Vedolizumab Monotherapy Vs Combination Therapy With Tacrolimus in UC

NCT02954159 | Terminated Phase 3 Results DMC FDA Drug

• 1 other identifier: 2016-101742
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this study is to assess if a combination therapy of tacrolimus and vedolizumab is superior to vedolizumab monotherapy for induction of remission in moderate to severe UC, and its effect on long and short-term outcomes including colectomy rate. Secondary aim of this study is to assess the safety of tacrolimus as an induction agent in patients with UC.

Conditions

Ulcerative Colitis

Outcome Measures

Primary Outcomes (1)

• Clinical Response

  Steroid-free clinical response at week 6 after starting vedolizumab, defined as a reduction in the Mayo Clinic score of at least 3 points and a decrease of at least 30% from the baseline score, with a decrease of at least 1 point on the rectal bleeding subscale or an absolute rectal bleeding score of 0 or 1 while off steroids.

  week 6

Secondary Outcomes (1)

• Clinical Response

  week 14

Other Outcomes (2)

• Mayo UC Score

  Screening, Week 2, 6, 8, 14, 30

• Short Inflammatory Bowel Disease Questionnaire

  Screening, Week 6, 14, 30

Study Arms (2)

Treatment arm

ACTIVE COMPARATOR

vedolizumab at standard regimen with concomitant induction treatment of tacrolimus (starting 0.05 mg per Kg twice daily)

Drug: Tacrolimus; Drug: Vedolizumab

Placebo Arm

PLACEBO COMPARATOR

vedolizumab at standard regimen with placebo.

Drug: Vedolizumab; Other: Placebo

Interventions

Tacrolimus DRUG

Oral tacrolimus tablet starting at 0.05mg/kg twice daily, with dose adjustments aiming for serum trough levels of 10-15 ng/ml during the first 2 weeks, and 5-10ng/ml subsequently.

Also known as: Prograf

Treatment arm

Vedolizumab DRUG

Intravenous Vedolizumab 300 mg at week 0, 2 and 6 followed by the same dose every 8 weeks. This drug will be given as per standard of care.

Also known as: Entyvio

Placebo Arm; Treatment arm

Placebo OTHER

Patients will be randomized 1:1 in Treatment arm (receive Tacrolimus) and Placebo Arm.

Placebo Arm

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients aged 18 to 65 years with a confirmed diagnosis of UC.
• Diagnosis of UC established at least 6 months before enrollment or evidence of chronicity in colonic biopsies.
• Patients with UC disease extent beyond 15 cm (must involve at least the sigmoid colon)
• In female patients:
• Post-menopausal for ≥1 year before screening, or
• Surgically sterile, or
• Agree to be on a contraceptive method from the screening visit through 4 weeks after discontinuing tacrolimus (or placebo), or
• Completely abstain from heterosexual intercourse.
• In male patients:
• o Agreement not to father a child through 4 weeks after discontinuing tacrolimus (through contraception or abstinence).
• Moderate to severe UC
• Mayo Clinic partial UC score of 6 to 12, with a baseline sigmoidoscopy sub-score of at least 2, and disease that extended 15 cm or more from the anal verge.
• Steroid dependent patients (Appendix 1)
• Steroid naïve or steroid responsive
• Patients are planned to start vedolizumab as part of their clinical care.

You may not qualify if:

• Positive stool test for parasites or stool culture for pathologic bacteria within 30 days prior to enrollment.
• Evidence or history of Clostridium Difficile infection within 60 days prior to enrollment.
• Active Cytomegalovirus (CMV) infection evidenced by a positive CMV PCR in serum and/or positive immunohistochemistry stain in colonic tissue.
• Uncontrolled hypertension.
• Chronic kidney disease (defined as a glomerular filtration rate \< 60 mL/min, calculated using the Modification of Diet in Renal Disease (MDRD) formula)
• Chronic liver disease.
• A refractory electrolyte disorder (e.g. hypomagnesemia).
• Persistent hypomagnesemia that does not respond to oral magnesium supplementation defined as a value \<1.3 mEq/L in two separate readings, despite the administration of oral magnesium \[10 meq of slow-release magnesium chloride three times per day for 48 hours\].
• Persistent hypophosphatemia defined as levels \<2.2 mg/dL in two separate readings, 48 hours apart despite phosphate supplementation (sodium phosphate/potassium phosphate 500 mg up to three times daily for 48 hours).
• Creatinine values of 1.5 mg/dL in 2 separate readings.
• Established diagnosis of diabetes mellitus.
• Clinical or radiological evidence of megacolon.
• Intestinal perforation, or abdominal abscess within 3 months prior to enrollment.
• Active clinically significant bacterial infection (within 30 days of enrollment).
• Personal history of total or sub-total colectomy.

Sponsors & Collaborators

• Medical College of Wisconsin: lead
• Takeda: collaborator

Study Sites (1)

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

MeSH Terms

Conditions

Colitis, Ulcerative

Interventions

Tacrolimus; vedolizumab

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Inflammatory Bowel Diseases; Colonic Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Limitations and Caveats

Study was stopped due to lack of enrollment. 4 subjects were enrolled. A Amendment was needed sooner to lessen patient burden/time or increase patient compensation.

Results Point of Contact

• Title: Andres Yarur, MD; Principal Investigator
• Organization: Medical College Of Wisconsin

ayarur@mcw.edu

414-955-6858

Study Officials

• Andres J Yarur, MD

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor, Dept of Gastroenterology

Study Record Dates

• First Submitted: October 14, 2016
• First Posted: November 3, 2016
• Study Start: May 18, 2017
• Primary Completion: January 31, 2019
• Study Completion: January 31, 2019
• Last Updated: September 3, 2020
• Results First Posted: September 3, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)