Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

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
Last Update Posted : August 27, 2018
Sponsor:
Information provided by (Responsible Party):
Takeda

Brief Summary:
The purpose of this study is to assess the effect of vedolizumab subcutaneous (vedolizumab SC) maintenance treatment in participants with moderately to severely active ulcerative colitis (UC) who achieved clinical response following administration of vedolizumab intravenous (vedolizumab IV) induction therapy.

Condition or disease Intervention/treatment Phase
Colitis, Ulcerative Drug: Vedolizumab IV 300 mg Drug: Placebo IV Drug: Vedolizumab SC 108 mg Drug: Placebo SC Phase 3

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 will enroll approximately 400 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. 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.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 384 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : January 8, 2016
Actual Primary Completion Date : May 30, 2018
Actual Study Completion Date : August 21, 2018

Resource links provided by the National Library of Medicine

Drug Information available for: Vedolizumab

Arm Intervention/treatment
Experimental: Vedolizumab SC 108 mg Maintenance Arm

Open-label Induction: vedolizumab IV 300 mg, infusion at Week 0 (Day 1) and Week 2 (Day 15)

Double-blind Maintenance:

  • vedolizumab SC 108 mg injection Q2W starting at Week 6 up to Week 50, and
  • matching placebo to vedolizumab IV infusion Q8W starting at Week 6 up to Week 46.
Drug: Vedolizumab IV 300 mg
Drug: Placebo IV
Drug: Vedolizumab SC 108 mg
Experimental: Vedolizumab IV 300 mg Maintenance Arm

Open-label Induction: vedolizumab IV 300 mg, infusion at Week 0 (Day 1) and Week 2 (Day 15)

Double-blind Maintenance:

  • vedolizumab IV 300mg, infusion at Week 6 up to Week 50, and
  • matching placebo to vedolizumab IV infusion Q8W starting at Week 6 up to Week 46.
Drug: Vedolizumab IV 300 mg
Drug: Placebo SC
Placebo Comparator: Placebo (IV and SC) Maintenance Arm

Open-label Induction: vedolizumab IV 300 mg, infusion, at Week 0 (Day 1) and Week 2 (Day 15)

Double-blind Maintenance:

  • placebo matching to vedolizumab IV infusion Q8W starting at Week 6 up to Week 46, and
  • placebo matching to vedolizumab SC injection Q2W starting at Week 6 up to Week 50.
Drug: Vedolizumab IV 300 mg
Drug: Placebo IV
Drug: Placebo SC



Primary Outcome Measures :
  1. Percentage of Participants Achieving Clinical Remission at Week 52 for vedolizumab SC and placebo [ Time Frame: Week 52 ]
    Clinical remission is defined as a complete Mayo score of ≤2 points and no individual subscore greater than >1 point.


Secondary Outcome Measures :
  1. Percentage of Participants Achieving Mucosal Healing at Week 52 [ Time Frame: Week 52 ]
    Mucosal healing is defined as Mayo endoscopic subscore ≤1 point

  2. 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.

  3. 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.

  4. 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.

  5. Percentage of Tumor Necrosis Factor-alpha (TNF-α) Antagonist Naive Participants Achieving Clinical Remission at Week 52 [ Time Frame: Week 52 ]
    Clinical remission is defined as a complete Mayo score of ≤2 points and no individual subscore greater than >1 point.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02611830


  Show 174 Study Locations
Sponsors and Collaborators
Takeda
Investigators
Layout table for investigator information
Study Director: Medical Director Clinical Science Takeda

Layout table for additonal information
Responsible Party: Takeda
ClinicalTrials.gov Identifier: NCT02611830     History of Changes
Other Study ID Numbers: 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 )
First Posted: November 23, 2015    Key Record Dates
Last Update Posted: August 27, 2018
Last Verified: August 2018

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Takeda:
Drug therapy

Additional relevant MeSH terms:
Layout table for MeSH terms
Colitis
Colitis, Ulcerative
Ulcer
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Intestinal Diseases
Pathologic Processes
Inflammatory Bowel Diseases
Vedolizumab
Gastrointestinal Agents