Study of Vedolizumab (MLN0002) in Patients With Moderate to Severe Crohn's Disease (GEMINI II)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT00783692
First received: October 31, 2008
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: Factorial 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 took part in the study at 285 investigative sites worldwide from 23 December 2008 to 08 May 2012. The Induction Phase contained 2 cohorts. The eligibility criteria for both cohorts were identical. The purpose of Cohort 2 was to provide enough responders to power the Maintenance Phase primary efficacy analysis.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
In Cohort 1, eligible patients who met entry criteria were randomized to treatment with double-blind vedolizumab 300 mg or placebo in a 3:2 ratio. All Cohort 2 patients were treated with open-label vedolizumab. In the Maintenance Phase participants were assigned to treatment groups based on their Induction Phase treatment and response to therapy.

Reporting Groups
  Description
Placebo In the Induction Phase participants in Cohort 1 were randomized to receive double-blind placebo intravenous infusions at Week 0 and Week 2. Participants continued to receive placebo every 4 weeks from Week 6 through Week 50 during the Maintenance Phase, regardless of treatment response during induction.
Induction Phase: DB Vedolizumab In the Induction Phase participants in Cohort 1 were randomized to receive double-blind (DB) vedolizumab 300 mg, administered by intravenous infusion at Week 0 and Week 2.
Induction Phase: OL Vedolizumab In the Induction Phase participants in Cohort 2 received open-label (OL) vedolizumab 300 mg, administered by intravenous infusion at Week 0 and Week 2.
Maintenance Phase: Placebo Participants who received vedolizumab during the Induction Phase and demonstrated a clinical response at Week 6 were then randomized to receive double-blind treatment with placebo every 4 weeks up to Week 50 during the Maintenance Phase.
Maintenance Phase: Vedolizumab Q8W Participants who received vedolizumab during the Induction Phase and demonstrated a clinical response at Week 6 were then randomized to receive double-blind treatment with vedolizumab 300 mg every 8 weeks (Q8W) at Weeks 6, 14, 22, 30, 38, and 46, and, to maintain blinding, placebo infusions at Weeks 10, 18, 26, 34, 42, and 50.
Maintenance Phase: Vedolizumab Q4W Participants who received vedolizumab during the Induction Phase and demonstrated a clinical response at Week 6 were then randomized to receive double-blind treatment with vedolizumab 300 mg every 4 weeks (Q4W) from Week 6 to Week 50.
Maintenance Phase: Non-Responders Participants who received vedolizumab during the Induction Phase who did not demonstrate a clinical response at Week 6 received open-label treatment with vedolizumab 300 mg every 4 weeks from Week 6 to Week 50.

Participant Flow for 2 periods

Period 1:   Induction Phase
    Placebo     Induction Phase: DB Vedolizumab     Induction Phase: OL Vedolizumab     Maintenance Phase: Placebo     Maintenance Phase: Vedolizumab Q8W     Maintenance Phase: Vedolizumab Q4W     Maintenance Phase: Non-Responders  
STARTED     148     220     748     0     0     0     0  
Treated     148     220     747     0     0     0     0  
COMPLETED     137     199     674     0     0     0     0  
NOT COMPLETED     11     21     74     0     0     0     0  
Adverse Event                 7                 9                 24                 0                 0                 0                 0  
Protocol Violation                 0                 0                 1                 0                 0                 0                 0  
Lack of Efficacy                 1                 3                 28                 0                 0                 0                 0  
Withdrawal by Subject                 3                 9                 16                 0                 0                 0                 0  
Lost to Follow-up                 0                 0                 3                 0                 0                 0                 0  
Other                 0                 0                 2                 0                 0                 0                 0  

Period 2:   Maintenance Phase
    Placebo     Induction Phase: DB Vedolizumab     Induction Phase: OL Vedolizumab     Maintenance Phase: Placebo     Maintenance Phase: Vedolizumab Q8W     Maintenance Phase: Vedolizumab Q4W     Maintenance Phase: Non-Responders  
STARTED     137     0     0     153     154     154     412  
COMPLETED     42     0     0     64     73     82     163  
NOT COMPLETED     95     0     0     89     81     72     249  
Adverse Event                 7                 0                 0                 15                 12                 9                 38  
Protocol Violation                 0                 0                 0                 1                 2                 3                 4  
Lack of Efficacy                 79                 0                 0                 64                 58                 48                 177  
Withdrawal by Subject                 7                 0                 0                 7                 6                 9                 24  
Lost to Follow-up                 2                 0                 0                 1                 3                 2                 5  
Other                 0                 0                 0                 1                 0                 1                 1  



  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 Induction Phase Safety Population, defined as all participants, in both Cohort 1 and Cohort 2, who received any amount of study drug in the Induction Phase (Weeks 0 to 6), according to the actual study drug received.

Reporting Groups
  Description
Placebo In the Induction Phase participants in Cohort 1 were randomized to receive double-blind placebo intravenous infusions at Week 0 and Week 2.
Induction Phase: DB Vedolizumab In the Induction Phase participants in Cohort 1 were randomized to receive double-blind (DB) vedolizumab 300 mg, administered by intravenous infusion at Week 0 and Week 2.
Induction Phase: OL Vedolizumab In the Induction Phase participants in Cohort 2 received open-label (OL) vedolizumab 300 mg, administered by intravenous infusion at Week 0 and Week 2.
Total Total of all reporting groups

Baseline Measures
    Placebo     Induction Phase: DB Vedolizumab     Induction Phase: OL Vedolizumab     Total  
Number of Participants  
[units: participants]
  148     220     747     1115  
Age  
[units: years]
Mean ± Standard Deviation
  38.6  ± 13.16     36.3  ± 11.57     35.6  ± 12.01     36.1  ± 12.12  
Age, Customized  
[units: participants]
       
< 35 years     67     111     404     582  
≥ 35 years     81     109     343     533  
Age, Customized  
[units: participants]
       
< 65 years     142     218     732     1092  
≥ 65 years     6     2     15     23  
Gender  
[units: participants]
       
Female     79     115     401     595  
Male     69     105     346     520  
Ethnicity (NIH/OMB)  
[units: participants]
       
Hispanic or Latino     5     2     19     26  
Not Hispanic or Latino     139     214     712     1065  
Unknown or Not Reported     4     4     16     24  
Race/Ethnicity, Customized  
[units: participants]
       
White     124     182     689     995  
Black     3     3     17     23  
Asian     19     35     35     89  
Other     2     0     6     8  
Region of Enrollment  
[units: participants]
       
Australia     5     10     30     45  
Austria     4     3     7     14  
Belgium     12     17     41     70  
Bulgaria     5     7     2     14  
Canada     22     12     103     137  
Czech Republic     11     16     53     80  
Denmark     0     2     8     10  
Estonia     1     2     3     6  
France     4     3     37     44  
Germany     0     1     49     50  
Greece     0     0     2     2  
Hong Kong     2     0     0     2  
Hungary     9     17     47     73  
Iceland     0     0     4     4  
India     10     19     5     34  
Ireland     0     0     2     2  
Israel     2     4     12     18  
Italy     1     0     13     14  
Korea, Republic of     3     12     11     26  
Latvia     0     2     0     2  
Malaysia     1     3     5     9  
Netherlands     0     0     7     7  
New Zealand     4     5     3     12  
Norway     0     0     13     13  
Poland     7     6     14     27  
Romania     0     1     4     5  
Russian Federation     4     9     15     28  
Serbia     0     0     3     3  
Singapore     1     0     0     1  
Slovakia     3     5     10     18  
South Africa     3     3     14     20  
Spain     1     0     6     7  
Sweden     0     1     8     9  
Switzerland     0     1     9     10  
Taiwan     0     0     3     3  
Turkey     2     3     1     6  
Ukraine     3     4     9     16  
United Kingdom     0     0     6     6  
United States     28     52     188     268  
Body Weight  
[units: kg]
Mean ± Standard Deviation
  68.7  ± 18.90     67.1  ± 19.07     70.8  ± 19.56     69.8  ± 19.42  
Body Mass Index (BMI)  
[units: kg/m^2]
Mean ± Standard Deviation
  23.7  ± 5.77     23.1  ± 5.62     24.2  ± 6.02     23.9  ± 5.93  
Duration of Crohn's Disease (CD)  
[units: years]
Mean ± Standard Deviation
  8.2  ± 7.80     9.2  ± 8.18     9.2  ± 7.63     9.0  ± 7.77  
Duration of Crohn's Disease - Categorical  
[units: participants]
       
< 1 year     12     12     45     69  
≥ 1 to < 3 years     27     48     126     201  
≥ 3 to < 7 years     45     49     191     285  
≥ 7 years     64     111     385     560  
Baseline Disease Activity – Crohn’s Disease Activity Index (CDAI) [1]
[units: units on a scale]
Mean ± Standard Deviation
  324.6  ± 78.08     327.3  ± 70.67     322.2  ± 67.17     323.6  ± 69.37  
Baseline Disease Activity – Categorical  
[units: participants]
       
CDAI ≤ 330     81     119     418     618  
CDAI > 330     66     100     325     491  
Missing     1     1     4     6  
Baseline C-reactive Protein (CRP) [2]
[units: mg/L]
Mean ± Standard Deviation
  23.6  ± 27.85     24.1  ± 27.23     20.4  ± 27.40     21.5  ± 27.45  
Baseline CRP - Categorical  
[units: participants]
       
≤ 2.87 mg/L     20     37     130     187  
> 2.87 to ≤ 5 mg/L     14     25     75     114  
> 5 to ≤ 10 mg/L     28     38     160     226  
> 10 mg/L     85     120     382     587  
Missing     1     0     0     1  
Baseline Fecal Calprotectin [3]
[units: μg/g]
Mean ± Standard Deviation
  1421.2  ± 2076.11     1839.9  ± 2624.92     1050.1  ± 1558.93     1254.2  ± 1908.82  
Baseline Fecal Calprotectin - Categorical  
[units: participants]
       
≤ 250 μg/g     34     51     201     286  
> 250 to ≤ 500 μg/g     27     25     112     164  
> 500 μg/g     81     134     406     621  
Missing     6     10     28     44  
Disease Localization  
[units: participants]
       
Ileum only     21     37     123     181  
Colon only     43     62     211     316  
Ileocolonic (both ileum and colon)     84     121     413     618  
History of Prior Surgery for Crohn's Disease  
[units: participants]
       
Yes     54     98     314     466  
No     94     122     433     649  
History of Fistulizing Disease  
[units: participants]
       
Yes     56     90     264     410  
No     92     130     483     705  
Draining Fistula at Baseline  
[units: participants]
       
Yes     23     38     104     165  
All Closed     2     1     8     11  
No     123     181     635     939  
Smoking Status  
[units: participants]
       
Current smoker     34     54     210     298  
Nonsmoker (never smoked)     85     120     351     556  
Former smoker     29     46     185     260  
Missing     0     0     1     1  
Baseline Extraintestinal Manifestations  
[units: participants]
       
Yes     107     133     456     696  
No     41     87     291     419  
History of Extraintestinal Manifestations  
[units: participants]
       
Yes     123     177     619     919  
No     25     43     128     196  
[1]

Number of participants for whom baseline CDAI scores were available were 147, 219, and 743, respectively.

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] Baseline CRP data was only available for 147 participants in the placebo arm.
[3] Number of participants for whom baseline fecal calprotectin data were available were 142, 210, and 719, respectively.



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Induction Phase: Percentage of Participants Achieving Clinical Remission at Week 6   [ Time Frame: Week 6 ]

2.  Primary:   Induction Phase: Percentage of Participants With Enhanced Clinical Response at Week 6   [ Time Frame: Baseline and Week 6 ]

3.  Primary:   Maintenance Phase: Percentage of Participants Achieving Clinical Remission at Week 52   [ Time Frame: Week 52 ]

4.  Secondary:   Induction Phase: Change From Baseline in C-Reactive Protein (CRP) Levels at Week 6   [ Time Frame: Baseline and Week 6 ]

5.  Secondary:   Maintenance Phase: Percentage of Participants With Enhanced Clinical Response at Week 52   [ Time Frame: Baseline and Week 52 ]

6.  Secondary:   Maintenance Phase: Percentage of Participants in Corticosteroid-free Clinical Remission at Week 52   [ Time Frame: Week 52 ]

7.  Secondary:   Maintenance Phase: Percentage of Participants With Durable Clinical Remission   [ Time Frame: Assessed every 4 weeks from Week 6 to Week 50, and at Week 52 ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
  Hide 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
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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: NCT00783692     History of Changes
Other Study ID Numbers: C13007, 2008-002783-33, U1111-1157-7675, CTRI/2009/091/000135, NMRR-08-1047-2202, 09/H1102/65, NL25208.096.08, C13007CTIL
Study First Received: October 31, 2008
Results First Received: June 19, 2014
Last Updated: June 19, 2014
Health Authority: United States: Food and Drug Administration