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Tocilizumab for Patients With Giant Cell Arteritis

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ClinicalTrials.gov Identifier: NCT01450137
Recruitment Status : Completed
First Posted : October 12, 2011
Results First Posted : February 12, 2019
Last Update Posted : February 12, 2019
Sponsor:
Collaborators:
University of Bern
Roche Pharma AG
Information provided by (Responsible Party):
University Hospital Inselspital, Berne

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Giant Cell Arteritis
Interventions Drug: Tocilizumab + Glucocorticoids (GCs)
Drug: Placebo + Glucocorticoids (GCs)
Enrollment 30
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Tocilizumab Placebo
Hide Arm/Group Description

Tocilizumab 8mg/kg every 4 weeks until week 52.

Tocilizumab + Glucocorticoids (GCs): Tocilizumab 8mg/kg every 4 weeks until week 52.

Placebo every 4 weeks until week 52.

Placebo + Glucocorticoids (GCs): Placebo every 4 weeks until week 52.

Period Title: Up to Week 12
Started 20 10
Completed 18 7
Not Completed 2 3
Reason Not Completed
Adverse Event             2             1
Withdrawal by Subject             0             2
Period Title: Week 12 to Study End
Started 18 7
Completed 18 5
Not Completed 0 2
Reason Not Completed
Death             0             1
Withdrawal by Subject             0             1
Arm/Group Title Tocilizumab Placebo Total
Hide Arm/Group Description

Tocilizumab 8mg/kg every 4 weeks until week 52.

Tocilizumab + Glucocorticoids (GCs): Tocilizumab 8mg/kg every 4 weeks until week 52.

Placebo every 4 weeks until week 52.

Placebo + Glucocorticoids (GCs): Placebo every 4 weeks until week 52.

Total of all reporting groups
Overall Number of Baseline Participants 20 10 30
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 20 participants 10 participants 30 participants
71.3  (8.9) 68.8  (16.9) 70.5  (11.9)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants 10 participants 30 participants
Female
13
  65.0%
8
  80.0%
21
  70.0%
Male
7
  35.0%
2
  20.0%
9
  30.0%
Body Mass Index (BMI)  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 20 participants 10 participants 30 participants
23.6  (3.0) 27.9  (3.7) 25.0  (3.8)
New onset giant cell arteritis  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants 10 participants 30 participants
16
  80.0%
7
  70.0%
23
  76.7%
Biopsy of the temporal artery  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants 10 participants 30 participants
Normal
5
  25.0%
0
   0.0%
5
  16.7%
Abnormal
13
  65.0%
8
  80.0%
21
  70.0%
Not done
2
  10.0%
2
  20.0%
4
  13.3%
Thoracoabdominal MR angiography  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants 10 participants 30 participants
Normal
9
  45.0%
2
  20.0%
11
  36.7%
Abnormal
11
  55.0%
6
  60.0%
17
  56.7%
Not done
0
   0.0%
2
  20.0%
2
   6.7%
Symptoms and signs of giant cell arteritis  
Measure Type: Count of Participants
Unit of measure:  Participants
Fever >= 38°C Number Analyzed 20 participants 10 participants 30 participants
1
   5.0%
1
  10.0%
2
   6.7%
Weight loss > 2kg within 4 weeks Number Analyzed 20 participants 10 participants 30 participants
6
  30.0%
3
  30.0%
9
  30.0%
Night sweats Number Analyzed 20 participants 10 participants 30 participants
3
  15.0%
2
  20.0%
5
  16.7%
Headache Number Analyzed 20 participants 10 participants 30 participants
13
  65.0%
5
  50.0%
18
  60.0%
Scalp tenderness Number Analyzed 20 participants 10 participants 30 participants
9
  45.0%
1
  10.0%
10
  33.3%
Claudication of tongue Number Analyzed 20 participants 10 participants 30 participants
2
  10.0%
0
   0.0%
2
   6.7%
Masseter muscle claudication Number Analyzed 20 participants 10 participants 30 participants
11
  55.0%
4
  40.0%
15
  50.0%
Claudication of upper limbs Number Analyzed 20 participants 10 participants 30 participants
4
  20.0%
2
  20.0%
6
  20.0%
Claudication of lower limbs Number Analyzed 20 participants 10 participants 30 participants
0
   0.0%
2
  20.0%
2
   6.7%
Visual impairment Number Analyzed 20 participants 10 participants 30 participants
5
  25.0%
2
  20.0%
7
  23.3%
Blood pressure   [1] 
Mean (Standard Deviation)
Unit of measure:  mmHg
Systolic right arm Number Analyzed 20 participants 9 participants 29 participants
130.6  (18.0) 137.7  (16.4) 132.8  (17.5)
Diastolic right arm Number Analyzed 20 participants 9 participants 29 participants
74.3  (11.8) 77.7  (15.2) 75.3  (12.8)
Systolic left arm Number Analyzed 19 participants 8 participants 27 participants
131.3  (16.3) 136.9  (13.0) 132.9  (15.3)
Diastolic left arm Number Analyzed 19 participants 8 participants 27 participants
75.1  (11.5) 82.8  (8.5) 77.3  (11.1)
[1]
Measure Analysis Population Description: Missing data.
Erythrocyte sedimentation rate  
Median (Inter-Quartile Range)
Unit of measure:  Mm/h
Number Analyzed 20 participants 10 participants 30 participants
69.0
(45.5 to 80.0)
40.0
(27.3 to 68.8)
54.5
(40.0 to 80.0)
C-reactive protein  
Median (Inter-Quartile Range)
Unit of measure:  mg/L
Number Analyzed 20 participants 10 participants 30 participants
25.5
(16.8 to 50.3)
39.0
(23.5 to 64.3)
31.5
(19.8 to 54.3)
1.Primary Outcome
Title Number of Patients That Have Achieved Complete Remission of Disease
Hide Description [Not Specified]
Time Frame 12 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized patients, intention-to-treat
Arm/Group Title Tocilizumab Placebo
Hide Arm/Group Description:

Tocilizumab 8mg/kg every 4 weeks until week 52.

Tocilizumab + Glucocorticoids (GCs): Tocilizumab 8mg/kg every 4 weeks until week 52.

Placebo every 4 weeks until week 52.

Placebo + Glucocorticoids (GCs): Placebo every 4 weeks until week 52.

Overall Number of Participants Analyzed 20 10
Measure Type: Count of Participants
Unit of Measure: Participants
17
  85.0%
4
  40.0%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tocilizumab, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0301
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 0.45
Confidence Interval (2-Sided) 95%
0.11 to 0.79
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Number of Relapse Free Patients
Hide Description [Not Specified]
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized patients, intention-to-treat
Arm/Group Title Tocilizumab Placebo
Hide Arm/Group Description:

Tocilizumab 8mg/kg every 4 weeks until week 52.

Tocilizumab + Glucocorticoids (GCs): Tocilizumab 8mg/kg every 4 weeks until week 52.

Placebo every 4 weeks until week 52.

Placebo + Glucocorticoids (GCs): Placebo every 4 weeks until week 52.

Overall Number of Participants Analyzed 20 10
Measure Type: Count of Participants
Unit of Measure: Participants
17
  85.0%
2
  20.0%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tocilizumab, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0010
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 0.65
Confidence Interval (2-Sided) 95%
0.36 to 0.94
Estimation Comments [Not Specified]
3.Secondary Outcome
Title Cumulative Dose of GCs in mg/kg
Hide Description cumulative weight-adapted prednisolone dose
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized patients, intention-to-treat
Arm/Group Title Tocilizumab Placebo
Hide Arm/Group Description:

Tocilizumab 8mg/kg every 4 weeks until week 52.

Tocilizumab + Glucocorticoids (GCs): Tocilizumab 8mg/kg every 4 weeks until week 52.

Placebo every 4 weeks until week 52.

Placebo + Glucocorticoids (GCs): Placebo every 4 weeks until week 52.

Overall Number of Participants Analyzed 20 10
Median (Inter-Quartile Range)
Unit of Measure: mg/kg
43
(39 to 52)
110
(88 to 150)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tocilizumab, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0005
Comments [Not Specified]
Method Wilcoxon (Mann-Whitney)
Comments [Not Specified]
4.Secondary Outcome
Title Restricted Mean Survival Time to First Relapse After Induction of Remission
Hide Description [Not Specified]
Time Frame 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized patients, intention-to-treat
Arm/Group Title Tocilizumab Placebo
Hide Arm/Group Description:

Tocilizumab 8mg/kg every 4 weeks until week 52.

Tocilizumab + Glucocorticoids (GCs): Tocilizumab 8mg/kg every 4 weeks until week 52.

Placebo every 4 weeks until week 52.

Placebo + Glucocorticoids (GCs): Placebo every 4 weeks until week 52.

Overall Number of Participants Analyzed 20 10
Mean (95% Confidence Interval)
Unit of Measure: Weeks
50
(46 to 54)
25
(11 to 38)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tocilizumab, Placebo
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0005
Comments [Not Specified]
Method z-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 25
Confidence Interval (2-Sided) 95%
11 to 39
Estimation Comments Difference between restricted mean survival time at 12 months
Time Frame 1 year
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Tocilizumab Placebo
Hide Arm/Group Description

Tocilizumab 8mg/kg every 4 weeks until week 52.

Tocilizumab + Glucocorticoids (GCs): Tocilizumab 8mg/kg every 4 weeks until week 52.

Placebo every 4 weeks until week 52.

Placebo + Glucocorticoids (GCs): Placebo every 4 weeks until week 52.

All-Cause Mortality
Tocilizumab Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   0/20 (0.00%)      1/10 (10.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
Tocilizumab Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   7/20 (35.00%)      5/10 (50.00%)    
Blood and lymphatic system disorders     
Glucocorticoid related hyperglycaemia and myopathia   1/20 (5.00%)  1 2/10 (20.00%)  2
Cardiac disorders     
Cardiovascular disease   1/20 (5.00%)  1 2/10 (20.00%)  3
Gastrointestinal disorders     
Gastrointestinal disease   3/20 (15.00%)  3 1/10 (10.00%)  1
Infections and infestations     
Infectious disease   1/20 (5.00%)  1 0/10 (0.00%)  0
Injury, poisoning and procedural complications     
Osteoporotic fracture   0/20 (0.00%)  0 1/10 (10.00%)  2
Musculoskeletal and connective tissue disorders     
Back pain   0/20 (0.00%)  0 1/10 (10.00%)  2
Skin and subcutaneous tissue disorders     
Skin disease   1/20 (5.00%)  1 0/10 (0.00%)  0
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 0%
Tocilizumab Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   11/20 (55.00%)      6/10 (60.00%)    
Blood and lymphatic system disorders     
Glucocorticoid-related hyperglycaemia and myopathia   1/20 (5.00%)  2 1/10 (10.00%)  1
Cardiac disorders     
Cardiovascular disease   0/20 (0.00%)  0 2/10 (20.00%)  2
Gastrointestinal disorders     
Gastrointestinal disease   1/20 (5.00%)  1 0/10 (0.00%)  0
Infections and infestations     
Infectious disease   7/20 (35.00%)  9 1/10 (10.00%)  1
Injury, poisoning and procedural complications     
Osteoporotic fracture   1/20 (5.00%)  1 1/10 (10.00%)  1
Musculoskeletal and connective tissue disorders     
Musculoskeletal disease   4/20 (20.00%)  5 3/10 (30.00%)  6
Reproductive system and breast disorders     
Cystic lesion mamma   1/20 (5.00%)  1 0/10 (0.00%)  0
Skin and subcutaneous tissue disorders     
Skin disease   0/20 (0.00%)  0 2/10 (20.00%)  2
Indicates events were collected by systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Prof Peter M Villiger
Organization: Department of Rheumatology, Immunology and Allergology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
EMail: peter.villiger@insel.ch
Layout table for additonal information
Responsible Party: University Hospital Inselspital, Berne
ClinicalTrials.gov Identifier: NCT01450137     History of Changes
Other Study ID Numbers: 168/10
First Submitted: October 3, 2011
First Posted: October 12, 2011
Results First Submitted: July 3, 2017
Results First Posted: February 12, 2019
Last Update Posted: February 12, 2019