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Study of Vedolizumab (MLN0002) in Patients With Moderate to Severe Ulcerative Colitis (GEMINI I)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier:
NCT00783718
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: Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, Investigator);   Primary Purpose: Treatment
Condition: Ulcerative Colitis
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 211 investigative sites worldwide. 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   149   225   521   0   0   0   0 
COMPLETED   135   218   485   0   0   0   0 
NOT COMPLETED   14   7   36   0   0   0   0 
Adverse Event                4                0                7                0                0                0                0 
Protocol Violation                1                1                6                0                0                0                0 
Lack of Efficacy                5                2                14                0                0                0                0 
Withdrawal by Subject                3                4                8                0                0                0                0 
Lost to Follow-up                1                0                1                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   135   0   0   126   122   125   330 
COMPLETED   30   0   0   48   77   84   135 
NOT COMPLETED   105   0   0   78   45   41   195 
Adverse Event                12                0                0                15                7                6                16 
Protocol Violation                1                0                0                0                0                0                2 
Lack of Efficacy                83                0                0                61                31                33                155 
Withdrawal by Subject                6                0                0                2                5                2                20 
Lost to Follow-up                3                0                0                0                2                0                2 



  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.
Baseline characteristics are provided for 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 0-6), 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. 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 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 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]
 149   225   521   895 
Age 
[Units: Years]
Mean (Standard Deviation)
 41.2  (12.50)   40.1  (13.11)   40.1  (13.27)   40.3  (13.09) 
Age, Customized 
[Units: Participants]
       
< 35   53   86   214   353 
≥ 35   96   139   307   542 
Age, Customized 
[Units: Participants]
       
< 65   142   217   503   862 
≥ 65   7   8   18   33 
Gender 
[Units: Participants]
       
Female   57   93   220   370 
Male   92   132   301   525 
Race/Ethnicity, Customized 
[Units: Participants]
       
White   115   183   436   734 
Black   2   5   5   12 
Asian   32   36   67   135 
Other   0   1   13   14 
Race/Ethnicity, Customized 
[Units: Participants]
       
Hispanic or Latino   5   10   31   46 
Not Hispanic or Latino   140   211   481   832 
Not reported   4   4   9   17 
Region of Enrollment 
[Units: Participants]
       
Australia   7   17   29   53 
Austria   4   3   12   19 
Belgium   7   14   35   56 
Bulgaria   2   1   3   6 
Canada   16   14   62   92 
Czech Republic   7   12   19   38 
Denmark   2   7   5   14 
Estonia   1   4   5   10 
France   1   3   13   17 
Germany   0   1   16   17 
Greece   0   1   4   5 
Hong Kong   0   0   1   1 
Hungary   2   6   8   16 
Iceland   0   1   2   3 
India   18   16   24   58 
Ireland   0   0   1   1 
Israel   0   1   1   2 
Italy   1   9   11   21 
Korea, Republic of   5   10   26   41 
Latvia   1   2   0   3 
Malaysia   5   2   2   9 
Netherlands   1   0   2   3 
New Zealand   0   5   6   11 
Norway   2   1   6   9 
Poland   2   6   52   60 
Russian Federation   9   15   25   49 
Singapore   0   0   1   1 
South Africa   4   5   10   19 
Spain   0   0   2   2 
Switzerland   2   1   3   6 
Turkey   0   3   3   6 
United Kingdom   2   0   4   6 
United States   47   64   127   238 
Body Weight [1] 
[Units: Kg]
Mean (Standard Deviation)
 72.4  (17.65)   72.4  (17.11)   74.2  (19.32)   73.4  (18.51) 
[1] Body weight data only available for 148 participants in the placebo arm.
Body Mass Index (BMI) [1] 
[Units: Kg/m^2]
Mean (Standard Deviation)
 24.6  (5.11)   24.9  (4.85)   25.3  (6.05)   25.1  (5.62) 
[1] BMI data only available for 148 participants in the placebo arm.
Duration of Ulcerative Colitis [1] 
[Units: Years]
Mean (Standard Deviation)
 7.1  (7.25)   6.1  (5.08)   7.2  (6.61)   6.9  (6.39) 
[1] Duration of ulcerative colitis data only available for 519 participants in the Induction Phase: OL Vedolizumab arm.
Categorical Duration of Ulcerative Colitis 
[Units: Participants]
       
< 1 year   13   13   38   64 
≥1 - < 3 years   44   63   121   228 
≥ 3 - < 7 years   39   77   163   279 
≥ 7 years   53   72   197   322 
Missing   0   0   2   2 
Baseline Mayo Score [1] 
[Units: Units on a scale]
Mean (Standard Deviation)
 8.6  (1.68)   8.5  (1.78)   8.6  (1.76)   8.6  (1.75) 
[1] The Mayo Score is a standard assessment tool to measure ulcerative colitis disease activity in clinical trials. The index consists of 4 components: two that are patient reported (rectal bleeding and stool frequency), a global assessment by the physician, and an endoscopic subscore. Each component is scored on a scale from 0 to 3 and the complete score ranges from 1 to 12 (higher scores indicate greater disease activity).
Baseline Disease Activity 
[Units: Participants]
       
Complete Mayo score < 6   5   6   14   25 
Complete Mayo score of 6 to 8 (inclusive)   70   105   249   424 
Complete Mayo score of 9 to 12 (inclusive)   74   114   258   446 
Baseline Fecal Calprotectin [1] 
[Units: μg/g]
Mean (Standard Deviation)
 2369.9  (3258.82)   2552.2  (3800.36)   1442.7  (1855.61)   1868.8  (2753.28) 
[1] Number of participants for whom baseline fecal calprotectin data were available were 139, 213, and 505, respectively.
Categorical Baseline Fecal Calprotectin 
[Units: Participants]
       
≤ 250 μg/g   27   37   94   158 
> 250 to ≤ 500 μg/g   20   20   82   122 
> 500 μg/g   92   156   329   577 
Missing   10   12   16   38 
Disease Localization 
[Units: Participants]
       
Proctosigmoiditis   22   25   69   116 
Left-sided colitis   59   92   188   339 
Extensive colitis   18   25   66   109 
Pancolitis   50   83   198   331 
Smoking Status 
[Units: Participants]
       
Current smoker   11   12   32   55 
Nonsmoker   88   145   322   555 
Former smoker   50   68   167   285 
History of Extraintestinal Manifestations 
[Units: Participants]
       
Yes   44   74   180   298 
No   105   151   341   597 


  Outcome Measures
  Show All Outcome Measures

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

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

3.  Secondary:   Induction Phase: Percentage of Participants in Clinical Remission at Week 6   [ Time Frame: Week 6 ]

4.  Secondary:   Induction Phase: Percentage of Participants With Mucosal Healing at Week 6   [ Time Frame: Week 6 ]

5.  Secondary:   Maintenance Phase: Percentage of Participants With Durable Clinical Response   [ Time Frame: Baseline, Week 6 and Week 52 ]

6.  Secondary:   Maintenance Phase: Percentage of Participants With Mucosal Healing at Week 52   [ Time Frame: Week 52 ]

7.  Secondary:   Maintenance Phase: Percentage of Participants With Durable Clinical Remission   [ Time Frame: Week 6 and Week 52 ]

8.  Secondary:   Maintenance Phase: Percentage of Participants With Corticosteroid-free Remission at Week 52   [ Time Frame: Week 52 ]


  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


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

Responsible Party: Millennium Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT00783718     History of Changes
Other Study ID Numbers: C13006
U1111-1156-8422 ( Registry Identifier: WHO )
2008-002782-32 ( EudraCT Number )
NL25207.096.08 ( Registry Identifier: CCMO )
CTRI/2009/091/000128 ( Registry Identifier: CTRI )
NMRR-08-1046-2201 ( Registry Identifier: NMRR )
C13006CTIL ( Other Identifier: Israel MoH )
09/H1102/66 ( Registry Identifier: NRES )
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