Colitis, Ulcerative, Crohn's Disease
Conditions
Keywords
Drug therapy
Brief summary
The main aim of the study is to check for long-term side effects of Vedolizumab Subcutaneous (also known as Vedolizumab SC) in people with ulcerative colitis (UC) and Crohn's disease (CD). Vedolizumab SC will be given as an injection just under the skin. This type of injection is called a subcutaneous injection or SC for short. Another aim of the study is to collect information on whether the participant's condition remains under control or improves during and after treatment with Vedolizumab SC. Participants who previously took part in studies MLN0002SC-3027 or MLN0002SC-3031 will be invited to visit the study clinic. At this visit, the study doctor will check if each participant can take part in this study. For those who can take part, participants will receive a subcutaneous injection of vedolizumab SC either once a week or once every 2 weeks. How often each participant receives vedolizumab SC will depend on their results from the previous study and on how active their condition is. Participants might be able to self-inject vedolizumab SC after being trained by the study doctors. During this study, the dose of vedolizumab SC might be increased for participants whose condition worsens. Participants will continue treatment with vedolizumab SC until it is approved in their particular country, the participant decides to stop treatment, or the sponsor stops the study. If the sponsor stops the study before vedolizumab SC is approved in all countries, the sponsor will make sure all affected participants will have access to vedolizumab SC outside of the study. After their final dose of vedolizumab SC, participants will visit the clinic 18 weeks later for a final check-up. Then, the clinic will telephone the participants 6 months after their final dose of vedolizumab SC to check if they have any health problems.
Detailed description
The drug being tested in this study is called vedolizumab subcutaneous (vedolizumab SC). Vedolizumab SC is being tested to assess its long-term safety and effectiveness in treating participants with UC or CD. This study will look at the long-term side effects and response/remission of UC and CD in participants who received vedolizumab SC in a prior vedolizumab SC study. The study will enroll up to 692 patients. All participants enrolled in this study will have previously participated in the MLN0002SC-3027 or MLN0002SC-3031 study. Participants who completed the Maintenance Period (Week 52) in their previous study, or who did not achieve a clinical response at Week 6 but who did achieve a clinical response at Week 14 after having received a third vedolizumab IV infusion at Week 6 in their previous study, will receive open-label vedolizumab SC 108 mg, once every 2 weeks (Q2W). Participants who withdrew early from the Maintenance Period of their previous study due to disease worsening or need for rescue medications will receive open-label vedolizumab SC 108 mg, once every week (QW). Participants receiving SC 108 mg Q2W who experience treatment failure (disease worsening or need for rescue medications while in the current study will be dose escalated to vedolizumab SC 108 mg QW. This multi-center trial will be conducted worldwide. Participation in this vedolizumab SC study will continue until vedolizumab SC becomes commercially available, the participant withdraws from the study, or the sponsor decides to close the study. Participants will make multiple visits to the clinic, plus a final visit 18 weeks after last dose of study drug for a follow-up assessment. Participants will also participate in a long-term safety follow-up, by phone, at 6 months after the last dose of study drug.
Interventions
DRUGVedolizumab SC
Vedolizumab SC 108 mg injection
Sponsors
Takeda
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1\. Prior participation in Study MLN0002SC-3027 or MLN0002SC-3031, and, in the opinion of the investigator, tolerated the study drug well. Early withdrawal from Study MLN0002SC-3027 or MLN0002SC-3031 must have been due to treatment failure during the Maintenance Period.
Exclusion criteria
1. Surgical intervention for IBD during or after participation in Study MLN0002SC-3027 or MLN0002SC-3031, or at any time during this study. 2. Chronic or severe infection, or, any new, unstable, or uncontrolled cardiovascular, pulmonary, hepatic, renal, gastrointestinal, genitourinary, hematological, coagulation, immunological, endocrine/metabolic, neurologic, oncologic, or other medical disorder developed during or after participation in a prior vedolizumab study that, in the opinion of the investigator, would confound the study results or compromise participant safety. 3. Withdrawal from Study MLN0002SC-3027 or MLN0002SC-3031 due to a study-drug related adverse event (AE).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs Adjusted by Duration of Participant's Exposure to Long-term Vedolizumab Treatment | Up to 97.9 months | A TEAE was defined as an adverse event (AE) that started or worsened on or after study Day 1 (defined as day first dosed) and no more than 18 weeks after the last dose of study drug. An SAE was defined as any untoward medical occurrence that occurs at any dose and resulted in death, was life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was an important medical event such as acute liver failure, pulmonary hypertension, or confirmed or suspected transmission of an infectious agent by a medicinal product. Participant years is defined as the total exposure-time of the participants in the respective treatment group. Incidence per 100 participant years is defined as (Number of participants with events\*100/participant years). As per planned analysis, data for this outcome measure is grouped and presented per disease condition. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Adverse Events of Special Interest (AESIs) Adjusted by Duration of Participant's Exposure to Long-term Vedolizumab Treatment | Up to 97.9 months | AESIs included hypersensitivity reactions (including injections site reactions), serious infections, malignancies, hepatotoxicity (abnormal liver function test) and progressive multifocal leukoencephalopathy (PML). Participant years is defined as the total exposure-time of the participants in the respective treatment group. Incidence per 100 participant years is defined as (Number of participants with events\*100/participant years). As per planned analysis, data for this outcome measure is grouped and presented per disease condition. |
| Number of Participants With Ulcerative Colitis Achieving Partial Mayo Scoring Clinical Response at Week 48 | Week 48 | Clinical response is defined as a decrease in the partial Mayo score of at least 2 points and ≥25% from baseline, with an accompanying decrease in rectal bleeding subscore of ≥1 point from baseline or absolute rectal bleeding subscore of ≤1 point. As per planned analysis, data for this outcome measure is grouped and presented for participants with ulcerative colitis. |
| Number of Participants With Crohn's Disease Achieving Clinical Response Based on Harvey-Bradshaw Index (HBI) Scores at Week 48 | Week 48 | Clinical response is defined as a decrease in HBI score of ≥3 points from baseline in CD participants (randomized early terminator CD participants only \[defined as randomized CD participants withdrawn from the parent study between Week 6 and Week 52\]). As per planned analysis, data for this outcome measure is grouped and presented for participants with Crohn's disease. |
| Number of Participants With Ulcerative Colitis Achieving Clinical Remission Based on Partial Mayo Score | Week 48 | Clinical remission is defined as a partial Mayo score of ≤2 with no individual subscore \>1. As per planned analysis, data for this outcome measure is grouped and presented for participants with ulcerative colitis. |
| Number of Participants With Crohn's Disease Achieving Clinical Remission Based on Harvey-Bradshaw Index (HBI) Scores | Week 48 | Clinical remission is defined as total HBI score of ≤4 points. As per planned analysis, data for this outcome measure is grouped and presented for participants with Crohn's disease. |
Countries
Argentina, Australia, Belgium, Bosnia and Herzegovina, Brazil, Bulgaria, Canada, Croatia, Czechia, Denmark, Estonia, Germany, Hungary, Israel, Italy, Japan, Lithuania, Mexico, Netherlands, Poland, Romania, Russia, Serbia, Slovakia, South Africa, South Korea, Spain, Sweden, Taiwan, Turkey (Türkiye), Ukraine, United Kingdom, United States
Participant flow
Recruitment details
Participants took part in the study at various investigative sites globally from 15 April 2016 to 12 June 2024.
Pre-assignment details
Participants who had previously participated in Study MLN0002SC-3027 \[NCT02611830\] or MLN0002SC-3031 \[NCT02611817\] and were eligible to participate received vedolizumab subcutaneously (SC) \[either 108 milligrams (mg) once every two weeks (Q2W) or once per week (QW)\] in the disease groups of Ulcerative Colitis and Crohn's Disease in this study. Data is presented accordingly.
Participants by arm
| Arm | Count |
|---|---|
| Ulcerative Colitis: Vedolizumab 108 mg Participants with UC who completed the Maintenance Phase in MLN0002SC-3027 (Week 52 assessment) or who did not achieve a clinical response at Week 6 in MLN0002SC-3027 but who did achieve a clinical response at Week 14 of the parent study after having received a third vedolizumab IV infusion at Week 6 in the parent study received vedolizumab SC 108 mg Q2W in this study whereas participants who withdrew early from the Maintenance Phase (at Week 14 onwards) in MLN0002SC-3027 due to disease worsening or need for rescue medications received vedolizumab SC 108 mg QW. | 288 |
| Crohn's Disease: Vedolizumab 108 mg Participants with CD who completed the Maintenance Phase in MLN0002SC-3031 (Week 52 assessment) or who did not achieve a clinical response at Week 6 in MLN0002SC-3031 but who did achieve a clinical response at Week 14 of the parent study after having received a third vedolizumab IV infusion at Week 6 in the parent study received vedolizumab SC 108 mg Q2W in this study whereas participants who withdrew early from the Maintenance Phase (at Week 14 onwards) in MLN0002SC-3031 due to disease worsening or need for rescue medications received vedolizumab SC 108 mg QW. | 458 |
| Total | 746 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 22 | 42 |
| Overall Study | Lack of Efficacy | 81 | 146 |
| Overall Study | Leukopenia or Lymphopenia | 1 | 0 |
| Overall Study | Lost to Follow-up | 4 | 10 |
| Overall Study | Pregnancy | 3 | 7 |
| Overall Study | Reason Not Specified | 13 | 21 |
| Overall Study | Significant Protocol Deviation | 0 | 1 |
| Overall Study | Site Termination | 3 | 3 |
| Overall Study | Withdrawal by Subject | 36 | 66 |
Baseline characteristics
| Characteristic | Ulcerative Colitis: Vedolizumab 108 mg | Crohn's Disease: Vedolizumab 108 mg | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 23 Participants | 18 Participants | 41 Participants |
| Age, Categorical Between 18 and 65 years | 265 Participants | 440 Participants | 705 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 3 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 34 Participants | 94 Participants | 128 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 253 Participants | 361 Participants | 614 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) Asian | 58 Participants | 28 Participants | 86 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 9 Participants | 11 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 226 Participants | 417 Participants | 643 Participants |
| Sex: Female, Male Female | 120 Participants | 214 Participants | 334 Participants |
| Sex: Female, Male Male | 168 Participants | 244 Participants | 412 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 163 | 0 / 60 | 0 / 65 | 2 / 239 | 0 / 117 | 0 / 102 |
| other Total, other adverse events | 94 / 163 | 41 / 60 | 55 / 65 | 151 / 239 | 78 / 117 | 90 / 102 |
| serious Total, serious adverse events | 29 / 163 | 12 / 60 | 24 / 65 | 55 / 239 | 35 / 117 | 31 / 102 |
Outcome results
Primary
Number of Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs Adjusted by Duration of Participant's Exposure to Long-term Vedolizumab Treatment
A TEAE was defined as an adverse event (AE) that started or worsened on or after study Day 1 (defined as day first dosed) and no more than 18 weeks after the last dose of study drug. An SAE was defined as any untoward medical occurrence that occurs at any dose and resulted in death, was life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, was an important medical event such as acute liver failure, pulmonary hypertension, or confirmed or suspected transmission of an infectious agent by a medicinal product. Participant years is defined as the total exposure-time of the participants in the respective treatment group. Incidence per 100 participant years is defined as (Number of participants with events\*100/participant years). As per planned analysis, data for this outcome measure is grouped and presented per disease condition.
Time frame: Up to 97.9 months
Population: The SAF included all participants who had received at least 1 dose of study medication during this study (MLN0002SC-3030).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ulcerative Colitis: Vedolizumab 108 mg | Number of Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs Adjusted by Duration of Participant's Exposure to Long-term Vedolizumab Treatment | TEAEs | 22.9 events per 100 participant years |
| Ulcerative Colitis: Vedolizumab 108 mg | Number of Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs Adjusted by Duration of Participant's Exposure to Long-term Vedolizumab Treatment | Serious TEAEs | 6.5 events per 100 participant years |
| Crohn's Disease: Vedolizumab 108 mg | Number of Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs Adjusted by Duration of Participant's Exposure to Long-term Vedolizumab Treatment | TEAEs | 28.0 events per 100 participant years |
| Crohn's Disease: Vedolizumab 108 mg | Number of Treatment Emergent Adverse Events (TEAEs) and Serious TEAEs Adjusted by Duration of Participant's Exposure to Long-term Vedolizumab Treatment | Serious TEAEs | 8.7 events per 100 participant years |
Secondary
Number of Adverse Events of Special Interest (AESIs) Adjusted by Duration of Participant's Exposure to Long-term Vedolizumab Treatment
AESIs included hypersensitivity reactions (including injections site reactions), serious infections, malignancies, hepatotoxicity (abnormal liver function test) and progressive multifocal leukoencephalopathy (PML). Participant years is defined as the total exposure-time of the participants in the respective treatment group. Incidence per 100 participant years is defined as (Number of participants with events\*100/participant years). As per planned analysis, data for this outcome measure is grouped and presented per disease condition.
Time frame: Up to 97.9 months
Population: The SAF included all participants who had received at least 1 dose of study medication during this study (MLN0002SC-3030).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ulcerative Colitis: Vedolizumab 108 mg | Number of Adverse Events of Special Interest (AESIs) Adjusted by Duration of Participant's Exposure to Long-term Vedolizumab Treatment | 16.3 events per 100 participant years |
| Crohn's Disease: Vedolizumab 108 mg | Number of Adverse Events of Special Interest (AESIs) Adjusted by Duration of Participant's Exposure to Long-term Vedolizumab Treatment | 17.4 events per 100 participant years |
Secondary
Number of Participants With Crohn's Disease Achieving Clinical Remission Based on Harvey-Bradshaw Index (HBI) Scores
Clinical remission is defined as total HBI score of ≤4 points. As per planned analysis, data for this outcome measure is grouped and presented for participants with Crohn's disease.
Time frame: Week 48
Population: FAS included all enrolled participants of this study MLN0002SC-3030.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ulcerative Colitis: Vedolizumab 108 mg | Number of Participants With Crohn's Disease Achieving Clinical Remission Based on Harvey-Bradshaw Index (HBI) Scores | 217 Participants |
Secondary
Number of Participants With Crohn's Disease Achieving Clinical Response Based on Harvey-Bradshaw Index (HBI) Scores at Week 48
Clinical response is defined as a decrease in HBI score of ≥3 points from baseline in CD participants (randomized early terminator CD participants only \[defined as randomized CD participants withdrawn from the parent study between Week 6 and Week 52\]). As per planned analysis, data for this outcome measure is grouped and presented for participants with Crohn's disease.
Time frame: Week 48
Population: FAS included all enrolled participants of this study MLN0002SC-3030. Overall number analyzed is the number of randomized CD participants withdrawn from the parent study between Week 6 and Week 52.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ulcerative Colitis: Vedolizumab 108 mg | Number of Participants With Crohn's Disease Achieving Clinical Response Based on Harvey-Bradshaw Index (HBI) Scores at Week 48 | 32 Participants |
Secondary
Number of Participants With Ulcerative Colitis Achieving Clinical Remission Based on Partial Mayo Score
Clinical remission is defined as a partial Mayo score of ≤2 with no individual subscore \>1. As per planned analysis, data for this outcome measure is grouped and presented for participants with ulcerative colitis.
Time frame: Week 48
Population: FAS included all enrolled participants of this study MLN0002SC-3030.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ulcerative Colitis: Vedolizumab 108 mg | Number of Participants With Ulcerative Colitis Achieving Clinical Remission Based on Partial Mayo Score | 150 Participants |
Secondary
Number of Participants With Ulcerative Colitis Achieving Partial Mayo Scoring Clinical Response at Week 48
Clinical response is defined as a decrease in the partial Mayo score of at least 2 points and ≥25% from baseline, with an accompanying decrease in rectal bleeding subscore of ≥1 point from baseline or absolute rectal bleeding subscore of ≤1 point. As per planned analysis, data for this outcome measure is grouped and presented for participants with ulcerative colitis.
Time frame: Week 48
Population: Full Analysis Set (FAS) included all enrolled participants of this study MLN0002SC-3030. Overall number of participants analyzed is the number of participants with data available for analyses.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ulcerative Colitis: Vedolizumab 108 mg | Number of Participants With Ulcerative Colitis Achieving Partial Mayo Scoring Clinical Response at Week 48 | 168 Participants |