Placebo-Controlled Study of Brazikumab in Participants With Moderately to Severely Active Ulcerative Colitis

NCT03616821 | Terminated Phase 2 Results DMC FDA Drug

• 3 other identifiers: D5272C00001Legacy #3151-201-0082018-001605-93
• Study Type: interventional
• Target: 242
• Locations: 19 countries
• Sites: 125

Brief Summary

The present study (D5272C00001/Legacy #3151-201-008) aims to evaluate the efficacy and safety of brazikumab in patients with moderately to severely active UC and will include assessments of clinical responses as demonstrated by improvement of symptoms and of colonic mucosal appearance as observed on endoscopy

Conditions

Ulcerative Colitis; IBD

Outcome Measures

Primary Outcomes (1)

• Clinical Remission

  Efficacy was assessed using the Mayo Scoring System for assessment of Ulcerative Colitis. The Mayo score assesses * stool frequency, * rectal bleeding, * endoscopic findings, and * physician's assessment of disease activity. Each of these four subscores can be scored as 0, 1, 2, or 3, where 0 is a normal finding and 3 corresponds to severe disease. The Mayo score has been modified (modified Mayo Score, mMS) to specify no friability in the endoscopy subscore of 1 (mild disease). Clinical Remission is defined by the mMS at Week 10: * Endoscopy subscore = 0 or 1, AND * Rectal bleeding subscore = 0, AND * Stool frequency subscore = 0 or 1, AND at least a 1-point decrease from baseline Further, if the patient * discontinue treatment prematurely for any reason * takes rescue treatment or meet the rescue criteria * uses prohibited medication the patient is considered as unsuccessfully treated and imputed as non-responder

  at Week 10

Secondary Outcomes (21)

• Sustained Clinical Remission

  Week 10 and 54

• CS-free Clinical Remission

  Week 54

• Clinical Response

  Week 10

• Endoscopic Improvement

  Week 10

• Serum Concentrations of Brazikumab (Induction)

  through week 10

Other Outcomes (1)

• Physical Examination

  through week 68

Study Arms (3)

Brazikumab Dose 1

EXPERIMENTAL

Intravenous brazikumab on day 1, day 15, and day 43 followed by Subcutaneous brazikumab every 4 weeks beginning on day 71 through week 50

Drug: Brazikumab

Brazikumab Dose 2

EXPERIMENTAL

Intravenous brazikumab on day 1, day 15, and day 43 followed by Subcutaneous brazikumab every 4 weeks beginning on day 71 through Week 50

Drug: Brazikumab

Placebo

PLACEBO COMPARATOR

Intravenous placebo on day 1, day 15, and day 43 followed by Subcutaneous every 4 weeks beginning on day 71 through Week 50.

Drug: Placebo

Interventions

Brazikumab DRUG

Intravenous brazikumab on day 1, day 15, and day 43 followed by Subcutaneous brazikumab every 4 weeks beginning on day 71 through Week 50

Brazikumab Dose 1; Brazikumab Dose 2

Placebo DRUG

Intravenous placebo on day 1, day 15, and day 43 followed by Subcutaneous placebo every 4 weeks beginning on Day 71 through Week 50.

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to provide informed consent
• Aged 18 to 80 years of age
• Diagnosis of UC with an onset of symptoms for a minimum of 3 months prior to Screening
• Evidence of UC extending proximal to the rectum (≥ 15 cm of involved colon)
• Moderately to severely active UC as defined by:
• Average daily mMS Stool Frequency subscore ≥ 1 AND Average daily mMS Rectal Bleeding subscore ≥ 1
• Modified Mayo endoscopic subscore of ≥ 2 based on a full colonoscopy within 14 days prior to randomization.
• 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 and for at least 18 weeks after the last dose of study intervention.
• 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 and negative QFT-TB during Screening.

You may not qualify if:

• 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.
• Criterion deleted as part of Amendment 5 v6.0
• 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).

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (125)

Research Site

Phoenix, Arizona, 85037, United States

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Tucson, Arizona, 85712, United States

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Little Rock, Arkansas, 72212, United States

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Chula Vista, California, 91911, United States

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Lancaster, California, 93534, United States

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Lincoln, California, 95648, United States

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Mission Hills, California, 91345, United States

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Poway, California, 92064, United States

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Colorado Springs, Colorado, 80907, United States

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Clearwater, Florida, 33756, United States

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Inverness, Florida, 34452, United States

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Kissimmee, Florida, 34741, United States

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Lakeland, Florida, 33813, United States

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Miami, Florida, 33157, United States

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Miami, Florida, 33165, United States

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Miami Lakes, Florida, 33016, United States

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Naples, Florida, 34102, United States

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New Port Richey, Florida, 34653, United States

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Tampa, Florida, 33614, United States

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Tampa, Florida, 33626, United States

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Atlanta, Georgia, 30328, United States

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Gurnee, Illinois, 60031, United States

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Oak Lawn, Illinois, 60453, United States

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Brownsburg, Indiana, 46112, United States

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Evansville, Indiana, 47715, United States

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Shawnee Mission, Kansas, 66226, United States

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Topeka, Kansas, 66606, United States

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Baton Rouge, Louisiana, 70809, United States

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Marrero, Louisiana, 70072, United States

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Shreveport, Louisiana, 71105, United States

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Wyoming, Michigan, 49519, United States

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Biloxi, Mississippi, 39531, United States

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Las Vegas, Nevada, 89106, United States

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Las Vegas, Nevada, 89123, United States

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New York, New York, 10016, United States

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Sunnyside, New York, 11104, United States

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Morehead City, North Carolina, 28557, United States

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Beachwood, Ohio, 44122, United States

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Springfield, Ohio, 45503, United States

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Oklahoma City, Oklahoma, 73112, United States

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Uniontown, Pennsylvania, 15401, United States

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Amarillo, Texas, 79109, United States

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Carrollton, Texas, 75007, United States

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Houston, Texas, 77017, United States

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Houston, Texas, 77058, United States

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Houston, Texas, 77598, United States

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Humble, Texas, 77346, United States

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Pflugerville, Texas, 78660, United States

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San Antonio, Texas, 78229, United States

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San Antonio, Texas, 78258, United States

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North Chesterfield, Virginia, 23236, United States

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Chicoutimi, Quebec, G7H 5H6, Canada

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Brno, 636 00, Czechia

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České Budějovice, 370 01, Czechia

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Hradec Králové, 500 12, Czechia

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Ostrava, 702 00, Czechia

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Hamburg, 20251, Germany

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Kiel, 24105, Germany

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Ulm, 89081, Germany

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Debrecen, 4032, Hungary

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Bangalore, 560054, India

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Hyderabad, 500032, India

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Jaipur, 302001, India

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New Delhi, 110075, India

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Rajkot, 360004, India

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Surat, 395002, India

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Haifa, 31096, Israel

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Jerusalem, 9103102, Israel

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Petah Tikva, 4941492, Israel

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Milan, 20132, Italy

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Negrar, 37024, Italy

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Rho, 20017, Italy

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Roma, 00168, Italy

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Asahikawa-shi, 070-8610, Japan

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Chiba, 260-8677, Japan

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Fukuoka, 810-8563, Japan

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Fukuyama-shi, Japan

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Hakodate-shi, 040-8585, Japan

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Kasama-shi, 309-1793, Japan

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Kashiwa-shi, 277-0871, Japan

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Koshigaya-shi, 343-8555, Japan

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Kure-shi, 737-0023, Japan

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Minatoku, 108-8642, Japan

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Nagaoka-shi, 940-2085, Japan

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Onga-gun, 807-0051, Japan

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Sapporo, 064-0919, Japan

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Takarazuka-shi, 665-0827, Japan

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Bydgoszcz, 85-079, Poland

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Chojnice, 89-600, Poland

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Częstochowa, 42-202, Poland

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Gdansk, 80-382, Poland

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Krakow, 31-513, Poland

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Ksawerów, 95-054, Poland

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Piaseczno, 05-500, Poland

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Poznan, 60-702, Poland

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Rzeszów, 35-302, Poland

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Sopot, 81-756, Poland

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Torun, 87-100, Poland

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Warsaw, 00-189, Poland

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Warsaw, 03-580, Poland

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Wroclaw, 52-210, Poland

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San Juan, 00927, Puerto Rico

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Aramil, 624002, Russia

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Izhevsk, 426035, Russia

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Moscow, 115419, Russia

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Novosibirsk, 630007, Russia

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Perm, 614000, Russia

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Tomsk, 634050, Russia

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Košice, 04013, Slovakia

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Bloemfontein, 9301, South Africa

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Cape Town, 7500, South Africa

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Cape Town, 7708, South Africa

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Plumstead, 7800, South Africa

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Busan, 48108, South Korea

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Daegu, 42415, South Korea

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Seoul, 03722, South Korea

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Seoul, 06351, South Korea

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Seoul, 06973, South Korea

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Wŏnju, 26426, South Korea

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Valencia, 46010, Spain

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Taichung, 40447, Taiwan

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Taipei, 100, Taiwan

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Kyiv, 03680, Ukraine

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Vinnytsia, 21009, Ukraine

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West Bromwich, B71 4HJ, United Kingdom

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Related Links

• CRS Synopsis
• SAP
• CSP

MeSH Terms

Conditions

Colitis, Ulcerative

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Inflammatory Bowel Diseases; Colonic Diseases; Intestinal Diseases

Limitations and Caveats

The study was early terminated and development of brazikumab stopped. Following cessation of development all study related dosing was immediately stopped. Site data cleaning engagement proved challenging. A patient centric approach was taken to focus data cleaning on key safety variables (adverse events). However, the database was locked with unclean data for the outcome measures. Please be aware that the data submitted needs to be considered with the data quality in mind.

Results Point of Contact

• Title: Global Clinical Lead
• Organization: AstraZeneca

information.center@astrazeneca.com

1-877-240-9479

Study Officials

• Kathy Bohannon

  AstraZeneca

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Global, multicenter, randomized, double-blind, placebo-controlled, parallel-group, Phase 2 study

Study Record Dates

• First Submitted: August 1, 2018
• First Posted: August 6, 2018
• Study Start: August 7, 2018
• Primary Completion: October 23, 2023
• Study Completion: October 23, 2023
• Last Updated: June 23, 2026
• Results First Posted: June 23, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Locations

ES (1); RU (6); GB (1); CA (1); PL (14); UA (2); TW (2); JP (14); PR (1); DE (3); KR (6); IN (6); HU (1); CZ (4); ZA (4); US (51); IL (3); SL (1); IT (4)