A Study of Vedolizumab in Children and Teenagers With Moderate to Severe Crohn's Disease (CD) (A Randomized, Double-Blind, Phase 3 Study to Evaluate the Efficacy and Safety of Vedolizumab Intravenous as Maintenance Therapy in Pediatric Subjects With...
Vedolizumab is a medicine that helps to reduce inflammation and pain in the digestive system in adults. In this study, children and teenagers with moderate to severe Crohn’s Disease will be treated with vedolizumab. The main aim of the study is to check if participants achieve remission after study treatment with vedolizumab. Remission means symptoms improve or disappear and an endoscopy shows no or limited signs of disease. Participants will receive 3 infusions of vedolizumab over 6 weeks. Then, those who have a clinical response will receive 1 of 3 doses of vedolizumab once every 8 weeks. They will receive the same dose every time.
- The participants has moderately to severely active CD, unresponsive or intolerant to their current standard of care (SOC).
- The participants weigh ≥10 kg at the time of screening and enrollment into the study.
- Participants with moderately to severely active Crohn's disease (CD) diagnosed at least 1 month before screening, defined by a Pediatric Crohn's Disease Activity Index (PCDAI) >30 and an simple endoscopic score for Crohn's Disease (SES-CD) >6 (or an SES-CD ≥4 if disease is confined to terminal ileum).
- Participants who have failed, lost response to, or been intolerant to treatment with at least 1 of the following agents: corticosteroids, immunomodulators (eg, azathioprine (AZA), 6-mercaptopurine (6-MP), methotrexate [MTX]), and/or tumor necrosis factor (TNF)-α antagonist therapy (eg, infliximab, adalimumab). This includes participants who are dependent on corticosteroids or exclusive or partial enteral nutrition to control symptoms and who are experiencing worsening of disease in the moderate-to-severe range when attempting to wean off corticosteroids or discontinue exclusive enteral nutrition.
- Participants with extensive colitis or pancolitis of >8 years' duration or left-sided colitis of >12 years' duration must have documented evidence of a negative surveillance colonoscopy within 12 months before screening.
- Participants with vaccinations that are up-to-date based on the countrywide accepted schedule of childhood vaccines.
- Participants who have received either (1) an investigational biologic (other than those listed in Exclusion Criterion #1) within 60 days or 5 half-lives before screening (whichever is longer); or (2) an approved biologic or biosimilar agent within 2 weeks before the first dose of study drug or at any time during the screening period.
- Participants with active cerebral/meningeal disease, signs/symptoms or history of progressive multifocal leukoencephalopathy (PML) or any other major neurological disorders including stroke, multiple sclerosis, brain tumor or neurodegenerative disease.
- The participants had a clinically significant infection (eg, pneumonia, pyelonephritis, coronavirus disease 2019 [COVID-19]) within 30 days prior to first dose of study drug.
- The participants has received any live vaccinations within 30 days prior to first dose.
- Participants who currently require surgical intervention or are anticipated to require surgical intervention for CD during this study.
- Participants who have had subtotal or total colectomy or have a jejunostomy, ileostomy, colostomy, ileo-anal pouch, known fixed stenosis of the intestine, short bowel syndrome, or >3 small intestine resections.
- Participants with a current diagnosis of indeterminate colitis.
- Participants with clinical features suggesting monogenic very early-onset inflammatory bowel disease.
- Active or latent tuberculosis (TB), as evidenced by a diagnostic TB test performed within 30 days of screening or during the screening Period that is positive, defined as:
- Positive QuantiFERON test or 2 successive indeterminate QuantiFERON tests, OR
- A TB skin test reaction ≥5 mm.
- The participants has chronic hepatitis B virus (HBV) infection or chronic hepatitis C virus (HCV) infection.
- The participants has any identified congenital or acquired immunodeficiency (eg, common variable immunodeficiency, human immunodeficiency virus [HIV] infection, organ transplantation).
- The participant has evidence of dysplasia or history of malignancy other than a successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma or localized carcinoma in situ of the cervix.
- Participants with positive stool studies for ova and/or parasites or stool culture at screening visit.
- Participants with positive Clostridium difficile stool test at screening visit.
Study description/explanation of participation:
In this study, children and teenagers with moderate to severe Crohn’s disease will be treated with vedolizumab, a medicine that helps to reduce inflammation and pain in the digestive system in adults. The main aim of the study is to check if participants’ symptoms improve or disappear, and an endoscopy shows no or limited signs of disease after study treatment with vedolizumab. 120 participants will enroll onto the study.
Description of treatment (mechanism of action):
In people with Crohn’s disease, there's an increased number of white blood cells entering the GI tract. The increased number of white blood cells causes inflammation in the GI tract. This inflammation can lead to the symptoms most commonly seen in people who have ulcerative colitis. Vedolizumab works by focusing in the GI tract to help control damaging inflammation, it binds to a protein on the GI-directed white blood cells, keeping them from entering the GI tract. With fewer white blood cells in the GI tract, vedolizumab helps reduce inflammation and symptoms.
Patient participation requirements:
In this study, the participant will take part in the following periods and visits:
- Screening (up to 28 days)
- Induction Period (14 weeks)
- Maintenance Period (40 weeks)
- End of Study/Early Termination Visit (at week 54 or study discontinuation
- In addition, if the participant does not have a clinical response (get better from study treatment) or discontinues from the study at any time during the Induction or Maintenance Periods, he/she may have:
- Follow-Up Safety Visit (18 weeks after last dose) and
- Long-Term Follow-Up (LTFU) (every 6months for 2years after last dose)
- The participant will receive the study drug as an IV infusion (slow injection into the veins) during the Induction and Maintenance Periods of the study.
Some of the procedures participants will be asked to complete are listed below.
- Completed an informed consent/pediatric assent form to participate. This will be done before any study procedures are performed. These forms contain important details about the study and is signed by a parent/guardian to provide consent for their child (the participant) to participate in the study. Consent can be withdrawn at any time during the study.
- Allergy reaction card: This card contains several questions about any allergies the participant may have.
- Provide Demographics and Medical History information about the participant’s age, race, and gender will be collected, as well as answer questions about past and present medical conditions, surgeries, and previous vaccinations.
- Report any medicines and procedures taken in the past
- Provide information about CD biologics history by answering questions about the participant’s past and present CD
- Complete Tanner Staging, this scale is used to measure sexual maturity by age and gender, and the participant’s stage of puberty
- Physical Examination including weight, height, and vital signs
- Concomitant Medications and Procedures information collection
- IRT Assessment, the participant’s recorded data will be added into the IRT system
- PTE Assessment, the participant will be taken immediately after signing the informed consent/pediatric assent. A PTE is any unfavorable change in the participant’s health that happens before they take the investigational drug
- AE assessment documents any unfavorable changes in the participant’s health. The change may or may not be caused by the investigational drug
- Endoscopy is a procedure to examine a person’s digestive tract
- Colonoscopy is an exam to detect changes or abnormalities in the large intestine and rectum
Possible risks and side effects:
All drugs have the possibility of problems and unwanted or bad side effects that are unknown at this time and could possibly happen. There may be risks from the study drug to an unborn child or breastfeeding infant that are not currently known; therefore, it is important to read the section on pregnancy carefully, even if your child is a boy.
Vedolizumab Side Effects
Participants will receive vedolizumab during the study. In intravenous studies to date, vedolizumab has been
Well-tolerated (how well you can stand the side effects). The most common side effects from
controlled clinical studies, reported in 10% to 20% of participants, include the following:
- Worsening of CD in patients with CD
- Common cold
- Joint pain
No side effects have been seen in more than 20% of participants who received at least 1 dose of vedolizumab.
Since many of these symptoms are commonly reported in patients with CD, it is unclear which may be related to vedolizumab, which may be related to participants’ CD, or which may happen by chance. It is not known if the side effects seen in adults will be like those seen in children. In addition to the risks listed above, vedolizumab and the study procedures may have unknown risks. There is always the possibility that participants will have a side effect that is currently unknown or not expected.
There is a greater chance of participants getting an infection, having a hard time fighting off an infection, or reactivation of an old infection (where participants had an infection before, it got better, then it comes back). Serious infections have occurred. People with inflammatory bowel disease have an increased risk for colon cancer; less than 1% of participants who received vedolizumab as part of the CD clinical studies were diagnosed with cancer, including colon cancer. It is also not known whether the cancer happened by chance or whether vedolizumab helped cause the cancer.
Study Procedure Risks
Risks Associated with Endoscopy (Colonoscopy): The following are possible discomforts (aches and pain or soreness) or risks associated with a colonoscopy:
- Heavy or ongoing bleeding from biopsy or removal of polyp (a small growth)
- Abdominal (belly) cramping, pain, or bloating
- Peritonitis (inflammation of the lining of the abdominal cavity)
- Perforation (a hole) in the intestinal wall. Surgery may be needed if a perforation occurs.
- Nausea, vomiting, bloating, or rectal irritation (uncomfortableness) caused by the bowel cleansing preparation (medicines used to clean out your child’s intestines)
- Side effects, such as drowsiness (sleepiness), from the sedative or pain medicine
Risks Associated with General Anesthetic (done during colonoscopy): The following are possible discomforts or risks associated with general anesthetic:
- Nausea and vomiting
- Postoperative delirium (confusion when regaining consciousness)
- Hypothermia (chills and shivering)
Risks Associated with Infusion Site Reactions (IV administration): An infusion site reaction is a localized reaction (meaning it only affects the area where the injection was given) that occurs along the vein or surrounding area where the study drug is infused. Symptoms that can happen with an infusion site reaction may include redness, tenderness, warmth, itching, or discomfort. An additional risk could happen as a result of the study drug leaking out from the blood vessel where it was infused, which would cause pain, blistering, and severe skin damage.
Risks Associated with Blood Draws: During blood sample collection, participants may have pain and/or bruising where the needle was inserted into the skin. Although rare, excess (too much) bleeding, blood clots, and infections where the needle was inserted into the skin may happen. Dizziness and/or fainting may also happen during or shortly after the blood is taken.
Risks Associated with TB Skin Tests: Side effects are uncommon from the TB skin test. However, a person who has been exposed to TB germs may occasionally have a reaction, which may cause some mild itching, swelling, or irritation. These kinds of reactions should disappear in 1 to 2 weeks. Rarely, in people who have been exposed to TB germs in the past, blisters or ulcers may happen and should be reported to your child’s study doctor for treatment. Allergic reactions can occur but are extremely rare.