Efficacy, Safety, Pharmacokinetics and Immunogenicity Study of Abatacept Administered Intravenously to Treat Active Polyarticular-course Juvenile Idiopathic Arthritis in Japan

• Sponsor: Bristol-Myers Squibb (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01835470
• Collaborator: Ono Pharmaceutical Co. Ltd (Industry)
• Enrollment: 23
• Locations: 13
• Arm: 1
• Actual Duration (Months): 59.7
• Patients Per Site: 1.8
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the efficacy of Abatacept after intravenous administration in Japanese children and adolescents with active juvenile idiopathic arthritis who have a history of an inadequate response or intolerance to Methotrexate or biologics

Condition or Disease	Intervention/Treatment	Phase
Juvenile Idiopathic Arthritis	Drug: Abatacept	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 23 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase III, Multicenter, Open-Label Study to Assess Efficacy, Safety, Pharmacokinetics and Immunogenicity of Abatacept Administered Intravenously in Japanese Children and Adolescents With Active Juvenile Idiopathic Arthritis Who Have a History of an Inadequate Response or Intolerance to Methotrexate or Biologics
• Actual Study Start Date: Aug 9, 2013
• Actual Primary Completion Date: Nov 24, 2015
• Actual Study Completion Date: Jul 30, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Abatacept Abatacept 10 mg/kg (for body weight less than 75 kg), 750 mg (for body weight between 75 and 100 kg), and 1g (for body weight above 100kg) intravenous infusion on Week 0 (Day 1), Week 2 (Day 15), Week 4 (Day 29) and every 4 weeks (28 days) thereafter up to the end of the study	Drug: Abatacept; Other Names: BMS-188667 ONO-4164

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Experiencing a American College of Rheumatology (ACR) Pediatric 30 Response at Week 16 [Week 16 (Day 113)]

   American College of Rheumatology (ACR) pediatric (PED) 30 response was defined as '≥30% improvement' and '≥3 of the 6 Juvenile Idiopathic Arthritis (JIA) core set' and ≥30% worsening in not more than 1 of the 6 JIA core set variables. JIA core set variables defined as the number of active joints, number of joints with Limit of Motion (LOM), physician's global assessment of disease severity, patient global assessment of overall well being, parent assessment of physical function, and acute phase reactant value. A non-responder imputation was applied.

Secondary Outcome Measures

1. Percentage of Participants Experiencing a American College of Rheumatology Pediatric 50, 70, 90 Response or Inactive Disease at Week 16 [Week 16 (Day 113)]

   ACR PED 50 response is defined as '≥50% improvement' and '≥3 of the 6 Juvenile Idiopathic Arthritis (JIA) core set' and ≥30% worsening in not more than 1 of the 6 JIA core set variables. ACR PED 70 response is defined as '≥70% improvement' and '≥3 of the 6 JIA core set' and ≥30% worsening in not more than 1 of the 6 JIA core set variables. ACR PED 90 response is defined as '≥90% improvement' and '≥3 of the 6 JIA core set' and ≥30% worsening in not more than 1 of the 6 JIA core set variables. Inactive disease status is defined as no active joints, physician's global assessment of disease severity equal or less than 10mm and C-reactive protein (CRP) within normal limits (0.3 mg/dL). A non-responder imputation is applied. mm=millimeter; mg/dL=milligrams/deciliter

2. Median Percentage of Improvement From Baseline in Physical Function as Assessed by the Childhood Health Assessment Questionnaire (CHAQ) Disability Index at Week 16 [Week 16 (Day 113)]

   Physical function was evaluated using the disability section of the Childhood Health Assessment Questionnaire (CHAQ). The questionnaire was derived from the adult HAQ. The disability section assessed physical functions in 8 domains: dressing and grooming, arising, eating, walking, hygiene, reach, grip and common activities. The questions were evaluated on a 4-point scale: 0 = without any difficulty, 1 = with some difficulty, 2 = with much difficulty and 3 =unable to do. Higher scores indicate greater dysfunction. A disability index was calculated as the mean of the 8 functional scales. The percentage of Improvement from baseline was calculated using the following equation: (Baseline value - Post-baseline value) / Baseline value x 100.

3. Number of Participants With Death, Serious Adverse Events (SAEs), Drug-Related SAEs, Discontinuation Due to Drug-Related SAEs, Drug-Related Adverse Events (AEs), and Discontinuation Due to Drug-Related AEs During the Short Term Period [Day 1 up to 56 days post Week 16 (Day 113); approximately 6 months]

   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. SAEs also include hospitalizations for elective surgical procedures. Drug-related=related or missing relationship to study drug. Data includes all events from the date of the first dose of the study drug up to 56 days post the last dose of the study drug in the short-term period or start of the long-term period, whichever occurred first.

4. Maximum Observed Concentration (Cmax) of Abatacept During the Short Term Period [9 time points up to Week 16 (Day 113)]

   Cmax was obtained from the serum concentration versus time data after intravenous administration of abatacept. Blood samples were collected at 0 hour (pre-dose) on Days 15 and 29 and at 0 hour (pre-dose) and 0.5 hours (post dose) on Days 57, 85, and 113. A blood sample was also collected on an interim visit that occurred on any day between Day 92 and Day 110. ug/mL=micrograms/milliliter

5. Trough Observed Concentration (Ctrough) of Abatacept During the Short Term Period [9 time points up to Week 16 (Day 113)]

   Blood samples were collected at 0 hour (pre-dose) on Days 15 and 29 and at 0 hour (pre-dose) and 0.5 hours (post dose) on Days 57, 85, and 113. A blood sample was also collected on an interim visit that occurred on any day between Day 92 and Day 110. ug/mL=micrograms/milliliter

6. Number of Participants With Positive Immunogenicity During the Short Term Period [Day 1 up to Week 16 (Day 113)]

   A positive immunogenicity response for 'Cytotoxic T-lymphocyte antigen (CTLA4), Immunoglobulin (Ig)', 'Ig and/or Junction Region', respectively = (1) missing baseline immunogenicity measurement and positive analytical laboratory reported immunogenicity response post-baseline (2) negative baseline immunogenicity response and positive analytical laboratory reported immunogenicity response post-baseline (3) positive baseline immunogenicity response and positive analytical laboratory reported immunogenicity response post-baseline with titer value strictly greater than the baseline titer value. Assessment based on assay cutpoint value. Serum samples were collected prior to study medication at Week 0 (Day 1), Week 8 (Day 57), and Week 16 (Day 113) in the short term period. Participants who early discontinued from the study or complete and did not switch to commercial abatacept had a serum sample collected on final visit or early termination visit, 28, 84 and 168 days after the last dose.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 4 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subjects who have a history of an inadequate therapeutic response or intolerance in the opinion of the examining physician to at least one biologics or Methotrexate (MTX).

• Diagnosis of Juvenile Idiopathic Arthritis (JIA) by International League of Associations for Rheumatology (ILAR) criteria as oligoarticular, polyarticular Rheumatoid Factor (RF+), polyarticular (RF-), or systemic with a polyarticular-course.

• Men and women, ages 4 to 17 years, inclusive at enrollment.

• Subjects must have a history of at least 5 joints with active disease and must have currently active articular disease as defined by:

1. ≥2 active joints (e.g. presence of swelling, or if no swelling is present, limitation of motion (LOM) accompanied by pain, tenderness, or both) at screening and at Week 0 (Day 1).

2. ≥2 joints with LOM at screening and at Week 0 (Day 1).

Exclusion Criteria:

• Systemic onset JIA with any of the following manifestations within the last 6 months prior to enrollment: intermittent fever due to JIA, rheumatoid rash, hepatosplenomegaly, pleuritis, pericarditis, or macrophage activation syndrome.

• Presence of any other rheumatic disease or major chronic infectious/inflammatory/immunologic disease (e.g. inflammatory bowel disease, psoriatic arthritis, spondyloarthropathy, hypogammaglobulinemia, or systemic lupus erythematosus, etc.)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Local Institution	Oobu-shi	Aichi	Japan	4748710
2	Local Institution	Sapporo-shi	Hokkaido	Japan	0048618
3	Local Institution	Sapporo-shi	Hokkaido	Japan	0608648
4	Local Institution	Kobe	Hyogo	Japan	6500047
5	Local Institution	Kagoshima-shi	Kagoshima	Japan	8908520
6	Local Institution	Yokohama-shi	Kanagawa	Japan	2328555
7	Local Institution	Yokohama-shi	Kanagawa	Japan	2360004
8	Local Institution	Sendai-shi	Miyagi	Japan	9893126
9	Local Institution	Niigata-shi	Niigata	Japan	9518520
10	Local Institution	Nakagami-gun	Okinawa	Japan	9030215
11	Local Institution	Takatsuki-shi	Osaka	Japan	5698686
12	Local Institution	Bunkyo-ku	Tokyo	Japan	1138603
13	Local Institution	Shinjuku-ku	Tokyo	Japan	1620054

Sponsors and Collaborators

• Bristol-Myers Squibb
• Ono Pharmaceutical Co. Ltd

Investigators

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

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

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

Publications

None provided.

• Responsible Party: Bristol-Myers Squibb
• ClinicalTrials.gov Identifier: NCT01835470
• Other Study ID Numbers: IM101-365
• First Posted: Apr 19, 2013
• Last Update Posted: Feb 26, 2021
• Last Verified: Feb 1, 2021

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

Study Results

Participant Flow

Recruitment Details	23 participants were enrolled and 20 participants were treated. Reason for non-treatment was that 3 participants no longer met study criteria.

Arm/Group Title	Abatacept
Arm/Group Description	Abatacept 10 mg/kg (for body weight less than 75 kg), 750 mg (for body weight between 75 and 100 kg), and 1g (for body weight above 100kg) intravenous infusion on Week 0 (Day 1), Week 2 (Day 15), Week 4 (Day 29) and every 4 weeks (28 days) thereafter up to the end of the study
Period Title: Short Term Treatment Period (to Week 16)
STARTED	20
COMPLETED	20
NOT COMPLETED	0
Period Title: Short Term Treatment Period (to Week 16)
STARTED	20
COMPLETED	16
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	Abatacept
Arm/Group Description	Abatacept 10 mg/kg (for body weight less than 75 kg), 750 mg (for body weight between 75 and 100 kg), and 1g (for body weight above 100kg) intravenous infusion on Week 0 (Day 1), Week 2 (Day 15), Week 4 (Day 29) and every 4 weeks (28 days) thereafter up to the end of the study
Overall Participants	20
Age (Count of Participants)
<=18 years	20 100%
Between 18 and 65 years	0 0%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	10.2 (3.24)
Sex: Female, Male (Count of Participants)
Female	15 75%
Male	5 25%
Race/Ethnicity, Customized (Count of Participants)
Japanese	20 100%
Region of Enrollment (Number) [Number]
Japan	20 100%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Experiencing a American College of Rheumatology (ACR) Pediatric 30 Response at Week 16
Description	American College of Rheumatology (ACR) pediatric (PED) 30 response was defined as '≥30% improvement' and '≥3 of the 6 Juvenile Idiopathic Arthritis (JIA) core set' and ≥30% worsening in not more than 1 of the 6 JIA core set variables. JIA core set variables defined as the number of active joints, number of joints with Limit of Motion (LOM), physician's global assessment of disease severity, patient global assessment of overall well being, parent assessment of physical function, and acute phase reactant value. A non-responder imputation was applied.
Time Frame	Week 16 (Day 113)

Outcome Measure Data

Analysis Population Description

All Treated Participants: All participants who received at least one dose of study medication

Arm/Group Title	Abatacept
Arm/Group Description	Abatacept 10 mg/kg (for body weight less than 75 kg), 750 mg (for body weight between 75 and 100 kg), and 1g (for body weight above 100kg) intravenous infusion on Week 0 (Day 1), Week 2 (Day 15), Week 4 (Day 29) and every 4 weeks (28 days) thereafter up to the end of the study
Measure Participants	20
Number (95% Confidence Interval) [percentage of participants]	90.0 450%

2. Secondary Outcome

Title	Percentage of Participants Experiencing a American College of Rheumatology Pediatric 50, 70, 90 Response or Inactive Disease at Week 16
Description	ACR PED 50 response is defined as '≥50% improvement' and '≥3 of the 6 Juvenile Idiopathic Arthritis (JIA) core set' and ≥30% worsening in not more than 1 of the 6 JIA core set variables. ACR PED 70 response is defined as '≥70% improvement' and '≥3 of the 6 JIA core set' and ≥30% worsening in not more than 1 of the 6 JIA core set variables. ACR PED 90 response is defined as '≥90% improvement' and '≥3 of the 6 JIA core set' and ≥30% worsening in not more than 1 of the 6 JIA core set variables. Inactive disease status is defined as no active joints, physician's global assessment of disease severity equal or less than 10mm and C-reactive protein (CRP) within normal limits (0.3 mg/dL). A non-responder imputation is applied. mm=millimeter; mg/dL=milligrams/deciliter
Time Frame	Week 16 (Day 113)

Outcome Measure Data

Analysis Population Description

All Treated Participants: All participants who received at least one dose of study medication

Arm/Group Title	Abatacept
Arm/Group Description	Abatacept 10 mg/kg (for body weight less than 75 kg), 750 mg (for body weight between 75 and 100 kg), and 1g (for body weight above 100kg) intravenous infusion on Week 0 (Day 1), Week 2 (Day 15), Week 4 (Day 29) and every 4 weeks (28 days) thereafter up to the end of the study
Measure Participants	20
ACR PED 50	75.0 375%
ACR PED 70	70.0 350%
ACR PED 90	35.0 175%
Inactive Disease	25.0 125%

3. Secondary Outcome

Title	Median Percentage of Improvement From Baseline in Physical Function as Assessed by the Childhood Health Assessment Questionnaire (CHAQ) Disability Index at Week 16
Description	Physical function was evaluated using the disability section of the Childhood Health Assessment Questionnaire (CHAQ). The questionnaire was derived from the adult HAQ. The disability section assessed physical functions in 8 domains: dressing and grooming, arising, eating, walking, hygiene, reach, grip and common activities. The questions were evaluated on a 4-point scale: 0 = without any difficulty, 1 = with some difficulty, 2 = with much difficulty and 3 =unable to do. Higher scores indicate greater dysfunction. A disability index was calculated as the mean of the 8 functional scales. The percentage of Improvement from baseline was calculated using the following equation: (Baseline value - Post-baseline value) / Baseline value x 100.
Time Frame	Week 16 (Day 113)

Outcome Measure Data

Analysis Population Description

All Treated Participants: All participants who received at least one dose of study medication

Arm/Group Title	Abatacept
Arm/Group Description	Abatacept 10 mg/kg (for body weight less than 75 kg), 750 mg (for body weight between 75 and 100 kg), and 1g (for body weight above 100kg) intravenous infusion on Week 0 (Day 1), Week 2 (Day 15), Week 4 (Day 29) and every 4 weeks (28 days) thereafter up to the end of the study
Measure Participants	20
Median (Inter-Quartile Range) [percentage of improvement from baseline]	43.18

4. Secondary Outcome

Title	Number of Participants With Death, Serious Adverse Events (SAEs), Drug-Related SAEs, Discontinuation Due to Drug-Related SAEs, Drug-Related Adverse Events (AEs), and Discontinuation Due to Drug-Related AEs During the Short Term Period
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. SAEs also include hospitalizations for elective surgical procedures. Drug-related=related or missing relationship to study drug. Data includes all events from the date of the first dose of the study drug up to 56 days post the last dose of the study drug in the short-term period or start of the long-term period, whichever occurred first.
Time Frame	Day 1 up to 56 days post Week 16 (Day 113); approximately 6 months

Outcome Measure Data

Analysis Population Description

All Treated Participants: All participants who received at least one dose of study medication

Arm/Group Title	Abatacept
Arm/Group Description	Abatacept 10 mg/kg (for body weight less than 75 kg), 750 mg (for body weight between 75 and 100 kg), and 1g (for body weight above 100kg) intravenous infusion on Week 0 (Day 1), Week 2 (Day 15), Week 4 (Day 29) and every 4 weeks (28 days) thereafter up to the end of the study.
Measure Participants	20
Death	0 0%
SAEs	2 10%
Drug-Related SAEs	1 5%
Discontinuation Due to Drug-Related SAEs	0 0%
Drug-Related AEs	5 25%
Discontinuation Due to Drug-Related AEs	0 0%

5. Secondary Outcome

Title	Maximum Observed Concentration (Cmax) of Abatacept During the Short Term Period
Description	Cmax was obtained from the serum concentration versus time data after intravenous administration of abatacept. Blood samples were collected at 0 hour (pre-dose) on Days 15 and 29 and at 0 hour (pre-dose) and 0.5 hours (post dose) on Days 57, 85, and 113. A blood sample was also collected on an interim visit that occurred on any day between Day 92 and Day 110. ug/mL=micrograms/milliliter
Time Frame	9 time points up to Week 16 (Day 113)

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) Analysis Population: All participants who received at least one dose of study medication and who had at least one adequate PK result reported after start of study medication. The 'n' signifies those participants who received study drug and were evaluated for this measure (each group respectively).

Arm/Group Title	Abatacept
Arm/Group Description	Abatacept 10 mg/kg (for body weight less than 75 kg), 750 mg (for body weight between 75 and 100 kg), and 1g (for body weight above 100kg) intravenous infusion on Week 0 (Day 1), Week 2 (Day 15), Week 4 (Day 29) and every 4 weeks (28 days) thereafter up to the end of the study
Measure Participants	20
Day 57	163.13 (26.22)
Day 85	172.43 (23.15)
Day 113	167.85 (18.42)

6. Secondary Outcome

Title	Trough Observed Concentration (Ctrough) of Abatacept During the Short Term Period
Description	Blood samples were collected at 0 hour (pre-dose) on Days 15 and 29 and at 0 hour (pre-dose) and 0.5 hours (post dose) on Days 57, 85, and 113. A blood sample was also collected on an interim visit that occurred on any day between Day 92 and Day 110. ug/mL=micrograms/milliliter
Time Frame	9 time points up to Week 16 (Day 113)

Outcome Measure Data

Analysis Population Description

Pharmacokinetic (PK) Analysis Population: All participants who received at least one dose of study medication and who had at least one adequate PK result reported after start of study medication. The 'n' signifies those participants who received study drug and were evaluated for this measure (each group respectively).

Arm/Group Title	Abatacept
Arm/Group Description	Abatacept 10 mg/kg (for body weight less than 75 kg), 750 mg (for body weight between 75 and 100 kg), and 1g (for body weight above 100kg) intravenous infusion on Week 0 (Day 1), Week 2 (Day 15), Week 4 (Day 29) and every 4 weeks (28 days) thereafter up to the end of the study
Measure Participants	20
Day 15	25.50 (27.61)
Day 29	38.64 (29.08)
Day 57	17.24 (36.63)
Day 85	16.79 (40.01)
Day 113	15.56 (36.61)

7. Secondary Outcome

Title	Number of Participants With Positive Immunogenicity During the Short Term Period
Description	A positive immunogenicity response for 'Cytotoxic T-lymphocyte antigen (CTLA4), Immunoglobulin (Ig)', 'Ig and/or Junction Region', respectively = (1) missing baseline immunogenicity measurement and positive analytical laboratory reported immunogenicity response post-baseline (2) negative baseline immunogenicity response and positive analytical laboratory reported immunogenicity response post-baseline (3) positive baseline immunogenicity response and positive analytical laboratory reported immunogenicity response post-baseline with titer value strictly greater than the baseline titer value. Assessment based on assay cutpoint value. Serum samples were collected prior to study medication at Week 0 (Day 1), Week 8 (Day 57), and Week 16 (Day 113) in the short term period. Participants who early discontinued from the study or complete and did not switch to commercial abatacept had a serum sample collected on final visit or early termination visit, 28, 84 and 168 days after the last dose.
Time Frame	Day 1 up to Week 16 (Day 113)

Outcome Measure Data

Analysis Population Description

Immunogenicity analysis population: All participants who received at least one dose of study medication and who had at least one immunogenicity result reported after start of study medication

Arm/Group Title	Abatacept
Arm/Group Description	Abatacept 10 mg/kg (for body weight less than 75 kg), 750 mg (for body weight between 75 and 100 kg), and 1g (for body weight above 100kg) intravenous infusion on Week 0 (Day 1), Week 2 (Day 15), Week 4 (Day 29) and every 4 weeks (28 days) thereafter up to the end of the study
Measure Participants	20
Number [participants]	0 0%

Adverse Events

Time Frame	During the cumulative period which is from the first dose date up to 56 days beyond the last dose of study medication in the LT period for participants entering the LT or up to 56 days beyond the last dose of study medication in the ST period for participants not entering the LT period
Adverse Event Reporting Description	From September 2013 to July 2018 (approximately 61 months)
Arm/Group Title	IV ABATACEPT
Arm/Group Description
All Cause Mortality
	IV ABATACEPT
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	IV ABATACEPT
	Affected / at Risk (%)	# Events
Total	6/20 (30%)
Infections and infestations
ENTEROCOLITIS VIRAL	1/20 (5%)
GASTROENTERITIS	1/20 (5%)
VARICELLA	1/20 (5%)
VIRAL TONSILLITIS	1/20 (5%)
Injury, poisoning and procedural complications
LOWER LIMB FRACTURE	1/20 (5%)
Musculoskeletal and connective tissue disorders
JUVENILE IDIOPATHIC ARTHRITIS	2/20 (10%)
Other (Not Including Serious) Adverse Events
	IV ABATACEPT
	Affected / at Risk (%)	# Events
Total	20/20 (100%)
Eye disorders
DRY EYE	2/20 (10%)
Gastrointestinal disorders
ABDOMINAL PAIN	2/20 (10%)
ABDOMINAL PAIN UPPER	2/20 (10%)
APHTHOUS ULCER	2/20 (10%)
CONSTIPATION	2/20 (10%)
DIARRHOEA	5/20 (25%)
NAUSEA	4/20 (20%)
STOMATITIS	7/20 (35%)
TOOTHACHE	2/20 (10%)
VOMITING	3/20 (15%)
General disorders
PYREXIA	4/20 (20%)
Immune system disorders
SEASONAL ALLERGY	5/20 (25%)
Infections and infestations
ANGULAR CHEILITIS	2/20 (10%)
BRONCHITIS	5/20 (25%)
CONJUNCTIVITIS	3/20 (15%)
ENTEROCOLITIS VIRAL	2/20 (10%)
GASTROENTERITIS	4/20 (20%)
INFLUENZA	10/20 (50%)
NASOPHARYNGITIS	17/20 (85%)
PHARYNGITIS	12/20 (60%)
RHINITIS	3/20 (15%)
UPPER RESPIRATORY TRACT INFECTION	4/20 (20%)
VIRAL PHARYNGITIS	3/20 (15%)
Injury, poisoning and procedural complications
ARTHROPOD BITE	2/20 (10%)
CONTUSION	6/20 (30%)
LIGAMENT SPRAIN	7/20 (35%)
SKIN ABRASION	2/20 (10%)
Investigations
INFLUENZA B VIRUS TEST POSITIVE	2/20 (10%)
Musculoskeletal and connective tissue disorders
ARTHRALGIA	5/20 (25%)
BACK PAIN	2/20 (10%)
MYALGIA	2/20 (10%)
PAIN IN EXTREMITY	2/20 (10%)
TENDONITIS	2/20 (10%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
SKIN PAPILLOMA	3/20 (15%)
Nervous system disorders
HEADACHE	7/20 (35%)
Respiratory, thoracic and mediastinal disorders
COUGH	3/20 (15%)
EPISTAXIS	3/20 (15%)
RHINITIS ALLERGIC	3/20 (15%)
RHINORRHOEA	2/20 (10%)
UPPER RESPIRATORY TRACT INFLAMMATION	6/20 (30%)
Skin and subcutaneous tissue disorders
ACNE	5/20 (25%)
ALOPECIA	2/20 (10%)
DERMATITIS	2/20 (10%)
DRY SKIN	2/20 (10%)
ECZEMA	2/20 (10%)
PURPURA	2/20 (10%)
RASH	3/20 (15%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Bristol-Myers Squibb Co. agreements with investigators vary; constant is our right to embargo communications regarding trial results prior to public release for a period ≤60 days from submittal for review. We will not prohibit investigators from publishing, but will prohibit the disclosure of previously undisclosed confidential information other than study results, and request postponement of single-center publications until after disclosure of the clinical trial's primary publication.