Study of Vedolizumab in Patients With Moderate to Severe Crohn's Disease (GEMINI III)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT01224171
First received: October 18, 2010
Last updated: June 19, 2014
Last verified: June 2014
Results First Received: June 19, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator);   Primary Purpose: Treatment
Condition: Crohn's Disease
Interventions: Drug: vedolizumab
Other: Placebo

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Participants with moderately to severely active Crohn's Disease took part in the study at 107 sites worldwide from 24 November 2010 to 12 April 2012. Approximately 75% of participants were to have previously failed tumor necrosis factor alpha (TNFα) antagonist therapy and approximately 25% were to have been naïve to TNFα antagonist therapy.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants were randomized 1:1 to receive either 300 mg vedolizumab or placebo. Randomization to treatment assignment was stratified by the presence or absence of previous failure of TNFα antagonist therapy or naïve to TNFα antagonist therapy, concomitant use of oral corticosteroids and concomitant use of immunomodulators.

Reporting Groups
  Description
Placebo Participants received placebo intravenous infusion at Weeks 0, 2 and 6.
Vedolizumab Participants received 300 mg intravenous vedolizumab at Weeks 0, 2, and 6.

Participant Flow:   Overall Study
    Placebo     Vedolizumab  
STARTED     207     209  
TNFα Antagonist Failure Population     157 [1]   158 [1]
COMPLETED     192 [2]   196 [2]
NOT COMPLETED     15     13  
Adverse Event                 8                 4  
Protocol Violation                 0                 1  
Lack of Efficacy                 5                 1  
Withdrawal of Consent                 2                 4  
Lost to Follow-up                 0                 3  
[1] Previously failed (inadequate response, loss of response, or intolerance) TNFα antagonist therapy
[2] Completed study is defined as patients who completed the Week 10 assessments.



  Baseline Characteristics
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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.
The Overall Intent-to-treat (ITT) Population consisted of all randomized participants who received any amount of blinded study drug.

Reporting Groups
  Description
Placebo Participants received placebo intravenous infusion at Weeks 0, 2 and 6.
Vedolizumab Participants received 300 mg intravenous vedolizumab at Weeks 0, 2, and 6.
Total Total of all reporting groups

Baseline Measures
    Placebo     Vedolizumab     Total  
Number of Participants  
[units: participants]
  207     209     416  
Age  
[units: years]
Mean ± Standard Deviation
  37.1  ± 13.15     38.6  ± 12.14     37.9  ± 12.66  
Age, Customized  
[units: participants]
     
< 35 years     105     88     193  
≥ 35 years     102     121     223  
Age, Customized  
[units: participants]
     
< 65 years     202     206     408  
≥ 65 years     5     3     8  
Gender  
[units: participants]
     
Female     118     118     236  
Male     89     91     180  
Ethnicity (NIH/OMB)  
[units: participants]
     
Hispanic or Latino     4     4     8  
Not Hispanic or Latino     199     204     403  
Unknown or Not Reported     4     1     5  
Race/Ethnicity, Customized  
[units: participants]
     
White     186     188     374  
Black     5     4     9  
Asian     9     9     18  
Other     7     6     13  
Not Reported     0     2     2  
Body Weight  
[units: kg]
Mean ± Standard Deviation
  71.3  ± 19.22     69.5  ± 17.76     70.4  ± 18.50  
Body Mass Index  
[units: kg/m^2]
Mean ± Standard Deviation
  24.6  ± 6.13     24.0  ± 5.13     24.3  ± 5.65  
Geographic Region  
[units: participants]
     
North America     95     102     197  
Western/Northern Europe     37     38     75  
Central Europe     46     41     87  
Eastern Europe     15     10     25  
Asia/Australia/Africa     14     18     32  
Duration of Crohn's Disease (CD)  
[units: years]
Mean ± Standard Deviation
  10.0  ± 7.98     10.6  ± 8.75     10.3  ± 8.37  
Duration of Crohn's Disease - Categorical  
[units: participants]
     
< 1 year     12     11     23  
≥ 1 to < 3 years     25     28     53  
≥ 3 to < 7 years     52     52     104  
≥ 7 years     118     118     236  
Baseline Disease Activity – Crohn’s Disease Activity Index (CDAI) [1]
[units: units on a scale]
Mean ± Standard Deviation
  301.3  ± 54.97     313.9  ± 53.17     307.7  ± 54.38  
Baseline Disease Activity – Categorical  
[units: participants]
     
CDAI ≤ 330     148     132     280  
CDAI > 330     59     77     136  
C-reactive Protein (CRP)  
[units: mg/L]
Mean ± Standard Deviation
  18.5  ± 21.98     19.0  ± 23.17     18.8  ± 22.56  
CRP - Categorical  
[units: participants]
     
≤ 2.87 mg/L     41     46     87  
> 2.87 to ≤ 5 mg/L     19     14     33  
> 5 to ≤ 10 mg/L     42     48     90  
> 10 mg/L     105     101     206  
Fecal Calprotectin [2]
[units: μg/g]
Mean ± Standard Deviation
  1426.5  ± 2357.76     1148.1  ± 1878.58     1288.0  ± 2134.79  
Fecal Calprotectin - Categorical  
[units: participants]
     
≤ 250 μg/g     47     52     99  
> 250 to ≤ 500 μg/g     35     35     70  
> 500 μg/g     124     117     241  
Missing     1     5     6  
Disease Localization  
[units: participants]
     
Ileum only     29     33     62  
Colon only     52     48     100  
Ileocolonic (both ileum and colon)     126     128     254  
History of Prior Surgery for Crohn's Disease  
[units: participants]
     
Yes     89     92     181  
No     118     117     235  
Smoking Status  
[units: participants]
     
Current Smoker     58     65     123  
Never Smoked     102     93     195  
Former Smoker     47     51     98  
History of Fistulizing Disease  
[units: participants]
     
Yes     77     71     148  
No     130     138     268  
Draining Fistula at Baseline  
[units: participants]
     
Yes     25     25     50  
All Closed     0     1     1  
No Fistula     182     183     365  
Extraintestinal Manifestations at Baseline  
[units: participants]
     
Yes     130     116     246  
No     77     93     170  
[1] Baseline disease activity represents the baseline CDAI score. The CDAI is a numerical calculation derived from the sum of products from a list of 8 disease variables: number of liquid stools, extent of abdominal pain, general well-being, occurrence of extraintestinal symptoms, need for antidiarrheal drugs, presence of abdominal masses, hematocrit, and body weight. CDAI scores range from 0 to ~600 points with lower scores indicating disease remission and higher scores indicating disease worsening.
[2] Number of participants for whom baseline fecal calprotectin data were available were 206 and 204, respectively.



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Percentage of Participants in Clinical Remission in the Tumor Necrosis Factor Alpha (TNFα) Antagonist Failure Subpopulation   [ Time Frame: Week 6 ]

2.  Secondary:   Percentage of Participants in Clinical Remission at Week 6 in the Overall Population   [ Time Frame: Week 6 ]

3.  Secondary:   Percentage of Participants in Clinical Remission at Week 10 in the TNFα Antagonist Failure Subpopulation   [ Time Frame: Week 10 ]

4.  Secondary:   Percentage of Participants in Clinical Remission at Week 10 in the Overall Population   [ Time Frame: Week 10 ]

5.  Secondary:   Percentage of Participants With Sustained Clinical Remission in the TNFα Antagonist Failure Population   [ Time Frame: Week 6 and Week 10 ]

6.  Secondary:   Percentage of Participants With Sustained Clinical Remission in the Overall Population   [ Time Frame: Week 6 and Week 10 ]

7.  Secondary:   Percentage of Participants With Enhanced Clinical Response at Week 6 in the TNFα Antagonist Failure Subpopulation   [ Time Frame: Baseline and Week 6 ]

8.  Secondary:   Number of Participants With Adverse Events (AEs)   [ Time Frame: From the date of first study drug administration to Week 22, through the 14 March 2012 database lock date. At the time of this database lock, 7 patients had completed Week 10 or early termination assessments but not Week 22 assessments. ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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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
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  More Information
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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: Medical Director
Organization: Millennium Pharmaceuticals Inc.
phone: 800-778-2860
e-mail: clinicaltrialregistry@tpna.com


No publications provided by Millennium Pharmaceuticals, Inc.

Publications automatically indexed to this study:

Responsible Party: Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT01224171     History of Changes
Other Study ID Numbers: C13011, U1111-1158-2581, 2009-016488-12, NL34356.078.10
Study First Received: October 18, 2010
Results First Received: June 19, 2014
Last Updated: June 19, 2014
Health Authority: United States: Food and Drug Administration