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Ulcerative ColitisPhase 2NCT02913508

Vedolizumab Subcutaneous (SC) Versus Intravenous (IV) in Ulcerative Colitis or Crohn's Disease

A Phase 2 study testing Vedolizumab intravenous injection and Vedolizumab subcutaneous injection in people with Ulcerative Colitis and Crohn's Disease, run by Takeda.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

The purpose of this study is to assess the bioavailability and pharmacokinetics (PK) of multiple doses of vedolizumab subcutaneous (SC) compared to vedolizumab intravenous (IV). Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Ulcerative Colitis, Crohn's Disease
What is being tested?
Vedolizumab intravenous injection and Vedolizumab subcutaneous injection
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
Apr 2014to Dec 2015
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 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • General Inclusion Criteria
  • In the opinion of the investigator, the participant is capable of understanding and complying with protocol requirements.
  • The participant or, when applicable, the participant's legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedure.
  • Is aged 18 to 80 years, inclusive.
  • The male or female participant is voluntarily able to give informed consent.
  • A male participant who is nonsterilized and sexually active with a female partner of childbearing potential agrees to use adequate contraception from signing of informed consent throughout the duration of the study and for 18 weeks after last dose.
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  • A female participant of childbearing potential who is sexually active with a nonsterilized male partner agrees to use routinely adequate contraception from signing of informed consent throughout the duration of the study and for 18 weeks after last dose.
  • Has a diagnosis of ulcerative colitis (UC) established at least 3 months prior to randomization by clinical and endoscopic evidence and corroborated by a histopathology report.
  • Has moderately to severely active UC as determined by a partial Mayo score of 3 to 9 within 7 days prior to the first dose of study drug.
  • Has evidence of UC extending proximal to the rectum (≥15 cm of involved colon).
  • Participants with extensive colitis or pancolitis of >8 years duration or left-sided colitis of >12 years duration must have documented evidence that a surveillance colonoscopy with random and targeted biopsies was performed within 18 months of the initial screening visit (may be performed during screening).
  • Participants with a family history of colorectal cancer, personal history of increased colorectal cancer risk, age >50 years, or other known risk factor for colorectal cancer must be up-to-date on colorectal cancer surveillance (may be performed during screening).
  • Participants may be receiving a therapeutic dose of the following drugs:
  • Oral or topical (rectal) 5-aminosalicylate (5-ASA) compounds provided that the dose has been stable for the 2 weeks immediately prior to randomization;
  • Oral corticosteroid therapy (prednisone at a stable dose ≤30 mg/day, budesonide at a dose ≤9 mg/day or equivalent steroid) provided that the dose has been stable for the 4 weeks immediately prior to randomization if corticosteroids have just been initiated, or for the 2 weeks immediately prior to randomization if corticosteroids are being tapered;
  • Topical (rectal) corticosteroid enemas/suppositories;
  • Azathioprine or 6-mercaptopurin provided that the dose has been stable for the 8 weeks immediately prior to randomization;
  • Antidiarrheals (eg, loperamide, diphenoxylate with atropine) for control of chronic diarrhea;
  • Probiotics (eg, Culturelle, S. boulardii) provided that the dose has been stable for the 2 weeks immediately prior to randomization;
  • Antibiotics used for the treatment of inflammatory bowel disease (IBD) (ie, ciprofloxacin, metronidazole).
  • Has a diagnosis of Crohn's Disease (CD) established at least 3 months prior to randomization by clinical and endoscopic evidence and corroborated by a histopathology report. Cases of CD established at least 3 months prior to randomization for which a histopathology report is not available will be considered based on the weight of the evidence supporting the diagnosis and excluding other potential diagnoses, and must be discussed with the sponsor on a case-by-case basis prior to randomization.
  • Has moderately to severely active CD as determined by Crohn's Disease Activity Index (CDAI) score of 220 to 450 within 7 days prior to the first dose of study drug and 1 of the following:
  • C-reactive protein (CRP) level >2.87 mg/L during the Screening Period, OR;
  • Ileocolonoscopy with photographic documentation of a minimum of 3 nonanastomotic ulcerations (each >0.5 cm in diameter) or 10 aphthous ulcerations (involving a minimum of 10 contiguous cm of intestine) consistent with CD, within 4 months prior to randomization, OR;
  • Fecal calprotectin >250 mcg/g stool during the Screening Period in conjunction with Computed Tomography (CT) enterography, magnetic resonance (MR) enterography, contrast-enhanced small bowel radiography, or wireless capsule endoscopy revealing Crohn's ulcerations (aphthae not sufficient), within 4 months prior to screening (participants with evidence of fixed stenosis or small bowel stenosis with prestenotic dilation should not be included).
  • Has CD involvement of the ileum and/or colon, at a minimum.
  • Participants with extensive colitis or pancolitis of >8 years duration or limited colitis of >12 years duration must have documented evidence that a surveillance colonoscopy with random and targeted biopsies was performed within 18 months of randomization (may be performed during screening).
  • Participants with a family history of colorectal cancer, personal history of increased colorectal cancer risk, age >50 years, or other known risk factor for colorectal cancer must be up-to-date on colorectal cancer surveillance (may be performed during screening).
  • Participants may be receiving a therapeutic dose of the following drugs:
  • Oral or topical (rectal) 5-ASA compounds provided that the dose has been stable for the 2 weeks immediately prior to randomization;
  • Oral corticosteroid therapy (prednisone at a stable dose ≤30 mg/day, budesonide at a dose ≤9 mg/day, or equivalent steroid) provided that the dose has been stable for the 4 weeks immediately prior to randomization if corticosteroids have just been initiated, or for the 2 weeks immediately prior to randomization if corticosteroids are being tapered;
  • Topical (rectal) corticosteroid enemas/suppositories;
  • Antibiotics used for the treatment of IBD (ie, ciprofloxacin, metronidazole);
  • Azathioprine or 6-mercaptopurin provided that the dose has been stable for the 8 weeks immediately prior to randomization;
  • Methotrexate provided that the dose has been stable for the 8 weeks immediately prior to randomization;
  • Antidiarrheals (eg, loperamide, diphenoxylate with atropine) for control of chronic diarrhea;
  • Probiotics (eg, Culturelle, S. boulardii) provided that the dose has been stable for the 2 weeks immediately prior to randomization.

Who cannot join

  • Gastrointestinal Exclusion Criteria:
  • Evidence of abdominal abscess at the initial Screening Visit.
  • Extensive colonic resection, subtotal or total colectomy.
  • History of >3 small bowel resections or diagnosis of short bowel syndrome.
  • Have received tube feeding, defined formula diets, or parenteral alimentation within 21 days prior to the administration of the first dose of study drug.
  • Ileostomy, colostomy, or known fixed symptomatic stenosis of the intestine.
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  • Within 30 days prior to randomization, have received any of the following for the treatment of underlying disease: a) Any investigational or approved nonbiologic therapy for UC or CD (eg, cyclosporine, thalidomide) other than those specified in the protocol.
  • Within 60 days prior to randomization, have received any of the following:
  • Infliximab,
  • Certolizumabpegol,
  • Adalimumab,
  • Golimumab,
  • Any other investigational or approved biological agent, other than local injections for non IBD conditions (eg, intra-ocular injections for the treatment of wet macular degeneration).
  • Evidence of or treatment for clostridium difficile infection or other intestinal pathogen within 28 days prior to randomization.
  • Currently require or are anticipated to require major surgical intervention during the study.
  • History or evidence of adenomatous colonic polyps that have not been removed.
  • History or evidence of colonic mucosal dysplasia.
  • Infectious Disease Exclusion Criteria
  • Has a positive test result for hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV), or a known history of human immunodeficiency virus infection (HIV) at Screening.
  • Active or latent tuberculosis (TB), regardless of treatment history, as evidenced by any of the following:
  • History of TB,
  • A positive diagnostic TB test within 1 month of randomization defined as:
  • a positive QuantiFERON® test or 2 successive indeterminate QuantiFERON® tests, OR ii. a tuberculin skin test reaction ≥10 mm (≥5 mm in participants receiving the equivalent of >15 mg/day prednisone), c. Chest X-ray within 3 months of randomization in which active or latent pulmonary tuberculosis cannot be excluded.
  • Any identified congenital or acquired immunodeficiency (eg, common variable immunodeficiency, human immunodeficiency virus [HIV] infection, organ transplantation).
  • Any live vaccinations within 30 days prior to study drug administration except for the influenza vaccine.
  • Clinically significant extra-intestinal infection (eg, pneumonia, pyelonephritis) or abdominal abscess within 30 days of the initial Screening visit.
  • General Exclusion Criteria
  • Previous exposure to vedolizumab.
  • Is an immediate family member, study site employee, or is in a dependent relationship with a study site employee who is involved in conduct of this study (eg, spouse, parent, child, sibling) or may consent under duress.
  • Has a positive test for drug screening.
  • Any prior exposure to natalizumab, efalizumab, or rituximab.
  • Female participants who are lactating or have a positive serum pregnancy test during the Screening period or a positive urine pregnancy test on Day 1 prior to study drug administration.
  • Any unstable or uncontrolled cardiovascular, pulmonary, hepatic, renal, gastrointestinal, genitourinary, hematological, coagulation, immunological, endocrine/metabolic, or other medical disorder that, in the opinion of the investigator, would confound the study results or compromise participant's safety.
  • Had any surgical procedure requiring general anesthesia within 30 days prior to randomization or is planning to undergo major surgery during the study period.
  • Any history of malignancy, except for the following:
  • adequately-treated nonmetastatic basal cell skin cancer;
  • squamous cell skin cancer that has been adequately treated and that has not recurred for at least 1 year prior to randomization; and
  • history of cervical carcinoma in situ that has been adequately treated and that has not recurred for at least 3 years prior to randomization. Participants with remote history of malignancy (eg, >10 years since completion of curative therapy without recurrence) will be considered based on the nature of the malignancy and the therapy received and must be discussed with the sponsor on a case-by-case basis prior to randomization.
  • History of any major neurological disorders, including but not limited to stroke, multiple sclerosis, brain tumor, or neurodegenerative disease.
  • Positive progressive multifocal leukoencephalopathy (PML) subjective symptom checklist prior to the administration of the first dose of study drug.
  • Any of the following laboratory abnormalities during the Screening period:
  • Hemoglobin level <8 g/dL,
  • White blood cell (WBC) count <3 x 10^9/L,
  • Lymphocyte count <0.5 x 10^9/L,
  • Platelet count <100 x 10^9/L or >1200 x10^9/L,
  • Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 x the upper limit of normal (ULN),
  • Alkalinephosphatase>3xULN,
  • Serum creatinine >2 x ULN,
  • Albumin <2.0 g/dL (<20 g/L).
  • Current or recent history (within 1 year prior to randomization) of alcohol dependence or illicit drug use.
  • Active psychiatric problems that, in the investigator's opinion, may interfere with compliance with the study procedures.
  • Unable to attend all the study visits or comply with study procedures.

About this study

Official title: A Randomized, Open Label Phase 2 Study to Assess Pharmacokinetics, Pharmacodynamics, Immunogenicity, Safety and Exploratory Efficacy of Vedolizumab Subcutaneous Compared to Vedolizumab Intravenous in Subjects With Moderately to Severely Active Ulcerative Colitis or Crohn's Disease

The purpose of this study is to assess the bioavailability and pharmacokinetics (PK) of multiple doses of vedolizumab subcutaneous (SC) compared to vedolizumab intravenous (IV).

Read the detailed description

The drug being tested in this study is called vedolizumab. Vedolizumab is being tested to determine its availability and reaction in the body of people who have moderately to severely active Ulcerative Colitis (UC) or Crohn's Disease (CD). This study will look at the availability and reaction of vedolizumab in people who are administered the treatment subcutaneously (SC) compared people who are administered the treatment intravenously (IV).

The study will enroll approximately 200 patients with moderately to severely active UC or CD. Participants will be randomly assigned (by chance, like flipping a coin) to one of the five treatment groups:

  • vedolizumab 300 mg IV
  • vedolizumab 300 mg IV and vedolizumab 160 mg SC
  • vedolizumab 300 mg IV and vedolizumab 108 mg SC
  • vedolizumab 480 mg SC and vedolizumab 160 mg SC
  • vedolizumab 324 mg SC and vedolizumab 108 mg SC

All participants will receive one of the treatments they are assigned to at various treatment visits throughout the study.

This multi-centre trial will be conducted in North America, Europe and Asia. The overall time to participate in this study is approximately 41 weeks in addition to a follow-up survey that will be administered every 6 months for 2 years. Participants will make 16 visits to the clinic, including a safety follow-up assessment 18 weeks after last dose of study drug.

Being tested
Vedolizumab intravenous injection, Vedolizumab subcutaneous injection
Keywords
Drug therapy
Medical subject headings
Colitis, Ulcerative, Crohn Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Vedolizumab intravenous injectionDrug

    Also called MLN0002, Entyvio

    Vedolizumab intravenous injection

  • Vedolizumab subcutaneous injectionDrug

    Also called MLN0002SC

    Vedolizumab subcutaneous injection

Study groups in NCT02913508
Study groupRoleWhat they receive
Vedolizumab 300 mg IV Q8WExperimentalVedolizumab 300 mg, intravenously, at Weeks 0 and 2, and then every 8 weeks (Q8W) (Weeks 6 and 14).
Receives: Drug: Vedolizumab intravenous injection
Vedolizumab 300 mg IV / 160 mg SC Q3WExperimentalVedolizumab 300 mg, intravenously, at Weeks 0 and 2, then vedolizumab 160 mg, subcutaneously (SC), every 3 weeks (Q3W) (Weeks 6, 9, 12, 15 and 18).
Receives: Drug: Vedolizumab intravenous injection; Drug: Vedolizumab subcutaneous injection
Vedolizumab 300 mg IV / 108 mg SC Q2WExperimentalVedolizumab 300 mg, intravenously, at Weeks 0 and 2, then vedolizumab 108 mg, subcutaneously, every 2 weeks (Q2W) (Weeks 6, 8, 10, 12, 14, 16, 18 and 20).
Receives: Drug: Vedolizumab intravenous injection; Drug: Vedolizumab subcutaneous injection
Vedolizumab 480 mg SC / 160 mg SC Q3WExperimentalVedolizumab 480 mg, subcutaneously, at Weeks 0 and 2, then vedolizumab 160 mg, subcutaneously, every 3 weeks (Weeks 6, 9, 12, 15 and 18).
Receives: Drug: Vedolizumab subcutaneous injection
Vedolizumab 324 mg SC / 108 mg SC Q2WExperimentalVedolizumab 324 mg, subcutaneously, at Weeks 0 and 2, then vedolizumab 108 mg, subcutaneously, every 2 weeks (Weeks 6, 8, 10, 12, 14, 16, 18 and 20).
Receives: Drug: Vedolizumab subcutaneous injection

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Average Concentration of Vedolizumab Over the Dosing Interval at Steady-State (Cavg, ss)

    Cavg, ss is defined as the average concentration over the dosing interval at steady-state, calculated as area under the serum concentration-time curve over the dosing interval at steady-state(AUCss)/Tau, where Tau is the dosing interval.

    Measured: Week 0 up to Week 22

  2. Average Concentration of Vedolizumab Over the Dosing Interval from Week 0 to Week 6 (Cavg[wk0-6])

    Area under the serum concentration-time curve from Week 0 to Week 6, calculated using the linear trapezoidal rule.

    Measured: Week 0 to Week 6

Secondary outcomes (4)

  1. Percentage of Participants with Positive Human Antihuman Antibody (HAHA) During the Study

    Measured: Pre-dose at Weeks 0, 2, 6, 10, 18, 22 and 38

  2. Percentage of Participants with Positive Neutralizing Human Antihuman Antibody (HAHA) During the Study

    Only participants with positive HAHA will be evaluated for positive neutralizing HAHA.

    Measured: Pre-dose at Weeks 0, 2, 6, 10, 18, 22 and 38

  3. Percent Saturation of Mucosal Addressin Cell Adhesion Molecule-1 (MAdCAM-1) at Week 6

    Measured: Week 6

  4. Percent Saturation of Mucosal Addressin Cell Adhesion Molecule-1 (MAdCAM-1) at Week 22

    Measured: Week 22

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted23 Sep 2016 (estimated)
  2. Study startApr 2014
  3. Primary completionDec 2015 (estimated)
  4. Study completionDec 2015 (estimated)

Resources

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
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02913508
Sponsor's protocol ID
MLN0002SC_201
Other IDs
2013-003030-32, U1111-1146-5451
Status last verified
Sep 2016
First submitted
22 Sep 2016
Last updated
23 Sep 2016
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Vedolizumab intravenous injection and Vedolizumab subcutaneous injection in people with Ulcerative Colitis and Crohn's Disease, run by Takeda.

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 37 inclusion and 52 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 23 Sep 2016. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. 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?

Average Concentration of Vedolizumab Over the Dosing Interval at Steady-State (Cavg, ss) (time frame: Week 0 up to Week 22). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02913508.

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 23 Sep 2016.

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