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Efficacy and Safety of Two Treatment Algorithms in Adults With Moderate to Severe Crohn's Disease (CALM)

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ClinicalTrials.gov Identifier: NCT01235689
Recruitment Status : Completed
First Posted : November 5, 2010
Results First Posted : December 7, 2017
Last Update Posted : January 16, 2018
Sponsor:
Information provided by (Responsible Party):
AbbVie ( AbbVie (prior sponsor, Abbott) )

Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition: Crohn's Disease
Interventions: Biological: Adalimumab
Drug: Prednisone
Drug: Azathioprine

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations

This study was conducted at 59 sites in Canada, European Union, Israel, Japan, Russia, South Africa, Switzerland, Turkey, and the Ukraine.

The study included a screening period, up to 8 weeks of prednisone run-in treatment, a 48-week post-randomization treatment period, and a 70 day follow-up phone call or clinic visit.


Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment

A total of 252 participants were enrolled and received study treatment, of whom

  • 165 entered the prednisone run-in

    • 157 randomized (45 prior to Week 9, 112 at Week 9)
    • 8 discontinued prior to randomization.
  • 87 randomized at Baseline.

Randomization was stratified by smoking status, weight, and disease duration.


Reporting Groups
  Description
Clinically Driven Management

Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI) and corticosteroid use.

Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.

Participants who randomized at Week 9 meeting success criteria started with no therapy; participants who randomized prior to Week 9 or who randomized at Week 9 but did not meet the success criteria began treatment with adalimumab.

Therapy was escalated according to pre-specified failure criteria using less stringent criteria:

At Key Visit 1 the criteria for management of disease activity were a CDAI decrease ≥ 70 (CR-70) compared to Baseline or CDAI < 200 at 1 week prior to the visit. At Key Visits 3, 4, and 5 (every 12 weeks after Key visit 1), the criteria for a change in treatment were a CDAI decrease of ≥ 100 (CR-100) compared to Baseline or CDAI < 200, and absence of prednisone during the preceding week.

Tight Control Management

Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI), high sensitivity C-reactive protein (hs-CRP), fecal calprotectin, and corticosteroid use.

Participants received customized therapy that could include prednisone, adalimumab, and azathioprine. Participants who randomized at Week 9 meeting success criteria started with no therapy; participants who randomized prior to Week 9 or who randomized at Week 9 but did not meet the success criteria began treatment with adalimumab.

Therapy was escalated according to pre-specified tight control criteria: At Key Visit 1 the success criteria were CDAI < 150, hs-CRP, < 5 mg/L, fecal calprotectin < 250 μg/g, and absence of prednisone use. At Key Visits 3, 4, and 5 (every 12 weeks after Key visit 1), the criteria were CDAI < 150, hs-CRP < 5 mg/L, fecal calprotectin < 250 μg/g, and absence of prednisone during the preceding week.


Participant Flow:   Overall Study
    Clinically Driven Management   Tight Control Management
STARTED   122 [1]   122 [1] 
Early Randomized (Baseline to Week 9)   63   69 
Randomized at Week 9   59   53 
COMPLETED   93   90 
NOT COMPLETED   29   32 
Adverse Event                12                16 
Lack of Efficacy                12                5 
Withdrawal by Subject                3                4 
Lost to Follow-up                1                2 
Miscellaneous                1                5 
[1] Total randomized includes participants who randomized at Week 9 and earlier.



  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
Clinically Driven Management

Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI) and corticosteroid use.

Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.

Tight Control Management

Participants randomized to receive management of disease activity using criteria based on Crohn's Disease Activity Index (CDAI), high sensitivity C-reactive protein (hs-CRP), fecal calprotectin, and corticosteroid use.

Participants received customized therapy that could include prednisone, adalimumab, and azathioprine.

Total Total of all reporting groups

Baseline Measures
   Clinically Driven Management   Tight Control Management   Total 
Overall Participants Analyzed 
[Units: Participants]
 122   122   244 
Age 
[Units: Years]
Mean (Standard Deviation)
 31.10  (11.40)   32.10  (11.97)   31.60  (11.67) 
Age, Customized 
[Units: Participants]
Count of Participants
     
< 40 years      97  79.5%      96  78.7%      193  79.1% 
40 to < 65 years      23  18.9%      24  19.7%      47  19.3% 
≥ 65 years      2   1.6%      2   1.6%      4   1.6% 
Sex: Female, Male 
[Units: Participants]
Count of Participants
     
Female      69  56.6%      72  59.0%      141  57.8% 
Male      53  43.4%      50  41.0%      103  42.2% 
Race/Ethnicity, Customized 
[Units: Participants]
Count of Participants
     
White      113  92.6%      113  92.6%      226  92.6% 
Black      2   1.6%      3   2.5%      5   2.0% 
Asian      3   2.5%      2   1.6%      5   2.0% 
American Indian/Alaska Native      0   0.0%      0   0.0%      0   0.0% 
Native Hawaiian or other Pacific Islander      0   0.0%      0   0.0%      0   0.0% 
Multi-race      1   0.8%      1   0.8%      2   0.8% 
Other      3   2.5%      3   2.5%      6   2.5% 
Weight 
[Units: Participants]
Count of Participants
     
< 70 kg      79  64.8%      81  66.4%      160  65.6% 
≥ 70 kg      43  35.2%      41  33.6%      84  34.4% 
Current Tobacco Use 
[Units: Participants]
Count of Participants
     
Yes      33  27.0%      31  25.4%      64  26.2% 
No      89  73.0%      91  74.6%      180  73.8% 
Disease Duration 
[Units: Participants]
Count of Participants
     
≤ 2 years      106  86.9%      106  86.9%      212  86.9% 
> 2 years      16  13.1%      16  13.1%      32  13.1% 
Crohn's Disease Endoscopy Index of Severity (CDEIS) [1] 
[Units: Units on a scale]
Mean (Standard Deviation)
 14.26  (6.925)   13.38  (6.049)   13.82  (6.503) 
[1] CDEIS is an index for determining the severity of Crohn's disease. The CDEIS considers deep ulcerations, superficial ulcerations, ulcerated and non-ulcerated surface, and the presence of ulcerated/non-ulcerated stenosis evaluated in 5 pre-defined segments of the colon (ileum, ascending colon, transverse colon, descending colon and sigmoid loop, and rectum). The score ranges from 0 to 44 where higher scores indicate more severe endoscopic activity.
Crohn's Disease Activity Index (CDAI) [1] 
[Units: Units on a scale]
Mean (Standard Deviation)
 267.7  (58.35)   273.3  (59.48)   270.5  (58.86) 
[1] CDAI is a tool used to quantify the symptoms of patients with Crohn's disease. Participants were asked to record the frequency of stools, abdominal pain and general well-being on a daily basis. In addition to the diary data, the investigator assessed the following for the calculation of CDAI: presence of complications, the use of antidiarrheal medicines, presence of an abdominal mass, hematocrit, and body weight. The CDAI is the sum of the products of each item multiplied by a weighting factor and generally ranges from 0 up to 600, where higher scores indicate more severe disease.


  Outcome Measures

1.  Primary:   Percentage of Participants With Mucosal Healing and No Deep Ulcerations   [ Time Frame: 48 weeks after Randomization ]

2.  Secondary:   Percentage of Participants in Deep Remission 48 Weeks After Randomization   [ Time Frame: 48 weeks after Randomization ]

3.  Secondary:   Percentage of Participants in Biologic Remission 48 Weeks After Randomization   [ Time Frame: 48 weeks after Randomization ]

4.  Secondary:   Percentage of Participants With Mucosal Healing 48 Weeks After Randomization   [ Time Frame: 48 weeks after Randomization ]

5.  Secondary:   Percentage of Participants With Mucosal Healing and CDEIS < 4 in Every Segment 48 Weeks After Randomization   [ Time Frame: 48 weeks after Randomization ]

6.  Secondary:   Percentage of Participants With Complete Mucosal Healing 48 Weeks After Randomization   [ Time Frame: 48 weeks after Randomization ]

7.  Secondary:   Percentage of Participants With Endoscopic Response 48 Weeks After Randomization   [ Time Frame: 48 weeks after Randomization ]

8.  Secondary:   Change From Baseline in CDEIS at 48 Weeks After Randomization   [ Time Frame: Baseline and 48 weeks after Randomization ]

9.  Secondary:   Change From Baseline in CDAI Over Time   [ Time Frame: Baseline and 4 and 8 weeks during the prednisone run-in, and 2, 6, 11, 14, 18, 23, 26, 30, 35, 38, 42, and 48 weeks after Randomization. ]

10.  Secondary:   Time to Crohn's Disease Flare   [ Time Frame: From Randomization to 48 weeks after Randomization ]

11.  Secondary:   Time to Clinical Remission   [ Time Frame: From Randomization through 48 weeks after Randomization ]

12.  Secondary:   Time to Steroid-free Remission   [ Time Frame: From Randomization through 48 weeks after Randomization ]

13.  Secondary:   Percentage of Participants in Clinical Remission Over Time   [ Time Frame: Baseline and 4 and 8 weeks during the prednisone run-in, and 2, 6, 11, 14, 18, 23, 26, 30, 35, 38, 42, and 48 weeks after Randomization. ]

14.  Secondary:   Percentage of Participants in Steroid-free Remission Over Time   [ Time Frame: 11, 14, 18, 23, 26, 30, 35, 38, 42, and 48 weeks after Randomization. ]

15.  Secondary:   Time to All-cause Hospitalization   [ Time Frame: From Randomization through 48 weeks after Randomization ]

16.  Secondary:   Time to Crohn's Disease-related Hospitalization or Hospitalization Due to Adverse Event Relating to Study Medication   [ Time Frame: From Randomization through 48 weeks after Randomization ]

17.  Secondary:   Number of Major Crohn's Disease-related Surgeries After Randomization   [ Time Frame: From Randomization through 48 weeks after Randomization ]

18.  Secondary:   Number of Crohn's Disease-related Hospitalizations After Randomization   [ Time Frame: From Randomization through 48 weeks after Randomization ]

19.  Secondary:   Number of All-cause Hospitalizations After Randomization   [ Time Frame: From Randomization through 48 weeks after Randomization ]

20.  Secondary:   Total Length of Stay in Hospital for All-cause Hospitalizations   [ Time Frame: From Randomization through 48 weeks after Randomization ]

21.  Secondary:   Total Length of Stay in Hospital for Crohn's Disease-related Hospitalizations   [ Time Frame: From Randomization through 48 weeks after Randomization ]

22.  Secondary:   Number of Crohn's Disease-related Surgical Procedures After Randomization   [ Time Frame: From Randomization through 48 weeks after Randomization ]

23.  Secondary:   Time to Crohn's Disease-related Hospitalization Due to Emergency   [ Time Frame: From Randomization through 48 weeks after Randomization ]

24.  Secondary:   Number of Crohn's Disease-related Hospitalizations Due to Emergency   [ Time Frame: From Randomization through 48 weeks after Randomization ]

25.  Secondary:   Change in Crohn's Disease Behavior According to Montreal Classification   [ Time Frame: From Baseline to 48 weeks after Randomization ]

26.  Secondary:   Change From Baseline in High Sensitivity C-Reactive Protein (Hs-CRP) Over Time   [ Time Frame: Baseline and 8 weeks during the prednisone run-in, and 11, 23, 35, and 48 weeks after Randomization. ]

27.  Secondary:   Change in Fecal Calprotectin From Baseline to 48 Weeks After Randomization   [ Time Frame: Baseline and 48 weeks after Randomization ]

28.  Secondary:   Total Dose of Prednisone   [ Time Frame: From Baseline through 48 weeks after Randomization ]

29.  Secondary:   Change From Baseline in Quality of Life in Inflammatory Bowel Disease Questionnaire (IBDQ) Total Score   [ Time Frame: Baseline and 48 weeks after Randomization ]

30.  Secondary:   Change From Baseline in Work Productivity Activity Index - Crohn's Disease (WPAI:CD)   [ Time Frame: Baseline and 48 weeks after Randomization ]

31.  Secondary:   Change From Baseline in Patient Health Questionnaire - 9 (PHQ9)   [ Time Frame: Baseline and 48 weeks after Randomization ]

32.  Secondary:   Change From Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) Score   [ Time Frame: Baseline and 48 weeks after Randomization ]

33.  Secondary:   Change From Baseline in Short-Form 36 (SF-36) Physical Component Summary and Mental Component Summary Scores   [ Time Frame: Baseline and 48 weeks after Randomization ]


  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: Global Medical Services
Organization: AbbVie (prior sponsor Abbott)
phone: 800-633-9110


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

Responsible Party: AbbVie ( AbbVie (prior sponsor, Abbott) )
ClinicalTrials.gov Identifier: NCT01235689     History of Changes
Other Study ID Numbers: M11-271
2010-020137-10 ( EudraCT Number )
First Submitted: November 4, 2010
First Posted: November 5, 2010
Results First Submitted: October 30, 2017
Results First Posted: December 7, 2017
Last Update Posted: January 16, 2018