Clinical trial NCT01988961: A Study to Evaluate the Accuracy of a Subset of the Length-109 Probe Set Panel (a Genetic Test) in Predicting Response to Golimumab in Participants With Moderately to Severely Active Ulcerative Colitis
Official title: A Phase 2a Open-Label Study to Evaluate Prediction of Response to Golimumab Using a Transcriptomic Profile in Subjects With Moderately to Severely Active Ulcerative Colitis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colitis, Ulcerative
Keywords: Colitis, Ulcerative
Golimumab
CNTO148
SIMPONI
Length-109 Probe Set Panel
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2013-11-20
Enrollment: 103
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the accuracy of a subset of the length-109 probe set panel (a genetic test) in predicting response to golimumab treatment in participants with moderately to severely active ulcerative colitis (UC).

Detailed description: The study drug, golimumab, belongs to a group of medicines known as tumor necrosis factor (TNF) inhibitors and is approved in the United States, European Union, and Canada for treatment of UC. Studies have shown that people respond differently to treatment with TNF inhibitors and furthermore, some people may not actually respond to treatment. Tests which could predict the likelihood of response to golimumab prior to treatment would be of benefit to people with UC. This is an open label (physicians and participants know the identity of the assigned treatment), multicenter study to evaluate the accuracy of a genetic test (a subset of the length-109 probe set panel) in predicting response to golimumab treatment in patients with moderately to severely active UC. The study will consist of a screening phase, an open label treatment phase (Week 0 to Week 50), and a follow-up visit at Week 58. A subset of the length-109 probe set panel will be tested on samples obtained from colonic biopsies taken prior to treatment with golimumab for all participants at screening. All participants enrolled in the study will receive subcutaneous golimumab from Week 0 to Week 50; at the discretion of the investigator, participants will be given the option to self-administer golimumab from Week 6 onwards. Blood and fecal samples will be taken at various time points during the study; colonic biopsies will be taken at screening, Week 6, and Week 30; and endoscopies will be performed at Week 0, Week 6, and Week 30. The study duration for each participant is expected to be approximately 58 weeks. Participant safety will be monitored throughout the study.

Eligibility criteria: Inclusion Criteria:

* Must have the following: a clinical diagnosis of moderately to severely active ulcerative colitis (UC), defined as a baseline Mayo score of 6 to 12 (inclusive), for at least 3 months prior to screening; and a screening endoscopy with a \> = 2 endoscopy sub score of the Mayo score as determined by a central reading of the video endoscopy
* Prior or current medication for UC must be as per protocol
* Prior to the screening endoscopy or the earliest entry in the Mayo diary card (whichever of these 2 events comes first) the following conditions must be met: per protocol requirements for treatment with 6-mercaptopurine, azathioprine, or methotrexate; per protocol requirements for treatment with oral 5-aminosalicylate or oral corticosteroids; treatment must have been discontinued for at least 2 weeks for rectal corticosteroids, rectal 5-aminosalicylate compounds, parenteral corticosteroids, total parenteral nutrition, pentoxifylline, thalidomide or related agents, and antibiotics for the treatment of UC; and treatment with 6-thioguanine must have been discontinued for at least 4 weeks
* Must have had a colonoscopy as per the time frame described in the protocol for the following: extensive colitis for \> = 8 years; disease limited to the left side of the colon for \> = 10 years; participants \> = 45 years of age to assess for the presence of adenomatous polyps
* Must meet the tuberculosis and hepatitis B virus screening criteria as defined in the protocol

Exclusion Criteria:

* The presence of any of the following: severe extensive colitis; UC limited to the rectum only or to \<20 cm of the colon; a stoma; a fistula (or history of a fistula); symptomatic colonic or small bowel obstruction; adenomatous colonic polyps (or history of adenomatous colonic polyps); or indeterminate colitis or clinical findings suggestive of Crohn's disease
* History of extensive colonic resection (eg, less than 30 cm of colon remaining) or colonic mucosal dysplasia; requires (or has required within the 2 months prior to screening) surgery for active gastrointestinal bleeding, peritonitis, intestinal obstruction, intra abdominal or pancreatic abscess requiring surgical drainage
* Have received the following concomitant or previous medical therapies: biologic therapy targeted at tumor necrosis factor alpha (eg, infliximab, adalimumab, golimumab, etanercept, certolizumab); natalizumab within 12 months of first golimumab administration; agents that deplete B- or T-cells (eg, rituximab, alemtuzumab, or visilizumab) within 12 months of first golimumab administration, or continue to manifest depletion of B- or T-cells more than 12 months after completion of therapy with lymphocyte depleting agents; cyclosporine, tacrolimus, sirolimus, or mycophenolate mofetil within 8 weeks prior to first administration of golimumab; vedolizumab within 8 weeks prior to first golimumab administration; apheresis (ie, Adacolumn apheresis) within 2 weeks prior to first administration of golimumab; any investigational drug within 4 weeks prior to first administration of golimumab or within 5 half-lives of the investigational agent, whichever is longer; or oral corticosteroids at a dose of greater than 40 mg of prednisone or its equivalent per day
* Have received, or are expected to receive, any live viral or bacterial vaccination within 8 weeks (or longer as indicated in the package insert of the relevant vaccine) prior to the first administration of golimumab or have had Bacille Calmette-Guerin (BCG) vaccination within 12 months of screening
* History of, or currently active illness, considered to be clinically significant by the Investigator or any other illness that the Investigator considers should exclude the participant from the study or that could interfere with the interpretation of the study results

Primary outcomes:
measure: The area under the Receiver Operating Characteristic curve of a subset of the length-109 probe set panel as a predictor of mucosal healing at Week 6.
timeFrame: Week 6
Secondary outcomes:
measure: The area under the Receiver Operating Characteristic curve of a subset of the length-109 probe set panel as a predictor of clinical response at Week 6 and at Week 30
timeFrame: Week 6 and Week 30
measure: The area under the Receiver Operating Characteristic curve of a subset of the length-109 probe set panel as a predictor of clinical remission at Week 6 and at Week 30
timeFrame: Week 6 and Week 30
measure: The area under the Receiver Operating Characteristic curve of a subset of the length-109 probe set panel as a predictor of mucosal healing at Week 30
timeFrame: Week 30
Other outcomes:
Locations:
city: La Jolla
country: United States
state: California
city: National City
country: United States
state: California
city: Denver
country: United States
state: Colorado
city: Golden
country: United States
state: Colorado
city: Maitland
country: United States
state: Florida
city: Winter Park
country: United States
state: Florida
city: Zephyrhills
country: United States
state: Florida
city: Suwanee
country: United States
state: Georgia
city: Idaho Falls
country: United States
state: Idaho
city: Crestview Hills
country: United States
state: Kentucky
city: Rochester
country: United States
state: Minnesota
city: Kansas City
country: United States
state: Missouri
city: Cincinnati
country: United States
state: Ohio
city: Columbia
country: United States
state: South Carolina
city: Chesapeake
country: United States
state: Virginia
city: Gent
country: Belgium
city: Leuven
country: Belgium
city: Roeselare
country: Belgium
city: Rousse
country: Bulgaria
city: Sofia
country: Bulgaria
city: Victoria
country: Canada
state: British Columbia
city: London
country: Canada
state: Ontario
city: Vaughan
country: Canada
state: Ontario
city: Hradec Kralove
country: Czech Republic
city: Praha 10
country: Czech Republic
city: Grenoble
country: France
city: Lille Cedex
country: France
city: Paris
country: France
city: Hannover
country: Germany
city: Kiel
country: Germany
city: Budapest
country: Hungary
city: Gyula
country: Hungary
city: Mosonmagyarovar
country: Hungary
city: Amsterdam
country: Netherlands
city: Sittard-Geleen
country: Netherlands
city: Elblag
country: Poland
city: Lodz
country: Poland
city: Staszow
country: Poland
city: Wroclaw
country: Poland
city: Moscow
country: Russian Federation
city: Nizhny Novgorod
country: Russian Federation
city: St Petersburg
country: Russian Federation
city: Kharkov
country: Ukraine
city: Kyiv
country: Ukraine
city: Vinnitsya
country: Ukraine
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References:
citation: Li K, Strauss R, Marano C, Greenbaum LE, Friedman JR, Peyrin-Biroulet L, Brodmerkel C, De Hertogh G. A Simplified Definition of Histologic Improvement in Ulcerative Colitis and its Association With Disease Outcomes up to 30 Weeks from Initiation of Therapy: Post Hoc Analysis of Three Clinical Trials. J Crohns Colitis. 2019 Aug 14;13(8):1025-1035. doi: 10.1093/ecco-jcc/jjz022.
citation: Telesco SE, Brodmerkel C, Zhang H, Kim LL, Johanns J, Mazumder A, Li K, Baribaud F, Curran M, Strauss R, Paxson B, Plevy S, Davison T, Knight L, Dibben S, Schreiber S, Sandborn W, Rutgeerts P, Siegel CA, Reinisch W, Greenbaum LE. Gene Expression Signature for Prediction of Golimumab Response in a Phase 2a Open-Label Trial of Patients With Ulcerative Colitis. Gastroenterology. 2018 Oct;155(4):1008-1011.e8. doi: 10.1053/j.gastro.2018.06.077. Epub 2018 Jul 4.