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

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ClinicalTrials.gov Identifier: NCT00534495
Recruitment Status : Completed
First Posted : September 26, 2007
Results First Posted : December 11, 2015
Last Update Posted : December 11, 2015
Sponsor:
Collaborator:
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Information provided by (Responsible Party):
Norman Ilowite, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Juvenile Idiopathic Arthritis
Intervention Biological: Rilonacept
Enrollment 71
Recruitment Details  
Pre-assignment Details 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
Hide 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
Reason Not Completed
randomized in error             0             1             0
Period Title: All Active Treatment Phase Week 4-24
Started 36 34 0
Completed 32 25 0
Not Completed 4 9 0
Reason Not Completed
Adverse Event             1             0             0
Lack of Efficacy             1             7             0
Lost to Follow-up             1             1             0
Withdrawal by Subject             1             1             0
Period Title: Long Term Ext. Phase Week 24-month 21
Started 0 0 40
Completed 0 0 29
Not Completed 0 0 11
Reason Not Completed
Adverse Event             0             0             1
Lack of Efficacy             0             0             5
Withdrawal by Subject             0             0             3
non compliance             0             0             2
Arm/Group Title Rilonacept Placebo Total
Hide 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 Number of Baseline Participants 36 35 71
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 36 participants 35 participants 71 participants
9.5  (4.6) 10.5  (4.4) 10  (4.5)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 36 participants 35 participants 71 participants
Female
23
  63.9%
23
  65.7%
46
  64.8%
Male
13
  36.1%
12
  34.3%
25
  35.2%
Race/Ethnicity, Customized   [1] 
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 36 participants 35 participants 71 participants
Black 5 7 12
White 25 23 48
Other 6 5 11
Hispanic 7 5 12
Non-Hispanic 29 30 59
[1]
Measure Description: Black ,white and Other are races Hispanic and Non-Hispanic are ethnicities. All patients were counted twice.
Disease Duration  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 36 participants 35 participants 71 participants
2.6  (3.6) 2.6  (3.1) 2.6  (3.4)
No.of joints with active disease  
Mean (Standard Deviation)
Unit of measure:  Joints
Number Analyzed 36 participants 35 participants 71 participants
11.7  (9.6) 10.5  (7.6) 11.1  (8.6)
Prior medications  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 36 participants 35 participants 71 participants
Corticosteroids 30 33 63
Methotrexate 21 26 47
Leflunomide 1 2 3
Infliximab 5 6 11
Etanercept 12 16 28
Abatacept 5 4 9
Anakinra 13 13 26
unknown Anakinra 4 4 8
Disease characteristics in the past  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 36 participants 35 participants 71 participants
Incomplete Macrophage Activation Syndrome 1 3 4
Complete Macrophage Activation Syndrome 1 1 2
Serositis 9 8 17
Systemic JIA rash 32 33 65
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
Hide Description [Not Specified]
Time Frame At Week 12
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Rilonacept Placebo
Hide 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

Overall Number of Participants Analyzed 36 35
Median (Inter-Quartile Range)
Unit of Measure: weeks
4
(2 to 10)
8 [1] 
(6 to NA)
[1]
not estimable too few events
2.Primary Outcome
Title Number of Serious Adverse Events,Adverse Events, Infections, Development of MAS
Hide Description [Not Specified]
Time Frame At Weeks 0- 24
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Rilonacept Placebo Long Term Extension 24 Weeks to 21 Months
Hide 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

[Not Specified]
Overall Number of Participants Analyzed 36 35 40
Measure Type: Number
Unit of Measure: events
Serious Adverse Events 4 2 8
Adverse Events 98 186 110
Infections 27 31 37
MAS 1 0 0
3.Secondary Outcome
Title Number of Participants With Response as Determined by JIA ACR50 and JIA ACR70
Hide Description [Not Specified]
Time Frame At Week 4 and week 12
Hide Outcome Measure Data
Hide 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
Hide 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

Overall Number of Participants Analyzed 35 33
Measure Type: Number
Unit of Measure: participants
week 4 ,ACR 50 21 10
week 12, ACR 50 26 13
week 4 ,ACR 70 21 10
week 12,ACR 70 28 19
4.Secondary Outcome
Title Pediatric Quality of Life Inventory
Hide Description Visual Analog Score (0-100 mm) 0 very well , 100 very poor
Time Frame At Weeks 4, 12 and 24
Hide Outcome Measure Data
Hide 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
Hide 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

[Not Specified]
Overall Number of Participants Analyzed 36 35 57
Median (Inter-Quartile Range)
Unit of Measure: units on a scale
week 4
12
(3 to 23)
34
(15 to 67)
NA [1] 
(NA to NA)
week 12
3.5
(0 to 17)
8
(2 to 38)
NA [1] 
(NA to NA)
week 24
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
7
(1 to 29)
baseline
49.5
(33 to 65)
53.0
(28 to 68)
NA [1] 
(NA to NA)
[1]
At week 24 both arms were combined
5.Secondary Outcome
Title Physical Function as Determined by Childhood Health Assessment Questionnaire ( CHAQ)
Hide 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
Hide Outcome Measure Data
Hide 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
Hide 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

[Not Specified]
Overall Number of Participants Analyzed 36 35 57
Median (Inter-Quartile Range)
Unit of Measure: units on a scale
week 4
0.43
(0.00 to 1.13)
0.88
(0.38 to 1.63)
NA [1] 
(NA to NA)
week 12
0.25
(0.00 to 0.88)
0.25
(0.00 to 1.25)
NA [1] 
(NA to NA)
week 24
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
0.13
(0.00 to 1.00)
baseline
1.00
(0.75 to 1.63)
1.25
(0.50 to 1.63)
NA [1] 
(NA to NA)
[1]
Groups were combined at week 24
6.Secondary Outcome
Title Number of Participants With Presence of Systemic Features ( Fever, Rash)
Hide Description [Not Specified]
Time Frame At Weeks 4, 12 and 24
Hide Outcome Measure Data
Hide 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
Hide 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

[Not Specified]
Overall Number of Participants Analyzed 36 35 57
Measure Type: Number
Unit of Measure: participants
Fever at week 4 3 5 NA [1] 
Rash at week 4 3 8 NA [1] 
Fever at week12 4 1 NA [1] 
Rash at week 12 3 1 NA [1] 
week 24 Fever NA [2]  NA [2]  NA [2] 
week 24 Rash NA [3]  NA [3]  4
baseline Fever 10 6 NA [1] 
beseline Rash 15 15 NA [1] 
[1]
data not collected
[2]
not collected
[3]
both groups were combined at 24 weeks
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
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
Hide 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

[Not Specified]
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 (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/--   --/--   --/-- 
Show Serious Adverse Events Hide 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 (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   1/36 (2.78%)   1/35 (2.86%)   3/35 (8.57%)   1/33 (3.03%)   6/40 (15.00%) 
Blood and lymphatic system disorders           
Histiocytosis,hematophagic   0/36 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  0/33 (0.00%)  1/40 (2.50%) 
Cardiac disorders           
Pericarditis   0/36 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  0/33 (0.00%)  1/40 (2.50%) 
Gastrointestinal disorders           
Abnormal Liver Function Test   0/36 (0.00%)  0/35 (0.00%)  1/35 (2.86%)  0/33 (0.00%)  0/40 (0.00%) 
Gastroenteritis ,Salmonela   0/36 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  0/33 (0.00%)  1/40 (2.50%) 
Infections and infestations           
Pyrexia   0/36 (0.00%)  0/35 (0.00%)  1/35 (2.86%)  0/33 (0.00%)  0/40 (0.00%) 
Variccela   0/36 (0.00%)  0/35 (0.00%)  1/35 (2.86%)  0/33 (0.00%)  0/40 (0.00%) 
Musculoskeletal and connective tissue disorders           
Juvenile Arthritis   1/36 (2.78%)  1/35 (2.86%)  0/35 (0.00%)  1/33 (3.03%)  1/40 (2.50%) 
Psychiatric disorders           
Mental status Changes   0/36 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  0/33 (0.00%)  1/40 (2.50%) 
Respiratory, thoracic and mediastinal disorders           
Viral uper respiratory tract infestion   0/36 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  0/33 (0.00%)  1/40 (2.50%) 
Pharingitis,Streptoccocal   0/36 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  0/33 (0.00%)  1/40 (2.50%) 
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
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 (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   9/36 (25.00%)   19/35 (54.29%)   27/35 (77.14%)   28/33 (84.85%)   28/40 (70.00%) 
Gastrointestinal disorders           
Abdominal pain ,upper  [1]  1/36 (2.78%)  2/35 (5.71%)  3/35 (8.57%)  1/33 (3.03%)  0/40 (0.00%) 
Nausea  [1]  0/36 (0.00%)  1/35 (2.86%)  1/35 (2.86%)  2/33 (6.06%)  3/40 (7.50%) 
Vomiting  [1]  1/36 (2.78%)  2/35 (5.71%)  1/35 (2.86%)  2/33 (6.06%)  4/40 (10.00%) 
Abdominal pain   0/36 (0.00%)  0/35 (0.00%)  3/35 (8.57%)  1/33 (3.03%)  3/40 (7.50%) 
diarrhoea   0/36 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  2/33 (6.06%)  0/40 (0.00%) 
General disorders           
Headache  [1]  1/36 (2.78%)  6/35 (17.14%)  1/35 (2.86%)  4/33 (12.12%)  3/40 (7.50%) 
injection site reaction   2/36 (5.56%)  7/35 (20.00%)  2/35 (5.71%)  3/33 (9.09%)  0/40 (0.00%) 
Fatigue   0/36 (0.00%)  1/35 (2.86%)  1/35 (2.86%)  2/33 (6.06%)  0/40 (0.00%) 
Non Cardiac chest pain   0/36 (0.00%)  3/35 (8.57%)  1/35 (2.86%)  4/33 (12.12%)  0/40 (0.00%) 
Pain   0/36 (0.00%)  1/35 (2.86%)  0/35 (0.00%)  2/33 (6.06%)  2/40 (5.00%) 
Immune system disorders           
Rash  [1]  2/36 (5.56%)  1/35 (2.86%)  1/35 (2.86%)  3/33 (9.09%)  1/40 (2.50%) 
Infections and infestations           
Pyrexia  [1]  0/36 (0.00%)  1/35 (2.86%)  5/35 (14.29%)  1/33 (3.03%)  1/40 (2.50%) 
Urinary tract infections   0/36 (0.00%)  0/35 (0.00%)  3/35 (8.57%)  1/33 (3.03%)  0/40 (0.00%) 
Investigations           
Body temperature increased   0/36 (0.00%)  2/35 (5.71%)  3/35 (8.57%)  2/33 (6.06%)  0/40 (0.00%) 
Blood fibrinogen dicreased   0/36 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  4/33 (12.12%)  0/40 (0.00%) 
Alanine amino transferase Increased   0/36 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  0/33 (0.00%)  2/40 (5.00%) 
Aspartate Amino transferase increased   0/36 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  0/33 (0.00%)  2/40 (5.00%) 
Musculoskeletal and connective tissue disorders           
Arthralgia  [1]  0/36 (0.00%)  1/35 (2.86%)  2/35 (5.71%)  6/33 (18.18%)  1/40 (2.50%) 
Joint swelling   0/36 (0.00%)  0/35 (0.00%)  0/35 (0.00%)  2/33 (6.06%)  3/40 (7.50%) 
Nervous system disorders           
Dizziness   0/36 (0.00%)  1/35 (2.86%)  0/35 (0.00%)  2/33 (6.06%)  0/40 (0.00%) 
Respiratory, thoracic and mediastinal disorders           
Cough  [1]  0/36 (0.00%)  1/35 (2.86%)  2/35 (5.71%)  3/33 (9.09%)  2/40 (5.00%) 
Pharyngitis,Streptococcal  [1]  0/36 (0.00%)  0/35 (0.00%)  2/35 (5.71%)  2/33 (6.06%)  4/40 (10.00%) 
Upper Respiratory tract infection  [1]  0/36 (0.00%)  1/35 (2.86%)  5/35 (14.29%)  9/33 (27.27%)  2/40 (5.00%) 
Rhinorea   1/36 (2.78%)  1/35 (2.86%)  2/35 (5.71%)  4/33 (12.12%)  0/40 (0.00%) 
Nasal Congestion   0/36 (0.00%)  0/35 (0.00%)  2/35 (5.71%)  2/33 (6.06%)  0/40 (0.00%) 
dyspnea   0/36 (0.00%)  1/35 (2.86%)  0/35 (0.00%)  2/33 (6.06%)  0/40 (0.00%) 
Skin and subcutaneous tissue disorders           
dry skin   1/36 (2.78%)  0/35 (0.00%)  1/35 (2.86%)  2/33 (6.06%)  0/40 (0.00%) 
Erythema   0/36 (0.00%)  2/35 (5.71%)  1/35 (2.86%)  2/33 (6.06%)  0/40 (0.00%) 
Indicates events were collected by systematic assessment
[1]
Adverse events
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.
Results Point of Contact
Name/Title: Dr.Norman T.Ilowite
Organization: Children's Hospital at Montefiore
Phone: 718-696-2602
Responsible Party: Norman Ilowite, National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
ClinicalTrials.gov Identifier: NCT00534495     History of Changes
Other Study ID Numbers: N01 AR070015
268200700015C-2-0-0 ( U.S. NIH Grant/Contract )
HHSN2682007000015C
First Submitted: September 24, 2007
First Posted: September 26, 2007
Results First Submitted: November 5, 2015
Results First Posted: December 11, 2015
Last Update Posted: December 11, 2015