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Trial record 42 of 130 for:    GCA

A 3-arm Proof of Concept Study of AIN457, ACZ885 or Corticosteroids in Patients With Polymyalgia Rheumatica

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01364389
Recruitment Status : Terminated (Data did not show that the two biologic treatments impacted PMR disease activity to the same degree as steroid treatment within a 2-week treatment period.)
First Posted : June 2, 2011
Results First Posted : March 4, 2015
Last Update Posted : May 4, 2018
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Polymyalgia Rheumatica
Inflammatory Diseases
Interventions Drug: AIN457
Drug: ACZ885
Drug: Prednisone
Drug: Placebo
Enrollment 16
Recruitment Details  
Pre-assignment Details  
Arm/Group Title ACZ885 AIN457 Prednisone
Hide Arm/Group Description On day 1, patients received a single intravenous dose of ACZ885 3mg/kg along with a placebo intravenous infusion in a double dummy manner to maintain the blind. On day 15, partial and complete responders continued in the open label phase of this treatment arm where they were eligible to receive one re-dose of ACZ885 upon confirmed disease flare. Non-responders started a 20 mg dose cycle of prednisone or prednisolone followed by standard steroid tapering. On day 1, patients received a single intravenous dose of AIN457 3mg/kg along with a placebo intravenous infusion in a double dummy manner to maintain the blind. On day 15, partial and complete responders continued in the open label phase of this treatment arm where they were eligible to receive one re-dose of AIN457 upon confirmed disease flare. Non-responders started a 20 mg dose cycle of prednisone or prednisolone followed by standard steroid tapering. On day 1, patients received daily oral doses of prednisone 20 mg along with daily oral placebo doses to in a double-dummy manner to maintain the blind. On day 15, partial and complete responders continued in the study and tapered their steroid treatment according to standard care. Non-responders were discontinued from the study.
Period Title: Overall Study
Started 5 6 5
Pharmacodynamic (PD) Analysis Set 5 6 4 [1]
Completed 3 5 4
Not Completed 2 1 1
Reason Not Completed
Withdrawal by Subject             0             1             0
Protocol deviation             0             0             1
Administrative problems             1             0             0
Adverse Event             1             0             0
[1]
One patient excluded: did not receive study drug; received placebo caps. and infusion only in error.
Arm/Group Title ACZ885 AIN457 Prednisone Total
Hide Arm/Group Description On day 1, patients received a single intravenous dose of ACZ885 3mg/kg along with a placebo intravenous infusion in a double dummy manner to maintain the blind. On day 15, partial and complete responders continued in the open label phase of this treatment arm where they were eligible to receive one re-dose of ACZ885 upon confirmed disease flare. Non-responders started a 20 mg dose cycle of prednisone or prednisolone followed by standard steroid tapering. On day 1, patients received a single intravenous dose of AIN457 3mg/kg along with a placebo intravenous infusion in a double dummy manner to maintain the blind. On day 15, partial and complete responders continued in the open label phase of this treatment arm where they were eligible to receive one re-dose of AIN457 upon confirmed disease flare. Non-responders started a 20 mg dose cycle of prednisone or prednisolone followed by standard steroid tapering. On day 1, patients received daily oral doses of prednisone 20 mg along with daily oral placebo doses to in a double-dummy manner to maintain the blind. On day 15, partial and complete responders continued in the study and tapered their steroid treatment according to standard care. Non-responders were discontinued from the study. Total of all reporting groups
Overall Number of Baseline Participants 5 6 5 16
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 5 participants 6 participants 5 participants 16 participants
67.2  (9.09) 68.8  (8.61) 69.4  (7.89) 68.5  (8.02)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 5 participants 6 participants 5 participants 16 participants
Female
4
  80.0%
2
  33.3%
5
 100.0%
11
  68.8%
Male
1
  20.0%
4
  66.7%
0
   0.0%
5
  31.3%
1.Primary Outcome
Title Polymyalgia Rheumatica Activity Score (PMR-AS)
Hide Description The efficacy of a single dose of AIN457 and ACZ885 (canakinumab) was measured by the polymyalgia rheumatica activity score. A composite PMR-AS was developed from the following components: measure of C-reactive protein (CRP), measure of Erythrocyte Sedimentation Rate (ESR), assessment of early morning stiffness, assessment of the patient’s elevation on upper limbs, patient’s assessment of pain, and physician’s global assessment of disease activity. Treatment effect was measured by the percent reduction in PMR-AS. N=3 for the ACZ885 arm because CRP values at Day 15 were missing for 2 participants.
Time Frame Baseline, Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacodynamic (PD) Analysis Set: This set included participants who received at least one dose of study medication and had no major protocol deviation that may impact the PD data.
Arm/Group Title ACZ885 AIN457 Prednisone
Hide Arm/Group Description:
On day 1, patients received a single intravenous dose of ACZ885 3mg/kg along with a placebo intravenous infusion in a double dummy manner to maintain the blind. On day 15, partial and complete responders continued in the open label phase of this treatment arm where they were eligible to receive one re-dose of ACZ885 upon confirmed disease flare. Non-responders started a 20 mg dose cycle of prednisone or prednisolone followed by standard steroid tapering.
On day 1, patients received a single intravenous dose of AIN457 3mg/kg along with a placebo intravenous infusion in a double dummy manner to maintain the blind. On day 15, partial and complete responders continued in the open label phase of this treatment arm where they were eligible to receive one re-dose of AIN457 upon confirmed disease flare. Non-responders started a 20 mg dose cycle of prednisone or prednisolone followed by standard steroid tapering.
On day 1, patients received daily oral doses of prednisone 20 mg along with daily oral placebo doses to in a double-dummy manner to maintain the blind. On day 15, partial and complete responders continued in the study and tapered their steroid treatment according to standard care. Non-responders were discontinued from the study.
Overall Number of Participants Analyzed 3 6 4
Least Squares Mean (Standard Error)
Unit of Measure: Percent reduction
64.5  (0.68) 51.7  (0.47) 91.9  (86.2)
2.Secondary Outcome
Title Time to Partial Clinical Response
Hide Description

The time to partial clinical response was assessed in patients who received a single dose of AIN457 or ACZ885 (canakinumab). Daily monitoring (home-based) of CRP was performed. This outcome shows the percentage of patients who achieved a partial clinical response at Day 15. A participant was defined as a partial responder if the participant had:

>50% reduction in patient global assessment visual analogue scale (VAS) compared with baseline and morning stiffness < 60 minutes.

Time Frame Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
PD analysis set
Arm/Group Title ACZ885 AIN457 Prednisone
Hide Arm/Group Description:
On day 1, patients received a single intravenous dose of ACZ885 3mg/kg along with a placebo intravenous infusion in a double dummy manner to maintain the blind. On day 15, partial and complete responders continued in the open label phase of this treatment arm where they were eligible to receive one re-dose of ACZ885 upon confirmed disease flare. Non-responders started a 20 mg dose cycle of prednisone or prednisolone followed by standard steroid tapering.
On day 1, patients received a single intravenous dose of AIN457 3mg/kg along with a placebo intravenous infusion in a double dummy manner to maintain the blind. On day 15, partial and complete responders continued in the open label phase of this treatment arm where they were eligible to receive one re-dose of AIN457 upon confirmed disease flare. Non-responders started a 20 mg dose cycle of prednisone or prednisolone followed by standard steroid tapering.
On day 1, patients received daily oral doses of prednisone 20 mg along with daily oral placebo doses to in a double-dummy manner to maintain the blind. On day 15, partial and complete responders continued in the study and tapered their steroid treatment according to standard care. Non-responders were discontinued from the study.
Overall Number of Participants Analyzed 5 6 4
Measure Type: Number
Unit of Measure: Percentage of participants
20.0 16.7 75.0
3.Secondary Outcome
Title Time to Complete Clinical Response
Hide Description The time to complete clinical response was assessed in patients who received a single dose of AIN457 or ACZ885 (canakinumab). Daily monitoring (home-based) of CRP was performed. This outcome shows the percentage of patients who achieved a complete clinical response at Day 15. A participant was defined as a complete responder if the participant had: >70% reduction in patient global assessment VAS compared with baseline, morning stiffness < 30 min, CRP < 1.0 mg/dL and/or ESR < 30 mm/1st hr.
Time Frame Day 15
Hide Outcome Measure Data
Hide Analysis Population Description
PD analysis set
Arm/Group Title ACZ885 AIN457 Prednisone
Hide Arm/Group Description:
On day 1, patients received a single intravenous dose of ACZ885 3mg/kg along with a placebo intravenous infusion in a double dummy manner to maintain the blind. On day 15, partial and complete responders continued in the open label phase of this treatment arm where they were eligible to receive one re-dose of ACZ885 upon confirmed disease flare. Non-responders started a 20 mg dose cycle of prednisone or prednisolone followed by standard steroid tapering.
On day 1, patients received a single intravenous dose of AIN457 3mg/kg along with a placebo intravenous infusion in a double dummy manner to maintain the blind. On day 15, partial and complete responders continued in the open label phase of this treatment arm where they were eligible to receive one re-dose of AIN457 upon confirmed disease flare. Non-responders started a 20 mg dose cycle of prednisone or prednisolone followed by standard steroid tapering.
On day 1, patients received daily oral doses of prednisone 20 mg along with daily oral placebo doses to in a double-dummy manner to maintain the blind. On day 15, partial and complete responders continued in the study and tapered their steroid treatment according to standard care. Non-responders were discontinued from the study.
Overall Number of Participants Analyzed 5 6 4
Measure Type: Number
Unit of Measure: Percentage of participants
0.0 0.0 25.0
4.Secondary Outcome
Title Time to First Flare
Hide Description [Not Specified]
Time Frame 6 months
Outcome Measure Data Not Reported
5.Secondary Outcome
Title Number of Flares Over a 6 Month Period
Hide Description [Not Specified]
Time Frame 6 months
Outcome Measure Data Not Reported
6.Secondary Outcome
Title Cumulative and/or Mean Steroid Dose Over a 6 Month Period
Hide Description [Not Specified]
Time Frame 6 months
Outcome Measure Data Not Reported
7.Secondary Outcome
Title Number of Patients Who Experienced Adverse Events, Serious Adverse Events and Deaths
Hide Description [Not Specified]
Time Frame 6 months
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set: This set included all participants who received at least one dose of study medication.
Arm/Group Title ACZ885 AIN457 Prednisone
Hide Arm/Group Description:
On day 1, patients received a single intravenous dose of ACZ885 3mg/kg along with a placebo intravenous infusion in a double dummy manner to maintain the blind. On day 15, partial and complete responders continued in the open label phase of this treatment arm where they were eligible to receive one re-dose of ACZ885 upon confirmed disease flare. Non-responders started a 20 mg dose cycle of prednisone or prednisolone followed by standard steroid tapering.
On day 1, patients received a single intravenous dose of AIN457 3mg/kg along with a placebo intravenous infusion in a double dummy manner to maintain the blind. On day 15, partial and complete responders continued in the open label phase of this treatment arm where they were eligible to receive one re-dose of AIN457 upon confirmed disease flare. Non-responders started a 20 mg dose cycle of prednisone or prednisolone followed by standard steroid tapering.
On day 1, patients received daily oral doses of prednisone 20 mg along with daily oral placebo doses to in a double-dummy manner to maintain the blind. On day 15, partial and complete responders continued in the study and tapered their steroid treatment according to standard care. Non-responders were discontinued from the study.
Overall Number of Participants Analyzed 5 6 5
Measure Type: Number
Unit of Measure: Participants
Adverse Events (serious and non-serious) 3 2 5
Serious Adverse Events 0 0 0
Deaths 0 0 0
8.Secondary Outcome
Title Pharmacokinetics of AIN457 and ACZ885
Hide Description [Not Specified]
Time Frame Day 15
Outcome Measure Data Not Reported
9.Secondary Outcome
Title Comparison Between the Initial Response to AIN457 and ACZ885 and the Response After Re-dosing of AIN457 and ACZ885
Hide Description [Not Specified]
Time Frame 6 months
Outcome Measure Data Not Reported
10.Secondary Outcome
Title Effect on Health-related Quality of Life
Hide Description [Not Specified]
Time Frame 6 months
Outcome Measure Data Not Reported
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title ACZ885 3mg/kg AIN457 3mg/kg Prednisone 20mg
Hide Arm/Group Description On day 1, patients received a single intravenous dose of ACZ885 3mg/kg along with a placebo intravenous infusion in a double dummy manner to maintain the blind. On day 15, partial and complete responders continued in the open label phase of this treatment arm where they were eligible to receive one re-dose of ACZ885 upon confirmed disease flare. Non-responders started a 20 mg dose cycle of prednisone or prednisolone followed by standard steroid tapering. On day 1, patients received a single intravenous dose of AIN457 3mg/kg along with a placebo intravenous infusion in a double dummy manner to maintain the blind. On day 15, partial and complete responders continued in the open label phase of this treatment arm where they were eligible to receive one re-dose of AIN457 upon confirmed disease flare. Non-responders started a 20 mg dose cycle of prednisone or prednisolone followed by standard steroid tapering. On day 1, patients received daily oral doses of prednisone 20 mg along with daily oral placebo doses to in a double-dummy manner to maintain the blind. On day 15, partial and complete responders continued in the study and tapered their steroid treatment according to standard care. Non-responders were discontinued from the study.
All-Cause Mortality
ACZ885 3mg/kg AIN457 3mg/kg Prednisone 20mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
ACZ885 3mg/kg AIN457 3mg/kg Prednisone 20mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/5 (0.00%)   0/6 (0.00%)   0/5 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
ACZ885 3mg/kg AIN457 3mg/kg Prednisone 20mg
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   3/5 (60.00%)   2/6 (33.33%)   5/5 (100.00%) 
Ear and labyrinth disorders       
Vertigo  1  0/5 (0.00%)  0/6 (0.00%)  1/5 (20.00%) 
Eye disorders       
Eye pain  1  0/5 (0.00%)  1/6 (16.67%)  0/5 (0.00%) 
Gastrointestinal disorders       
Abdominal pain upper  1  0/5 (0.00%)  0/6 (0.00%)  1/5 (20.00%) 
Dyspepsia  1  0/5 (0.00%)  1/6 (16.67%)  0/5 (0.00%) 
Gastrooesophageal reflux disease  1  1/5 (20.00%)  0/6 (0.00%)  0/5 (0.00%) 
Oral mucosal blistering  1  0/5 (0.00%)  0/6 (0.00%)  1/5 (20.00%) 
Toothache  1  1/5 (20.00%)  0/6 (0.00%)  0/5 (0.00%) 
Infections and infestations       
Bronchitis  1  0/5 (0.00%)  0/6 (0.00%)  1/5 (20.00%) 
Nasopharyngitis  1  0/5 (0.00%)  1/6 (16.67%)  0/5 (0.00%) 
Sinusitis  1  1/5 (20.00%)  0/6 (0.00%)  0/5 (0.00%) 
Upper respiratory tract infection  1  1/5 (20.00%)  0/6 (0.00%)  1/5 (20.00%) 
Investigations       
Blood pressure increased  1  0/5 (0.00%)  1/6 (16.67%)  0/5 (0.00%) 
Weight increased  1  0/5 (0.00%)  0/6 (0.00%)  1/5 (20.00%) 
Metabolism and nutrition disorders       
Type 2 diabetes mellitus  1  0/5 (0.00%)  1/6 (16.67%)  0/5 (0.00%) 
Musculoskeletal and connective tissue disorders       
Arthralgia  1  1/5 (20.00%)  1/6 (16.67%)  1/5 (20.00%) 
Arthritis  1  0/5 (0.00%)  0/6 (0.00%)  1/5 (20.00%) 
Joint swelling  1  1/5 (20.00%)  1/6 (16.67%)  0/5 (0.00%) 
Muscle spasms  1  0/5 (0.00%)  0/6 (0.00%)  1/5 (20.00%) 
Seronegative arthritis  1  0/5 (0.00%)  1/6 (16.67%)  0/5 (0.00%) 
Nervous system disorders       
Headache  1  0/5 (0.00%)  1/6 (16.67%)  1/5 (20.00%) 
Lethargy  1  0/5 (0.00%)  1/6 (16.67%)  0/5 (0.00%) 
Presyncope  1  0/5 (0.00%)  0/6 (0.00%)  1/5 (20.00%) 
Psychiatric disorders       
Insomnia  1  1/5 (20.00%)  0/6 (0.00%)  0/5 (0.00%) 
Sleep disorder  1  0/5 (0.00%)  1/6 (16.67%)  1/5 (20.00%) 
Respiratory, thoracic and mediastinal disorders       
Oropharyngeal pain  1  1/5 (20.00%)  0/6 (0.00%)  0/5 (0.00%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
This study was terminated because the data did not show that the two biologic treatments impacted PMR disease activity to the same degree as steroid treatment within a 2-week treatment period.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
Layout table for additonal information
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT01364389     History of Changes
Other Study ID Numbers: CPJMR0012201
2010-019395-73 ( EudraCT Number )
First Submitted: March 10, 2011
First Posted: June 2, 2011
Results First Submitted: February 17, 2015
Results First Posted: March 4, 2015
Last Update Posted: May 4, 2018