A Study of Vedolizumab (MLN0002) in Patients With Moderate to Severe Crohn's Disease (GEMINI II)
Summary: This multicenter, phase 3, randomized, blinded, placebo-controlled study in patients with moderately to severely active CD comprises two phases:
The Induction Phase, designed to establish the efficacy and safety of vedolizumab (MLN0002) for the induction of clinical response and remission; and the Maintenance Phase, designed to establish the efficacy and safety of vedolizumab(MLN0002) for the maintenance of clinical response and remission.
| HR#: |
18653 |
| PRINCIPAL INVESTIGATOR: |
Brenda J. Hoffman, , MD, FACP, FACG |
| SPONSOR: |
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| TARGET ENROLLMENT: |
3 |
| DISEASE TYPE: |
Crohns Disease |
| BODY LOCATION(S): |
Large Intestine, |
| PRIMARY OBJECTIVE: |
Primary Outcome Measures:
Proportion of patients in clinical remission [ Time Frame: Week 6 & 52 ] |
| SECONDARY OBJECTIVE(S): |
Secondary Outcome Measures:
Proportion of patients with enhanced clinical response [ Time Frame: Week 6 & 52 ] |
| INCLUSION CRITERIA: |
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1
| Age 18 to 80. |
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2
| Male or female patient who is voluntarily able to give informed consent. |
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3
| Female patients who: a. are post-menopausal for at least 1 year before the screening visit, OR b. are surgically sterile, OR c. if they are of childbearing potential, agree to practice 2 effective methods of contraception, at the same time, from the time of signing the informed consent form through 6 months after the last dose of study drug, OR agree to completely abstain from heterosexual intercourse.Male patients, even if surgically sterilized (ie, status post-vasectomy), who: a. agree to practice effective barrier contracetpion during the entire study treatment period and through 6 months after the last dose of study drug, OR b. agree to completely abstain from heterosexual intercourse. |
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4
| Diagnosis of Crohn's disease established at least 6 months prior to enrollment by clinical and endoscopic evidence and corroborated by a histopathology report. Cases of Crohn's disease established at least 12 months prior to enrollment 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 enrollment. |
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5
| Moderately to severely active Crohn's disease as determined by a CDAI score of 220 to 480 within 7 days prior to the first dose of study drug and 1 of the following: a. CRP level >2.87 mg/L during the screening period OR b. ileocolonoscopy with photographic documentation of a minimum of 3 non-anastomotic ulcerations (each >0.5cm in diameter; apthous ulcerations are not sufficient) consistent with CD within 4 months prior to screening |
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6
| CD involvement of the ileum and/or colon, at a minimum. |
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| Patients with extensive colitis or pancolitis of >8 years duration or limited colitis of >12 years duration must have documented evidence that a surveillance colonoscopy was performed within 12 months of the initial screening visit (may be performed during screening). |
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8
| Patients with a family history of colorectal cancer, personal history of increased colorectal cancer risk, age >50 years, or other known risk factor must be up-to-date on colorectal cancer surveillance (may be performed during screening). |
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9
| Demonstrated, over the previous 5 year period, an inadequate response to, loss of response to, or intolerance of at least one of the following agents as defined below:
-immunomodulators: signs and symptoms of persistently active disease despite a history of at least one 8 week regimen of oral azathioprine (=1.5mg/kg) or 6-mercaptopurine mg/kg (=0.75mg/kg) OR; signs and symptoms of persistently active disease despite a history of at least one 8 week regimen of methotrexate (=12.5mg/week) OR; history of intolerance of at least one immunomodulator (including, but not limited to nausea/vomiting, abdominal pain, pancreatitis, LFT abnormalities, lymphopenia, TPMT genetic mutation, infection)
-TNFa antagonists- signs and symptoms of persistent active disease despite a history of at least one 4 week induction regimen of one of the following agents: infliximab 5mg/kgIV 2 doses at least 2 weeks apart; adalimumb one 80mg SC dose followed by one 40mg dose at least 2 weeks apart; certolizumab pegol 400mg SC 2 doses at least 2 weeks apart OR; recurrentce of symptoms during scheduled maintenance dosing following prior clinical benefit (discontinuation despite clinical benefit does not qualify) OR; history of intolerance of at least one TNF antagonist (including, but not limited to infusion-related reaction, demyelination, congestive heart failure, infection). |
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| May be receiving a therapeutic dose of the following drugs: A. oral 5-ASA compounds provided that the dose has been stable for the 2 weeks immediately prior to enrollment; B. oral corticosteroid therapy (prednisone at a stable dose =30mgday, budesonide at a stable dose =9mg/day, or equivalent steroid) provided that the dose has been stable for the 4 weeks immediately prior to enrollment if corticosteroids have just been initiated, or for the 2 weeks immediately prior to enrollment if corticosteroids are being tapered; C. probiotics (eg, Culturelle, Saccharomyces boulardii) provided that the dose has been stable for the 2 weeks immediately prior to enrollment; D. Antidiarrheals (eg, loperamide, diphenoxylate with atropine) for control of chronic diarrhea; E. Azathioprine or 6-mercaptopurine (only permitted for Cohort 1 patients) provided that the dose has been stable for the 8 weeks immediately prior to enrollment; F. Methotrexate (only permitted for Cohort 1 patients) provided that the dose has been stable for the 8 weeks immediately prior to enrollment; G. Antibiotics used for the treatment of CD (ie, ciprofloxacin, metronidazole) provided that the dose has been stable for the 2 weeks immediately prior to enrollment. |
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| EXCLUSION CRITERIA: |
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1
| Evidence of abdominal abscess at the initial screening visit. |
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2
| Extensive colonic resection, subtotal or total colectomy. |
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3
| History of >3 small bowel resections or diagnosis of short bowel syndrome. |
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4
| Have received tube feeding, defined formula diets, or parenteral alimentation within 21 days prior to the administration of the first dose of study drug. |
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5
| Ileostomy, colostomy, or known fixed symptomatic stenosis of the intestine. |
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6
| 6. Within 30 days prior to enrollment, have received any of the following for the treatment of underlying disease: A. Non-biologic therapies (eg, cyclosporine, thalidomide); B. A non-biologic investigational therapy; C. An approved non-biologic therapy in an investigational protocol; D. Adalimumab. |
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7
| Within 60 days prior to enrollment, have received any of the following: A. infliximab; B. Certolizumab pegol; C. Any other investigational or approved biological agent. |
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8
| Any prior exposure to natalizumab or rituximab. |
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9
| Use of topical (rectal) treatment with 5-ASA or corticosteroid enemas/suppositories within 2 weeks of the administration of the first dose of study drug. |
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10
| Evidence of or treatment for C. difficile infection within 60 days or other intestinal pathogen within 30 days prior to enrollment. |
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11
| Currently require or are anticipated to require surgical intervention for CD during the study. |
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12
| History or evidence of adenomatous colonic polyps that have not been removed. |
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13
| History or evidence of colonic mucosal dysplasia. |
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14
| Diagnosis of ulcerative colitis or indeterminate colitis. |
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15
| Chronic hepatitis B or C infection. |
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16
| Active or latent tuberculosis, regardless of treatment history, as evidenced by any of the following: A. history of tuberculosis; B. a positive diagnostic tuberculosis (TB) test within one month of enrollment defined as: a positive QuantiFERON test or 2 successive indeterminate QuantiFERON tests OR a tuberculin skin test reaction =10mm (=5mm in patients receiving the equivalent of >15mg/day prednisone); C. Chest X-ray within 3 months of enrollment in which active or latent pulmonary tuberculosis cannot be excluded. |
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17
| Any identified congenital or acquired immunodeficiency (eg, common variable immunodeficiency, human immunodeficiency virus [HIV] infection, organ transplantation). |
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18
| Any live vaccinations within 30 days prior to study drug administration except for the influenza vaccine. |
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19
| Clinically significant extra-intestinal infection (eg, pneumonia, pyelonephritis) within 30 days of the initial screening visit. |
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20
| Previous exposure to MLN0002. |
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21
| Female patients who are lactating or have a positive serum pregnancy test durng the screening period or a positive urine pregnancy test on Day 1 prior to study drug administration. |
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22
| Any unstable or uncontrolled cardiovascular, pulmonary, hepatic, renal, gastrointestinal, genitourinary, hematological, coagulation, immunological, endocrine/metabolic, or other medicatl disorder that, in the opinion of the investigator, would confound the study results or compromise patient safety. |
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23
| Had any surgical procedure requiring general anesthesia within 30 days prior to enrollment or is planning to undergo major surgery during the study period. |
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24
| Any history of malignancy, except for the following: a. adequately-treated non-metastatic basal cell skin cancer; b. any other type of non-melanoma skin cancer that has been adequately treated and that has not recurred for at least 1 year prior to enrollment; and c. history of cervical carcinoma in situ that has been adequately treated and that has no recurred for at least 3 years prior to enrollment. |
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25
| History of any major neurological disorders, including stroke, multiple sclerosis, brain tumor, or neurodegenerative disease. |
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26
| Positive PML subjective symptom checklist prior to the administration of the first dose of study drug. |
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27
| Any of the following laboratory abnormalities during the screening period: a. Hemoglobin level <8g/dL; b. WBC count <3 x 10^9/L; c. Lymphocyte count <0.5 x10^9/L; d. Platelet count <100 x 10^9/L or >1200 x 10^9/L; e. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 x the upper limit of normal (ULN); f. Alkaline phosphatase >3 x ULN; g. Serum creatinine >2 x ULN. |
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28
| Current or recent history (within one year prior to enrollment) of alcohol dependence or illicit drug use. |
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29
| Active psychiatric problems that, in the investigator's opinion, may interfere with compliance with the study procedures. |
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30
| Unable to attend all the study visits or comply with study procedures. |
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| TREATMENT GROUPS: |
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| LENGTH OF STUDY: |
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| CONTACTS: |
- Rebekah Whichard, , BA, CCRC (Primary Study Coordinator)
(843) 876-7233 or richreb@musc.edu
- Kyle Orrell, MSHP (DDC Research Program Manager)
843-876-4303 or orrell@musc.edu
- Brenda J. Hoffman, , MD, FACP, FACG (Principal Investigator)
(843) 876-4265 or hoffmanb@musc.edu
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