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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
History of Changes
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  
Number of Participants  
[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)  
Body Mass Index (BMI) [2]
[units: kg/m^2]
Mean (Standard Deviation) 		  24.6  (5.11)     24.9  (4.85)     25.3  (6.05)     25.1  (5.62)  
Duration of Ulcerative Colitis [3]
[units: years]
Mean (Standard Deviation) 		  7.1  (7.25)     6.1  (5.08)     7.2  (6.61)     6.9  (6.39)  
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 [4]
[units: units on a scale]
Mean (Standard Deviation) 		  8.6  (1.68)     8.5  (1.78)     8.6  (1.76)     8.6  (1.75)  
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 [5]
[units: μg/g]
Mean (Standard Deviation) 		  2369.9  (3258.82)     2552.2  (3800.36)     1442.7  (1855.61)     1868.8  (2753.28)  
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  
[1] Body weight data only available for 148 participants in the placebo arm.
[2] BMI data only available for 148 participants in the placebo arm.
[3] Duration of ulcerative colitis data only available for 519 participants in the Induction Phase: OL Vedolizumab arm.
[4] 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).
[5] Number of participants for whom baseline fecal calprotectin data were available were 139, 213, and 505, respectively.



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

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

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

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

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

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

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

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


  Serious Adverse Events
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  Other Adverse Events
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  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