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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
  Hide Participant Flow

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 
Overall Participants Analyzed 
[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) 
[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.

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) [1] 
[Units: mg/L]
Mean (Standard Deviation)
 23.6  (27.85)   24.1  (27.23)   20.4  (27.40)   21.5  (27.45) 
[1] Baseline CRP data was only available for 147 participants in the placebo arm.
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 [1] 
[Units: μg/g]
Mean (Standard Deviation)
 1421.2  (2076.11)   1839.9  (2624.92)   1050.1  (1558.93)   1254.2  (1908.82) 
[1] Number of participants for whom baseline fecal calprotectin data were available were 142, 210, and 719, respectively.
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 


  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


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

Responsible Party: Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT00783692     History of Changes
Other Study ID Numbers: C13007
2008-002783-33 ( EudraCT Number )
U1111-1157-7675 ( Registry Identifier: WHO )
CTRI/2009/091/000135 ( Registry Identifier: CTRI )
NMRR-08-1047-2202 ( Registry Identifier: NMRR )
09/H1102/65 ( Registry Identifier: NRES )
NL25208.096.08 ( Registry Identifier: CCMO )
C13007CTIL ( Other Identifier: Israel MoH )
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