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Efficacy, Safety and Tolerability of ACZ885 in Patients With Active Rheumatoid Arthritis

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ClinicalTrials.gov Identifier: NCT00424346
Recruitment Status : Completed
First Posted : January 19, 2007
Results First Posted : June 19, 2013
Last Update Posted : February 10, 2014
Sponsor:
Information provided by (Responsible Party):
Novartis

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition: Rheumatoid Arthritis
Interventions: Drug: Canakinumab
Drug: Placebo

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
277 patients were randomized in core (CACZ885A2201): 71 were assigned to ACZ885 600 mg intravenous(iv) + 300 mg subcutaneous each 2 weeks(sc q2wk), 66 to ACZ885 300 mg sc q2wk, 69 to ACZ885 150 mg sc q4wk, 71 to placebo. 3 were randomized but not treated. All other 274 (98.9%) were treated and had post-baseline efficacy data.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Enrollment in core & CACZ885A2201E2 was determined by how many entered first extension study. Study protocols did not mandate that patients continue treatment in the extension phase and furthermore the reason for not continuing from the Core to the Extension phase was not capture. A total of 6.6% completed extensions.

Reporting Groups
  Description
Canakinumab 600 mg IV + 300 mg q2wk Participants received canakinumab 600 mg intravenous (IV) loading dose on Day 1 and 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg every 4 weeks. Participants in this treatment group who participated in the Extension Phase are represented in the 'Canakinumab 300 mg q2wk' treatment group in the Extension Phase table below.
Canakinumab 300 mg q2wk Participants received canakinumab 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.
Canakinumab 150 mg q4wk Participants received canakinumab 150 mg subcutaneous injections every 4 weeks (q4wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.
Placebo Participants received placebo subcutaneous injections every 2 weeks for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.

Participant Flow for 2 periods

Period 1:   Core Study
    Canakinumab 600 mg IV + 300 mg q2wk   Canakinumab 300 mg q2wk   Canakinumab 150 mg q4wk   Placebo
STARTED   71   64   69   70 
COMPLETED   62   56   65   63 
NOT COMPLETED   9   8   4   7 
Adverse Event                5                3                1                1 
Abnormal Laboratory Values                0                1                0                0 
Lack of Efficacy                1                3                0                4 
Withdrawal by Subject                1                0                0                2 
Lost to Follow-up                1                1                0                0 
Administrative Problems                1                0                1                0 
Protocol Violation                0                0                2                0 

Period 2:   Extension Phase
    Canakinumab 600 mg IV + 300 mg q2wk   Canakinumab 300 mg q2wk   Canakinumab 150 mg q4wk   Placebo
STARTED   0 [1]   110 [2]   59   58 
COMPLETED   0   8   4   3 
NOT COMPLETED   0   102   55   55 
Adverse Event                0                9                5                4 
Lack of Efficacy                0                16                14                11 
Withdrawal by Subject                0                5                3                4 
Lost to Follow-up                0                2                0                0 
Administrative Problems                0                69                32                35 
Death                0                0                0                1 
Protocol Violation                0                1                1                0 
[1] Participants are represented in the Canakinumab 300 mg q2wk treatment group.
[2] Includes participants who completed the Core phase in the Canakinumab 600 mg IV + 300 mg q2wk group.



  Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Canakinumab 600 mg IV + 300 mg q2wk Participants received canakinumab 600 mg intravenous (IV) loading dose on Day 1 and 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg every 4 weeks.
Canakinumab 300 mg q2wk Participants received canakinumab 300 mg subcutaneous injections every 2 weeks (q2wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.
Canakinumab 150 mg q4wk Participants received canakinumab 150 mg subcutaneous injections every 4 weeks (q4wk) for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.
Placebo Participants received placebo subcutaneous injections every 2 weeks for 12 weeks in the Core Phase. In the Extension Phase, participants received 300 mg canakinumab every 4 weeks subcutaneously, until a protocol amendment in January 2009 decreased the dose to 150 mg subcutaneous injection every 4 weeks.
Total Total of all reporting groups

Baseline Measures
   Canakinumab 600 mg IV + 300 mg q2wk   Canakinumab 300 mg q2wk   Canakinumab 150 mg q4wk   Placebo   Total 
Overall Participants Analyzed 
[Units: Participants]
 71   64   69   70   274 
Age, Customized [1] 
[Units: Participants]
         
≥18 - <41 years   5   5   7   7   24 
≥41 - <65 years   50   31   43   43   167 
≥65 - <75 years   11   18   16   16   61 
≥75 years   5   10   3   4   22 
[1] Demographics for the Core Study population. The number of patients in the core phase was 274.
Age, Customized [1] [2] 
[Units: Participants]
         
≥18 - <41 years   NA [2]   7   6   6   19 
≥41 - <65 years   NA [2]   66   39   38   143 
≥65 - <75 years   NA [2]   25   12   12   49 
≥75 years   NA [2]   12   2   2   16 
[1] Demographics for the Extension study population. The number of participants in the optional extension phase was less than the overall number of baseline participants who started the study. Total number of patients is 227.
[2] This group did not exist in the extension studies, only in core.
Gender [1] 
[Units: Participants]
         
Female   60   57   56   52   225 
Male   11   7   13   18   49 
[1] Demographics for the Core Study population.
Gender [1] 
[Units: Participants]
         
Female   0   94   47   44   185 
Male   0   16   12   14   42 
[1] Demographics for the Extension study population. The number of patients in the optional extension phase was less than the overall number of baseline participants who started the study. Total number of patients is 227.


  Outcome Measures

1.  Primary:   Percentage of American College of Rheumatology [ACR] 50 Criteria Responders at Week 12   [ Time Frame: Baseline and Week 12 ]

2.  Primary:   Percentage of American College of Rheumatology [ACR] 20 Criteria Responders During the Extension Phase   [ Time Frame: Baseline and Weeks 24, 36, 48, 60, 72, 88, 100, 112 and 124 ]

3.  Primary:   Percentage of American College of Rheumatology [ACR] 50 Criteria Responders During the Extension Phase   [ Time Frame: Baseline and Weeks 24, 36, 48, 60, 72, 88, 100, 112 and 124 ]

4.  Primary:   Percentage of American College of Rheumatology [ACR] 70 Criteria Responders During the Extension Phase   [ Time Frame: Baseline and Weeks 24, 36, 48, 60, 72, 88, 100, 112 and 124 ]

5.  Primary:   Change From Baseline in Disease Activity Score (DAS) 28 During the Extension Phase   [ Time Frame: Baseline and Weeks 24, 72 and 112 ]

6.  Secondary:   Percentage of American College of Rheumatology [ACR] 50 Criteria Responders at Weeks 2, 4 and 8   [ Time Frame: Baseline and Weeks 2, 4 and 8 ]

7.  Secondary:   Percentage of American College of Rheumatology [ACR] 20 Criteria Responders   [ Time Frame: Baseline and Weeks 2, 4, 8 and 12 ]

8.  Secondary:   Percentage of American College of Rheumatology [ACR] 70 Criteria Responders   [ Time Frame: Baseline and Weeks 2, 4, 8 and 12 ]

9.  Secondary:   Number of Distinct Responders According to ACR20, ACR50 and ACR70 Criteria at Week 12   [ Time Frame: Baseline and Week 12 ]

10.  Secondary:   Change From Baseline in Swollen 28-joint Count   [ Time Frame: Baseline and Weeks 2, 4, 8 and 12 ]

11.  Secondary:   Change From Baseline in Tender 28-joint Count   [ Time Frame: Baseline and Weeks 2, 4, 8 and 12 ]

12.  Secondary:   Change From Baseline in Patient’s Pain Intensity   [ Time Frame: Baseline and Weeks 2, 4, 8 and 12 ]

13.  Secondary:   Change From Baseline in Patient’s Global Assessment of Disease Activity   [ Time Frame: Baseline and Weeks 2, 4, 8 and 12 ]

14.  Secondary:   Change From Baseline in Physician’s Global Assessment of Disease Activity   [ Time Frame: Baseline and Weeks 2, 4, 8 and 12 ]

15.  Secondary:   Change From Baseline in Health Assessment Questionnaire (HAQ) Score   [ Time Frame: Baseline and Weeks 2, 4, 8 and 12 ]

16.  Secondary:   Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels   [ Time Frame: Baseline and Weeks 2, 4, 8 and 12 ]

17.  Secondary:   Change From Baseline in Disease Activity Score (DAS) 28   [ Time Frame: Baseline and Weeks 2, 4, 8 and 12 ]

18.  Secondary:   Change From Baseline in Erythrocyte Sedimentation Rate   [ Time Frame: Baseline and Weeks 2, 4, 8 and 12 ]

19.  Secondary:   Change From Baseline in Rheumatoid Factor Concentration   [ Time Frame: Baseline and Weeks 4, 8 and 12 ]

20.  Secondary:   Change From Baseline in Short Form 36 Health Survey (SF-36)   [ Time Frame: Baseline and Weeks 2, 4, 8 and 12 ]

21.  Secondary:   Change From Baseline in Functional Assessment of Chronic Illness Therapy- Fatigue (FACIT-F)   [ Time Frame: Baseline and Weeks 2, 4, 8 and 12 ]

22.  Secondary:   Number of Distinct Responders According to ACR20, ACR50 and ACR70 Criteria at the End of the Extension Study   [ Time Frame: Baseline and End of Study (up to 124 weeks) ]

23.  Secondary:   Change From Baseline in Swollen 28-joint Count During the Extension Study   [ Time Frame: Baseline and Weeks 24, 36, 48, 60, 72, 88, 100, 112 and 124. ]

24.  Secondary:   Change From Baseline in Tender 28-joint Count During the Extension Study   [ Time Frame: Baseline and Weeks 24, 36, 48, 60, 72, 88, 100, 112 and 124. ]

25.  Secondary:   Change From Baseline in Patient's Pain Intensity During the Extension Study   [ Time Frame: Baseline and Weeks 24, 36, 48, 60, 72, 88, 100, 112 and 124. ]

26.  Secondary:   Change From Baseline in Patient's Global Assessment of Disease Activity During the Extension Study   [ Time Frame: Baseline and Weeks 24, 36, 48, 60, 72, 88, 100, 112 and 124. ]

27.  Secondary:   Change From Baseline in Physician's Global Assessment of Disease Activity During the Extension Study   [ Time Frame: Baseline and Weeks 24, 36, 48, 60, 72, 88, 100, 112 and 124. ]

28.  Secondary:   Change From Baseline in Health Assessment Questionnaire (HAQ) Score During the Extension Study   [ Time Frame: Baseline and Weeks 24, 36, 48, 60, 72, 88, 100, 112 and 124. ]

29.  Secondary:   Change From Baseline in High-sensitive C-Reactive Protein (hsCRP) Levels During the Extension Study   [ Time Frame: Baseline and Weeks 24, 36, 48, 60, 72, 88, 100, 112 and 124. ]

30.  Secondary:   Change From Baseline in Erythrocyte Sedimentation Rate During the Extension Study   [ Time Frame: Baseline and Weeks 24, 36, 48, 60, 72 and 88. ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information

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 agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Study Director
Organization: Novartis Pharmaceuticals
phone: 862-778-8300


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Novartis
ClinicalTrials.gov Identifier: NCT00424346     History of Changes
Obsolete Identifiers: NCT00471198, NCT00784628
Other Study ID Numbers: CACZ885A2201
CACZ885A2201E1
CACZ885A2201E2
First Submitted: January 17, 2007
First Posted: January 19, 2007
Results First Submitted: April 2, 2013
Results First Posted: June 19, 2013
Last Update Posted: February 10, 2014