A 54-Week, Multicenter, Randomized, Double-blind, Placebo Controlled, Parallel-group Phase 2 Study to Assess the Efficacy and Safety of Brazikumab in Participants With Moderately to Severely Active Ulcerative Colitis (EXPEDITION Lead-In)
The purpose of this study is to evaluate the efficacy and safety of brazikumab versus placebo to induce clinical remission based on endoscopic improvement, rectal bleeding, and stool frequency scores in participants with moderate to severe UC who have failed or are intolerant to conventional therapy.
- Ability to sign informed consent
- 18-80 years of age
- Have a diagnosis of ulcerative colitis with an onset of symptoms for a minimum of 3 months prior to screening for the study.
- Moderately to severely active UC (signs and symptoms and colonoscopy findings)
- Participant had an inadequate response or intolerance to intervention with conventional treatment or prior biological treatment or demonstrated CS dependence for the treatment of UC. For participants who have previously used biological treatment, a participant may have failed up to 3 biologics that include up to 2 different mechanisms of action.
- Participants taking 5-aminosalicylates, oral prednisone (or equivalent), oral budesonide, or immunomodulators must be at a stable dose or discontinued. Topical (rectal) aminosalicylic acid or topical (rectal) steroids should be discontinued.
- Female participants of childbearing potential must have a negative urine pregnancy test prior to administration of study intervention and must agree to use a highly effective method of birth control throughout the study
- Women not of childbearing potential are defined as women who are either permanently sterilized (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy), or who are postmenopausal.
- Non sterilized males who are sexually active with a female partner of childbearing potential should use condoms during treatment and until the end of relevant systemic exposure in the male participant, plus a further 18 weeks.
- No known history of active TB or latent TB without completion of appropriate intervention.
- Participant has UC limited to the rectum (ie, not beyond 15 cm of the anal verge).
- Current diagnosis of fulminant colitis, a diagnosis of CD or indeterminate colitis, presence or history of a fistula consistent with CD, primary sclerosing cholangitis, celiac disease, or untreated bile acid malabsorption. Participants with a history of toxic megacolon within 12 months of screening are excluded.
- History of subtotal colectomy with ileorectostomy or colectomy with ileoanal pouch, Koch pouch, ileostomy, or other prior colonic resection, or need for surgical intervention for control of UC anticipated within 6 months.
- Participant has received the following treatment:
- Infliximab: within 8 weeks prior to randomization.
- Adalimumab, certolizumab pegol, or golimumab: within 8 weeks prior to randomization.
- Vedolizumab or ustekinumab within 12 weeks of randomization.
- Other prohibited medication, biologic or small molecule treatment within 5 half-lives prior to randomization.
- Fecal microbiota transplantation: within 8 weeks prior to randomization.
- Except for ustekinumab, prior exposure to any biologic agent targeting IL-12 or IL-23.
- Known history of allergy to the study intervention formulation or any of its excipients or components of the delivery device, or to any other biologic therapy.
- Participant received cyclosporine, mycophenolate mofetil, sirolimus (rapamycin), thalidomide, tacrolimus (FK-506), or tofacitinib within 2 weeks prior to Screening.
- Participants who received IV or intramuscular steroids within 2 weeks prior to Screening.
- Participant is currently enrolled in another investigational device or drug study, or is within 35 days or 5 half-lives, whichever is longer, since ending another investigational device or drug study(s), or receiving other investigational agent(s).
- Participant received a transfusion of blood, plasma, or platelets within 30 days prior to Screening.
- Participant received a Bacille Calmette-Guérin vaccination within 12 months of randomization or any other live vaccine less than 4 weeks prior to randomization.
- Participant has any of the following criteria related to infections:
- Evidence of a recent systemic fungal infection, requiring inpatient hospitalization, and/or antifungal treatment.
- Any infection requiring hospitalization or treatment with IV anti-infectives within 4 weeks of Screening.
- Cytomegalovirus or Epstein-Barr virus infection that has not resolved within 8 weeks prior to Screening.
- Clinically significant chronic infection that has not resolved within 8 weeks of Screening
- Nonserious infection requiring oral anti-infectives within 2 weeks prior to randomization must be further discussed with study medical monitor.
- Clinical evidence of or suspected to have an abscess during Screening.
- Any underlying condition that predisposes the participant to infections.
- Participant had previous allogenic bone marrow transplant or history of organ or cell-based transplantation.
- Clinically significant active infection or signs/symptoms of infection that has the potential to worsen with immunosuppressive therapy.
- Signs or symptoms of ongoing infection due to intestinal pathogens
- Participant has known or suspected history of chronic use of NSAIDs and/or opiates, drug, or alcohol abuse.
- History of cancer with the following exceptions: history of basal cell carcinoma and/or squamous cell carcinoma of the skin OR carcinoma in situ of the cervix; with apparent successful curative therapy, greater than 12 months prior to Screening.
- Clinically significant cardiovascular conditions.
- Prolonged QTcF interval or conditions leading to additional risk for QT prolongation.
- Clinically significant kidney disease
- Abnormal laboratory results at Screening as defined in the study protocol
- Participant is pregnant or breastfeeding or plans to become pregnant during the study.
- Participant has other known, pre-existing, clinically significant medical conditions that are not associated with UC and are uncontrolled with standard treatment.
- Participant has any disorder that may compromise the ability of the participant to give written informed consent and/or to comply with all required study procedures.
- Employees of the clinical study site or any other individuals involved with the conduct of the study, or immediate family members of such individuals.
Study description/explanation of participation:
Participants with moderate to severely active ulcerative colitis (UC) may be eligible to participate in a clinical study comparing brazikumab, an investigational drug (investigational means the treatment is not approved for use) to placebo, an inactive dummy treatment given in the same way as brazikumab for up to 1 ½ years. Participants who meet eligibility criteria will be randomly assigned (by chance) to brazikumab or placebo (referred to as study drug) and will not know which treatment they are taking. Participants will receive induction doses of intravenous (through a vein) study drug at their first treatment visit (baseline), Week 2, and Week 6 followed by subcutaneous (administered under the skin) study drug every 4 weeks until Week 48.
- Brazikumab high dose IV (Weeks 0, 2, and 6), then SC from Week 12 and every 4 weeks through Week 50.
- Brazikumab low dose IV (Weeks 0, 2, and 6), then SC from Week 12 and every 4 weeks through Week 50.
- Placebo: placebo IV (Weeks 0, 2, and 6), then SC from Week 12 and every 4 weeks through Week 50.
If you meet specific study criteria and may benefit from receiving brazikumab, you may be able to participate in a separate extension study after you finish treatment in this study.
Description of treatment or intervention (mechanism of action):
Brazikumab is a type of protein called an antibody and is designed to stick to another protein called interleukin-23 (IL-23). IL-23 is known to play a role in causing inflammation in patients with UC. By sticking to IL-23, it is hoped that brazikumab will stop IL-23 from working, thereby helping to reduce the symptoms of UC.
Patient participation requirements:
- Attend all study visits
- Tell the study doctor about how you are feeling and what medications you are taking
- Follow the directions of the study doctor and research team
- Complete questionnaires on a daily electronic diary honestly and bring the diary to each study visit
- Do not participate in any other research studies while you are a participant in this study
Possible risks and side effects:
This is the first study of brazikumab in UC, however brazikumab has been investigated for use in Crohn’s Disease. It is not approved in any countries and safety and efficacy have not been established. In past studies common side effects (occurring at a rate of 1 in 10 to 1 in 100 participants) included headache, nasopharyngitis (common cold), joint pain, dizziness, asthenia (lack of energy, abnormal physical weakness), skin rash, upper respiratory infections, and muscle pain.
Other potential risks associated with drugs that affect the immune response are serious infections, allergic reactions, malignancies, and infusion reactions (during the IV portion of the study).