Crohn's DiseasePhase 2NCT02834754
Vedolizumab Post Op Study
A Phase 2 study testing Vedolizumab in people with Crohn's Disease, run by Marc Schwartz at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Crohn's Disease
- What is being tested?
- Vedolizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Dec 2018to 1 May 2019
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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
Who cannot join
- 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
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- 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).
- Have a history of lymphoproliferative disease including lymphoma, or signs or symptoms suggestive of possible lymphoproliferative disease such as lymphadenopathy of unusual size or location (eg, nodes in the posterior triangle of the neck, intraclavicular, epitrochlear, or periaortic area), or splenomegaly.
- Have had a known substance abuse (drug or alcohol) or dependency within the previous 3 years, history of noncompliance to medical regimens, or other condition/circumstance that could interfere with the subject's adherence to protocol requirements (eg, psychiatric disease, lack of motivation, travel, etc).
- Are unable to or unwilling to undergo multiple venipunctures because of poor tolerability or lack of easy access
- Have had a chronic or recurrent infectious disease including, but not limited to, chronic renal infection, chronic chest infection (eg, bronchiectasis), sinusitis, recurrent urinary tract infection (recurrent pyelonephritis or chronic nonremitting cystitis), open, draining, or infected skin wound, or ulcer.
- Have had a serious infection (eg, hepatitis, pneumonia, or pyelonephritis), have been hospitalized for an infection, or have been treated with intravenous (IV) antibiotics for an infection within 2 months prior to randomization. The exception being participants whose infection is a direct consequence of their Crohn's disease and will be completely resolved with surgery, e.g. participants with an abscess related to penetrating Crohn's disease of the terminal ileum who have no sign of infection after surgery. Less serious infections (eg, acute upper respiratory tract infection, enteric infections without signs or symptoms or simple urinary tract infection) need not be considered exclusions at the discretion of the investigator.
- Have a serious concomitant illness that could interfere with the subject's participation in the trial.
- Current use of prescription doses or chronic and frequent use of over-the-counter doses of nonsteroidal anti-inflammatory drugs (NSAIDs), except low-dose aspirin for prevention of heart attacks, unstable angina, or transient ischemic attacks.
- Have ulcerative colitis.
- Are participating in another investigative trial during participation in this trial.
- Use of any investigational drug within 30 days prior to randomization or within 5 half-lives of the investigational agent, whichever is longer.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pittsburgh
Pittsburgh, Pennsylvania, 15213
About this study
Official title: A Randomized, Double-blind, Placebo Controlled Study of Vedolizumab for the Prevention of Post-operative Crohn's Disease Recurrence
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.
Read the detailed description
Study aims: To determine the efficacy of vedolizumab in preventing mucosal recurrence of Crohn's disease in patients undergoing resective surgery.
Methods: This is a randomized, placebo-controlled 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 or placebo. Patients will receive the first infusion of vedolizumab (300 mg) or placebo (1:1 randomization) 2-4 weeks after surgery. Subsequent infusions of vedolizumab or placebo will occur at 2, 6, 14, 22, 30, 38, 46, and 54 weeks after the first infusion. The primary assessment for determination of drug efficacy will be presence or absence of mucosal inflammation (representing active Crohn's disease) at the ileocolonic anastomosis and neo-terminal ileum. This assessment will be made by colonoscopic inspection one year after surgery. Patients with an elevated fecal calprotectin at week 22 will undergo a 6-month post-operative clinical colonoscopy to assess for endoscopic recurrence.
Subject population: Patients scheduled for resectional surgery for ileal or ileocolonic Crohn's disease will be eligible for the study. Subjects will be male or female who are 18 years of age or older.
- Conditions
- Crohn's Disease
- Being tested
- Vedolizumab, placebo
- Keywords
- post-operative
- Medical subject headings
- Crohn Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VedolizumabDrug
Also called entyvio
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
placeboDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Vedolizumab | Experimental | Vedolizumab infusions at weeks 0, 2, and 6 weeks, then every 8 weeks for 52 weeks Receives: Drug: Vedolizumab |
| placebo | Placebo comparator | Placebo infusions at weeks 0, 2, and 6 weeks, then every 8 weeks for 52 weeks Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 54 weeks
Secondary outcomes (2)
clinical remission
CDAI <150
Measured: 54 weeks
Histologic remission
Geboes score
Measured: 54 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jul 2016 (estimated)
- Study start1 Dec 2018
- Primary completion1 May 2019
- Study completion1 May 2019
Why it stopped: Limited time for enrollment of required number of subjects
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Crohn's DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Marc Schwartz
- Sponsor type
- University, hospital or other
- Collaborators
- Takeda
- Responsible party
- Sponsor-investigator, Marc Schwartz, University of Pittsburgh
- Investigators
- Marc B Schwartz, MD, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02834754
- Sponsor's protocol ID
- PRO16030443
- Status last verified
- May 2020
- First submitted
- 12 Jul 2016
- Last updated
- 14 May 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-blind, Placebo Controlled Study of Vedolizumab for the Prevention of Post-operative Crohn's Disease Recurrence
- ClinicalTrials.gov ID
- NCT02834754
- Acronym / sponsor ID
- PRO16030443
- Conditions
- Crohn's Disease
- Keywords
- post-operative
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Limited time for enrollment of required number of subjects
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Marc SchwartzUniversity, hospital or other
- Collaborators
- Takeda
- Study start
- 1 Dec 2018 (actual)
- Primary completion
- 1 May 2019 (actual)
- Study completion
- 1 May 2019 (actual)
- First posted
- 15 Jul 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Study aims: To determine the efficacy of vedolizumab in preventing mucosal recurrence of Crohn's disease in patients undergoing resective surgery.
Methods: This is a randomized, placebo-controlled 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 or placebo. Patients will receive the first infusion of vedolizumab (300 mg) or placebo (1:1 randomization) 2-4 weeks after surgery. Subsequent infusions of vedolizumab or placebo will occur at 2, 6, 14, 22, 30, 38, 46, and 54 weeks after the first infusion. The primary assessment for determination of drug efficacy will be presence or absence of mucosal inflammation (representing active Crohn's disease) at the ileocolonic anastomosis and neo-terminal ileum. This assessment will be made by colonoscopic inspection one year after surgery. Patients with an elevated fecal calprotectin at week 22 will undergo a 6-month post-operative clinical colonoscopy to assess for endoscopic recurrence.
Subject population: Patients scheduled for resectional surgery for ileal or ileocolonic Crohn's disease will be eligible for the study. Subjects will be male or female who are 18 years of age or older.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Vedolizumab | Experimental | Drug: VedolizumabVedolizumab infusions at weeks 0, 2, and 6 weeks, then every 8 weeks for 52 weeks |
| placebo | Placebo comparator | Drug: placeboPlacebo infusions at weeks 0, 2, and 6 weeks, then every 8 weeks for 52 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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).
Key exclusion criteria (25 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VedolizumabAlso: entyvioVedolizumab 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 | Drug | Vedolizumab |
| placeboCurrently 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. | Drug | placebo |
Primary outcome
Endoscopic remission
Time frame: 54 weeks
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.
2 secondary outcomes
clinical remission
Time frame: 54 weeks
Histologic remission
Time frame: 54 weeks
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2020.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marc B Schwartz, MD principal investigator
University of Pittsburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Vedolizumab in people with Crohn's Disease, run by Marc Schwartz at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 25 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 14 May 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Endoscopic remission (time frame: 54 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 May 2020.