Clinical trial NCT04919252: Efficacy and Safety of Vedolizumab in Biologic-naïve Korean Patients With Moderate to Severe Inflammatory Bowel Disease
Official title: Efficacy and Safety of Vedolizumab in Biologic-naïve Korean Patients With Moderate to Severe Inflammatory Bowel Disease
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Crohn's Disease and Ulcerative Colitis
Keywords: inflammatory bowel disease
Lead sponsor: Yonsei University
Sponsor class: OTHER
First posted: 2021-06-09
Enrollment: 60
Sex: ALL
Minimum age (years): 19
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: If subjects voluntarily consent to participation in the study, those who are finally determined to be eligible for the study after whether all of the inclusion criteria and none of the exclusion criteria are met is checked will receive the study drug. Efficacy and safety will be evaluated at baseline, baseline, 2 weeks, 6 weeks, 14 weeks, 22 weeks, 30 weeks, 38 weeks, 46 weeks, and 54 weeks.

Detailed description: This study, which is designed as a multicenter, open-label, single-arm, phase 3b clinical trial, is intended to evaluate the efficacy and safety of vedolizumab in biologic-naïve Korean patients with moderate-to-severe bowel disease.

The study is conducted with a single arm, and the subjects to be recruited consist of 30 patients with Crohn's disease and 30 patients with ulcerative colitis (considering dropout rate of 20%).

The total period after the subject enrollment is 54 weeks, and a total of 10 visits are made with screening, baseline, 2 weeks, 6 weeks, 14 weeks, 22 weeks, 30 weeks, 38 weeks, 46 weeks, and 54 weeks.

* Crohn's disease (CD): If a subject does not respond to vedolizumab 300mg iv 0, 2, and 6 weeks for induction, an additional dose of vedolizumab 300 mg will be given at week 10. On the other hand, Maintenance therapy should be continued every 8 weeks from week 14 in responding patients, and for some patients who have experienced a decrease in their response, it can be given every 4 weeks.The maximum dosing period is 54 weeks.
* Ulcerative colitis (UC): If a subject responds to vedolizumab 300mg iv 0, 2, and 6 weeks for induction, maintenance therapy should be continued every 8 weeks from week 14, and for some patients who have experienced a decrease in their response, it can be given every 4 weeks.The maximum dosing period is 54 weeks.

Eligibility criteria: Inclusion Criteria:

1. Adults aged ≥ 19 years to ≤ 70 years
2. Patients with moderate-to-severe active Crohn's disease or ulcerative colitis who are unresponsive to, become unresponsive to, or have no tolerability to universal treatment (with corticosteroids, immunomodulators, etc.)

   * CDAI (Crohn's Disease Activity Index) ≥ 220 for Crohn's disease
   * Complete Mayo score ≥ 6 for ulcerative colitis

Exclusion Criteria:

1. A history of total colectomy
2. Acute severe UC(Ulcerative Colitis)
3. A potential for a bowel resection surgery within 3 months
4. Pregnancy and breastfeeding
5. Prior use of any biologics including anti-TNFs, ustekinumab, and tofacitinib
6. A history of solid cancer and blood cancer within 5 years
7. Positive for active or latent tuberculosis (However, screening is possible if active tuberculosis is excluded and after at least 4 weeks of latent tuberculosis treatment.)
8. Active severe infections such as sepsis, cytomegalovirus, listeriosis, and opportunistic infections such as progressive multifocal leukoencephalopathy (PML).
9. Hypersensitivity to vedolizumab or its substances (e.g., dyspnoea, bronchospasm, redness, and increased heart rate)
10. Experience of treatment with a drug or a medical device due to participation in another clinical trial within 3 months from the date of consent
11. A woman of childbearing potential who has a positive pregnancy test (Urine-hCG or Serum hCG) at a screening visit or does not agree to use at least one of medically acceptable, effective contraceptive methods\*. However, females who reached menopause at least one year ago or turned out infertile due to an operation should be excluded.

    \*Effective contraceptive methods: intrauterine devices (e.g., IUD, mirena), dual barrier methods (diaphragm or condom/femidom + spermicide), and parenteral contraceptives. Continuing only sexual abstinence is not viewed as an acceptable method.
12. A woman of childbearing potential who neither practices adequate contraception nor agrees to continue its use for at least 18 weeks after the last dose of the study drug.
13. Those decided by the investigator to be not eligible for this study

Primary outcomes:
measure: Clinical remission rate (%) at 14 weeks after commencement of vedolizumab treatment in induction phase
timeFrame: 14 weeks
measure: Clinical remission rate (%) at 54 weeks in maintenance phase
timeFrame: 54 weeks
Secondary outcomes:
measure: Response rate of dose intensification at 54 weeks in inadequate responders at 6 weeks
timeFrame: 6 weeks, 54 weeks
measure: Mucosal healing rate at 14 weeks and 54 weeks
timeFrame: 14 weeks, 54 weeks
measure: Steroid free remission rate at 54 weeks
timeFrame: 54 weeks
measure: Transmural healing rate at 14 weeks and 54 weeks for Crohn's Disease
timeFrame: 14 weeks, 54 weeks
measure: Correlation of CRP(C-reactive protein) level with clinical remission at 54 weeks.
timeFrame: 54 weeks
measure: Correlation of fecal calprotectin level with clinical remission at 54 weeks
timeFrame: 54 weeks
measure: Correlation of endoscopic severity with clinical remission at 54 weeks
timeFrame: 54 weeks
measure: Correlation of radiologic severity with clinical remission at 54 weeks
timeFrame: 54 weeks
measure: Correlation of CDAI(Crohn's Disease Activity Index) score with clinical remission at 54 weeks
timeFrame: 54 weeks
measure: Correlation of Mayo score with clinical remission at 54 weeks
timeFrame: 54 weeks
measure: Changes in fecal microbiota after vedolizumab treatment: Microbiota change will be compared with baseline status using α diversity and β diversity.
timeFrame: Baseline, 14 weeks, 54 weeks
measure: QoL(Quality of Life): IBDQ(Inflammatory Bowel Disease Questionnaire)
timeFrame: Baseline, 14 weeks, 54 weeks
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Yonsei University Health System, Severance Hospital
Study officials:
affiliation: Severance Hospital of Yonsei University College of Medicine
name: Jae hee Cheon, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: