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Efficacy and Safety of Vedolizumab Subcutaneously (SC) as Maintenance Therapy in Ulcerative Colitis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02611830
Recruitment Status : Completed
First Posted : November 23, 2015
Results First Posted : January 23, 2020
Last Update Posted : January 23, 2020
Sponsor:
Information provided by (Responsible Party):
Takeda

Tracking Information
First Submitted Date  ICMJE November 19, 2015
First Posted Date  ICMJE November 23, 2015
Results First Submitted Date  ICMJE May 29, 2019
Results First Posted Date  ICMJE January 23, 2020
Last Update Posted Date January 23, 2020
Actual Study Start Date  ICMJE December 18, 2015
Actual Primary Completion Date May 30, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 22, 2020)
Percentage of Participants Achieving Clinical Remission at Week 52 [ Time Frame: Week 52 ]
Clinical remission is defined as a complete Mayo score ≤ 2 points and no individual subscore > 1 point. The Mayo score is a standard assessment tool to measure ulcerative colitis disease activity in clinical trials. The index consists of 4 subscores: rectal bleeding, stool frequency, findings on endoscopy, and physician's global assessment. Each subscore is scored on a scale from 0 to 3 and the complete Mayo score ranges from 0 to 12 (higher scores indicate greater disease activity).
Original Primary Outcome Measures  ICMJE
 (submitted: November 19, 2015)
Percentage of Participants Achieving Clinical Remission at Week 52 for vedolizumab IV and plac [ Time Frame: Week 52 ]
Clinical remission is defined as a complete Mayo score of ≤2 points and no individual subscore greater than >1 point.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 22, 2020)
  • Percentage of Participants Achieving Mucosal Healing at Week 52 [ Time Frame: Week 52 ]
    Mucosal healing is defined as Mayo endoscopic subscore ≤1 point. The findings on endoscopy scale ranges from 0 to 3, where 0=normal or inactive disease 1=mild disease (erythema, decreased vascular pattern, mild friability) 2=moderate disease (marked erythema, lack of vascular pattern, friability, erosions) 3=severe disease (spontaneous bleeding, ulceration).
  • Percentage of Participants Achieving Durable Clinical Response at Week 6 and Week 52 [ Time Frame: Baseline, Weeks 6 and 52 ]
    Durable clinical response is defined as clinical response at both Weeks 6 and 52, where clinical response is defined as a reduction in complete Mayo score of ≥3 points and ≥30% from Baseline (Week 0) with an accompanying decrease in rectal bleeding subscore of ≥1 point or absolute rectal bleeding subscore of ≤1 point. The Mayo score is a standard assessment tool to measure ulcerative colitis disease activity in clinical trials. The index consists of 4 subscores: rectal bleeding, stool frequency, findings on endoscopy, and physician's global assessment. Each subscore is scored on a scale from 0 to 3 and the complete Mayo score ranges from 0 to 12 (higher scores indicate greater disease activity).
  • Percentage of Participants Achieving Durable Clinical Remission at Week 6 and Week 52 [ Time Frame: Weeks 6 and 52 ]
    Durable clinical remission is defined as clinical remission at both Weeks 6 and 52. Clinical remission is defined as a complete Mayo score of less than or equal to (≤) 2 points and no individual subscore greater than (>) 1 point. The Mayo score is a standard assessment tool to measure ulcerative colitis disease activity in clinical trials. The index consists of 4 subscores: rectal bleeding, stool frequency, findings on endoscopy, and physician's global assessment. Each subscore is scored on a scale from 0 to 3 and the complete Mayo score ranges from 0 to 12 (higher scores indicate greater disease activity).
  • Percentage of Participants Achieving Corticosteroid-free Remission at Week 52 [ Time Frame: Week 52 ]
    Corticosteroid-free remission is defined as participants using oral corticosteroids at Baseline (Week 0) who have discontinued oral corticosteroids and are in clinical remission at Week 52. Clinical remission is defined as a complete Mayo score of ≤ 2 points and no individual subscore > 1 point. The Mayo score is a standard assessment tool to measure ulcerative colitis disease activity in clinical trials. The index consists of 4 subscores: rectal bleeding, stool frequency, findings on endoscopy, and physician's global assessment. Each subscore is scored on a scale from 0 to 3 and the complete Mayo score ranges from 0 to 12 (higher scores indicate greater disease activity).
Original Secondary Outcome Measures  ICMJE
 (submitted: November 19, 2015)
  • Percentage of Participants Achieving Mucosal Healing at Week 52 [ Time Frame: Week 52 ]
    Mucosal healing is defined as Mayo endoscopic subscore ≤1 point
  • Percentage of Participants Achieving Durable Clinical Response [ Time Frame: Baseline and Weeks 6 and 52 ]
    Durable clinical response is defined as clinical response at Weeks 6 and 52, where clinical response is defined as a reduction in complete Mayo score of ≥3 points and ≥30% from Baseline (Week 0) with an accompanying decrease in rectal bleeding subscore of ≥1 point or absolute rectal bleeding subscore of ≤1 point.
  • Percentage of Participants Achieving Durable Clinical Remission [ Time Frame: Weeks 6 and 52 ]
    Durable clinical response is defined as clinical response at Weeks 6 and 52, where clinical response is defined as a reduction in complete Mayo score of ≥3 points and ≥30% from Baseline (Week 0) with an accompanying decrease in rectal bleeding subscore of ≥1 point or absolute rectal bleeding subscore of ≤1 point.
  • Percentage of Participants Achieving Corticosteroid-free Remission at Week 52 [ Time Frame: Baseline and Week 52 ]
    Corticosteroid-free remission is defined as participants using oral corticosteroids at Baseline (Week 0) who have discontinued oral corticosteroids and are in clinical remission at Week 52. Clinical remission is defined as a complete Mayo score of ≤2 points and no individual subscore greater than >1 point.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy and Safety of Vedolizumab Subcutaneously (SC) as Maintenance Therapy in Ulcerative Colitis
Official Title  ICMJE A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study, With a Vedolizumab IV Reference Arm, to Evaluate the Efficacy and Safety of Vedolizumab Subcutaneous as Maintenance Therapy in Subjects With Moderately to Severely Active Ulcerative Colitis Who Achieved Clinical Response Following Open-Label Vedolizumab Intravenous Therapy
Brief Summary The purpose of this study is to assess the effect of vedolizumab subcutaneous (vedolizumab SC) maintenance treatment on clinical remission at Week 52 in participants with moderately to severely active ulcerative colitis (UC) who achieved clinical response following administration of vedolizumab intravenous (vedolizumab IV) induction therapy.
Detailed Description

The drug being tested in this study is called vedolizumab subcutaneous (vedolizumab SC). Vedolizumab SC is being tested to treat people who have moderate to severely active ulcerative colitis. This study will look at clinical remission as well as mucosal healing, durable clinical response, durable clinical remission, and corticosteroid free remission in participants with UC who receive vedolizumab SC maintenance therapy after having achieved a clinical response to vedolizumab IV induction therapy.

The study enrolled 383 patients. All participants will enter into a 6-week Induction Phase where they will be administered open-label vedolizumab IV 300 mg via intravenous infusion (IV) at Week 0 (Day 1) and Week 2 (Day 15), and will then be assessed for a clinical response at Week 6. Participants who achieve a clinical response at Week 6 will be randomly assigned to one of the three treatment groups:

Vedolizumab SC 108 mg Q2W and Placebo IV Q8W Vedolizumab IV 300 mg Q8W and Placebo SC Q2W Placebo SC Q2W and Placebo IV Q8W

Participants who do not achieve a clinical response at Week 6 will not be randomized in to the Maintenance Period, and will receive a third infusion of vedolizumab IV 300 mg at Week 6.

This multi-center trial will be conducted worldwide. The overall time to participate in this study is up to 71 weeks (up to 4 weeks of screening, 52 weeks of treatment and 18 weeks of safety follow-up). 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.

After the Week 52 assessments, participants meeting protocol-defined criteria were eligible to enroll in Study MLN0002SC-3030 (NCT02620046; Long-term Safety) to receive open-label vedolizumab treatment. Participants who withdrew early (prior to Week 52) due to sustained nonresponse, disease worsening, or the need for rescue medications may also have been eligible for Study MLN0002SC-3030. Participants who did not enroll into Study MLN0002SC-3030 were to complete a final on-study safety assessment at Week 68 (or final safety visit 18 weeks after the last dose) in the Maintenance Phase of Study MLN0002SC-3027.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Colitis, Ulcerative
Intervention  ICMJE
  • Drug: Vedolizumab 300 mg IV
    Vedolizumab intravenous infusion
  • Drug: Placebo IV
    Vedolizumab intravenous infusion placebo
  • Drug: Vedolizumab 108 mg SC
    Vedolizumab subcutaneous injection
  • Drug: Placebo SC
    Vedolizumab subcutaneous injection placebo
Study Arms  ICMJE
  • Experimental: Maintenance Phase: Induction IV + Vedolizumab 108 mg SC
    Participants received vedolizumab 300 mg IV infusion in open-label induction phase and achieved clinical response at Week 6 were randomized to receive vedolizumab SC in maintenance phase. Vedolizumab SC, 108 mg, injection, Q2W and placebo-matching IV infusions, Q8W, starting at Week 6 up to approximately Week 50.
    Interventions:
    • Drug: Vedolizumab 300 mg IV
    • Drug: Placebo IV
    • Drug: Vedolizumab 108 mg SC
  • Experimental: Maintenance Phase: Induction IV + Vedolizumab 300 mg IV
    Participants received vedolizumab 300 mg IV infusion in open-label induction phase and achieved clinical response at Week 6 were randomized to receive vedolizumab IV in maintenance phase. Vedolizumab 300 mg, IV infusion, Q8W and placebo-matching SC injection, Q2W starting at Week 6 up to approximately Week 50.
    Interventions:
    • Drug: Vedolizumab 300 mg IV
    • Drug: Placebo SC
  • Experimental: Maintenance Phase: Induction IV + Placebo
    Participants received vedolizumab 300 mg IV infusion in open-label induction phase and achieved clinical response at Week 6 were randomized to receive placebo in maintenance phase. Placebo-matching subcutaneous (SC) injections, once every 2 weeks (Q2W) and placebo-matching IV infusions, once every 8 weeks (Q8W) starting at Week 6 up to approximately Week 50.
    Interventions:
    • Drug: Vedolizumab 300 mg IV
    • Drug: Placebo IV
    • Drug: Placebo SC
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 22, 2020)
383
Original Estimated Enrollment  ICMJE
 (submitted: November 19, 2015)
400
Actual Study Completion Date  ICMJE August 21, 2018
Actual Primary Completion Date May 30, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Diagnosis of ulcerative colitis (UC) established at least 6 months prior to screening, by clinical and endoscopic evidence and corroborated by a histopathology report.
  2. Moderately to severely active UC as determined by a complete Mayo score of 6-12 (with an endoscopic subscore ≥2)
  3. Evidence of UC extending proximal to the rectum (≥15 cm of involved colon).
  4. Inadequate response with, loss of response to, or intolerance to corticosteroids, immunomodulators, or Tumor Necrosis Factor-alpha (TNF-α) antagonists

Exclusion Criteria:

  1. Evidence of abdominal abscess or toxic megacolon at the initial Screening Visit.
  2. Extensive colonic resection, subtotal or total colectomy.
  3. Ileostomy, colostomy, or known fixed symptomatic stenosis of the intestine.
  4. Prior exposure to investigational or approved non-biologic therapies (eg, cyclosporine, tacrolimus, thalidomide, methotrexate or tofacitinib) for the treatment of underlying disease within 30 days or 5 half-lives of screening (whichever is longer).
  5. Prior exposure to any investigational or approved biologic or biosimilar agent within 60 days or 5 half-lives of screening (whichever is longer).
  6. Prior exposure to vedolizumab
  7. Surgical intervention for UC required at any time during the study.
  8. History or evidence of adenomatous colonic polyps that have not been removed or has a history or evidence of colonic mucosal dysplasia.
  9. Suspected or confirmed diagnosis of Crohn's entercolitis, indeterminate colitis, ischaemic colitis, radiation colitis, diverticular disease associated with colitis, or microscopic colitis.
  10. Active infections
  11. Chronic hepatitis B virus (HBV) infection or chronic hepatitis C virus (HCV) infection, HIV or tuberculosis (active or latent), identified congenital or acquired immunodeficiency. HBV immune participants (ie, being hepatitis B surface antigen [HBsAg] negative and hepatitis B antibody positive) may, however, be included.
  12. History of any major neurological disorders, including stroke, multiple sclerosis, brain tumor, demyelinating or neurodegenerative disease.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 80 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Australia,   Belgium,   Bosnia and Herzegovina,   Brazil,   Bulgaria,   Canada,   Croatia,   Czechia,   Denmark,   Estonia,   Germany,   Hungary,   Israel,   Italy,   Japan,   Korea, Republic of,   Lithuania,   Mexico,   Netherlands,   Poland,   Romania,   Russian Federation,   Serbia,   Slovakia,   Spain,   Sweden,   Turkey,   Ukraine,   United Kingdom,   United States
Removed Location Countries Colombia,   Czech Republic
 
Administrative Information
NCT Number  ICMJE NCT02611830
Other Study ID Numbers  ICMJE MLN0002SC-3027
2015-000480-14 ( EudraCT Number )
U1111-1168-0813 ( Registry Identifier: WHO )
16/LO/0089 ( Registry Identifier: NRES )
NL55501.056.15 ( Registry Identifier: CCMO )
JapicCTI-163222 ( Registry Identifier: JapicCTI )
189732 ( Registry Identifier: HC-CTD )
163300410A0046 ( Registry Identifier: NREC )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Takeda makes patient-level, de-identified data sets and associated documents available after applicable marketing approvals and commercial availability have been received, an opportunity for the primary publication of the research has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com/Approach for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.
Responsible Party Takeda
Study Sponsor  ICMJE Takeda
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Clinical Science Takeda
PRS Account Takeda
Verification Date January 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP