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) - Phase 2 Dose-finding UC Study

AstraZeneca AB0 个研究点目标入组 255 人开始时间: 2020年5月5日最近更新: 2023年10月30日

试验速览

阶段: 1 期
状态: 进行中（未招募）
发起方: AstraZeneca AB
入组人数: 255

研究概览入排标准研究者记录与标识符相似试验

研究概览

简要总结

暂无简介。

研究设计

研究类型: Interventional clinical trial of medicinal product

入排标准

性别: All

入选标准

•1.Ability to provide informed consent prior to any study procedures and willing and able to attend all study visits.
•2.Aged 18 to 80 years of age at the time of signing the informed consent.
•3.Diagnosis of UC with an onset of symptoms for a minimum of 3 months prior to Screening.
•4.Evidence of UC extending proximal to the rectum (= 15 cm of involved colon).
•5.Moderately to severely active UC as defined by (5a and 5b must be met):
•(a) Stool Frequency and Rectal Bleeding subscores will be obtained during Screening on an eDiary. The following criteria must also be met:
•i. Average daily mMS Stool Frequency subscore = 1 AND
•ii. Average daily mMS Rectal Bleeding subscore = 1
•(b) Modified Mayo endoscopic subscore of = 2 based on a full colonoscopy within 14 days prior to initial IRT randomization.
•6.Participant had an inadequate response or intolerance to intervention with conventional treatment (oral aminosalicylates, oral CS, azathioprine, methotrexate, or 6 mercaptopurine) 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.
•7.Where applicable, participants taking any of the following medications must be at a stable dose or discontinued:
•(a) Oral 5-aminosalicylates must be at a stable dose for 2 weeks prior to the screening colonoscopy.
•(b) Oral prednisone up to 25 mg/day or equivalent, must be at a stable dose for 2 weeks prior to the screening colonoscopy and kept stable until the Week 10 assessment.
•(c) Oral budesonide up to 9 mg/day, must be at a stable dose for 2 weeks prior to the screening colonoscopy and kept stable until the Week 10 assessment.
•(d) Topical (rectal) aminosalicylic acid (eg, mesalamine) or topical (rectal) steroids should be discontinued within 2 weeks prior to screening colonoscopy. Rectal therapies should not be restarted after the screening colonoscopy.
•(e) An immunomodulator: participants must have been on treatment for a minimum of 8 weeks and must be kept at stable doses as below:
•i. Azathioprine, must be at a stable dose for 4 weeks prior to screening, OR
•ii. 6-mercaptopurine, must be at a stable dose for 4 weeks prior to screening, OR
•iii. Methotrexate, must be at a stable dose for 4 weeks prior to screening.
•8.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 (confirmed by the investigator) from randomization throughout the study duration and for at least 18 weeks after last dose of study intervention
•9.Women not of childbearing potential are defined as women who are either permanently sterilized (hysterectomy, bilateral oophorectomy, or bilateral salpingectomy), or who are postmenopausal.
•10.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.
•11.No known history of active TB or latent TB without completion of appropriate intervention.
•Are the trial subjects under 18? no
•Number of subjects for this age range:
•F.1.2 Adults (18-64 years) yes
•F.1.2.1 Number of subjects for this age range 200
•F.1.3 Elderly (>=65 years) yes
•F.1.3.1 Number of subjects for this age range 55

排除标准

•1.Participant has UC limited to the rectum (ie, not beyond 15 cm of the anal verge).
•2.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.
•3.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.
•4.Participant has received the following treatment:
•(a) Infliximab: within 8 weeks prior to randomization.
•(b) Adalimumab, certolizumab pegol, or golimumab: within 8 weeks prior to randomization.
•(c) Vedolizumab or ustekinumab within 12 weeks of randomization.
•(d) Other prohibited medication, biologic or small molecule treatment within 5 half-lives prior to randomization.
•(e) Fecal microbiota transplantation: within 8 weeks prior to randomization.
•5.Except for ustekinumab, prior exposure to any biologic agent targeting IL-12 or IL-23 (risankizumab, brazikumab, mirikizumab, guselkumab, tildrakizumab).
•6.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.
•7.Participant received cyclosporine, mycophenolate mofetil, sirolimus (rapamycin), thalidomide, tacrolimus (FK-506), or tofacitinib within 2 weeks prior to Screening.
•8.Participants who received IV or intramuscular steroids within 2 weeks prior to Screening.
•9.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).
•10.Participant received a transfusion of blood, plasma, or platelets within 30 days prior to Screening.
•11.Participant received a Bacille Calmette-Guérin vaccination within 12 months of randomization or any other live vaccine less than 4 weeks prior to randomization.
•12.Participant has any of the following criteria related to infections:
•(a) Evidence of a recent systemic fungal infection, requiring inpatient hospitalization, and/or antifungal treatment.
•(b) Any infection requiring hospitalization or treatment with IV anti-infectives within 4 weeks of Screening.
•(c) Cytomegalovirus or Epstein-Barr virus infection that has not resolved within 8 weeks prior to Screening.
•(d) Clinically significant chronic infection that has not resolved within 8 weeks of Screening.
•(e) Nonserious infection requiring oral anti-infectives within 2 weeks prior to randomization must be further discussed with study medical monitor.
•(f) Clinical evidence of or suspected to have an abscess during Screening.
•(g) Any underlying condition that predisposes the participant to infections.
•(h) Participant had previous allogenic bone marrow transplant or history of organ or cell-based transplantation.
•(i) Clinically significant active infection or signs/symptoms of infection that has the potential to worsen with immunosuppressive therapy.
•(j) Signs or symptoms of ongoing infection due to intestinal pathogens.
•13.Participant has known or suspected history of chronic use of NSAIDs and/or opiates, drug, or alcohol abuse.
•14.History of cancer with the following exceptions:

研究者

发起方

AstraZeneca AB

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