1 0
High BUN; n=57, n=59 4 3
Low Na; n=64, n=62 0 1
Low K; n=64, n=62 1 1
Low Ca; n=64, n=61 1 0
Low Glu; n=45, n=38 0 2
High Glu; n=45, n=38 3 3
Low protein; n=64, n=61 0 1
High urine protein; n=58, n=58 4 1
High urine Glu; n=58, n=58 2 1
High urine blood; n=58, n=58 3 7
High leukocyte esterase; n=23, n=18 2 5
High urine RBC; n=24, n=17 4 4
High urine WBC; n=29, n=21 8 10
49.Secondary Outcome
Title MP; Number of Participants With Marked Chemistry and Urinalysis Laboratory Abnormalities
Hide Description Low=lower than LLN, High=greater than ULN. LLN/ULN= serum glucose (Glu): <65 mg/dL/ >220 mg/dL; fasting serum Glu: <0.8 x LLN/ >1.5 x ULN; total protein: < 0.9 x LLN/ >1.1 x ULN; albumin:<0.9 x LLN; uric acid: >1.5 x ULN. For Urinalysis (Urine protein, urine Glu, urine blood, leukocyte esterase, Red Blood Cells [RBCs], White Blood Cells [WBCs]): Use ≥2 when BL value missing or value ≥4, or when pre-dose=0 or 0.5. Use ≥3 when pre-dose=1. Use ≥4 when pre-dose=2 or 3
Time Frame Day IP-85 through Day MP-365
Hide Outcome Measure Data
Hide Analysis Population Description
The As Treated analysis population was used for all safety summaries and was defined to include all participants who received at least one infusion of study medication.
Arm/Group Title ABA 30/~10 mg/kg, MP ABA ~10 mg/kg, MP
Hide Arm/Group Description:
During IP, abatacept was administered intravenously (IV) on Days IP-1 and IP-15 at a dose of 30 mg/kg (fixed dose). Following this, on Days IP-29 and IP-57 abatacept was administered IV at a dose of ~10 mg/kg.
During IP, abatacept was administered IV on Days IP-1 and IP-15 at a dose of ~10 mg/kg (weight-tiered). On Days IP-29 and IP-57, abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered).
Overall Number of Participants Analyzed 65 66
Measure Type: Number
Unit of Measure: participants
Low Glu; n=45, n=38 0 2
High Glu; n=45, n=38 3 3
Low protein; n=64, n=61 0 1
High urine protein; n=58, n=58 4 1
High urine Glu; n=58, n=58 2 1
High urine blood; n=58, n=58 3 7
High leukocyte esterase; n=23, n=18 2 5
High urine RBC; n=24, n=17 4 4
High urine WBC; n=29, n=21 8 10
50.Secondary Outcome
Title OL; Number of Participants With Clinical Response Over Time
Hide Description The Mayo Scoring system ranges from 0 - 12 points and is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Higher Mayo scores indicate greater severity of disease. A clinical response is defined as a reduction from baseline in the Mayo score of ≥ 3 points and ≥ 30%, with an accompanying decrease in the rectal bleeding subscore of ≥ 1 point or absolute rectal bleeding subscore of ≤ 1 point.
Time Frame Day OL-1 through Day OL-729
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 infusion of open-label study medication at any time were included in the efficacy analyses of the OL. Number of Participants Analyzed=all participants in OL; n=number of evaluable participants.
Arm/Group Title ABA ~10 mg/kg, OL
Hide Arm/Group Description:
During OL, abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered) every 28 days beginning Day OL-1.
Overall Number of Participants Analyzed 347
Measure Type: Number
Unit of Measure: participants
Day OL-365 (n=163) 44
Day OL-729 (n=4) 0
51.Secondary Outcome
Title OL; Number of Participants With Clinical Remission Over Time
Hide Description The Mayo Scoring system ranges from 0 - 12 points and is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Higher Mayo scores indicate greater severity of disease. Clinical remission is defined as a Mayo score of ≤ 2 points with no individual subscore exceeding 1 point.
Time Frame Day OL-1 through Day OL-729
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 infusion of open-label study medication at any time were included in the efficacy analyses of the OL. Number of Participants Analyzed=all participants in OL; n=number of evaluable participants.
Arm/Group Title ABA ~10 mg/kg, OL
Hide Arm/Group Description:
During OL, abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered) every 28 days beginning Day OL-1.
Overall Number of Participants Analyzed 347
Measure Type: Number
Unit of Measure: participants
Day OL-365 (n=163) 18
Day OL-729 (n=4) 0
52.Secondary Outcome
Title OL; Number of Participants With Mayo Endoscopic Subscores Indicating Mucosal Healing (≤1 Point) During OL
Hide Description The Mayo Scoring system ranges from 0 - 12 points and is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Higher Mayo scores indicate greater severity of disease. Mucosal healing was defined as endoscopic subscore ≤ 1 point
Time Frame Open-Label Period (Day OL-1 through Day OL-729)
Hide Outcome Measure Data
Hide Analysis Population Description
Due to the early termination of the study after preliminary IP1C results were reviewed and the primary efficacy endpoint was not achieved, the secondary subgroup analyses of mucosal healing was not conducted for the OL as planned.
Arm/Group Title ABA ~10 mg/kg, MP Placebo, MP
Hide Arm/Group Description:
During MP, abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered) every 28 days beginning Day MP-1.
During the MP, placebo was administered IV every 28 days beginning Day MP-1 through Day MP-337.
Overall Number of Participants Analyzed 17 12
Measure Type: Number
Unit of Measure: participants
0 0
53.Secondary Outcome
Title OL; Number of Participants With Clinical Response or Clinical Remission Upon Retreatment With Abatacept Among Those Who Received Abatacept in the IP or MP Period
Hide Description The Mayo Scoring system (range 0-12 points, high scores=greater severity of disease) is a composite index consisting of 4 disease variables (stool frequency, rectal bleeding, endoscopy evaluation, and Physician's Global Assessment). Clinical response=reduction from baseline in the Mayo score of ≥ 3 points and ≥ 30%, with accompanying decrease in the rectal bleeding subscore of ≥ 1 point or absolute rectal bleeding subscore of ≤ 1 point. Clinical remission = Mayo score of ≤ 2 points with no individual subscore exceeding 1 point. Change from Baseline= post-Baseline - Baseline value.
Time Frame Last Study Visit (Day OL-729)
Hide Outcome Measure Data
Hide Analysis Population Description
Due to the early termination of the study after preliminary IP1C results were reviewed and the primary efficacy endpoint was not achieved, the secondary subgroup analyses of clinical efficacy upon retreatment with abatacept among participants who received study drug during the IP or MP was not conducted for the OL as planned.
Arm/Group Title ABA ~10 mg/kg, OL
Hide Arm/Group Description:
During OL, abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered) every 28 days beginning Day OL-1.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
54.Secondary Outcome
Title OL; Number of Participants With Abatacept-Induced Antibodies
Hide Description A electrochemiluminescent immunoassay screened sera for drug-specific antibodies, immunocompetition was used to identify specific anti-Abatacept reactivity. CTLA4 and Possibly Ig category=reactivity against extracellular domain of human CTLA4, constant regions of human IgG1, or both (CTLA4Ig; Abatacept molecule). Ig and/or Junction category=reactivity against constant regions and/or hinge region of human IgG1. Drug-induced seropositivity was defined as a post-baseline titer higher than Baseline, or any post-baseline positivity if Baseline value was missing.
Time Frame For participants receiving OL medication, all measurements starting after Day OL-1 (including follow-up visits and at 56 and 85 days after last dose)
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects with at least one post-baseline immunogenicity measurement during the study period were included in the immunogenicity data set. "Positive" was defined as "positive post-baseline IP-1" and with a titer value greater than the baseline titer value. Participants with missing baseline titer were assumed "negative" at baseline.
Arm/Group Title ABA ~10 mg/kg, OL
Hide Arm/Group Description:
During OL, abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered) every 28 days beginning Day OL-1.
Overall Number of Participants Analyzed 324
Measure Type: Number
Unit of Measure: participants
Total 66
CTLA4/Possibly Ig 59
Ig and/or Ig Junction 11
55.Secondary Outcome
Title OL; Number of Participants Using Corticosteroids During OL
Hide Description Participants taking oral corticosteroids (equivalent of ≤ 30 mg prednisone daily) must have met minimum treatment duration at entry into IP and had stable dose for ≥2 weeks prior to entry into the IP.
Time Frame Day OL-1 through Day OL-729
Hide Outcome Measure Data
Hide Analysis Population Description
Due to the early termination of the study after preliminary IP1C results were reviewed and the primary efficacy endpoint was not achieved, the secondary subgroup analyses of corticosteroid use was not conducted for the OL as planned.
Arm/Group Title ABA ~10 mg/kg, OL
Hide Arm/Group Description:
During OL, abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered) every 28 days beginning Day OL-1.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title ABA 30/~10 mg/kg,IP1C ABA 30/~10mg/kg,IP2C ABA 3 mg/kg,IP1C ABA ~10 mg/kg,IP1C ABA ~10mg/kg,IP2C ABA ~10mg/kg, MP ABA ~10 mg/kg, OL Placebo, IP1C Placebo, MP
Hide Arm/Group Description During IP, abatacept was administered intravenously (IV) on Days IP-1 and IP-15 at a dose of 30 mg/kg (fixed dose). On Days IP-29 and IP-57, abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered). During IP, abatacept was administered intravenously (IV) on Days IP-1 and IP-15 at a dose of 30 mg/kg (fixed dose). On Days IP-29 and IP-57, abatacept was administered IV at a dose of ~10 mg/kg. During IP, abatacept was administered IV on Days IP-1, IP-15, IP-29, and IP-57 at a dose of 3 mg/kg (fixed dose). During IP, abatacept was administered IV on Days IP-1,IP-15, IP-29, and IP-57 at a dose of ~10 mg/kg (weight-tiered). During IP, abatacept was administered IV on Days IP-1,IP-15, IP-29, and IP-57 at a dose of ~10 mg/kg (weight-tiered). During MP, abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered) every 28 days beginning Day MP-1. During OL, abatacept was administered IV at a dose of ~10 mg/kg (weight-tiered) every 28 days beginning Day OL-1. During the IP, placebo was administered IV on Days IP-1, IP-15, IP-29, and IP-57. During the MP, placebo was administered IV every 28 days beginning Day MP-1 through Day MP-337.
All-Cause Mortality
ABA 30/~10 mg/kg,IP1C ABA 30/~10mg/kg,IP2C ABA 3 mg/kg,IP1C ABA ~10 mg/kg,IP1C ABA ~10mg/kg,IP2C ABA ~10mg/kg, MP ABA ~10 mg/kg, OL Placebo, IP1C Placebo, MP
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
ABA 30/~10 mg/kg,IP1C ABA 30/~10mg/kg,IP2C ABA 3 mg/kg,IP1C ABA ~10 mg/kg,IP1C ABA ~10mg/kg,IP2C ABA ~10mg/kg, MP ABA ~10 mg/kg, OL Placebo, IP1C Placebo, MP
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   22/141 (15.60%)   6/51 (11.76%)   8/70 (11.43%)   20/139 (14.39%)   4/50 (8.00%)   7/65 (10.77%)   66/349 (18.91%)   7/140 (5.00%)   4/66 (6.06%) 
Blood and lymphatic system disorders                   
ANAEMIA  1  2/141 (1.42%)  1/51 (1.96%)  0/70 (0.00%)  1/139 (0.72%)  0/50 (0.00%)  0/65 (0.00%)  2/349 (0.57%)  0/140 (0.00%)  0/66 (0.00%) 
IRON DEFICIENCY ANAEMIA  1  0/141 (0.00%)  0/51 (0.00%)  0/70 (0.00%)  0/139 (0.00%)  0/50 (0.00%)  0/65 (0.00%)  1/349 (0.29%)  0/140 (0.00%)  0/66 (0.00%) 
Cardiac disorders                   
MYOCARDIAL INFARCTION  1  0/141 (0.00%)  0/51 (0.00%)  0/70 (0.00%)  0/139 (0.00%)  0/50 (0.00%)  0/65 (0.00%)  1/349 (0.29%)  0/140 (0.00%)  0/66 (0.00%) 
ACUTE CORONARY SYNDROME  1  0/141 (0.00%)  0/51 (0.00%)  0/70 (0.00%)  0/139 (0.00%)  0/50 (0.00%)  0/65 (0.00%)  1/349 (0.29%)  0/140 (0.00%)  0/66 (0.00%) 
Eye disorders                   
VISION BLURRED  1  1/141 (0.71%)  0/51 (0.00%)  0/70 (0.00%)  0/139 (0.00%)  0/50 (0.00%)  0/65 (0.00%)  0/349 (0.00%)  0/140 (0.00%)  0/66 (0.00%) 
Gastrointestinal disorders                   
COLITIS  1  0/141 (0.00%)  0/51 (0.00%)  0/70 (0.00%)  2/139 (1.44%)  0/50 (0.00%)  0/65 (0.00%)  1/349 (0.29%)  0/140 (0.00%)  0/66 (0.00%) 
DIARRHOEA  1  2/141 (1.42%)  0/51 (0.00%)  0/70 (0.00%)  0/139 (0.00%)  0/50 (0.00%)  0/65 (0.00%)  2/349 (0.57%)  0/140 (0.00%)  0/66 (0.00%) 
PROCTALGIA  1  1/141 (0.71%)  0/51 (0.00%)  0/70 (0.00%)  0/139 (0.00%)  0/50 (0.00%)  0/65 (0.00%)  0/349 (0.00%)  0/140 (0.00%)  0/66 (0.00%) 
PANCREATITIS  1  0/141 (0.00%)  0/51 (0.00%)  0/70 (0.00%)  0/139 (0.00%)  0/50 (0.00%)  0/65 (0.00%)  1/349 (0.29%)  0/140 (0.00%)  0/66 (0.00%) 
ABDOMINAL PAIN  1  0/141 (0.00%)  1/51 (1.96%)  0/70 (0.00%)  0/139 (0.00%)  0/50 (0.00%)  0/65 (0.00%)  0/349 (0.00%)  0/140 (0.00%)  0/66 (0.00%) 
CROHN'S DISEASE  1  0/141 (0.00%)  0/51 (0.00%)  0/70 (0.00%)  1/139 (0.72%)  0/50 (0.00%)  0/65 (0.00%)  0/349 (0.00%)  0/140 (0.00%)  0/66 (0.00%) 
COLITIS ULCERATIVE  1  13/141 (9.22%)  5/51 (9.80%)  5/70 (7.14%)  14/139 (10.07%)  4/50 (8.00%)  3/65 (4.62%)  42/349 (12.03%)  4/140 (2.86%)  1/66 (1.52%) 
RECTAL HAEMORRHAGE  1  1/141 (0.71%)  0/51 (0.00%)  0/70 (0.00%)  0/139 (0.00%)  0/50 (0.00%)  0/65 (0.00%)  1/349 (0.29%)  0/140 (0.00%)  0/66 (0.00%) 
ABDOMINAL PAIN LOWER  1  0/141 (0.00%)  0/51 (0.00%)  1/70 (1.43%)  0/139 (0.00%)  0/50 (0.00%)  0/65 (0.00%)  1/349 (0.29%)  0/140 (0.00%)  0/66 (0.00%) 
ABDOMINAL PAIN UPPER  1  0/141 (0.00%)  1/51 (1.96%)  0/70 (0.00%)  0/139 (0.00%)  0/50 (0.00%)  0/65 (0.00%)  0/349 (0.00%)  0/140 (0.00%)  0/66 (0.00%) 
General disorders                   
MALAISE  1  0/141 (0.00%)  0/51 (0.00%)  0/70 (0.00%)  0/139 (0.00%)  0/50 (0.00%)  0/65 (0.00%)  1/349 (0.29%)  0/140 (0.00%)  0/66 (0.00%) 
PYREXIA  1  0/141 (0.00%)  0/51 (0.00%)  0/70 (0.00%)  0/139 (0.00%)  0/50 (0.00%)  0/65 (0.00%)  1/349 (0.29%)  0/140 (0.00%)  0/66 (0.00%) 
ASTHENIA  1  0/141 (0.00%)  0/51 (0.00%)  1/70 (1.43%)  0/139 (0.00%)  0/50 (0.00%)  0/65 (0.00%)  0/349 (0.00%)  0/140 (0.00%)  0/66 (0.00%) 
INFUSION RELATED REACTION  1  0/141 (0.00%)  0/51 (0.00%)  0/70 (0.00%)  1/139 (0.72%)  0/50 (0.00%)  0/65 (0.00%)  0/349 (0.00%)  0/140 (0.00%)  0/66 (0.00%) 
Hepatobiliary disorders                   
CHOLECYSTITIS  1  0/141 (0.00%)  0/51 (0.00%)  0/70 (0.00%)  1/139 (0.72%)  0/50 (0.00%)  0/65 (0.00%)  0/349 (0.00%)  0/140 (0.00%)  0/66 (0.00%) 
HEPATIC FUNCTION ABNORMAL  1  0/141 (0.00%)  0/51 (0.00%)  0/70 (0.00%)  0/139 (0.00%)  0/50 (0.00%)  0/65 (0.00%)  1/349 (0.29%)  0/140 (0.00%)  0/66 (0.00%) 
Immune system disorders                   
HYPERSENSITIVITY  1  1/141 (0.71%)  0/51 (0.00%)  0/70 (0.00%)  0/139 (0.00%)  0/50 (0.00%)  0/65 (0.00%)  0/349 (0.00%)  0/140 (0.00%)  0/66 (0.00%) 
ANAPHYLACTIC REACTION  1  0/141 (0.00%)  0/51 (0.00%)  0/70 (0.00%)  0/139 (0.00%)  0/50 (0.00%)  0/65 (0.00%)  0/349 (0.00%)  1/140 (0.71%)  0/66 (0.00%) 
Infections and infestations                   
SEPSIS  1  0/141 (0.00%)  0/51 (0.00%)  0/70 (0.00%)  0/139 (0.00%)  0/50 (0.00%)  1/65 (1.54%)  1/349 (0.29%)  0/140 (0.00%)  0/66 (0.00%) 
VIRAEMIA  1  0/141 (0.00%)  0/51 (0.00%)  0/70 (0.00%)  0/139 (0.00%)  0/50 (0.00%)  0/65 (0.00%)  1/349 (0.29%)  0/140 (0.00%)  1/66 (1.52%) 
PNEUMONIA  1  1/141 (0.71%)  0/51 (0.00%)  0/70 (0.00%)  0/139 (0.00%)  0/50 (0.00%)  1/65 (1.54%)  1/349 (0.29%)  0/140 (0.00%)  0/66 (0.00%) 
SINUSITIS  1  0/141 (0.00%)  0/51 (0.00%)  0/70 (0.00%)  0/139 (0.00%)  0/50 (0.00%)  0/65 (0.00%)  1/349 (0.29%)  0/140 (0.00%)  0/66 (0.00%) 
VARICELLA  1  0/141 (0.00%)  0/51 (0.00%)  0/70 (0.00%)  0/139 (0.00%)  0/50 (0.00%)  1/65 (1.54%)  0/349 (0.00%)  0/140 (0.00%)  0/66 (0.00%) 
LISTERIOSIS  1  0/141 (0.00%)  0/51 (0.00%)  0/70 (0.00%)  0/139 (0.00%)  0/50 (0.00%)  0/65 (0.00%)  1/349 (0.29%)  0/140 (0.00%)  0/66 (0.00%) 
ANAL ABSCESS  1  0/141 (0.00%)  0/51 (0.00%)  0/70 (0.00%)  0/139 (0.00%)  0/50 (0.00%)  1/65 (1.54%)  0/349 (0.00%)  0/140 (0.00%)  0/66 (0.00%) 
APPENDICITIS  1  0/141 (0.00%)  0/51 (0.00%)  0/70 (0.00%)  0/139 (0.00%)  0/50 (0.00%)  1/65 (1.54%)  0/349 (0.00%)  0/140 (0.00%)  0/66 (0.00%) 
OTITIS MEDIA  1  0/141 (0.00%)  0/51 (0.00%)  0/70 (0.00%)  0/139 (0.00%)  0/50 (0.00%)  0/65 (0.00%)  1/349 (0.29%)  0/140 (0.00%)  0/66 (0.00%) 
SEPTIC SHOCK  1  1/141 (0.71%)  0/51 (0.00%)  0/70 (0.00%)  0/139 (0.00%)  0/50 (0.00%)  0/65 (0.00%)  0/349 (0.00%)  0/140 (0.00%)  0/66 (0.00%) 
HERPES ZOSTER  1  0/141 (0.00%)  0/51 (0.00%)  0/70 (0.00%)  0/139 (0.00%)  0/50 (0.00%)  0/65 (0.00%)  1/349 (0.29%)  0/140 (0.00%)  0/66 (0.00%) 
HIV INFECTION  1  0/141 (0.00%)  0/51 (0.00%)  0/70 (0.00%)  0/139 (0.00%)  0/50 (0.00%)  0/65 (0.00%)  1/349 (0.29%)  0/140 (0.00%)  0/66 (0.00%) 
PILONIDAL CYST  1  0/141 (0.00%)  0/51 (0.00%)  0/70 (0.00%)  0/139 (0.00%)  0/50 (0.00%)  0/65 (0.00%)  1/349 (0.29%)  0/140 (0.00%)  0/66 (0.00%) 
GASTROENTERITIS  1  1/141 (0.71%)  0/51 (0.00%)  0/70 (0.00%)  0/139 (0.00%)  0/50 (0.00%)  0/65 (0.00%)  1/349 (0.29%)  0/140 (0.00%)  0/66 (0.00%) 
LOBAR PNEUMONIA  1  0/141 (0.00%)  0/51 (0.00%)  0/70 (0.00%)  0/139 (0.00%)  0/50 (0.00%)  0/65 (0.00%)  1/349 (0.29%)  0/140 (0.00%)  0/66 (0.00%) 
VIRAL INFECTION  1  0/141 (0.00%)  0/51 (0.00%)  1/70 (1.43%)  0/139 (0.00%)  0/50 (0.00%)  0/65 (0.00%)  0/349 (0.00%)  0/140 (0.00%)  0/66 (0.00%) 
PELVIC INFECTION  1  0/141 (0.00%)  0/51 (0.00%)  0/70 (0.00%)  0/139 (0.00%)  0/50 (0.00%)  0/65 (0.00%)  1/349 (0.29%)  0/140 (0.00%)  0/66 (0.00%) 
ABDOMINAL ABSCESS  1  2/141 (1.42%)  0/51 (0.00%)  0/70 (0.00%)  0/139 (0.00%)  0/50 (0.00%)  0/65 (0.00%)  0/349 (0.00%)  0/140 (0.00%)  0/66 (0.00%) 
OTITIS MEDIA CHRONIC  1  0/141 (0.00%)  0/51 (0.00%)  0/70 (0.00%)  0/139 (0.00%)  0/50 (0.00%)  0/65 (0.00%)  0/349 (0.00%)  0/140 (0.00%)  1/66 (1.52%) 
CLOSTRIDIAL INFECTION  1  0/141 (0.00%)  0/51 (0.00%)  0/70 (0.00%)  0/139 (0.00%)  0/50 (0.00%)  1/65 (1.54%)  0/349 (0.00%)  0/140 (0.00%)  0/66 (0.00%) 
PNEUMONIA HERPES VIRAL  1  0/141 (0.00%)  0/51 (0.00%)  0/70 (0.00%)  0/139 (0.00%)  0/50 (0.00%)  1/65 (1.54%)  0/349 (0.00%)  0/140 (0.00%)  0/66 (0.00%) 
CYTOMEGALOVIRUS COLITIS  1  0/141 (0.00%)  0/51 (0.00%)  0/70 (0.00%)  0/139 (0.00%)  0/50 (0.00%)  0/65 (0.00%)  1/349 (0.29%)  0/140 (0.00%)  0/66 (0.00%) 
URINARY TRACT INFECTION  1  1/141 (0.71%)  0/51 (0.00%)  0/70 (0.00%)  0/139 (0.00%)  0/50 (0.00%)  0/65 (0.00%)  0/349 (0.00%)  0/140 (0.00%)  0/66 (0.00%) 
CLOSTRIDIUM DIFFICILE COLITIS  1  0/141 (0.00%)  0/51 (0.00%)  0/70 (0.00%)  0/139 (0.00%)  0/50 (0.00%)  0/65 (0.00%)  1/349 (0.29%)  0/140 (0.00%)  0/66 (0.00%) 
Injury, poisoning and procedural complications                   
ALCOHOL POISONING  1  0/141 (0.00%)  0/51 (0.00%)  0/70 (0.00%)  0/139 (0.00%)  0/50 (0.00%)  0/65 (0.00%)  1/349 (0.29%)  0/140 (0.00%)  0/66 (0.00%) 
ARTERIAL RESTENOSIS  1  0/141 (0.00%)  0/51 (0.00%)  0/70 (0.00%)  0/139 (0.00%)  0/50 (0.00%)  0/65 (0.00%)  1/349 (0.29%)  0/140 (0.00%)  0/66 (0.00%) 
ABDOMINAL WOUND DEHISCENCE  1  0/141 (0.00%)  0/51 (0.00%)  0/70 (0.00%)  1/139 (0.72%)  0/50 (0.00%)  0/65 (0.00%)  0/349 (0.00%)  0/140 (0.00%)  0/66 (0.00%) 
Investigations                   
HAEMOGLOBIN DECREASED  1  0/141 (0.00%)  0/51 (0.00%)  0/70 (0.00%)  0/139 (0.00%)  0/50 (0.00%)  0/65 (0.00%)  1/349 (0.29%)  0/140 (0.00%)  0/66 (0.00%) 
HEPATIC ENZYME INCREASED  1  0/141 (0.00%)  0/51 (0.00%)  0/70 (0.00%)  0/139 (0.00%)  0/50 (0.00%)  0/65 (0.00%)  0/349 (0.00%)  1/140 (0.71%)  0/66 (0.00%) 
Metabolism and nutrition disorders                   
DEHYDRATION  1  1/141 (0.71%)  0/51 (0.00%)  0/70 (0.00%)  0/139 (0.00%)  0/50 (0.00%)  0/65 (0.00%)  0/349 (0.00%)  1/140 (0.71%)  0/66 (0.00%) 
MALNUTRITION  1  1/141 (0.71%)  0/51 (0.00%)  0/70 (0.00%)  0/139 (0.00%)  0/50 (0.00%)  0/65 (0.00%)  0/349 (0.00%)  0/140 (0.00%)  0/66 (0.00%) 
Musculoskeletal and connective tissue disorders                   
BACK PAIN  1  0/141 (0.00%)  0/51 (0.00%)  0/70 (0.00%)  0/139 (0.00%)  0/50 (0.00%)  0/65 (0.00%)  1/349 (0.29%)  0/140 (0.00%)  0/66 (0.00%) 
ARTHRALGIA  1  0/141 (0.00%)  0/51 (0.00%)  0/70 (0.00%)  0/139 (0.00%)  0/50 (0.00%)  0/65 (0.00%)  1/349 (0.29%)  0/140 (0.00%)  0/66 (0.00%) 
FIBROMYALGIA  1  0/141 (0.00%)  0/51 (0.00%)  0/70 (0.00%)  1/139 (0.72%)  0/50 (0.00%)  0/65 (0.00%)  0/349 (0.00%)  0/140 (0.00%)  0/66 (0.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)                   
BREAST CANCER  1  0/141 (0.00%)  0/51 (0.00%)  0/70 (0.00%)  0/139 (0.00%)  0/50 (0.00%)  0/65 (0.00%)  0/349 (0.00%)  0/140 (0.00%)  1/66 (1.52%) 
BOWEN'S DISEASE  1  0/141 (0.00%)  0/51 (0.00%)  0/70 (0.00%)  0/139 (0.00%)  0/50 (0.00%)  0/65 (0.00%)  1/349 (0.29%)  0/140 (0.00%)  0/66 (0.00%) 
MALIGNANT MELANOMA  1  0/141 (0.00%)  0/51 (0.00%)  0/70 (0.00%)  0/139 (0.00%)  0/50 (0.00%)  0/65 (0.00%)  0/349 (0.00%)  1/140 (0.71%)  0/66 (0.00%) 
BASAL CELL CARCINOMA  1  1/141 (0.71%)  0/51 (0.00%)  0/70 (0.00%)  0/139 (0.00%)  0/50 (0.00%)  0/65 (0.00%)  2/349 (0.57%)  0/140 (0.00%)  0/66 (0.00%) 
CHRONIC MYELOID LEUKAEMIA  1  0/141 (0.00%)  0/51 (0.00%)  0/70 (0.00%)  0/139 (0.00%)  0/50 (0.00%)  0/65 (0.00%)  1/349 (0.29%)  0/140 (0.00%)  0/66 (0.00%) 
SQUAMOUS CELL CARCINOMA OF SKIN  1  0/141 (0.00%)  0/51 (0.00%)  0/70 (0.00%)  0/139 (0.00%)  0/50 (0.00%)  0/65 (0.00%)  1/349 (0.29%)  0/140 (0.00%)  0/66 (0.00%) 
Nervous system disorders                   
DIZZINESS  1  1/141 (0.71%)  0/51 (0.00%)  0/70 (0.00%)  0/139 (0.00%)  0/50 (0.00%)  0/65 (0.00%)  0/349 (0.00%)  0/140 (0.00%)  0/66 (0.00%) 
CEREBRAL ISCHAEMIA  1  0/141 (0.00%)  0/51 (0.00%)  0/70 (0.00%)  0/139 (0.00%)  0/50 (0.00%)  0/65 (0.00%)  1/349 (0.29%)  0/140 (0.00%)  0/66 (0.00%) 
Psychiatric disorders                   
ABNORMAL BEHAVIOUR  1  0/141 (0.00%)  0/51 (0.00%)  0/70 (0.00%)  0/139 (0.00%)  0/50 (0.00%)  0/65 (0.00%)  1/349 (0.29%)  0/140 (0.00%)  0/66 (0.00%) 
PERSONALITY CHANGE  1  0/141 (0.00%)  0/51 (0.00%)  0/70 (0.00%)  0/139 (0.00%)  0/50 (0.00%)  0/65 (0.00%)  1/349 (0.29%)  0/140 (0.00%)  0/66 (0.00%) 
Renal and urinary disorders                   
NEPHROLITHIASIS  1  0/141 (0.00%)