A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study, With a Vedolizumab IV Reference Arm, to Evaluate the Efficacy and Safety of Vedolizumab Subcutaneous as Maintenance Therapy in Patients With Moderately to Severely Active Ulcerative Colitis...
Published: 08/16/2017
General Information:
Full Study Title: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study, With a Vedolizumab IV Reference Arm, to Evaluate the Efficacy and Safety of Vedolizumab Subcutaneous as Maintenance Therapy in Patients With Moderately to Severely Active Ulcerative Colitis Who Achieved Clinical Response Following Open-Label Vedolizumab Intravenous Therapy. (3027)
The purpose of this study is to assess the effect of vedolizumab subcutaneous (vedolizumab SC) maintenance treatment in participants with moderately to severely active ulcerative colitis (UC) who achieved clinical response following administration of vedolizumab intravenous (vedolizumab IV) induction therapy.
Eligibility:
Key Inclusion Criteria:
- Diagnosis of UC established at least 6 months prior to screening, by clinical and endoscopic evidence and corroborated by a histopathology report
- Moderately to severely active UC as determined by a complete Mayo score of 6-12 (with endoscopic subscore > or = 2)
- Evidence of UC extending proximal to the rectum >or= cm of involved colon).
- Inadequate response with, loss of response to, or intolerance to: corticosteroids, immunomodulators, or tumor necrosis factor-alpha (TNF-a) antagonists.
Key Inclusion Criteria:
- Evidence of abdominal abscess or toxic megacolon at the initial screening visit.
- Extensive colonic resection, subtotal or total colectomy.
- Ileostomy, colostomy, or known fixed symptomatic stenosis of the intestine.
- Prior exposure to investigational or approved non-biologic therapies (e.g. cyclosporine, tacrolimus, thalidomide, methotrexate, or tofacitinib) for the treatment of underlying disease within 30 days or five half-lives of screening (whichever is longer).
- Prior exposure to any investigational or approved biologic or biosimilar agent within 60 days or five half-lives of screening (whichever is longer).
- Prior exposure to vedolizumab.
- Surgical intervention for UC anticipated at any time during the study.
- History or evidence of adenmomatous colonic polyps that have not been removed, or has a history or evidence of colonic mucosal dysplasia.
- Suspected or confirmed diagnosis of Crohn's enterocolits, indeterminate colitis, ischaemic colitis, radiation colitis, diverticular disease assocated with colitis, or microscopic colitis.
- Active infections
- Chronic hepatitis B or C infection, human immunodeficiency virus or tuberculosis (active or latent), identified congenital or acquired immunodeficiency.
- History of any major neurolgical disorder.
Study Details:
Study Description
The drug being tested in this study is called vedolizumab subcutaneous (vedolizumab SC). Vedolizumab SC is being tested to treat people who have moderate to severely active ulcerative colitis. This study will look at clinical remission as well as mucosal healing, durable clinical response, durable clinical remission, and corticosteroid free remission in participants with UC who receive vedolizumab SC maintenance therapy after having achieved a clinical response to vedolizumab IV induction therapy.
The study will enroll approximately 400 patients. All participants will enter into a 6 week induction Phase where they will be administered open-label vedolizumab IV 300 mg via intravenous infusion (IV) at Week 0 (Day 1) and Week 2 (Day 15), and will then assessed for a clinical response at Week 6. Participants who achieve a clinical response at Week 6 will be randomly assigned to one of the three treatment groups:
- Vedolizumab SC 108 mg Q2W and Placebo IV Q8W
- Vedolizumab IV 300 mg Q8W and Placebo SC Q2W
- Placebo SC Q2W and Placebo IV Q8W
Participants who do not achieve a clinical response at Week 6 will not be randomized in to the Maintenance Period, and will receive a third infusion of vedolizumab IV 300 mg at Week 6. If the subject responds to week 6 dose they will be enrolled into the open label MLN0002SC-3030 study. If the patient does not respond they will be discontinued. This multi-center trial will be conducted worldwide. The overall time to participate in this study is up to 71 weeks. Participants will make multiple visits to the clinic, plus a final visit 18 weeks after last dose of study drug for a follow-up assessment. Participants will also participate in a long-term safety follow-up, by phone, at 6 months after the last dose of study drug. Patients will have routine clinic visits where Physical exams will be completed, and vitals will be assessed. Blood, stool, and urine samples will be collected at select visits. An ECG and flexible sigmoidoscopy will performed at select visits. As well, quality of life assessments, and various other patient-reported outcome (PRO) measures will be collected at select visits. You will be asked about your health and any changes to your medications routinely.
Description of Treatment or Intervention (Mechanism of Action)
Vedolizumab impairs the migration of gut-homing leukocytes into GI mucosa and acts as a gut-selective immunomodulator.
Patient Participation Requirements
The overall time to participate in this study is up to 71 weeks
Possible Risks & Side Effects
Vedolizumab: The most common side effects from controlled clinical trials, reported in 10% - 20% of patients, include:
- worsening of Crohn’s disease in patients with Crohn’s disease
- worsening of Ulcerative Colitis in patients with Ulcerative Colitis
- common cold
- headache
- joint pain
Other side effects, reported in 2-9% of patients, include:
- nausea
- fever
- stomach pain
- upper respiratory tract infection
- tiredness
- vomiting
- low levels of red blood cells (anemia)
- cough
- back pain
- bronchitis (tubes that carry air to the lungs become inflamed and irritated)
- urinary tract infection
- dizziness
- diarrhea
- sinus infection
- flu
- flu-like illness
- rash
- sore throat
- itching
- swollen ankles
- pains in arms or legs
- stomach flu
- an infected cavity filled with pus near the anus or rectum (anal abscess)
- small tunnel which connects an infected gland inside the anus to an opening on the skin around the anus (anal fistula)
Allergic reactions may occur. Risks associated with an ileocolonoscopy/flexible sigmoidoscopy. Possible discomforts or risks associated with a colonoscopy or sigmoidoscopy:
- Cramping, pain, abdominal bloating (common).
- Nausea, vomiting, bloating, or rectal irritation caused by the bowel cleanse preparation (common).
- Side effects, like drowsiness following sedative or pain medication (less common).
- Peritonitis (inflammation of the lining of the abdominal cavity) (rare).
- Perforation (a hole) of the intestinal wall (rare). Surgery may be needed if a perforation occurs (rare).
Risks associated with infusion site reactions (IV administration). Symptoms associated with an infusion site reaction may include redness, tenderness, warmth, itching, or discomfort. Also, medication may leak out from the blood vessel where it was infused which may cause pain, blistering, and possible skin damage. Risks associated with injection site reactions (SC administration). Symptoms associated with an injection site reaction may include redness, tenderness, warmth, itching, discomfort, bleeding, or a nodule or hardening of the skin in the area surrounding where the medication was administered or severe skin or tissue damage.