Efficacy and Safety of Vedolizumab Subcutaneous (SC) as Maintenance Therapy in Crohn's Disease (CD)

• ClinicalTrials.gov Identifier: NCT02611817
• Recruitment Status: Completed
• First Posted: November 23, 2015
• Results First Posted: June 23, 2020
• Last Update Posted: May 25, 2022
• Sponsor: Takeda
• Information provided by (Responsible Party): Takeda

Tracking Information

• First Submitted Date: November 19, 2015
• First Posted Date: November 23, 2015
• Results First Submitted Date: May 5, 2020
• Results First Posted Date: June 23, 2020
• Last Update Posted Date: May 25, 2022
• Actual Study Start Date: January 4, 2016
• Actual Primary Completion Date: May 6, 2019 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 10, 2020)

Percentage of Participants Achieving Clinical Remission at Week 52 [ Time Frame: Week 52 ]

Clinical remission is defined as a Crohn's Disease Activity Index (CDAI) score less than or equal to (<=) 150 at Week 52. A CDAI is a multi-item instrument which measures severity of active Crohn's Disease monitored over 7 days includes participant reported symptoms, physician-assessed signs, and laboratory markers. CDAI score is equal to (=) sum of weighted scores for subjective items (number of liquid/soft stools, degree of abdominal pain, general well-being); and objective items (use of anti-diarrhoeal medication, abdominal mass, haematocrit, presence of extraintestinal manifestation, body weight). CDAI scores range approximately from 0 to 600, higher scores indicating greater disease activity.

Original Primary Outcome Measures (submitted: November 19, 2015)

Percentage of Participants Achieving Clinical Remission at Week 52 [ Time Frame: Week 52 ]

Clinical remission is defined as a Crohn's Disease Activity Index (CDAI) score ≤150 at Week 52.

Current Secondary Outcome Measures (submitted: June 10, 2020)

• Percentage of Participants Achieving Enhanced Clinical Response at Week 52 [ Time Frame: Week 52 ]
  Enhanced clinical response is defined as a decrease from Baseline of greater than or equal to (>=) 100 points in the CDAI score at Week 52. A CDAI is a multi-item instrument which measures severity of active CD monitored over 7 days includes participant reported symptoms, physician-assessed signs, and laboratory markers. CDAI score = Sum of weighted scores for subjective items (number of liquid/soft stools, degree of abdominal pain, general well-being); and objective items (use of anti-diarrhoeal medication, abdominal mass, haematocrit, presence of extraintestinal manifestation, body weight). CDAI scores range approximately from 0 to 600, higher scores indicating 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 CDAI score <=150 at Week 52. CDAI score = Sum of weighted scores for subjective items (number of liquid/soft stools, degree of abdominal pain, general well-being); and objective items (use of anti-diarrhoeal medication, abdominal mass, haematocrit, presence of extraintestinal manifestation, body weight). CDAI scores range approximately from 0 to 600, higher scores indicating greater disease activity.
• Percentage of TNF-alpha Antagonist Naive Participants Achieving Clinical Remission at Week 52 [ Time Frame: Week 52 ]
  Clinical remission is defined as CDAI score <=150 at Week 52. CDAI score = Sum of weighted scores for subjective items (number of liquid/soft stools, degree of abdominal pain, general well-being); and objective items (use of anti-diarrhoeal medication, abdominal mass, haematocrit, presence of extraintestinal manifestation, body weight). CDAI scores range approximately from 0 to 600, higher scores indicating greater disease activity.

Original Secondary Outcome Measures (submitted: November 19, 2015)

• Percentage of Participants Achieving Enhanced Clinical Response at Week 52 [ Time Frame: Baseline and Week 52 ]
  Enhanced clinical response is defined as a decrease from Baseline of ≥100 points in the Crohn's Disease Activity Index (CDAI) score at Week 52.
• Percentage of Participants Achieving Corticosteroid-free Remission [ Time Frame: Baseline and Week 52 ]
  Corticosteroid-free remission is defined as participants using oral corticosteroids at Baseline who have discontinued oral corticosteroids and are in clinical remission at Week 52. Clinical remission is defined as a Crohn's Disease Activity Index (CDAI) score ≤150 at Week 52.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Efficacy and Safety of Vedolizumab Subcutaneous (SC) as Maintenance Therapy in Crohn's Disease (CD)
• Official Title: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Vedolizumab Subcutaneous as Maintenance Therapy in Subjects With Moderately to Severely Active Crohn's Disease 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) as maintenance treatment in participants with moderately to severely active CD 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 SC. Vedolizumab SC is being tested to treat people who have moderate to severely active CD. This study will look at clinical remission, as well as enhanced clinical response and corticosteroid-free remission in participants with CD who receive vedolizumab SC maintenance therapy after having achieved a clinical response to vedolizumab IV induction therapy.

The study will enroll approximately 824 participants. All participants will enter a 6 week Induction Phase where they will be administered open-label vedolizumab IV 300 mg via IV infusion 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 two treatment groups:

• Vedolizumab SC 108 mg Maintenance Arm
• Placebo SC Maintenance Arm

Participants who do not achieve a clinical response will not be randomized into the Maintenance Period, and instead 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.

• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Crohn's Disease

Intervention

• Drug: Vedolizumab SC 108 mg
  Vedolizumab SC Injection.
• Drug: Placebo
  Vedolizumab placebo-matching SC injection.
• Drug: Vedolizumab IV 300 mg
  Vedolizumab IV Injection.

Study Arms

• Experimental: Vedolizumab SC 108 mg Maintenance Arm

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

  Double-blind Maintenance: vedolizumab SC 108 mg injection once every 2 weeks (Q2W) starting at Week 6 up to Week 50

  Interventions:

  • Drug: Vedolizumab SC 108 mg
  • Drug: Vedolizumab IV 300 mg
• Placebo Comparator: Placebo SC Maintenance Arm

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

  Double-blind Maintenance: matching placebo to vedolizumab SC injection Q2W starting at Week 6 up to Week 50

  Interventions:

  • Drug: Placebo
  • Drug: Vedolizumab IV 300 mg

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 22, 2018): 644
• Original Estimated Enrollment (submitted: November 19, 2015): 824
• Actual Study Completion Date: August 6, 2019
• Actual Primary Completion Date: May 6, 2019 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Diagnosis of CD established at least 3 months prior to screening by clinical and endoscopic evidence corroborated by a histopathology report.

2. Moderately to severely active CD as determined by a CDAI score of 220 to 450 and 1 of the following:

   • C-reactive protein (CRP) level greater than (>) 2.87 milligram per liter (mg/L) OR
   • Ileocolonoscopy with photographic documentation of a minimum of 3 nonanastomotic ulcerations (each >0.5 centimeter [cm] in diameter) or 10 aphthous ulcerations (involving a minimum of 10 contiguous cm of intestine) consistent with CD OR
   • Fecal calprotectin >250 microgram per gram (mcg/g) stool during the screening period in conjunction with computed tomography enterography (CTE), magnetic resonance enterography (MRE), contrast-enhanced small bowel radiography, or wireless capsule endoscopy revealing CD ulcerations (aphthae not sufficient).
3. CD involvement of the ileum and/or colon, at a minimum.
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 at Screening.
2. Extensive colonic resection, subtotal or total colectomy.
3. History of >3 small bowel resections or diagnosis of short bowel syndrome.
4. Ileostomy, colostomy, or known fixed symptomatic stenosis of the intestine.
5. Prior exposure to investigational or approved non-biologic therapies (example, cyclosporine, tacrolimus, thalidomide, or tofacitinib) for the treatment of underlying disease within 30 days or 5 half-lives of screening (whichever is longer).
6. Prior exposure to any investigational or approved biologic or biosimilar agent within 60 days or 5 half-lives of screening (whichever is longer).
7. Prior exposure to vedolizumab.
8. Surgical intervention for CD required at any time during the study.
9. History or evidence of adenomatous colonic polyps that have not been removed, or of colonic mucosal dysplasia.
10. Suspected or confirmed diagnosis of ulcerative colitis, indeterminate colitis, ischaemic colitis, radiation colitis, diverticular disease associated with colitis, or microscopic colitis.
11. Active infections.
12. Chronic hepatitis B virus (HBV) or C (HCV) infection, tuberculosis (TB) (active or latent), or congenital or acquired immunodeficiency. HBV immune participants (that is, being hepatitis B surface antigen [HBsAg] negative and hepatitis B antibody positive) may, however, be included.
13. History of any major neurological disorders, including stroke, multiple sclerosis, brain tumor, or neurodegenerative disease.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Belgium, Bosnia and Herzegovina, Brazil, Bulgaria, Canada, Czechia, Denmark, Estonia, Germany, Hungary, Israel, Italy, Japan, Korea, Republic of, Lithuania, Mexico, Netherlands, Poland, Romania, Russian Federation, Serbia, Slovakia, South Africa, Sweden, Taiwan, Turkey, Ukraine, United Kingdom, United States
• Removed Location Countries: Argentina, Czech Republic, Spain

Administrative Information

• NCT Number: NCT02611817
• Other Study ID Numbers: MLN0002SC-3031; U1111-1168-0845 ( Registry Identifier: WHO ); 2015-000481-58 ( EudraCT Number ); NL55774.056.16 ( Registry Identifier: CCMO ); 16/LO/0090 ( Registry Identifier: NRES ); MLN0002SC-3031CTID ( Registry Identifier: Israel ); 163300410A0045 ( Registry Identifier: NREC ); 189748 ( Registry Identifier: HC-CTD ); MOH_2017-01-05_000039 ( Other Identifier: CRS ); JapicCTI-163386 ( Registry Identifier: JapicCTI )
• 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

• Plan to Share IPD: Yes
• Plan Description: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Supporting Materials: Informed Consent Form (ICF)
• Supporting Materials: Clinical Study Report (CSR)
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/ For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.
• URL: https://vivli.org/ourmember/takeda/

• Current Responsible Party: Takeda
• Original Responsible Party: Same as current
• Current Study Sponsor: Takeda
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Medical Director Clinical Science; Takeda

• PRS Account: Takeda
• Verification Date: May 2022