Safety and Effectiveness of Rilonacept for Treating Systemic Juvenile Idiopathic Arthritis in Children and Young Adults

• Sponsor: Montefiore Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00534495
• Collaborator: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) (NIH)
• Enrollment: 71
• Location: 1
• Arms: 2
• Duration (Months): 55
• Patients Per Site Per Month: 1.3

Study Details

Study Description

Brief Summary

Systemic juvenile idiopathic arthritis (SJIA) is a type of arthritis that typically occurs before 16 years of age. SJIA usually involves heat, pain, swelling, and stiffness in the body's joints. It can also involve fever, rash, anemia, and inflammation in various parts of the body. Rilonacept is a drug that can reduce inflammation. The purpose of this study is to determine whether a rilonacept drug regimen initiated early is more effective than a similar rilonacept drug regimen initiated 4 weeks later when treating children and young adults with SJIA.

Condition or Disease	Intervention/Treatment	Phase
Juvenile Idiopathic Arthritis	Biological: Rilonacept	Phase 2

Detailed Description

The current standard treatment for SJIA includes nonsteroidal anti-inflammatory drugs (NSAIDS) and corticosteroids. However, in most people, NSAIDS do not completely control the disease. Also, no studies have been done to prove which medication or combination of medications is best to treat children and adolescents with SJIA. Interleukin-1 (IL-1), a protein secreted by certain cells in the body, assists in regulating immune and inflammatory responses. Too much IL-1 can be harmful and has been shown to play a role in the inflammation associated with a variety of diseases, including SJIA. Rilonacept is a drug that inhibits IL-1 activity. The purpose of this study is to determine whether a rilonacept drug regimen initiated early is more effective than a similar rilonacept drug regimen initiated 4 weeks later when treating children and young adults with SJIA. This study will also evaluate the safety of rilonacept, and various tissue samples will be collected from participants for future genetic studies.

This study will last 6 months. Participants will be randomly assigned to one of two groups:

• Group 1 participants will receive rilonacept injections at a dose of 4.4mg/kg at study entry (loading dose), then 2.2 mg/kg weekly until Week 4. At Week 4, they will receive a loading dose of placebo, followed by weekly rilonacept injections at 2.2 mg/kg for the duration of the study.

• Group 2 participants will receive placebo at study entry and then during the first 4 weeks of treatment. At Week 4, they will receive a loading dose of rilonacept injections of 4.4 mg/kg, followed by weekly rilonacept injections at a dose of 2.2 mg/kg for the duration of the study.

Participants will continue any previous corticosteroid therapy, but in tapering doses. All participants will attend study visits at Weeks 0, 2, 4, 6, 8, 10, 12, 14 and 24. Study visits will include a physical exam, joint exam, blood collection, interview, and questionnaires. Urine collection may occur for some female participants. Other evaluations may be performed by the participant's regular doctor. Throughout the study, participants will maintain at-home diaries to record fever, morning stiffness and pain, when rilonacept or placebo was taken, any side effects experienced from treatment, and any additional medications that were taken.

Study Design

• Study Type: Interventional
• Actual Enrollment: 71 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Randomized Placebo Phase Study of Rilonacept in the Treatment of Systemic Juvenile Idiopathic Arthritis (RAPPORT)
• Study Start Date: Nov 1, 2008
• Actual Primary Completion Date: Jun 1, 2013
• Actual Study Completion Date: Jun 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group 1 Loading dose of rilonacept (4.4mg/kg) at Week 0, followed by rilonacept 2.2 mg/kg/week for the remainder of the study	Biological: Rilonacept; 2.2 mg/kg subcutaneously; Other Names: IL-1 Trap Arcalyst
Placebo Comparator: Group 2 Placebo for 4 weeks, followed by rilonacept loading dose (4.4mg/kg), followed by rilonacept 2.2 mg/kg/week for the remainder of the study	Biological: Rilonacept; 2.2 mg/kg subcutaneously; Other Names: IL-1 Trap Arcalyst

Outcome Measures

Primary Outcome Measures

1. Time to Response to Treatment, as Determined by a Modified JIA ACR30 Requiring no Fever, Coupled With a Requirement for Corticosteroid Taper in Participants Who Are Taking Corticosteroids [At Week 12]

2. Number of Serious Adverse Events,Adverse Events, Infections, Development of MAS [At Weeks 0- 24]

Secondary Outcome Measures

1. Number of Participants With Response as Determined by JIA ACR50 and JIA ACR70 [At Week 4 and week 12]

2. Pediatric Quality of Life Inventory [At Weeks 4, 12 and 24]

   Visual Analog Score (0-100 mm) 0 very well , 100 very poor

3. Physical Function as Determined by Childhood Health Assessment Questionnaire ( CHAQ) [At Weeks 12 and 24]

   Childhood Health Assesment Questionairre dissability index (C-HAQ)-DI, Disability Index Calculation: The index is calculated by adding the scores for each of the categories and dividing by the number of categories answered. This gives a score in the 0 to 3.0 range. lower is better

4. Number of Participants With Presence of Systemic Features ( Fever, Rash) [At Weeks 4, 12 and 24]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Months to 19 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Fulfills International League Against Rheumatism (ILAR) criteria for SJIA

• Duration of SJIA lasting at least 6 weeks since onset

• Active disease as defined by at least two joints with active disease

• Not currently receiving methotrexate OR if taking methotrexate, the dose has remained stable or has been discontinued for 4 weeks prior to screening

• Has never received certain biologics OR if previously received biologics, discontinued etanercept for at least 4 weeks prior to screening and discontinued infliximab or adalimumab for at least 8 weeks prior to screening

• Not currently receiving corticosteroids OR if taking oral corticosteroids, the dose has remained stable between 2 and 60 mg/day for at least 2 weeks prior to screening

Exclusion Criteria:

• Past treatment with anakinra, rilonacept, or other biologic IL-1 inhibitor

• Treatment with other disease-modifying antirheumatic drugs (DMARDs) including, but not limited to, azathioprine, sulfasalazine, cyclosporine, and thalidomide within 4 weeks of screening

• Treatment with leflunomide without cholestyramine washout at the end of therapy

• Treatment with cyclophosphamide within 3 months of study entry

• Treatment with tacrolimus or tocilizumab within 4 weeks of study entry

• Treatment with rituximab within 6 months of study entry

• Treatment with intravenous immunoglobulin (IVIG) within 4 weeks of screening

• Kidney disease

• AST or ALT levels more than two times the upper limit of normal

• Bilirubin levels higher than 1.5 mg/dl

• Thrombocytopenia, leukopenia, or neutropenia

• Abnormal prothrombin time (PT) and partial thromboplastin time (PTT) tests

• Low levels of plasma fibrinogen

• Evidence of chronic recurrent infection or other significant, non-SJIA illness that might interfere with study participation

• Psychological or cognitive difficulties that might interfere with study participation

• Current drug or alcohol abuse

• Anticipated poor compliance to assigned study regimen

• Participation in another clinical trial within 30 days of study entry

• Major surgical procedure within 3 months of study entry

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Montefiore Medical Center	Bronx	New York	United States	10467

Sponsors and Collaborators

• Montefiore Medical Center
• National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Investigators

• Principal Investigator: Norman T. Ilowite, MD, Montefiore Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Norman Ilowite, Chief, Division of Rheumatology, Children's Hospital at Montefiore, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
• ClinicalTrials.gov Identifier: NCT00534495
• Other Study ID Numbers: N01 AR070015; 268200700015C-2-0-0; HHSN2682007000015C
• First Posted: Sep 26, 2007
• Last Update Posted: Dec 11, 2015
• Last Verified: Nov 1, 2015

• Keywords provided by Norman Ilowite, Chief, Division of Rheumatology, Children's Hospital at Montefiore, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS): Systemic Juvenile Idiopathic Arthritis; Juvenile Rheumatoid Arthritis; Systemic Juvenile Rheumatoid Arthritis
• Additional relevant MeSH terms: Arthritis; Arthritis, Juvenile; Rilonacept

Study Results

Participant Flow

Pre-assignment Detail	71 participants enrolled. 1 participant was erroneously randomized and was not included in the analysis. This patient was not exposed to study drug

Arm/Group Title	Rilonacept	Placebo	Long Term Extension All Participants
Arm/Group Description	Loading dose of rilonacept (4.4mg/kg) at Week 0, followed by rilonacept 2.2 mg/kg/week followed by a placebo loading dose and then rilonacept in the long term extension phase Rilonacept: 2.2 mg/kg subcutaneously	Placebo loading dose followed by maintenance dose for 4 weeks, followed by rilonacept loading dose (4.4mg/kg), followed by rilonacept 2.2 mg/kg/week for the long term extension Rilonacept: 2.2 mg/kg subcutaneously	All participants who benefited from rilonacept were eligible to enroll this phase and receive rilonacept 2.2mg/kg weekly
Period Title: Double Blind Placebo Phase Week 0-4
STARTED	36	35	0
COMPLETED	36	34	0
NOT COMPLETED	0	1	0
Period Title: Double Blind Placebo Phase Week 0-4
STARTED	36	34	0
COMPLETED	32	25	0
NOT COMPLETED	4	9	0
Period Title: Double Blind Placebo Phase Week 0-4
STARTED	0	0	40
COMPLETED	0	0	29
NOT COMPLETED	0	0	11

Baseline Characteristics

Arm/Group Title	Rilonacept	Placebo	Total
Arm/Group Description	Loading dose of rilonacept (4.4mg/kg) at Week 0, followed by rilonacept 2.2 mg/kg/week for the remainder of the study Rilonacept: 2.2 mg/kg subcutaneously	Placebo for 4 weeks, followed by rilonacept loading dose (4.4mg/kg), followed by rilonacept 2.2 mg/kg/week for the remainder of the study Rilonacept: 2.2 mg/kg subcutaneously	Total of all reporting groups
Overall Participants	36	35	71
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	9.5 (4.6)	10.5 (4.4)	10 (4.5)
Sex: Female, Male (Count of Participants)
Female	23 63.9%	23 65.7%	46 64.8%
Male	13 36.1%	12 34.3%	25 35.2%
Race/Ethnicity, Customized (Number) [Number]
Black	5 13.9%	7 20%	12 16.9%
White	25 69.4%	23 65.7%	48 67.6%
Other	6 16.7%	5 14.3%	11 15.5%
Hispanic	7 19.4%	5 14.3%	12 16.9%
Non-Hispanic	29 80.6%	30 85.7%	59 83.1%
Disease Duration (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	2.6 (3.6)	2.6 (3.1)	2.6 (3.4)
No.of joints with active disease (joints) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [joints]	11.7 (9.6)	10.5 (7.6)	11.1 (8.6)
Prior medications (participants) [Number]
Corticosteroids	30 83.3%	33 94.3%	63 88.7%
Methotrexate	21 58.3%	26 74.3%	47 66.2%
Leflunomide	1 2.8%	2 5.7%	3 4.2%
Infliximab	5 13.9%	6 17.1%	11 15.5%
Etanercept	12 33.3%	16 45.7%	28 39.4%
Abatacept	5 13.9%	4 11.4%	9 12.7%
Anakinra	13 36.1%	13 37.1%	26 36.6%
unknown Anakinra	4 11.1%	4 11.4%	8 11.3%
Disease characteristics in the past (participants) [Number]
Incomplete Macrophage Activation Syndrome	1 2.8%	3 8.6%	4 5.6%
Complete Macrophage Activation Syndrome	1 2.8%	1 2.9%	2 2.8%
Serositis	9 25%	8 22.9%	17 23.9%
Systemic JIA rash	32 88.9%	33 94.3%	65 91.5%

Outcome Measures

1. Primary Outcome

Title	Time to Response to Treatment, as Determined by a Modified JIA ACR30 Requiring no Fever, Coupled With a Requirement for Corticosteroid Taper in Participants Who Are Taking Corticosteroids
Time Frame	At Week 12

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rilonacept	Placebo
Arm/Group Description	Loading dose of rilonacept (4.4mg/kg) at Week 0, followed by rilonacept 2.2 mg/kg/week for the remainder of the study Rilonacept: 2.2 mg/kg subcutaneously	Placebo for 4 weeks, followed by rilonacept loading dose (4.4mg/kg), followed by rilonacept 2.2 mg/kg/week for the remainder of the study Rilonacept: 2.2 mg/kg subcutaneously
Measure Participants	36	35
Median (Inter-Quartile Range) [weeks]	4	8

2. Secondary Outcome

Title	Number of Participants With Response as Determined by JIA ACR50 and JIA ACR70
Time Frame	At Week 4 and week 12

Outcome Measure Data

Analysis Population Description

Participants in the study at week 4 (rilonacept 35 and placebo 33).Participants in the study at week 12 ( Rilonacept 33 and placebo 29).

Arm/Group Title	Rilonacept	Placebo
Arm/Group Description	Loading dose of rilonacept (4.4mg/kg) at Week 0, followed by rilonacept 2.2 mg/kg/week for the remainder of the study Rilonacept: 2.2 mg/kg subcutaneously	Placebo for 4 weeks, followed by rilonacept loading dose (4.4mg/kg), followed by rilonacept 2.2 mg/kg/week for the remainder of the study Rilonacept: 2.2 mg/kg subcutaneously
Measure Participants	35	33
week 4 ,ACR 50	21 58.3%	10 28.6%
week 12, ACR 50	26 72.2%	13 37.1%
week 4 ,ACR 70	21 58.3%	10 28.6%
week 12,ACR 70	28 77.8%	19 54.3%

3. Secondary Outcome

Title	Pediatric Quality of Life Inventory
Description	Visual Analog Score (0-100 mm) 0 very well , 100 very poor
Time Frame	At Weeks 4, 12 and 24

Outcome Measure Data

Analysis Population Description

At Week 4 ,36 Rilonacept and 34 Placebo patient. At week 12, Rilonacept 33 patients and Placebo 29.At baseline Rilonacept 36 and Placebo 35 participants.

Arm/Group Title	Rilonacept	Placebo	Week 24- All Subjects
Arm/Group Description	Loading dose of rilonacept (4.4mg/kg) at Week 0, followed by rilonacept 2.2 mg/kg/week for the remainder of the study Rilonacept: 2.2 mg/kg subcutaneously	Placebo for 4 weeks, followed by rilonacept loading dose (4.4mg/kg), followed by rilonacept 2.2 mg/kg/week for the remainder of the study Rilonacept: 2.2 mg/kg subcutaneously
Measure Participants	36	35	57
week 4	12	34	NA
week 12	3.5	8	NA
week 24	NA	NA	7
baseline	49.5	53.0	NA

4. Secondary Outcome

Title	Physical Function as Determined by Childhood Health Assessment Questionnaire ( CHAQ)
Description	Childhood Health Assesment Questionairre dissability index (C-HAQ)-DI, Disability Index Calculation: The index is calculated by adding the scores for each of the categories and dividing by the number of categories answered. This gives a score in the 0 to 3.0 range. lower is better
Time Frame	At Weeks 12 and 24

Outcome Measure Data

Analysis Population Description

36 Rilonacept and 35 placebo at baseline , 36 Rilonacept and 34 placebo at week 4, 33 Rilonacept and 29 placebo at week 12, and 57 combined at week 24.

Arm/Group Title	Rilonacept	Placebo	Week 24- All Subjects
Arm/Group Description	Loading dose of rilonacept (4.4mg/kg) at Week 0, followed by rilonacept 2.2 mg/kg/week for the remainder of the study Rilonacept: 2.2 mg/kg subcutaneously	Placebo for 4 weeks, followed by rilonacept loading dose (4.4mg/kg), followed by rilonacept 2.2 mg/kg/week for the remainder of the study Rilonacept: 2.2 mg/kg subcutaneously
Measure Participants	36	35	57
week 4	0.43	0.88	NA
week 12	0.25	0.25	NA
week 24	NA	NA	0.13
baseline	1.00	1.25	NA

5. Secondary Outcome

Title	Number of Participants With Presence of Systemic Features ( Fever, Rash)
Time Frame	At Weeks 4, 12 and 24

Outcome Measure Data

Analysis Population Description

At week 4 ,Rilonacept 36 and Placebo 34 participants , at week 12 , Rilonacept 33 and 29 Placebo participants , and at week 24 combined group with 57 participants, at baseline Rilonacept 36 and Placebo 35 participants.

Arm/Group Title	Rilonacept	Placebo	Week 24- All Subjects
Arm/Group Description	Loading dose of rilonacept (4.4mg/kg) at Week 0, followed by rilonacept 2.2 mg/kg/week for the remainder of the study Rilonacept: 2.2 mg/kg subcutaneously	Placebo for 4 weeks, followed by rilonacept loading dose (4.4mg/kg), followed by rilonacept 2.2 mg/kg/week for the remainder of the study Rilonacept: 2.2 mg/kg subcutaneously
Measure Participants	36	35	57
Fever at week 4	3 8.3%	5 14.3%	NA NaN
Rash at week 4	3 8.3%	8 22.9%	NA NaN
Fever at week12	4 11.1%	1 2.9%	NA NaN
Rash at week 12	3 8.3%	1 2.9%	NA NaN
week 24 Fever	NA NaN	NA NaN	NA NaN
week 24 Rash	NA NaN	NA NaN	4 5.6%
baseline Fever	10 27.8%	6 17.1%	NA NaN
beseline Rash	15 41.7%	15 42.9%	NA NaN

6. Primary Outcome

Title	Number of Serious Adverse Events,Adverse Events, Infections, Development of MAS
Time Frame	At Weeks 0- 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Rilonacept	Placebo	Long Term Extension 24 Weeks to 21 Months
Arm/Group Description	Loading dose of rilonacept (4.4mg/kg) at Week 0, followed by rilonacept 2.2 mg/kg/week for the remainder of the study Rilonacept: 2.2 mg/kg subcutaneously	Placebo for 4 weeks, followed by rilonacept loading dose (4.4mg/kg), followed by rilonacept 2.2 mg/kg/week for the remainder of the study Rilonacept: 2.2 mg/kg subcutaneously
Measure Participants	36	35	40
Serious Adverse Events	4	2	8
Adverse Events	98	186	110
Infections	27	31	37
MAS	1	0	0

Adverse Events

Arm/Group Title	Rilonacept Week (0-4)		Placebo Week (0-4)		Rilonacept Week (4-24)		Placebo Week (4-24)		Long Term Extension 24 Weeks to 21 Months
Arm/Group Description	Loading dose of rilonacept (4.4mg/kg) at Week 0, followed by rilonacept 2.2 mg/kg/week for the remainder of the study Rilonacept: 2.2 mg/kg subcutaneously		Placebo for 4 weeks, followed by rilonacept loading dose (4.4mg/kg), followed by rilonacept 2.2 mg/kg/week for the remainder of the study Rilonacept: 2.2 mg/kg subcutaneously		Loading dose of rilonacept (4.4mg/kg) at Week 0, followed by rilonacept 2.2 mg/kg/week for the remainder of the study Rilonacept: 2.2 mg/kg subcutaneously		Placebo for 4 weeks, followed by rilonacept loading dose (4.4mg/kg), followed by rilonacept 2.2 mg/kg/week for the remainder of the study Rilonacept: 2.2 mg/kg subcutaneously
All Cause Mortality
	Rilonacept Week (0-4)		Placebo Week (0-4)		Rilonacept Week (4-24)		Placebo Week (4-24)		Long Term Extension 24 Weeks to 21 Months
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Rilonacept Week (0-4)		Placebo Week (0-4)		Rilonacept Week (4-24)		Placebo Week (4-24)		Long Term Extension 24 Weeks to 21 Months
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/36 (2.8%)		1/35 (2.9%)		3/35 (8.6%)		1/33 (3%)		6/40 (15%)
Blood and lymphatic system disorders
Histiocytosis,hematophagic	0/36 (0%)		0/35 (0%)		0/35 (0%)		0/33 (0%)		1/40 (2.5%)
Cardiac disorders
Pericarditis	0/36 (0%)		0/35 (0%)		0/35 (0%)		0/33 (0%)		1/40 (2.5%)
Gastrointestinal disorders
Abnormal Liver Function Test	0/36 (0%)		0/35 (0%)		1/35 (2.9%)		0/33 (0%)		0/40 (0%)
Gastroenteritis ,Salmonela	0/36 (0%)		0/35 (0%)		0/35 (0%)		0/33 (0%)		1/40 (2.5%)
Infections and infestations
Pyrexia	0/36 (0%)		0/35 (0%)		1/35 (2.9%)		0/33 (0%)		0/40 (0%)
Variccela	0/36 (0%)		0/35 (0%)		1/35 (2.9%)		0/33 (0%)		0/40 (0%)
Musculoskeletal and connective tissue disorders
Juvenile Arthritis	1/36 (2.8%)		1/35 (2.9%)		0/35 (0%)		1/33 (3%)		1/40 (2.5%)
Psychiatric disorders
Mental status Changes	0/36 (0%)		0/35 (0%)		0/35 (0%)		0/33 (0%)		1/40 (2.5%)
Respiratory, thoracic and mediastinal disorders
Viral uper respiratory tract infestion	0/36 (0%)		0/35 (0%)		0/35 (0%)		0/33 (0%)		1/40 (2.5%)
Pharingitis,Streptoccocal	0/36 (0%)		0/35 (0%)		0/35 (0%)		0/33 (0%)		1/40 (2.5%)
Other (Not Including Serious) Adverse Events
	Rilonacept Week (0-4)		Placebo Week (0-4)		Rilonacept Week (4-24)		Placebo Week (4-24)		Long Term Extension 24 Weeks to 21 Months
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/36 (25%)		19/35 (54.3%)		27/35 (77.1%)		28/33 (84.8%)		28/40 (70%)
Gastrointestinal disorders
Abdominal pain ,upper	1/36 (2.8%)		2/35 (5.7%)		3/35 (8.6%)		1/33 (3%)		0/40 (0%)
Nausea	0/36 (0%)		1/35 (2.9%)		1/35 (2.9%)		2/33 (6.1%)		3/40 (7.5%)
Vomiting	1/36 (2.8%)		2/35 (5.7%)		1/35 (2.9%)		2/33 (6.1%)		4/40 (10%)
Abdominal pain	0/36 (0%)		0/35 (0%)		3/35 (8.6%)		1/33 (3%)		3/40 (7.5%)
diarrhoea	0/36 (0%)		0/35 (0%)		0/35 (0%)		2/33 (6.1%)		0/40 (0%)
General disorders
Headache	1/36 (2.8%)		6/35 (17.1%)		1/35 (2.9%)		4/33 (12.1%)		3/40 (7.5%)
injection site reaction	2/36 (5.6%)		7/35 (20%)		2/35 (5.7%)		3/33 (9.1%)		0/40 (0%)
Fatigue	0/36 (0%)		1/35 (2.9%)		1/35 (2.9%)		2/33 (6.1%)		0/40 (0%)
Non Cardiac chest pain	0/36 (0%)		3/35 (8.6%)		1/35 (2.9%)		4/33 (12.1%)		0/40 (0%)
Pain	0/36 (0%)		1/35 (2.9%)		0/35 (0%)		2/33 (6.1%)		2/40 (5%)
Immune system disorders
Rash	2/36 (5.6%)		1/35 (2.9%)		1/35 (2.9%)		3/33 (9.1%)		1/40 (2.5%)
Infections and infestations
Pyrexia	0/36 (0%)		1/35 (2.9%)		5/35 (14.3%)		1/33 (3%)		1/40 (2.5%)
Urinary tract infections	0/36 (0%)		0/35 (0%)		3/35 (8.6%)		1/33 (3%)		0/40 (0%)
Investigations
Body temperature increased	0/36 (0%)		2/35 (5.7%)		3/35 (8.6%)		2/33 (6.1%)		0/40 (0%)
Blood fibrinogen dicreased	0/36 (0%)		0/35 (0%)		0/35 (0%)		4/33 (12.1%)		0/40 (0%)
Alanine amino transferase Increased	0/36 (0%)		0/35 (0%)		0/35 (0%)		0/33 (0%)		2/40 (5%)
Aspartate Amino transferase increased	0/36 (0%)		0/35 (0%)		0/35 (0%)		0/33 (0%)		2/40 (5%)
Musculoskeletal and connective tissue disorders
Arthralgia	0/36 (0%)		1/35 (2.9%)		2/35 (5.7%)		6/33 (18.2%)		1/40 (2.5%)
Joint swelling	0/36 (0%)		0/35 (0%)		0/35 (0%)		2/33 (6.1%)		3/40 (7.5%)
Nervous system disorders
Dizziness	0/36 (0%)		1/35 (2.9%)		0/35 (0%)		2/33 (6.1%)		0/40 (0%)
Respiratory, thoracic and mediastinal disorders
Cough	0/36 (0%)		1/35 (2.9%)		2/35 (5.7%)		3/33 (9.1%)		2/40 (5%)
Pharyngitis,Streptococcal	0/36 (0%)		0/35 (0%)		2/35 (5.7%)		2/33 (6.1%)		4/40 (10%)
Upper Respiratory tract infection	0/36 (0%)		1/35 (2.9%)		5/35 (14.3%)		9/33 (27.3%)		2/40 (5%)
Rhinorea	1/36 (2.8%)		1/35 (2.9%)		2/35 (5.7%)		4/33 (12.1%)		0/40 (0%)
Nasal Congestion	0/36 (0%)		0/35 (0%)		2/35 (5.7%)		2/33 (6.1%)		0/40 (0%)
dyspnea	0/36 (0%)		1/35 (2.9%)		0/35 (0%)		2/33 (6.1%)		0/40 (0%)
Skin and subcutaneous tissue disorders
dry skin	1/36 (2.8%)		0/35 (0%)		1/35 (2.9%)		2/33 (6.1%)		0/40 (0%)
Erythema	0/36 (0%)		2/35 (5.7%)		1/35 (2.9%)		2/33 (6.1%)		0/40 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.