BMS-188667 in Children and Adolescents With Juvenile Rheumatoid Arthritis
Sponsor
Bristol-Myers Squibb (Industry)
Overall Status
Completed
CT.gov ID
NCT00095173
Collaborator
(none)
214
36
3
95
5.9
0.1
Study Details
Study Description
Brief Summary
The primary purpose of the clinical research study is to assess the safety of treating children and juvenile subjects with BMS-188667 (Abatacept). In addition, the study will assess the effectiveness of BMS-188667 in reducing disease activity of Juvenile Rheumatoid Arthritis (JRA) or Juvenile Idiopathic Arthritis (JIA) as measured by the time to occurrence of disease flare.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
214 participants
Allocation:
Randomized
Intervention Model:
Single Group Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Phase III, Multi-Center, Multi-National, Randomized Withdrawal Study to Evaluate the Safety and Efficacy of BMS-188667 in Children and Adolescents With Active Polyarticular Juvenile Rheumatoid Arthritis (JRA)
Study Start Date
:
Dec 1, 2003
Actual Primary Completion Date
:
Jun 1, 2006
Actual Study Completion Date
:
Nov 1, 2011
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Abatacept Double Blind Period |
Drug: Abatacept
IV infusions, IV, 10mg/kg body weight, every 4 weeks, 6 months (unless a disease flare discontinued the patient earlier).
Other Names:
|
| Placebo Comparator: Placebo Double Blind Period |
Drug: Placebo
IV infusions, IV, N/A, every 4 weeks, 6 months.
|
| Experimental: Abatacept - Open Label
|
Drug: Abatacept
Solution, intravenous, Approximately 10 mg/kg fixed dose, based on subject's body weight; 500 mg for subjects weighing < 60kg; 750 mg for subjects weighing 60 to 100 kg; and 1 gram for subjects weighing > 100 kg, monthly
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Time to Occurrence of Juvenile Rheumatoid Arthritis/Juvenile Idiopathic Arthritis (JRA/JIA) Disease Flare During Double-Blind Phase (Period B) [Period B (Day 113 to Day 282)]
Time to flare is defined as the elapsed number of days between the first dose date in Period B and the study day that disease flare is confirmed. All of the following criteria must be met to be defined as a flare: > 30% worsening in at least 3 of the 6 JRA/JIA core response variables > 30% improvement in not more than 1 of the 6 JRA/JIA core set variables ≥ 2 cm of worsening must be present if the Physician or Parent Global Assessment is used to define flare worsening in ≥ 2 joints must be present if the number of active joints or joints with limitation of motion is used to define flare based on changes in the surrogate marker, erythrocyte sedimentation rate (ESR)
Secondary Outcome Measures
- Number of Participants With a Juvenile Rheumatoid Arthritis/Juvenile Idiopathic Arthritis (JRA/JIA) Disease With a Flare During Double-Blind Phase (Period B) [Period B (Day 113 to Day 282)]
All of the following criteria must be met to be defined as a flare: > 30% worsening in at least 3 of the 6 JRA/JIA core response variables > 30% improvement in not more than 1 of the 6 JRA/JIA core set variables ≥ 2 cm of worsening must be present if the Physician or Parent Global Assessment is used to define flare worsening in ≥ 2 joints must be present if the number of active joints or joints with limitation of motion is used to define flare based on changes in the surrogate marker, erythrocyte sedimentation rate (ESR)
- Number of Participants With Serious Adverse Events (SAEs), Treatment-Related AEs, Deaths, Discontinuation of Study Drug Due to AEs During Open-Label Lead-In Phase (Period A) [Period A (Day 1 to Day 113)]
AE=any new unfavorable symptom, sign or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity or drug dependency/abuse; is life-threatening, an important medical event or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible or missing relationship to study drug. Death=during the study and up to 28 days past study discontinuation. The select AEs were determined using the Medical Dictionary for Regulatory Activities (MedDRA, v14.1).
- Number of Participants With Serious Adverse Events (SAEs), Treatment-Related AEs, Deaths, Discontinuation of Study Drug Due to AEs During Double-Blind Phase (Period B) [Period B (Day 113 to Day 282)]
AE=any new unfavorable symptom, sign or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity or drug dependency/abuse; is life-threatening, an important medical event or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible or missing relationship to study drug. Death=during the study and up to 28 days past study discontinuation. The select AEs were determined using the Medical Dictionary for Regulatory Activities (MedDRA, v14.1).
- Number of Participants With Serious Adverse Events (SAEs), Treatment-Related AEs, Deaths, Discontinuation of Study Drug Due to AEs During Open-Label Phase (Period C) [Period C (Day 282 to end of study)]
AE=any new unfavorable symptom, sign or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity or drug dependency/abuse; is life-threatening, an important medical event or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible or missing relationship to study drug. Death=during the study and up to 85 days past study discontinuation. The select AEs were determined using the Medical Dictionary for Regulatory Activities (MedDRA, v14.1).
- Median Percent Change From Baseline in JRA/JIA Core Set Variables During Double-Blind Phase (Period B) [Period B (Day 113 to Day 282)]
Percent change from baseline was calculated from the difference between post-baseline and baseline divided by baseline multiplied by 100 and reported as the range between 25th and 75th percentile, not full range; American College of Rheumatology (ACR) Pediatric 30 JRA/JIA core set variables include active joints, limited range of motion, physician global assessment of disease severity, parent global assessment of overall well-being, change in physical function as measured by the Childhood Health Assessment Questionnaire (CHAQ), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Disease activity was assessed by the physician and parent on a 0-100 mm visual analog scale (VAS). Low values represent low severity of disease and good well-being whereas high values represent highly severe disease and very poor well-being.
- Median Percent Change From Baseline in JRA/JIA Core Set Variables During Open-Label Phase (Period C) [Period C (Day 282 to end of study)]
Percent change from baseline was calculated from the difference between post-baseline and baseline divided by baseline multiplied by 100 and reported as the range between 25th and 75th percentile, not full range; American College of Rheumatology (ACR) Pediatric 30 JRA/JIA core set variables include active joints, limited range of motion, physician's global assessment of disease severity, parent global assessment of overall well-being, change in physical function as measured by the Childhood Health Assessment Questionnaire (CHAQ), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Disease activity was assessed by the physician and parent on a 0-100 mm visual analog scale (VAS). Low values represent low severity of disease and good well-being whereas high values represent highly severe disease and very poor well-being.
- Events of Special Interest During Open-Label Lead-In Phase (Period A), Including Infections, Peri-Infusional Adverse Events (AEs), Autoimmune Disorders and Malignancies [Period A (Day 1 to Day 113)]
The sponsor prospectively identified categories of AEs that may be associated with the use of immunomodulatory drugs including infections, peri-infusional AEs, autoimmune disorders, malignancies. Peri-infusional AEs are defined as those AEs of special interest occurring during the first 24 hours after the start of study drug infusion. Malignancies definitions were based on events in the MedDRA Maintenance and Support Services Organization (MSSO) malignancies Structured MedDRA Query (SMQ).Autoimmune disorders are in alignment with the pre-specified MedDRA codes of autoimmune disorders events of interest.
- Events of Special Interest During Double-Blind Phase (Period B), Including Infections, Peri-Infusional Adverse Events (AEs), Autoimmune Disorders and Malignancies [Period B (Day 113 to Day 282)]
The sponsor prospectively identified categories of AEs that may be associated with the use of immunomodulatory drugs including infections, peri-infusional AEs, autoimmune disorders, malignancies. Peri-infusional AEs are defined as those AEs of special interest occurring during the first 24 hours after the start of study drug infusion. Malignancies definitions were based on events in the MedDRA Maintenance and Support Services Organization (MSSO) malignancies Structured MedDRA Query (SMQ).Autoimmune disorders are in alignment with the pre-specified MedDRA codes of autoimmune disorders events of interest.
- Events of Special Interest During Open-Label Phase (Period C), Including Infections, Peri-Infusional Adverse Events (AEs), Autoimmune Disorders and Malignancies [Period C (Day 282 up to 56 days after the last dose of study medication)]
The sponsor prospectively identified categories of AEs that may be associated with the use of immunomodulatory drugs including infections, peri-infusional AEs, autoimmune disorders, malignancies. Peri-infusional AEs are defined as those AEs of special interest occurring during the first 24 hours after the start of study drug infusion. Malignancies definitions were based on events in the MedDRA Maintenance and Support Services Organization (MSSO) malignancies Structured MedDRA Query (SMQ).Autoimmune disorders are in alignment with the pre-specified MedDRA codes of autoimmune disorders events of interest.
- Percentage of Participants Achieving American College of Rheumatology (ACR) Pediatric 30 (ACRP30), ACR Pediatric 50, ACR Pediatric 70, ACR Pediatric 90, and Inactive Disease Status Erythrocyte Sedimentation Rate (ESR) Response Rate [Day 113, Day 282, and Day 2047]
The ACRP30 response criteria were defined as a ≥ 30% improvement over baseline in ESR. ACRP 50, 70, and 90 responses were defined similarly with 50%, 70%, and 90% improvements required, respectively.
- Number of Treated Participants With Marked Laboratory Abnormalities During Open-Label Lead-In Phase (Period A) [Period A (Day 1 to Day 113)]
Marked abnormalities were pre-defined as changes in lab tests that occurred after drug infusion and were reported relative to the normal range for each analyte. Hemoglobin, 11.6-14.8 grams per deciliter (g/dL);Hematocrit, 36.0-50.0 percent;Erythrocytes, 3.80-5.10x10*6 cells per microliter (c/uL);Platelets, 140-44 cells per liter (c/L);Leukocytes, 4.00-12.50 c/uL;Absolute Neutrophils + Bands, if <1.00x10^3 c/uL;Absolute Lymphocytes, if <0.72x10^3 or >7.50x10^3 c/uL;Absolute Eosinophils, if >0.750X10^3 c/uL;Alanine Aminotransferase, 0-40 units per liter (U/L);G-Glutamyl Transferase, 0-60 U/L;Bilirubin, 0.1-1.2 milligrams per deciliter (mg/dL);Blood Urea Nitrogen, 5.9-26.0 mg/dL;Creatinine, 0.50-1.50 mg/dL;Serum Potassium, 3.5-5.5 milliequivalents per liter (mEq/L);Serum Glucose, 65-99 mg/dL;Fasting Serum Glucose, 65-99 mg/dL;Total Protein, 6.0-8.5 g/dL;Albumin, 3.5-5.5 g/dL;Urine Protein, >=4;Urine Glucose, >=4;Urine Blood, >=4;Urine Red Blood Cells >=4;Urine White Blood Cells, >=4.
- Number of Treated Participants With Marked Laboratory Abnormalities During Double-Blind Phase (Period B) [Period B (Day 113 to Day 282)]
Marked abnormalities were pre-defined as changes in lab tests that occurred after drug infusion and were reported relative to the normal range for each analyte. Hemoglobin, 11.6-14.8 grams per deciliter (g/dL);Hematocrit, 36.0-50.0 percent;Erythrocytes, 3.80-5.10x10*6 cells per microliter (c/uL);Platelets, 140-44 cells per liter (c/L);Leukocytes, 4.00-12.50 c/uL;Absolute Neutrophils + Bands, if <1.00x10^3 c/uL;Absolute Lymphocytes, if <0.72x10^3 or >7.50x10^3 c/uL;Absolute Eosinophils, if >0.750X10^3 c/uL;Aspartate Aminotransferase, 0-40 units per liter (U/L); Alanine Aminotransferase, 0-40 U/L;Blood Urea Nitrogen, 5.9-26.0 mg/dL;Serum Sodium, 135-148 milliequivalents per liter (mEq/L);Serum Potassium, 3.5-5.5 mEq/L;Serum Glucose, 65-99 mg/dL;Fasting Serum Glucose, 65-99 mg/dL;Urine Protein, >=4;Urine Blood, >=4;Urine Red Blood Cells >=4;Urine White Blood Cells, >=4.
- Number of Treated Participants With Marked Laboratory Abnormalities During Open-Label Phase (Period C) [Period C (Day 282 to end of study)]
Marked abnormalities were pre-defined as changes in lab tests after drug infusion and relative to normal range. Hemoglobin,11.6-14.8grams per deciliter(g/dL);Hematocrit,36.0-50.0 percent;Erythrocytes,3.80-5.10x10*6 cells per microliter(c/uL);Platelets,140-44 cells per liter(c/L);Leukocytes,4.00-12.50c/uL;Absolute(Abs)Neutrophils+Bands,<1.00x10^3 c/uL;Abs Lymphocytes,<0.72x10^3 or>7.50x10^3 c/uL;Abs Eosinophils,>0.750X10^3 c/uL;Alkaline Phosphatase,0-40 units per liter(U/L);Aspartate Aminotransferase,0-40 U/L;Alanine Aminotransferase,0-40U/L;G-Glutamyl Transferase,0-60 U/L;Bilirubin, 0.1-1.2 milligrams per deciliter(mg/dL);Blood Urea Nitrogen,5.9-26.0 mg/dL;Creatinine, 0.50-1.50mg/dL;Inorganic Phosphorus,2.8-6.2 U/L;Serum Potassium,3.5-5.5 milliequivalents per liter(mEq/L);Serum Glucose,65-99 mg/dL;Fasting Serum Glucose,65-99 mg/dL;Total Protein, 6.0-8.5 g/dL;Albumin,3.5-5.5 g/dL;Urine Protein,>=4;Urine Glucose,>=4;Urine Blood,>=4;Urine Red Blood Cells>=4;Urine White Blood Cells,>=4.
- Number of Participants With Anti-Abatacept or Anti-CTLA4 Positive Responses Over Time During Open-Label Phase (Period C) [Period C (Day 282 to 85 days after the last dose of study medication)]
During Period C, blood samples for immunogenicity assessments were obtained just prior to the start of the IV infusion of abatacept at 3-month intervals during the first 2 years of Period C, at 6-month intervals thereafter, and again 28, 56, and 85 days after the last infusion. Direct-format, enzyme-linked immunosorbent assays (ELISAs) were used to evaluate the cytotoxic T-lymphocyte antigen 4 (CTLA4) and the anti-CTLA4-T antibody.
Eligibility Criteria
Criteria
Ages Eligible for Study:
6 Years
to 17 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Diagnosis of Juvenile Rheumatoid Arthritis or Juvenile Idiopathic Arthritis;
-
Current active arthritis;
-
Failed treatment with at least one disease modifying anti-rheumatic drug (DMARD);
-
Subjects must discontinue use of any DMARD other than methotrexate prior to the first dose of study medication
Exclusion Criteria:
-
Presence of infection or history of frequent acute or chronic infections;
-
Joint replacement surgery required during the study or history of surgery on more than 5 joints;
-
Live vaccines within 3 months of the first dose of study medication;
-
Unresolved serious bacterial infection or chronic bacterial infection;
-
Subjects who currently have intermittent fever due to JRA/JIA, rheumatoid rash, hepato-splenomegaly, pleuritis, pericarditis, or macrophage activation syndrome.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Omaha | Nebraska | United States | ||
| 2 | Livingston | New Jersey | United States | ||
| 3 | New Hyde Park | New York | United States | ||
| 4 | Valhalla | New York | United States | ||
| 5 | Cincinnati | Ohio | United States | ||
| 6 | Cleveland | Ohio | United States | ||
| 7 | Duncansville | Pennsylvania | United States | ||
| 8 | Dallas | Texas | United States | ||
| 9 | Seattle | Washington | United States | ||
| 10 | Milwaukee | Wisconsin | United States | ||
| 11 | Local Institution | Bregenz | Austria | ||
| 12 | Local Institution | Botucatu | Brazil | ||
| 13 | Local Institution | Rio de Janeiro | Brazil | ||
| 14 | Local Institution | Sao Paulo | Brazil | ||
| 15 | Local Institution | Paris | France | ||
| 16 | Local Institution | Strasbourg | France | ||
| 17 | Local Institution | Berlin | Germany | ||
| 18 | Local Institution | Bremen | Germany | ||
| 19 | Local Institution | Halle | Germany | ||
| 20 | Local Institution | Hamburg | Germany | ||
| 21 | Local Institution | Firenze | Italy | ||
| 22 | Local Institution | Genova | Italy | ||
| 23 | Local Institution | Milano | Italy | ||
| 24 | Local Institution | Napoli | Italy | ||
| 25 | Local Institution | Roma | Italy | ||
| 26 | Local Institution | Trieste | Italy | ||
| 27 | Local Institution | Guadalajara | Mexico | ||
| 28 | Local Institution | Mexico City | Mexico | ||
| 29 | Local Institution | Monterrey | Mexico | ||
| 30 | Local Institution | Puebla | Mexico | ||
| 31 | Local Institution | San Luis Potosi | Mexico | ||
| 32 | Local Institution | Lima | Peru | ||
| 33 | Local Institution | Lisboa | Portugal | ||
| 34 | Local Institution | La Coruna | Spain | ||
| 35 | Local Institution | Valencia | Spain | ||
| 36 | Local Institution | Lausanne | Switzerland |
Sponsors and Collaborators
- Bristol-Myers Squibb
Investigators
- Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00095173
Other Study ID Numbers:
- IM101-033
First Posted:
Nov 2, 2004
Last Update Posted:
Jan 18, 2017
Last Verified:
Nov 1, 2016
Keywords provided by Bristol-Myers Squibb
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | 214 enrolled; in Per A, 190 treated; 24 not treated due to screening failures.170 completed Per A, 123 responders qualified to enter Per B. One subject did not enter Per B; 122 responders were randomized, 60 abatacept and 62 placebo. 36 of 47 Per A non-responders re-entered at Per C. Protocol violation occurred; 5yr old participant. |
| Arm/Group Title | Abatacept (All Participants in Period A) | Abatacept (Period B) | Placebo (Period B) | Abatacept (Period A Non-Responders in Period C) | Abatacept (Period C) | Placebo (Period B) to Abatacept (Period C) |
|---|---|---|---|---|---|---|
| Arm/Group Description | Abatacept: 10 milligram per kilogram body weight (mg/kg), limited to a maximum 1000 mg for participants weighing >100kg; solution infused intravenously (IV), over 90 minutes, once every 2 weeks for 3 doses. | Abatacept: 10 milligram per kilogram body weight (mg/kg), limited to a maximum 1000 mg for participants weighing >100kg; solution infused intravenously (IV), over 90 minutes, once a month for 6 months or until they experienced a flare (Period B). | Placebo: Dextrose 5% in water (D5W) or normal saline (NS) IV infusion, once every 2 weeks for 3 doses, then monthly up to 6 months. Participants were seated or in supine position during infusion. | Participants not eligible to continue into Period B but re-entered in Period C. Abatacept: 10 milligram per kilogram body weight (mg/kg), limited to a maximum 1000 mg for participants weighing >100kg; solution infused intravenously (IV), over 90 minutes, once every two weeks for three doses (Period A) or once a month for up to 5 years (Period C). | Abatacept: 10 milligram per kilogram body weight (mg/kg), limited to a maximum 1000 mg for participants weighing >100kg; solution infused intravenously (IV), over 90 minutes, once a month for up to 5 years. | Participants from Period B Placebo group entering Period C. Abatacept: 10 milligram per kilogram body weight (mg/kg), limited to a maximum 1000 mg for participants weighing >100kg; solution infused intravenously (IV), over 90 minutes, once a month for up to 5 years. |
| Period Title: Open-Label Lead-In Phase (Period A) | ||||||
| STARTED | 190 | 0 | 0 | 0 | 0 | 0 |
| COMPLETED | 170 | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 20 | 0 | 0 | 0 | 0 | 0 |
| Period Title: Open-Label Lead-In Phase (Period A) | ||||||
| STARTED | 0 | 60 | 62 | 0 | 0 | 0 |
| COMPLETED | 0 | 49 | 31 | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 11 | 31 | 0 | 0 | 0 |
| Period Title: Open-Label Lead-In Phase (Period A) | ||||||
| STARTED | 0 | 0 | 0 | 36 | 58 | 59 |
| COMPLETED | 0 | 0 | 0 | 13 | 29 | 27 |
| NOT COMPLETED | 0 | 0 | 0 | 23 | 29 | 32 |
Baseline Characteristics
| Arm/Group Title | Abatacept (All Participants in Period A) |
|---|---|
| Arm/Group Description | Abatacept: 10 milligram per kilogram body weight (mg/kg), limited to a maximum 1000 mg for participants weighing >100kg; solution infused intravenously (IV), over 90 minutes,once every 2 weeks for 3 doses, then monthly up to 6 months unless a disease flare discontinued the patient earlier. |
| Overall Participants | 190 |
| Age (years) [Median (Full Range) ] | |
| Median (Full Range) [years] |
13.0
|
| Gender (Count of Participants) | |
| Female |
137
72.1%
|
| Male |
53
27.9%
|
Outcome Measures
| Title | Time to Occurrence of Juvenile Rheumatoid Arthritis/Juvenile Idiopathic Arthritis (JRA/JIA) Disease Flare During Double-Blind Phase (Period B) |
|---|---|
| Description | Time to flare is defined as the elapsed number of days between the first dose date in Period B and the study day that disease flare is confirmed. All of the following criteria must be met to be defined as a flare: > 30% worsening in at least 3 of the 6 JRA/JIA core response variables > 30% improvement in not more than 1 of the 6 JRA/JIA core set variables ≥ 2 cm of worsening must be present if the Physician or Parent Global Assessment is used to define flare worsening in ≥ 2 joints must be present if the number of active joints or joints with limitation of motion is used to define flare based on changes in the surrogate marker, erythrocyte sedimentation rate (ESR) |
| Time Frame | Period B (Day 113 to Day 282) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All treated participants |
| Arm/Group Title | Abatacept (Period B) | Placebo (Period B) |
|---|---|---|
| Arm/Group Description | Abatacept: 10 milligram per kilogram body weight (mg/kg), limited to a maximum 1000 mg for participants weighing >100kg; solution infused intravenously (IV), over 90 minutes, once a month for 6 months or until they experienced a flare. | Placebo: Dextrose 5% in water (D5W) or normal saline (NS) IV infusion, once every 2 weeks for 3 doses, then monthly up to 6 months. Participants were seated or in supine position during infusion. |
| Measure Participants | 60 | 62 |
| Median (Full Range) [months] |
NA
|
6
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Abatacept (Period B), Placebo (Period B) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.0002 |
| Comments | ||
| Method | Log Rank | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Hazard Ratio (HR) |
| Estimated Value | 0.31 | |
| Confidence Interval |
(2-Sided) 95% 0.16 to 0.59 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | Abatacept over placebo | |
| Title | Number of Participants With a Juvenile Rheumatoid Arthritis/Juvenile Idiopathic Arthritis (JRA/JIA) Disease With a Flare During Double-Blind Phase (Period B) |
|---|---|
| Description | All of the following criteria must be met to be defined as a flare: > 30% worsening in at least 3 of the 6 JRA/JIA core response variables > 30% improvement in not more than 1 of the 6 JRA/JIA core set variables ≥ 2 cm of worsening must be present if the Physician or Parent Global Assessment is used to define flare worsening in ≥ 2 joints must be present if the number of active joints or joints with limitation of motion is used to define flare based on changes in the surrogate marker, erythrocyte sedimentation rate (ESR) |
| Time Frame | Period B (Day 113 to Day 282) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All treated participants |
| Arm/Group Title | Abatacept (Period B) | Placebo (Period B) |
|---|---|---|
| Arm/Group Description | Abatacept: 10 milligram per kilogram body weight (mg/kg), limited to a maximum 1000 mg for participants weighing >100kg; solution infused intravenously (IV), over 90 minutes, once a month for 6 months or until they experienced a flare. | Placebo: Dextrose 5% in water (D5W) or normal saline (NS) IV infusion, once every 2 weeks for 3 doses, then monthly up to 6 months. Participants were seated or in supine position during infusion. |
| Measure Participants | 60 | 62 |
| Number [participants] |
12
6.3%
|
33
NaN
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Abatacept (Period B), Placebo (Period B) |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | <0.001 |
| Comments | ||
| Method | Chi-squared | |
| Comments | ||
| Title | Number of Participants With Serious Adverse Events (SAEs), Treatment-Related AEs, Deaths, Discontinuation of Study Drug Due to AEs During Open-Label Lead-In Phase (Period A) |
|---|---|
| Description | AE=any new unfavorable symptom, sign or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity or drug dependency/abuse; is life-threatening, an important medical event or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible or missing relationship to study drug. Death=during the study and up to 28 days past study discontinuation. The select AEs were determined using the Medical Dictionary for Regulatory Activities (MedDRA, v14.1). |
| Time Frame | Period A (Day 1 to Day 113) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All treated participants in Periods A |
| Arm/Group Title | Abatacept (All Participants in Period A) |
|---|---|
| Arm/Group Description | Abatacept: 10 milligram per kilogram body weight (mg/kg), limited to a maximum 1000 mg for participants weighing >100kg; solution infused intravenously (IV), over 90 minutes, once every 2 weeks for 3 doses. |
| Measure Participants | 190 |
| SAE |
6
3.2%
|
| Treatment-Related AE |
0
0%
|
| All Deaths |
0
0%
|
| Treatment-Related Deaths |
0
0%
|
| Discontinuation of Study Drug due to AEs |
1
0.5%
|
| Title | Number of Participants With Serious Adverse Events (SAEs), Treatment-Related AEs, Deaths, Discontinuation of Study Drug Due to AEs During Double-Blind Phase (Period B) |
|---|---|
| Description | AE=any new unfavorable symptom, sign or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity or drug dependency/abuse; is life-threatening, an important medical event or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible or missing relationship to study drug. Death=during the study and up to 28 days past study discontinuation. The select AEs were determined using the Medical Dictionary for Regulatory Activities (MedDRA, v14.1). |
| Time Frame | Period B (Day 113 to Day 282) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All treated participants in Periods B |
| Arm/Group Title | Abatacept (Period B) | Placebo (Period B) |
|---|---|---|
| Arm/Group Description | Abatacept: 10 milligram per kilogram body weight (mg/kg), limited to a maximum 1000 mg for participants weighing >100kg; solution infused intravenously (IV), over 90 minutes, once a month for 6 months or until they experienced a flare. | Placebo: Dextrose 5% in water (D5W) or normal saline (NS) IV infusion, once every 2 weeks for 3 doses, then monthly up to 6 months. Participants were seated or in supine position during infusion. |
| Measure Participants | 60 | 62 |
| SAE |
0
0%
|
2
NaN
|
| Treatment-Related AE |
0
0%
|
0
NaN
|
| All Deaths |
0
0%
|
0
NaN
|
| Treatment-Related Deaths |
0
0%
|
0
NaN
|
| Discontinuation of Study Drug due to AEs |
0
0%
|
0
NaN
|
| Title | Number of Participants With Serious Adverse Events (SAEs), Treatment-Related AEs, Deaths, Discontinuation of Study Drug Due to AEs During Open-Label Phase (Period C) |
|---|---|
| Description | AE=any new unfavorable symptom, sign or disease or worsening of a preexisting condition that may not have a causal relationship with treatment. SAE=a medical event that at any dose results in death, persistent or significant disability/incapacity or drug dependency/abuse; is life-threatening, an important medical event or a congenital anomaly/birth defect; or requires or prolongs hospitalization. Treatment-related=having certain, probable, possible or missing relationship to study drug. Death=during the study and up to 85 days past study discontinuation. The select AEs were determined using the Medical Dictionary for Regulatory Activities (MedDRA, v14.1). |
| Time Frame | Period C (Day 282 to end of study) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All treated participants in Period C |
| Arm/Group Title | Abatacept (Period A Non-Responders in Period C) | Abatacept (Period C) | Placebo (Period B) to Abatacept (Period C) |
|---|---|---|---|
| Arm/Group Description | Participants not eligible to continue into Period B but re-entered in Period C. Abatacept: 10 milligram per kilogram body weight (mg/kg), limited to a maximum 1000 mg for participants weighing >100kg; solution infused intravenously (IV), over 90 minutes, once every two weeks for three doses (Period A) and once a month for up to 5 years (Period C). | Abatacept: 10 milligram per kilogram body weight (mg/kg), limited to a maximum 1000 mg for participants weighing >100kg; solution infused intravenously (IV), over 90 minutes, once a month for up to 5 years. | Participants from Period B Placebo group entering Period C. Abatacept: 10 milligram per kilogram body weight (mg/kg), limited to a maximum 1000 mg for participants weighing >100kg; solution infused intravenously (IV), over 90 minutes, once a month for up to 5 years. |
| Measure Participants | 36 | 58 | 59 |
| SAE |
9
4.7%
|
9
NaN
|
12
NaN
|
| Treatment-Related AE |
2
1.1%
|
4
NaN
|
3
NaN
|
| All Deaths |
0
0%
|
0
NaN
|
1
NaN
|
| Treatment-Related Deaths |
0
0%
|
0
NaN
|
0
NaN
|
| Discontinuation of Study Drug due to AEs |
1
0.5%
|
2
NaN
|
3
NaN
|
| Title | Median Percent Change From Baseline in JRA/JIA Core Set Variables During Double-Blind Phase (Period B) |
|---|---|
| Description | Percent change from baseline was calculated from the difference between post-baseline and baseline divided by baseline multiplied by 100 and reported as the range between 25th and 75th percentile, not full range; American College of Rheumatology (ACR) Pediatric 30 JRA/JIA core set variables include active joints, limited range of motion, physician global assessment of disease severity, parent global assessment of overall well-being, change in physical function as measured by the Childhood Health Assessment Questionnaire (CHAQ), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Disease activity was assessed by the physician and parent on a 0-100 mm visual analog scale (VAS). Low values represent low severity of disease and good well-being whereas high values represent highly severe disease and very poor well-being. |
| Time Frame | Period B (Day 113 to Day 282) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All treated participants in Period B |
| Arm/Group Title | Abatacept (Period B) | Placebo (Period B) |
|---|---|---|
| Arm/Group Description | Abatacept: 10 milligram per kilogram body weight (mg/kg), limited to a maximum 1000 mg for participants weighing >100kg; solution infused intravenously (IV), over 90 minutes, once a month for 6 months or until they experienced a flare. | Placebo: Dextrose 5% in water (D5W) or normal saline (NS) IV infusion, once every 2 weeks for 3 doses, then monthly up to 6 months. Participants were seated or in supine position during infusion. |
| Measure Participants | 60 | 62 |
| Active Joints |
-20.9
|
50.00
|
| Joints with LOM |
0.00
|
50.00
|
| Physician Global Assessment |
-29.8
|
55.95
|
| Parent Global Assessment |
-11.2
|
8.39
|
| CHAQ Disability Index |
0.00
|
0.00
|
| ESR |
0.00
|
20.50
|
| CRP |
0.00
|
6.25
|
| Title | Median Percent Change From Baseline in JRA/JIA Core Set Variables During Open-Label Phase (Period C) |
|---|---|
| Description | Percent change from baseline was calculated from the difference between post-baseline and baseline divided by baseline multiplied by 100 and reported as the range between 25th and 75th percentile, not full range; American College of Rheumatology (ACR) Pediatric 30 JRA/JIA core set variables include active joints, limited range of motion, physician's global assessment of disease severity, parent global assessment of overall well-being, change in physical function as measured by the Childhood Health Assessment Questionnaire (CHAQ), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). Disease activity was assessed by the physician and parent on a 0-100 mm visual analog scale (VAS). Low values represent low severity of disease and good well-being whereas high values represent highly severe disease and very poor well-being. |
| Time Frame | Period C (Day 282 to end of study) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All treated participants in Period C |
| Arm/Group Title | Abatacept (Period A Non-Responders in Period C) | Abatacept (Period C) | Placebo (Period B) to Abatacept (Period C) |
|---|---|---|---|
| Arm/Group Description | Participants not eligible to continue into Period B but re-entered in Period C. Abatacept: 10 milligram per kilogram body weight (mg/kg), limited to a maximum 1000 mg for participants weighing >100kg; solution infused intravenously (IV), over 90 minutes, once every two weeks for three doses (Period A) and once a month for up to 5 years (Period C). | Abatacept: 10 milligram per kilogram body weight (mg/kg), limited to a maximum 1000 mg for participants weighing >100kg; solution infused intravenously (IV), over 90 minutes, once a month for up to 5 years. | Participants from Period B Placebo group entering Period C. Abatacept: 10 milligram per kilogram body weight (mg/kg), limited to a maximum 1000 mg for participants weighing >100kg; solution infused intravenously (IV), over 90 minutes, once a month for up to 5 years. |
| Measure Participants | 36 | 58 | 59 |
| Active Joints |
-26.7
|
-70.2
|
-82.4
|
| Joints with Limited Range of Motion |
0.00
|
-50.0
|
-71.4
|
| Physician Global Assessment of Disease Severity |
-31.9
|
-75.0
|
-81.8
|
| Parent Global Assessment of Overall Well-Being |
1.96
|
-62.7
|
-63.9
|
| CHAQ Disability Index |
14.14
|
-56.7
|
-45.5
|
| ESR |
20.87
|
-27.3
|
-24.2
|
| CRP |
0.00
|
-33.8
|
-27.8
|
| Title | Events of Special Interest During Open-Label Lead-In Phase (Period A), Including Infections, Peri-Infusional Adverse Events (AEs), Autoimmune Disorders and Malignancies |
|---|---|
| Description | The sponsor prospectively identified categories of AEs that may be associated with the use of immunomodulatory drugs including infections, peri-infusional AEs, autoimmune disorders, malignancies. Peri-infusional AEs are defined as those AEs of special interest occurring during the first 24 hours after the start of study drug infusion. Malignancies definitions were based on events in the MedDRA Maintenance and Support Services Organization (MSSO) malignancies Structured MedDRA Query (SMQ).Autoimmune disorders are in alignment with the pre-specified MedDRA codes of autoimmune disorders events of interest. |
| Time Frame | Period A (Day 1 to Day 113) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All treated participants in Period A |
| Arm/Group Title | Abatacept (All Participants in Period A) |
|---|---|
| Arm/Group Description | Abatacept: 10 milligram per kilogram body weight (mg/kg), limited to a maximum 1000 mg for participants weighing >100kg; solution infused intravenously (IV), over 90 minutes, once every 2 weeks for 3 doses. |
| Measure Participants | 190 |
| Infections and Infestations |
68
35.8%
|
| Peri-Infusional AEs |
30
15.8%
|
| Autoimmune Disorders |
2
1.1%
|
| Malignancies |
0
0%
|
| Title | Events of Special Interest During Double-Blind Phase (Period B), Including Infections, Peri-Infusional Adverse Events (AEs), Autoimmune Disorders and Malignancies |
|---|---|
| Description | The sponsor prospectively identified categories of AEs that may be associated with the use of immunomodulatory drugs including infections, peri-infusional AEs, autoimmune disorders, malignancies. Peri-infusional AEs are defined as those AEs of special interest occurring during the first 24 hours after the start of study drug infusion. Malignancies definitions were based on events in the MedDRA Maintenance and Support Services Organization (MSSO) malignancies Structured MedDRA Query (SMQ).Autoimmune disorders are in alignment with the pre-specified MedDRA codes of autoimmune disorders events of interest. |
| Time Frame | Period B (Day 113 to Day 282) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All treated participants in Period B |
| Arm/Group Title | Abatacept (Period B) | Placebo (Period B) |
|---|---|---|
| Arm/Group Description | Abatacept: 10 milligram per kilogram body weight (mg/kg), limited to a maximum 1000 mg for participants weighing >100kg; solution infused intravenously (IV), over 90 minutes, once a month for 6 months or until they experienced a flare. | Placebo: Dextrose 5% in water (D5W) or normal saline (NS) IV infusion, once every 2 weeks for 3 doses, then monthly up to 6 months. Participants were seated or in supine position during infusion. |
| Measure Participants | 60 | 62 |
| Infections and Infestations |
27
14.2%
|
27
NaN
|
| Peri-Infusional AEs |
2
1.1%
|
2
NaN
|
| Autoimmune Disorders |
0
0%
|
0
NaN
|
| Malignancies |
0
0%
|
0
NaN
|
| Title | Events of Special Interest During Open-Label Phase (Period C), Including Infections, Peri-Infusional Adverse Events (AEs), Autoimmune Disorders and Malignancies |
|---|---|
| Description | The sponsor prospectively identified categories of AEs that may be associated with the use of immunomodulatory drugs including infections, peri-infusional AEs, autoimmune disorders, malignancies. Peri-infusional AEs are defined as those AEs of special interest occurring during the first 24 hours after the start of study drug infusion. Malignancies definitions were based on events in the MedDRA Maintenance and Support Services Organization (MSSO) malignancies Structured MedDRA Query (SMQ).Autoimmune disorders are in alignment with the pre-specified MedDRA codes of autoimmune disorders events of interest. |
| Time Frame | Period C (Day 282 up to 56 days after the last dose of study medication) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All treated participants in Period C |
| Arm/Group Title | Abatacept (All Participants in Period C) |
|---|---|
| Arm/Group Description | Abatacept: 10 milligram per kilogram body weight (mg/kg), limited to a maximum 1000 mg for participants weighing >100kg; solution infused intravenously (IV), over 90 minutes, once a month for up to 5 years. |
| Measure Participants | 153 |
| Infections and Infestations |
120
63.2%
|
| Peri-Infusional AEs |
22
11.6%
|
| Autoimmune Disorders |
7
3.7%
|
| Malignancies |
1
0.5%
|
| Title | Percentage of Participants Achieving American College of Rheumatology (ACR) Pediatric 30 (ACRP30), ACR Pediatric 50, ACR Pediatric 70, ACR Pediatric 90, and Inactive Disease Status Erythrocyte Sedimentation Rate (ESR) Response Rate |
|---|---|
| Description | The ACRP30 response criteria were defined as a ≥ 30% improvement over baseline in ESR. ACRP 50, 70, and 90 responses were defined similarly with 50%, 70%, and 90% improvements required, respectively. |
| Time Frame | Day 113, Day 282, and Day 2047 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All treated participants |
| Arm/Group Title | Abatacept (Period A Non-Responders in Period C) | Abatacept (Period C) | Placebo (Period B) to Abatacept (Period C) |
|---|---|---|---|
| Arm/Group Description | Participants not eligible to continue into Period B but re-entered in Period C. Abatacept: 10 milligram per kilogram body weight (mg/kg), limited to a maximum 1000 mg for participants weighing >100kg; solution infused intravenously (IV), over 90 minutes, once every two weeks for three doses (Period A) and once a month for up to 5 years (Period C). | Abatacept: 10 milligram per kilogram body weight (mg/kg), limited to a maximum 1000 mg for participants weighing >100kg; solution infused intravenously (IV), over 90 minutes, once a month for up to 5 years. | Participants from Period B Placebo group entering Period C. Abatacept: 10 milligram per kilogram body weight (mg/kg), limited to a maximum 1000 mg for participants weighing >100kg; solution infused intravenously (IV), over 90 minutes, once a month for up to 5 years. |
| Measure Participants | 36 | 58 | 59 |
| ACR Pediatric 30 (ESR) at Day 113 |
0
0%
|
100
NaN
|
100
NaN
|
| ACR Pediatric 30 (ESR) at Day 282 |
NA
NaN
|
84.5
NaN
|
67.8
NaN
|
| ACR Pediatric 30 (ESR) at Day 2047 |
69.2
36.4%
|
97.0
NaN
|
86.7
NaN
|
| ACR Pediatric 50 (ESR) at Day 113 |
0
0%
|
65.5
NaN
|
88.1
NaN
|
| ACR Pediatric 50 (ESR) at Day 282 |
NA
NaN
|
79.3
NaN
|
52.5
NaN
|
| ACR Pediatric 50 (ESR) at Day 2047 |
69.2
36.4%
|
93.9
NaN
|
80.0
NaN
|
| ACR Pediatric 70 (ESR) at Day 113 |
0
0%
|
37.9
NaN
|
49.2
NaN
|
| ACR Pediatric 70 (ESR) at Day 282 |
NA
NaN
|
55.2
NaN
|
30.5
NaN
|
| ACR Pediatric 70 (ESR) at Day 2047 |
53.8
28.3%
|
78.8
NaN
|
63.3
NaN
|
| ACR Pediatric 90 (ESR) at Day 113 |
0
0%
|
17.2
NaN
|
22.0
NaN
|
| ACR Pediatric 90 (ESR) at Day 282 |
NA
NaN
|
41.4
NaN
|
15.3
NaN
|
| ACR Pediatric 90 (ESR) at Day 2047 |
38.5
20.3%
|
66.7
NaN
|
40.0
NaN
|
| Title | Number of Treated Participants With Marked Laboratory Abnormalities During Open-Label Lead-In Phase (Period A) |
|---|---|
| Description | Marked abnormalities were pre-defined as changes in lab tests that occurred after drug infusion and were reported relative to the normal range for each analyte. Hemoglobin, 11.6-14.8 grams per deciliter (g/dL);Hematocrit, 36.0-50.0 percent;Erythrocytes, 3.80-5.10x10*6 cells per microliter (c/uL);Platelets, 140-44 cells per liter (c/L);Leukocytes, 4.00-12.50 c/uL;Absolute Neutrophils + Bands, if <1.00x10^3 c/uL;Absolute Lymphocytes, if <0.72x10^3 or >7.50x10^3 c/uL;Absolute Eosinophils, if >0.750X10^3 c/uL;Alanine Aminotransferase, 0-40 units per liter (U/L);G-Glutamyl Transferase, 0-60 U/L;Bilirubin, 0.1-1.2 milligrams per deciliter (mg/dL);Blood Urea Nitrogen, 5.9-26.0 mg/dL;Creatinine, 0.50-1.50 mg/dL;Serum Potassium, 3.5-5.5 milliequivalents per liter (mEq/L);Serum Glucose, 65-99 mg/dL;Fasting Serum Glucose, 65-99 mg/dL;Total Protein, 6.0-8.5 g/dL;Albumin, 3.5-5.5 g/dL;Urine Protein, >=4;Urine Glucose, >=4;Urine Blood, >=4;Urine Red Blood Cells >=4;Urine White Blood Cells, >=4. |
| Time Frame | Period A (Day 1 to Day 113) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All treated participants in Period C evaluated for a specific analyte. |
| Arm/Group Title | Abatacept (All Participants in Period A) |
|---|---|
| Arm/Group Description | Abatacept: 10 milligram per kilogram body weight (mg/kg), limited to a maximum 1000 mg for participants weighing >100kg; solution infused intravenously (IV), over 90 minutes, once every two weeks for three doses. |
| Measure Participants | 190 |
| Hemoglobin (Low) n=189 |
2
1.1%
|
| Hematocrit (Low) n=189 |
2
1.1%
|
| Erythrocytes (Low) n=189 |
1
0.5%
|
| Platelets (Low) n=189 |
1
0.5%
|
| Platelet Count (High) n=189 |
2
1.1%
|
| Leukocytes (Low) n=189 |
9
4.7%
|
| Leukocytes (High) n=189 |
10
5.3%
|
| Absolute Neutrophils + Bands (Low) n=189 |
5
2.6%
|
| Absolute Lymphocytes (Low) n=189 |
9
4.7%
|
| Absolute Eosinophils (High) n=189 |
16
8.4%
|
| Alanine Aminotransferase (ALT, High) n=190 |
2
1.1%
|
| G-Glutamyl Transferase (GGT, High) n=190 |
1
0.5%
|
| Bilirubin (Total, High) n=190 |
1
0.5%
|
| Blood Urea Nitrogen (High) n=190 |
6
3.2%
|
| Creatinine (High) n=190 |
12
6.3%
|
| Potassium (High) n=190 |
4
2.1%
|
| Serum Glucose (Low) n=190 |
26
13.7%
|
| Serum Glucose (High) n=190 |
2
1.1%
|
| Fasting Serum Glucose (High) n=109 |
1
0.5%
|
| Total Protein (High) n=190 |
2
1.1%
|
| Albumin (Low) n=190 |
2
1.1%
|
| Urine Protein (High) n=190 |
12
6.3%
|
| Urine Glucose (High) n=190 |
1
0.5%
|
| Urine Blood (High) n=190 |
23
12.1%
|
| Urine White Blood Cells (High) n=75 |
9
4.7%
|
| Urine Red Blood Cells (High) n=75 |
25
13.2%
|
| Title | Number of Treated Participants With Marked Laboratory Abnormalities During Double-Blind Phase (Period B) |
|---|---|
| Description | Marked abnormalities were pre-defined as changes in lab tests that occurred after drug infusion and were reported relative to the normal range for each analyte. Hemoglobin, 11.6-14.8 grams per deciliter (g/dL);Hematocrit, 36.0-50.0 percent;Erythrocytes, 3.80-5.10x10*6 cells per microliter (c/uL);Platelets, 140-44 cells per liter (c/L);Leukocytes, 4.00-12.50 c/uL;Absolute Neutrophils + Bands, if <1.00x10^3 c/uL;Absolute Lymphocytes, if <0.72x10^3 or >7.50x10^3 c/uL;Absolute Eosinophils, if >0.750X10^3 c/uL;Aspartate Aminotransferase, 0-40 units per liter (U/L); Alanine Aminotransferase, 0-40 U/L;Blood Urea Nitrogen, 5.9-26.0 mg/dL;Serum Sodium, 135-148 milliequivalents per liter (mEq/L);Serum Potassium, 3.5-5.5 mEq/L;Serum Glucose, 65-99 mg/dL;Fasting Serum Glucose, 65-99 mg/dL;Urine Protein, >=4;Urine Blood, >=4;Urine Red Blood Cells >=4;Urine White Blood Cells, >=4. |
| Time Frame | Period B (Day 113 to Day 282) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All treated participants in Period B evaluated for a specific analyte. |
| Arm/Group Title | Abatacept (Period B) | Placebo (Period B) |
|---|---|---|
| Arm/Group Description | Abatacept: 10 milligram per kilogram body weight (mg/kg), limited to a maximum 1000 mg for participants weighing >100kg; solution infused intravenously (IV), over 90 minutes, once a month for 6 months or until they experienced a flare. | Placebo: Dextrose 5% in water (D5W) or normal saline (NS) IV infusion, once every 2 weeks for 3 doses, then monthly up to 6 months. Participants were seated or in supine position during infusion. |
| Measure Participants | 60 | 62 |
| Hemoglobin (Low) n=60, 61 |
1
0.5%
|
1
NaN
|
| Hematocrit (Low) n=60, 61 |
1
0.5%
|
1
NaN
|
| Erythrocytes (Low) n=60, 61 |
0
0%
|
1
NaN
|
| Platelets (Low) n-60, 61 |
4
2.1%
|
0
NaN
|
| Platelets (High) n=189 |
0
0%
|
1
NaN
|
| Leukocytes (Low) n=60, 61 |
1
0.5%
|
1
NaN
|
| Leukocytes (High) n=60, 61 |
1
0.5%
|
2
NaN
|
| Absolute Neutrophils + Bands (Low) n=60, 62 |
0
0%
|
1
NaN
|
| Absolute Lymphocytes (Low) n=60, 62 |
2
1.1%
|
3
NaN
|
| Absolute Eosinophils (High) n=60, 62 |
6
3.2%
|
4
NaN
|
| Aspartate Aminotransferase (AST, High) n=60, 62 |
1
0.5%
|
0
NaN
|
| Alanine Aminotransferase (ALT, High) n=60, 62 |
1
0.5%
|
0
NaN
|
| Blood Urea Nitrogen (High) n=60, 62 |
1
0.5%
|
1
NaN
|
| Serum Sodium (Low) n=60, 62 |
0
0%
|
1
NaN
|
| Serum Potassium (High) n=60, 62 |
2
1.1%
|
0
NaN
|
| Serum Glucose (Low) n=60, 62 |
4
2.1%
|
5
NaN
|
| Serum Glucose (High) n=60, 62 |
0
0%
|
1
NaN
|
| Fasting Serum Glucose (High) n=60, 62 |
1
0.5%
|
1
NaN
|
| Urine Protein (High) n=62 |
2
1.1%
|
2
NaN
|
| Urine Blood (High) n=60, 62 |
12
6.3%
|
6
NaN
|
| Urine White Blood Cells (High) n=24, 20 |
5
2.6%
|
2
NaN
|
| Urine Red Blood Cells (High) n=24, 20 |
6
3.2%
|
4
NaN
|
| Title | Number of Treated Participants With Marked Laboratory Abnormalities During Open-Label Phase (Period C) |
|---|---|
| Description | Marked abnormalities were pre-defined as changes in lab tests after drug infusion and relative to normal range. Hemoglobin,11.6-14.8grams per deciliter(g/dL);Hematocrit,36.0-50.0 percent;Erythrocytes,3.80-5.10x10*6 cells per microliter(c/uL);Platelets,140-44 cells per liter(c/L);Leukocytes,4.00-12.50c/uL;Absolute(Abs)Neutrophils+Bands,<1.00x10^3 c/uL;Abs Lymphocytes,<0.72x10^3 or>7.50x10^3 c/uL;Abs Eosinophils,>0.750X10^3 c/uL;Alkaline Phosphatase,0-40 units per liter(U/L);Aspartate Aminotransferase,0-40 U/L;Alanine Aminotransferase,0-40U/L;G-Glutamyl Transferase,0-60 U/L;Bilirubin, 0.1-1.2 milligrams per deciliter(mg/dL);Blood Urea Nitrogen,5.9-26.0 mg/dL;Creatinine, 0.50-1.50mg/dL;Inorganic Phosphorus,2.8-6.2 U/L;Serum Potassium,3.5-5.5 milliequivalents per liter(mEq/L);Serum Glucose,65-99 mg/dL;Fasting Serum Glucose,65-99 mg/dL;Total Protein, 6.0-8.5 g/dL;Albumin,3.5-5.5 g/dL;Urine Protein,>=4;Urine Glucose,>=4;Urine Blood,>=4;Urine Red Blood Cells>=4;Urine White Blood Cells,>=4. |
| Time Frame | Period C (Day 282 to end of study) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All treated participants in Period C evaluated for a specific analyte. |
| Arm/Group Title | Abatacept (All Participants in Period C) |
|---|---|
| Arm/Group Description | Abatacept: 10 milligram per kilogram body weight (mg/kg), limited to a maximum 1000 mg for participants weighing >100kg; solution infused intravenously (IV), over 90 minutes, once a month for up to 5 years. |
| Measure Participants | 153 |
| Hemoglobin (Low) n=153 |
12
6.3%
|
| Hematocrit (Low) n=153 |
8
4.2%
|
| Erythrocytes (Low) n=153 |
4
2.1%
|
| Platelet Count (Low) n=153 |
4
2.1%
|
| Platelet Count (High) n=153 |
5
2.6%
|
| Leukocytes (Low) n=153 |
20
10.5%
|
| Leukocytes (High) n=153 |
18
9.5%
|
| Absolute Neutrophils + Bands (Low) |
14
7.4%
|
| Absolute Lymphocytes (Low) n=153 |
21
11.1%
|
| Absolute Lymphocytes (High) n=153 |
5
2.6%
|
| Absolute Eosinophils (High) n=153 |
50
26.3%
|
| Alkaline Phosphatase (ALP, High) n=153 |
2
1.1%
|
| Aspartate Aminotransferase (AST, High) |
5
2.6%
|
| Alanine Aminotransferase (ALT, High) n=153 |
11
5.8%
|
| G-Glutamyl Transferase (GGT, High) n=153 |
6
3.2%
|
| Bilirubin (Total, High) n=153 |
3
1.6%
|
| Blood Urea Nitrogen (High) n=153 |
15
7.9%
|
| Creatinine (High) n=153 |
36
18.9%
|
| Potassium (High) n=153 |
10
5.3%
|
| Inorganic Phosphorus (High) n=153 |
4
2.1%
|
| Serum Glucose (Low) n=153 |
54
28.4%
|
| Serum Glucose (High) n=153 |
1
0.5%
|
| Fasting Serum Glucose (Low) n=100 |
11
5.8%
|
| Fasting Serum Glucose (High) n=100 |
7
3.7%
|
| Total Protein (Low) n=153 |
1
0.5%
|
| Total Protein (High) n=153 |
1
0.5%
|
| Albumin (Low) n=153 |
9
4.7%
|
| Urine Protein (High) n=153 |
35
18.4%
|
| Urine Glucose (High) n=153 |
1
0.5%
|
| Urine Blood (High) n=153 |
73
38.4%
|
| Urine White Blood Cells (High) n=117 |
49
25.8%
|
| Urine Red Blood Cells (High) n=117 |
86
45.3%
|
| Title | Number of Participants With Anti-Abatacept or Anti-CTLA4 Positive Responses Over Time During Open-Label Phase (Period C) |
|---|---|
| Description | During Period C, blood samples for immunogenicity assessments were obtained just prior to the start of the IV infusion of abatacept at 3-month intervals during the first 2 years of Period C, at 6-month intervals thereafter, and again 28, 56, and 85 days after the last infusion. Direct-format, enzyme-linked immunosorbent assays (ELISAs) were used to evaluate the cytotoxic T-lymphocyte antigen 4 (CTLA4) and the anti-CTLA4-T antibody. |
| Time Frame | Period C (Day 282 to 85 days after the last dose of study medication) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All treated participants who were evaluated for immunogenicity during Period C |
| Arm/Group Title | Abatacept (Period A Non-Responders in Period C) | Abatacept (Period C) | Placebo (Period B) to Abatacept (Period C) |
|---|---|---|---|
| Arm/Group Description | Participants not eligible to continue into Period B but re-entered in Period C. Abatacept: 10 milligram per kilogram body weight (mg/kg), limited to a maximum 1000 mg for participants weighing >100kg; solution infused intravenously (IV), over 90 minutes, once every two weeks for three doses (Period A) and once a month for up to 5 years (Period C). | Abatacept: 10 milligram per kilogram body weight (mg/kg), limited to a maximum 1000 mg for participants weighing >100kg; solution infused intravenously (IV), over 90 minutes, once a month for up to 5 years. | Participants from Period B Placebo group entering Period C. Abatacept: 10 milligram per kilogram body weight (mg/kg), limited to a maximum 1000 mg for participants weighing >100kg; solution infused intravenously (IV), over 90 minutes, once a month for up to 5 years. |
| Measure Participants | 33 | 57 | 58 |
| Anti-Abatacept, Overall on Treatment (n=31,54,54) |
1
0.5%
|
5
NaN
|
2
NaN
|
| Anti-Abatacept, Post-Treatment (n=25,41,38) |
0
0%
|
3
NaN
|
3
NaN
|
| Anti-CTLA4-T, Overall on Treatment (n=33,57,58) |
4
2.1%
|
4
NaN
|
4
NaN
|
| Anti-CTLA4-T, Overall Post-Treatment (n=27,46,42) |
4
2.1%
|
1
NaN
|
1
NaN
|
Adverse Events
| Time Frame | From first dose to last dose plus 56 days up to end of study (November 2011) | |||||||
|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Study initiated: February 2004; Study completed: November 2011 | |||||||
| Arm/Group Title | Abatacept (Only Period A) | Abatacept (Period A/Period C) | Abatacept (Period A/Period B) | Abatacept (Period A)/Placebo (Period B) | ||||
| Arm/Group Description | Participants treated in Period A but did not in Periods B or C. Abatacept: 10 milligram per kilogram body weight (mg/kg), limited to a maximum 1000 mg for participants weighing >100kg; solution infused intravenously (IV), over 90 minutes, once every 2 weeks for 3 doses. | Participants treated in Period A, not eligible to continue into Period B, but re-entered in Period C. Abatacept: 10 milligram per kilogram body weight (mg/kg), limited to a maximum 1000 mg for participants weighing >100kg; solution infused intravenously (IV), over 90 minutes, once every two weeks for three doses (Period A) and once a month for up to 5 years (Period C). | All participants treated with Abatacept in Periods A and B who may or may not have entered Period C. Abatacept: 10 milligram per kilogram body weight (mg/kg), limited to a maximum 1000 mg for participants weighing >100kg; solution infused intravenously (IV), over 90 minutes, once every 2 weeks for 3 doses, then once a month for 6 months. If participants entered Period C, treatment continued once a month for up to 5 years. | All participants treated with Abatacept in Period A, placebo in Period B, who may or may not have entered Period C. Placebo: Dextrose 5% in water (D5W) or normal saline (NS) IV infusion, once every 2 weeks for 3 doses, then monthly up to 6 months. Participants were seated or in supine position during infusion. If participants entered Period C, they were treated with Abatacept,10 milligram per kilogram body weight (mg/kg), limited to a maximum 1000 mg for participants weighing >100kg; solution infused intravenously (IV), over 90 minutes, once a month for up to 5 years. | ||||
All Cause Mortality |
||||||||
| Abatacept (Only Period A) | Abatacept (Period A/Period C) | Abatacept (Period A/Period B) | Abatacept (Period A)/Placebo (Period B) | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||
Serious Adverse Events |
||||||||
| Abatacept (Only Period A) | Abatacept (Period A/Period C) | Abatacept (Period A/Period B) | Abatacept (Period A)/Placebo (Period B) | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 4/32 (12.5%) | 10/36 (27.8%) | 9/60 (15%) | 14/62 (22.6%) | ||||
| Gastrointestinal disorders | ||||||||
| Abdominal pain | 0/32 (0%) | 0/36 (0%) | 1/60 (1.7%) | 0/62 (0%) | ||||
| Vomiting | 0/32 (0%) | 0/36 (0%) | 1/60 (1.7%) | 1/62 (1.6%) | ||||
| Nausea | 0/32 (0%) | 0/36 (0%) | 0/60 (0%) | 1/62 (1.6%) | ||||
| General disorders | ||||||||
| Fatigue | 0/32 (0%) | 0/36 (0%) | 0/60 (0%) | 1/62 (1.6%) | ||||
| Condition aggravated | 0/32 (0%) | 1/36 (2.8%) | 0/60 (0%) | 0/62 (0%) | ||||
| Pyrexia | 0/32 (0%) | 0/36 (0%) | 1/60 (1.7%) | 1/62 (1.6%) | ||||
| Immune system disorders | ||||||||
| Food allergy | 0/32 (0%) | 0/36 (0%) | 0/60 (0%) | 1/62 (1.6%) | ||||
| Hypersensitivity | 0/32 (0%) | 0/36 (0%) | 1/60 (1.7%) | 0/62 (0%) | ||||
| Infections and infestations | ||||||||
| Erysipelas | 0/32 (0%) | 0/36 (0%) | 0/60 (0%) | 1/62 (1.6%) | ||||
| Abscess limb | 0/32 (0%) | 1/36 (2.8%) | 0/60 (0%) | 0/62 (0%) | ||||
| Appendicitis | 0/32 (0%) | 0/36 (0%) | 2/60 (3.3%) | 0/62 (0%) | ||||
| Gastroenteritis | 0/32 (0%) | 0/36 (0%) | 0/60 (0%) | 1/62 (1.6%) | ||||
| Herpes zoster | 0/32 (0%) | 1/36 (2.8%) | 0/60 (0%) | 0/62 (0%) | ||||
| Meningitis bacterial | 0/32 (0%) | 1/36 (2.8%) | 0/60 (0%) | 0/62 (0%) | ||||
| Tooth abscess | 0/32 (0%) | 0/36 (0%) | 1/60 (1.7%) | 0/62 (0%) | ||||
| Arthritis bacterial | 0/32 (0%) | 1/36 (2.8%) | 0/60 (0%) | 1/62 (1.6%) | ||||
| Dengue fever | 0/32 (0%) | 1/36 (2.8%) | 0/60 (0%) | 0/62 (0%) | ||||
| Pyelonephritis | 0/32 (0%) | 1/36 (2.8%) | 1/60 (1.7%) | 0/62 (0%) | ||||
| Varicella | 0/32 (0%) | 1/36 (2.8%) | 0/60 (0%) | 1/62 (1.6%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Joint dislocation | 0/32 (0%) | 0/36 (0%) | 0/60 (0%) | 1/62 (1.6%) | ||||
| Overdose | 0/32 (0%) | 0/36 (0%) | 1/60 (1.7%) | 0/62 (0%) | ||||
| Multiple injuries | 0/32 (0%) | 0/36 (0%) | 0/60 (0%) | 1/62 (1.6%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Type 1 diabetes mellitus | 0/32 (0%) | 0/36 (0%) | 1/60 (1.7%) | 0/62 (0%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Arthritis | 0/32 (0%) | 3/36 (8.3%) | 3/60 (5%) | 0/62 (0%) | ||||
| Foot deformity | 0/32 (0%) | 0/36 (0%) | 1/60 (1.7%) | 1/62 (1.6%) | ||||
| Rheumatoid arthritis | 2/32 (6.3%) | 1/36 (2.8%) | 0/60 (0%) | 1/62 (1.6%) | ||||
| Torticollis | 0/32 (0%) | 1/36 (2.8%) | 0/60 (0%) | 0/62 (0%) | ||||
| Arthralgia | 0/32 (0%) | 1/36 (2.8%) | 1/60 (1.7%) | 1/62 (1.6%) | ||||
| Arthropathy | 0/32 (0%) | 0/36 (0%) | 0/60 (0%) | 1/62 (1.6%) | ||||
| Juvenile arthritis | 0/32 (0%) | 1/36 (2.8%) | 0/60 (0%) | 0/62 (0%) | ||||
| Synovial cyst | 0/32 (0%) | 0/36 (0%) | 0/60 (0%) | 1/62 (1.6%) | ||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Fibroadenoma of breast | 0/32 (0%) | 0/36 (0%) | 1/60 (1.7%) | 0/62 (0%) | ||||
| Acute lymphocytic leukaemia | 1/32 (3.1%) | 0/36 (0%) | 0/60 (0%) | 0/62 (0%) | ||||
| Nervous system disorders | ||||||||
| Encephalitis | 0/32 (0%) | 0/36 (0%) | 0/60 (0%) | 1/62 (1.6%) | ||||
| Temporal lobe epilepsy | 0/32 (0%) | 0/36 (0%) | 0/60 (0%) | 1/62 (1.6%) | ||||
| Multiple sclerosis | 0/32 (0%) | 0/36 (0%) | 0/60 (0%) | 1/62 (1.6%) | ||||
| Psychiatric disorders | ||||||||
| Suicide attempt | 0/32 (0%) | 0/36 (0%) | 0/60 (0%) | 1/62 (1.6%) | ||||
| Reproductive system and breast disorders | ||||||||
| Ovarian cyst | 1/32 (3.1%) | 0/36 (0%) | 0/60 (0%) | 0/62 (0%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Skin ulcer | 0/32 (0%) | 1/36 (2.8%) | 0/60 (0%) | 0/62 (0%) | ||||
| Vascular disorders | ||||||||
| Haematoma | 0/32 (0%) | 0/36 (0%) | 0/60 (0%) | 1/62 (1.6%) | ||||
Other (Not Including Serious) Adverse Events |
||||||||
| Abatacept (Only Period A) | Abatacept (Period A/Period C) | Abatacept (Period A/Period B) | Abatacept (Period A)/Placebo (Period B) | |||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 22/32 (68.8%) | 32/36 (88.9%) | 57/60 (95%) | 54/62 (87.1%) | ||||
| Blood and lymphatic system disorders | ||||||||
| Anaemia | 0/32 (0%) | 2/36 (5.6%) | 3/60 (5%) | 5/62 (8.1%) | ||||
| Leukopenia | 0/32 (0%) | 3/36 (8.3%) | 4/60 (6.7%) | 3/62 (4.8%) | ||||
| Eosinophilia | 0/32 (0%) | 4/36 (11.1%) | 5/60 (8.3%) | 6/62 (9.7%) | ||||
| Ear and labyrinth disorders | ||||||||
| Ear pain | 0/32 (0%) | 0/36 (0%) | 1/60 (1.7%) | 4/62 (6.5%) | ||||
| Eye disorders | ||||||||
| Cataract | 0/32 (0%) | 2/36 (5.6%) | 1/60 (1.7%) | 0/62 (0%) | ||||
| Conjunctivitis allergic | 0/32 (0%) | 0/36 (0%) | 4/60 (6.7%) | 0/62 (0%) | ||||
| Conjunctivitis | 0/32 (0%) | 4/36 (11.1%) | 5/60 (8.3%) | 4/62 (6.5%) | ||||
| Gastrointestinal disorders | ||||||||
| Diarrhoea | 2/32 (6.3%) | 8/36 (22.2%) | 11/60 (18.3%) | 15/62 (24.2%) | ||||
| Mouth ulceration | 2/32 (6.3%) | 1/36 (2.8%) | 3/60 (5%) | 4/62 (6.5%) | ||||
| Abdominal discomfort | 0/32 (0%) | 2/36 (5.6%) | 2/60 (3.3%) | 0/62 (0%) | ||||
| Abdominal pain | 1/32 (3.1%) | 6/36 (16.7%) | 8/60 (13.3%) | 8/62 (12.9%) | ||||
| Abdominal pain upper | 0/32 (0%) | 5/36 (13.9%) | 10/60 (16.7%) | 10/62 (16.1%) | ||||
| Duodenitis | 0/32 (0%) | 2/36 (5.6%) | 0/60 (0%) | 0/62 (0%) | ||||
| Gastritis | 0/32 (0%) | 6/36 (16.7%) | 6/60 (10%) | 5/62 (8.1%) | ||||
| Vomiting | 2/32 (6.3%) | 7/36 (19.4%) | 9/60 (15%) | 13/62 (21%) | ||||
| Aphthous stomatitis | 1/32 (3.1%) | 3/36 (8.3%) | 3/60 (5%) | 2/62 (3.2%) | ||||
| Dyspepsia | 0/32 (0%) | 1/36 (2.8%) | 4/60 (6.7%) | 3/62 (4.8%) | ||||
| Nausea | 6/32 (18.8%) | 5/36 (13.9%) | 9/60 (15%) | 12/62 (19.4%) | ||||
| General disorders | ||||||||
| Fatigue | 2/32 (6.3%) | 2/36 (5.6%) | 0/60 (0%) | 1/62 (1.6%) | ||||
| Chest pain | 0/32 (0%) | 2/36 (5.6%) | 2/60 (3.3%) | 2/62 (3.2%) | ||||
| Pain | 1/32 (3.1%) | 2/36 (5.6%) | 0/60 (0%) | 2/62 (3.2%) | ||||
| Chills | 0/32 (0%) | 0/36 (0%) | 3/60 (5%) | 1/62 (1.6%) | ||||
| Influenza like illness | 0/32 (0%) | 0/36 (0%) | 3/60 (5%) | 4/62 (6.5%) | ||||
| Pyrexia | 2/32 (6.3%) | 8/36 (22.2%) | 12/60 (20%) | 12/62 (19.4%) | ||||
| Infections and infestations | ||||||||
| Pneumonia | 0/32 (0%) | 2/36 (5.6%) | 0/60 (0%) | 0/62 (0%) | ||||
| Bacteriuria | 0/32 (0%) | 2/36 (5.6%) | 6/60 (10%) | 2/62 (3.2%) | ||||
| Pharyngitis streptococcal | 2/32 (6.3%) | 0/36 (0%) | 0/60 (0%) | 1/62 (1.6%) | ||||
| Pharyngotonsillitis | 0/32 (0%) | 2/36 (5.6%) | 3/60 (5%) | 1/62 (1.6%) | ||||
| Vulvovaginitis | 0/32 (0%) | 4/36 (11.1%) | 1/60 (1.7%) | 2/62 (3.2%) | ||||
| Fungal skin infection | 0/32 (0%) | 3/36 (8.3%) | 3/60 (5%) | 2/62 (3.2%) | ||||
| Impetigo | 0/32 (0%) | 3/36 (8.3%) | 2/60 (3.3%) | 2/62 (3.2%) | ||||
| Pneumonia primary atypical | 0/32 (0%) | 2/36 (5.6%) | 0/60 (0%) | 0/62 (0%) | ||||
| Rhinitis | 0/32 (0%) | 6/36 (16.7%) | 8/60 (13.3%) | 9/62 (14.5%) | ||||
| Gastroenteritis | 1/32 (3.1%) | 4/36 (11.1%) | 6/60 (10%) | 5/62 (8.1%) | ||||
| Tonsillitis | 0/32 (0%) | 6/36 (16.7%) | 7/60 (11.7%) | 3/62 (4.8%) | ||||
| Upper respiratory tract infection | 3/32 (9.4%) | 12/36 (33.3%) | 11/60 (18.3%) | 12/62 (19.4%) | ||||
| Urinary tract infection | 0/32 (0%) | 2/36 (5.6%) | 10/60 (16.7%) | 3/62 (4.8%) | ||||
| Lice infestation | 0/32 (0%) | 2/36 (5.6%) | 3/60 (5%) | 0/62 (0%) | ||||
| Pharyngitis | 0/32 (0%) | 3/36 (8.3%) | 10/60 (16.7%) | 13/62 (21%) | ||||
| Nasopharyngitis | 3/32 (9.4%) | 11/36 (30.6%) | 20/60 (33.3%) | 15/62 (24.2%) | ||||
| Sinusitis | 1/32 (3.1%) | 5/36 (13.9%) | 12/60 (20%) | 7/62 (11.3%) | ||||
| Paronychia | 2/32 (6.3%) | 3/36 (8.3%) | 3/60 (5%) | 2/62 (3.2%) | ||||
| Tinea versicolour | 0/32 (0%) | 1/36 (2.8%) | 3/60 (5%) | 1/62 (1.6%) | ||||
| Varicella | 0/32 (0%) | 1/36 (2.8%) | 3/60 (5%) | 3/62 (4.8%) | ||||
| Viral infection | 3/32 (9.4%) | 0/36 (0%) | 2/60 (3.3%) | 4/62 (6.5%) | ||||
| Bronchitis | 0/32 (0%) | 2/36 (5.6%) | 8/60 (13.3%) | 4/62 (6.5%) | ||||
| Influenza | 1/32 (3.1%) | 6/36 (16.7%) | 16/60 (26.7%) | 12/62 (19.4%) | ||||
| Otitis media acute | 0/32 (0%) | 2/36 (5.6%) | 1/60 (1.7%) | 3/62 (4.8%) | ||||
| Injury, poisoning and procedural complications | ||||||||
| Joint injury | 0/32 (0%) | 1/36 (2.8%) | 1/60 (1.7%) | 5/62 (8.1%) | ||||
| Arthropod bite | 0/32 (0%) | 2/36 (5.6%) | 0/60 (0%) | 2/62 (3.2%) | ||||
| Fall | 0/32 (0%) | 0/36 (0%) | 2/60 (3.3%) | 5/62 (8.1%) | ||||
| Investigations | ||||||||
| Alanine aminotransferase increased | 0/32 (0%) | 0/36 (0%) | 5/60 (8.3%) | 2/62 (3.2%) | ||||
| Transaminases increased | 0/32 (0%) | 1/36 (2.8%) | 3/60 (5%) | 1/62 (1.6%) | ||||
| Aspartate aminotransferase increased | 0/32 (0%) | 0/36 (0%) | 3/60 (5%) | 2/62 (3.2%) | ||||
| Metabolism and nutrition disorders | ||||||||
| Decreased appetite | 0/32 (0%) | 2/36 (5.6%) | 3/60 (5%) | 0/62 (0%) | ||||
| Musculoskeletal and connective tissue disorders | ||||||||
| Myalgia | 0/32 (0%) | 0/36 (0%) | 3/60 (5%) | 4/62 (6.5%) | ||||
| Torticollis | 0/32 (0%) | 2/36 (5.6%) | 1/60 (1.7%) | 0/62 (0%) | ||||
| Arthralgia | 0/32 (0%) | 1/36 (2.8%) | 1/60 (1.7%) | 4/62 (6.5%) | ||||
| Back pain | 0/32 (0%) | 3/36 (8.3%) | 5/60 (8.3%) | 2/62 (3.2%) | ||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||
| Skin papilloma | 1/32 (3.1%) | 0/36 (0%) | 3/60 (5%) | 4/62 (6.5%) | ||||
| Nervous system disorders | ||||||||
| Dizziness | 4/32 (12.5%) | 3/36 (8.3%) | 7/60 (11.7%) | 4/62 (6.5%) | ||||
| Headache | 7/32 (21.9%) | 10/36 (27.8%) | 14/60 (23.3%) | 11/62 (17.7%) | ||||
| Psychiatric disorders | ||||||||
| Insomnia | 2/32 (6.3%) | 0/36 (0%) | 0/60 (0%) | 1/62 (1.6%) | ||||
| Renal and urinary disorders | ||||||||
| Haematuria | 0/32 (0%) | 2/36 (5.6%) | 5/60 (8.3%) | 4/62 (6.5%) | ||||
| Dysuria | 0/32 (0%) | 0/36 (0%) | 4/60 (6.7%) | 4/62 (6.5%) | ||||
| Leukocyturia | 0/32 (0%) | 2/36 (5.6%) | 1/60 (1.7%) | 0/62 (0%) | ||||
| Reproductive system and breast disorders | ||||||||
| Vaginal discharge | 0/32 (0%) | 2/36 (5.6%) | 1/60 (1.7%) | 1/62 (1.6%) | ||||
| Respiratory, thoracic and mediastinal disorders | ||||||||
| Oropharyngeal pain | 4/32 (12.5%) | 3/36 (8.3%) | 8/60 (13.3%) | 8/62 (12.9%) | ||||
| Rhinitis allergic | 2/32 (6.3%) | 1/36 (2.8%) | 4/60 (6.7%) | 2/62 (3.2%) | ||||
| Cough | 4/32 (12.5%) | 7/36 (19.4%) | 10/60 (16.7%) | 13/62 (21%) | ||||
| Epistaxis | 2/32 (6.3%) | 2/36 (5.6%) | 0/60 (0%) | 0/62 (0%) | ||||
| Nasal congestion | 2/32 (6.3%) | 0/36 (0%) | 1/60 (1.7%) | 1/62 (1.6%) | ||||
| Dyspnoea | 0/32 (0%) | 2/36 (5.6%) | 0/60 (0%) | 0/62 (0%) | ||||
| Rhinorrhoea | 0/32 (0%) | 2/36 (5.6%) | 3/60 (5%) | 2/62 (3.2%) | ||||
| Skin and subcutaneous tissue disorders | ||||||||
| Pruritus | 1/32 (3.1%) | 2/36 (5.6%) | 2/60 (3.3%) | 1/62 (1.6%) | ||||
| Eczema | 2/32 (6.3%) | 0/36 (0%) | 2/60 (3.3%) | 4/62 (6.5%) | ||||
| Rash | 0/32 (0%) | 1/36 (2.8%) | 3/60 (5%) | 5/62 (8.1%) | ||||
| Dermatitis | 0/32 (0%) | 1/36 (2.8%) | 3/60 (5%) | 0/62 (0%) | ||||
| Vascular disorders | ||||||||
| Hypertension | 0/32 (0%) | 2/36 (5.6%) | 2/60 (3.3%) | 0/62 (0%) | ||||
| Flushing | 2/32 (6.3%) | 0/36 (0%) | 0/60 (0%) | 0/62 (0%) | ||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Bristol-Myers Squibb Study Director |
|---|---|
| Organization | Bristol-Myers Squibb |
| Phone | |
| Clinical.Trials@bms.com |
Responsible Party:
Bristol-Myers Squibb
ClinicalTrials.gov Identifier:
NCT00095173
Other Study ID Numbers:
- IM101-033
First Posted:
Nov 2, 2004
Last Update Posted:
Jan 18, 2017
Last Verified:
Nov 1, 2016