Vedolizumab Post Op Study

NCT02834754 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: PRO16030443
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

This is a pilot study that will determine the endoscopic recurrence of Crohn's disease 12 months after curative, resective ileal or ileocolonic surgery in patients receiving post-operative vedolizumab (Entyvio) or placebo. The investigators hypothesize that the administration of post-operative vedolizumab will decrease the endoscopic recurrence of Crohn's disease.

Conditions

Crohn's Disease

Keywords

post-operative

Outcome Measures

Primary Outcomes (1)

• Endoscopic remission

  During a follow up colonoscopy, the Rutgeerts' score will be used to assess for endoscopic remission. An endoscopy score of i0 or i1 will be considered endoscopic remission and a score of i2 or higher denotes endoscopic recurrence. The endoscopic scoring system is as follows: Grade 0 normal distal ileum, Grade 1 up to 5 small aphthous ulcers, Grade 2 six or more aphthous ulcers with skip areas either at the ilocolonic anastomosis or proximal to it, Grade 3 diffuse aphthous ileitis with diffusely inflamed mucosa and Grade 4 diffuse inflammation with larger ulcers, nodules, and/or narrowing.

  54 weeks

Secondary Outcomes (2)

• clinical remission

  54 weeks

• Histologic remission

  54 weeks

Study Arms (2)

Vedolizumab

EXPERIMENTAL

Vedolizumab infusions at weeks 0, 2, and 6 weeks, then every 8 weeks for 52 weeks

Drug: Vedolizumab

placebo

PLACEBO COMPARATOR

Placebo infusions at weeks 0, 2, and 6 weeks, then every 8 weeks for 52 weeks

Drug: placebo

Interventions

Vedolizumab DRUG

Vedolizumab is a monoclonal antibody developed by Millennium Pharmaceuticals, Inc for the treatment of ulcerative colitis and Crohn's disease. It binds to integrin α₄β₇. Blocking the α₄β₇ integrin results in gut-selective anti-inflammatory activity. Vedolizumab was been approved by the Food and Drug Administration (FDA) in 2014 for achieving clinical response, achieving clinical remission, and achieving corticosteroid-free remission in adult patients with moderately to severely active Crohn's disease. We believe that use of vedolizumab constitutes a non-significant risk to the research subject. The dose of vedolizumab administered is 300mg IV

Also known as: entyvio

Vedolizumab

placebo DRUG

Currently there are no clinical guidelines and no standard of care for the maintenance of surgically induced remission. There are no medications that have consistently been proven to be efficacious at preventing recurrent Crohn's disease and as such, no active equivalent arm is being used. Due to the lack of effective prophylactic therapy, many physicians and patients opt not to initiate medical therapy after surgery, rather wait until Crohn's disease recurs, or wait to perform a post-operative colonoscopy within 6-12 months of surgery, and decide on initiating Crohn's disease therapy based on endoscopic Rutgeerts; score. Therefore, acknowledging that many patients are not administered post-operative maintenance medications, we feel the placebo arm is justified.

placebo

Eligibility Criteria

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

You may qualify if:

• Are men or women \> 18 years of age at screening.
• Curative resection and ileocolonic anastomosis for Crohn's disease. Patients with isolated fibrostenotic (non-inflammatory) or minimal (not clinically significant) disease elsewhere in gastrointestinal that is not resected will also be included.
• Participants who have received pre-operative vedolizumab therapy may be included.
• Concomitant medications: All concomitant medications at the time of the surgery will be discontinued post-operatively.
• Men and women of childbearing potential must use adequate birth control measures (e.g., abstinence, oral contraceptives, intrauterine device, barrier method with spermicide, implantable or injectable contraceptives or surgical sterilization) for the duration of the study and should continue such precautions for 6 months after receiving the last infusion).
• Antibiotics for the treatment of Crohn's disease (eg. ciprofloxacin and metronidazole) are allowable but must be discontinued within 12 weeks after surgery. Antibiotics for the treatment of a concomitant infection are allowable throughout the duration of the study as long as the primary purpose of antibiotic therapy is not for the primary treatment of Crohn's disease.
• Screening laboratory tests must meet the screening criteria (Hemoglobin ≥ 8.5 g/dL, White blood cell (WBC) count ≥ 3.0 x 109/L, Neutrophils ≥ 1.0 x 109/L, Platelets ≥ 100 x 109/L, Lymphocyte count ≥ 0.5 x 109/L and SGOT (AST-aspartate aminotransferase) -\< 3 times upper normal limit).
• Are capable of providing written informed consent, and the consent must be obtained prior to conducting any protocol-specified procedures.
• Are willing to adhere to the study visit schedule and other protocol requirements.
• Participants who require a temporary diverting ileostomy and then takedown will be included. These would be participants who undergo resective surgery and primary ileocolonic anastomosis but require a temporary diverting ostomy proximal to the anastomotic site. Participants will be eligible for the study upon takedown of the diverting ileostomy

You may not qualify if:

• Participants with greater than 10 years of Crohn's disease requiring their FIRST resection of a short (\<10cm) fibrostenotic stricture. The rationale for excluding these participants is that historically this group of participants is at a very low risk of recurrence and therefore, would not be a group targeted for postoperative medical therapy.
• Macroscopically active disease at the anastomosis at the time of surgery.
• Presence of a stoma.
• Prior severe infusion reaction to vedolizumab, i.e. anaphylaxis, bronchospasm, or hypotension.
• History of anaphylaxis to other chimeric proteins.
• Any of the following medications taken within 12 weeks of surgery: cyclosporine, tacrolimus, sirolimus, mycophenolate mofetil, or other investigational drugs. Patients who have taken these medications more than 12 weeks prior to surgery will be allowed in the study
• At the time of screening participants with a positive stool culture for enteric pathogens, pathogenic ova or parasites, or Clostridium difficile toxin and have clinically significant signs of an enteric infection, i.e. diarrhea, fever, abdominal pain. participants will be eligible for enrollment if stool cultures are positive but do not have clinically significant signs or symptoms or infection and receive appropriate antibiotic treatment. A repeat stool culture will be obtained at the completion of antibiotic treatment.
• Women who are pregnant, nursing, or planning pregnancy during the trial or within 6 months after the last infusion (this includes father's who plan on fathering a child within 6 months after their last infusion).
• Have or have had an opportunistic infection (eg, herpes zoster \[shingles\], cytomegalovirus, Pneumocystis carinii, aspergillosis, histoplasmosis, or mycobacteria other than TB) within 6 months of screening.
• Have a chest radiograph within 3 months prior to screening that shows evidence of malignancy, infection, or any abnormalities.
• Documentation of seropositive for human immunodeficiency virus (HIV).
• Documentation of a positive test for hepatitis B surface antigen or a history of documented hepatitis C.
• Have current signs or symptoms of systemic lupus erythematosus, or severe, progressive, or uncontrolled renal, hepatic, hematologic, gastrointestinal, endocrine, pulmonary, cardiac, neurologic, or cerebral diseases.
• Presence of a transplanted solid organ (with the exception of a corneal transplant \> 3 months prior to randomization).
• Have any current known malignancy other than the condition being treated or have a history of malignancy within 5 years prior to screening (except for squamous or basal cell carcinoma of the skin that has been fully excised with no evidence of recurrence).

Sponsors & Collaborators

• Marc Schwartz: lead
• Takeda: collaborator

Study Sites (1)

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

MeSH Terms

Conditions

Crohn Disease

Interventions

vedolizumab

Condition Hierarchy (Ancestors)

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

Study Officials

• Marc B Schwartz, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: July 12, 2016
• First Posted: July 15, 2016
• Study Start: December 1, 2018
• Primary Completion: May 1, 2019
• Study Completion: May 1, 2019
• Last Updated: May 14, 2020

Record last verified: 2020-05

Locations

US (1)