Identification of Biomarkers of Janus Kinase Inhibitor Therapy in Patients With Ulcerative Colitis

NCT04576000 | Terminated FDA Drug

• 1 other identifier: RP1907
• Study Type: observational
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to provide new mechanistic insights into the molecular determinants of response or nonresponse to Janus Kinase inhibitor therapy and the biological heterogeneity that exists in Ulcerative Colitis. This study will include patients who are initiating Janus Kinase inhibitor therapy according to standard of care. This study consists of:

• Part 1: 8 or 10 week induction therapy followed by an 8-week maintenance therapy
• Part 2: Patients who continue Janus Kinas inhibitor therapy after part 1 will be followed further for a total of 2 years, or until discontinuation of Janus Kinase inhibitor therapy (whichever is first)

Conditions

Ulcerative Colitis

Outcome Measures

Primary Outcomes (3)

• Identify predictive fecal biomarkers that are associated with a change from baseline in UC-100 score

  The UC-100 is a composite disease activity index consisting of clinical, endoscopic, and histological findings. The UC-100 is calculated by summing the weighted Mayo Clinic Score (MCS) stool frequency and endoscopy subscores, and the Robarts Histopathology Index (RHI) score as follows: UC-100 Score = 1 + (16 X stool frequency) + (6 X endoscopic subscore) + (RHI score). The total UC-100 score ranges from 1 to 100, with higher scores representing more severe disease activity.

  8 or 10 weeks; 24 weeks

• Identify predictive blood biomarkers that are associated with a change from baseline in UC-100 score

  8 or 10 weeks; 24 weeks

• Identify predictive tissue biomarkers that are associated with a change from baseline in UC-100 score

  8 or 10 weeks; 24 weeks

Secondary Outcomes (20)

• Identify pharmacodynamic fecal biomarkers that are associated with a change from baseline in UC-100 score

  8 or 10 weeks, 24 weeks

• Identify pharmacodynamic blood biomarkers that are associated with a change from baseline in UC-100 score

  8 or 10 weeks, 24 weeks

• Identify pharmacodynamic tissue biomarkers that are associated with a change from baseline in UC-100 score

  8 or 10 weeks, 24 weeks

• Identify a fecal biomarker signature as a surrogate measure for change from baseline in UC-100 score

  8 or 10 weeks, 24 weeks

• Identify a blood biomarker signature as a surrogate measure for change from baseline in UC-100 score

  8 or 10 weeks, 24 weeks

Study Arms (1)

Open-Label Group

Eligible patients will include those who will be prescribed Janus Kinase inhibitor as part of their routine medical care.

Drug: Janus Kinase Inhibitor

Interventions

Janus Kinase Inhibitor DRUG

Janus Kinase inhibitor induction therapy will be administered according to Standard Of Care (SOC)

Open-Label Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

This study will involve subjects with moderately to severely active Ulcerative Colitis who will receive Janus Kinase inhibitor for at least 8 weeks, followed by Janus Kinase inhibitor maintenance therapy for an additional 8 weeks.

You may qualify if:

• years of age or older.
• Male or nonpregnant, nonlactating females.
• Diagnosis of Ulcerative Colitis for at least 3 months prior to screening.
• Moderately to severely active Ulcerative Colitis (total Mayo Clinic Score ≥ 6), with objective evidence of inflammation defined by a Mayo endoscopic subscore (MES) ≥ 2 and disease extending \> 15 cm from the anal verge.
• Physician plans to administer Janus Kinase inhibitor for at least 8 weeks of induction therapy as part of Standard of Care (SOC).
• Documentation of a negative test result for latent tuberculosis within the last 12 months, or according to routine clinical practice.
• Able to participate fully in all aspects of this clinical trial, including collection of tissue biopsies.
• Written informed consent must be obtained and documented.

You may not qualify if:

• Diagnosis of Crohn's disease or indeterminate colitis.
• An active, serious infection, including localized infections.
• Concomitant administration of biological therapies for Ulcerative Colitis or potent immunosuppressants, such as azathioprine and cyclosporine. Subjects with previous exposure to these treatments should undergo an appropriate washout period according to local practice prior to starting Janus Kinase inhibitor, in keeping with routine clinical practice.
• Hematology laboratory (e.g., absolute lymphocyte count, absolute neutrophil count, and hemoglobin that contraindicate the product label.
• Interval between live vaccinations and initiation of tofacitinib therapy should be in accordance with current vaccination guidelines regarding immunosuppressive agents.
• Serious underlying disease other than Ulcerative Colitis that in the opinion of the investigator may interfere with the subject's ability to participate fully in the study.

Sponsors & Collaborators

• Alimentiv Inc.: lead
• Alimentiv Translational Research Consortium: collaborator

Study Sites (1)

Amsterdam Medical Center, IBD Center

Amsterdam, North Halland, 1105 AZ, Netherlands

Location

Related Publications (4)

• Jairath V, Jeyarajah J, Zou G, Parker CE, Olson A, Khanna R, D'Haens GR, Sandborn WJ, Feagan BG. A composite disease activity index for early drug development in ulcerative colitis: development and validation of the UC-100 score. Lancet Gastroenterol Hepatol. 2019 Jan;4(1):63-70. doi: 10.1016/S2468-1253(18)30306-6. Epub 2018 Oct 18.

  PMID: 30343116 BACKGROUND

• Mosli MH, Feagan BG, Zou G, Sandborn WJ, D'Haens G, Khanna R, Shackelton LM, Walker CW, Nelson S, Vandervoort MK, Frisbie V, Samaan MA, Jairath V, Driman DK, Geboes K, Valasek MA, Pai RK, Lauwers GY, Riddell R, Stitt LW, Levesque BG. Development and validation of a histological index for UC. Gut. 2017 Jan;66(1):50-58. doi: 10.1136/gutjnl-2015-310393. Epub 2015 Oct 16.

  PMID: 26475633 BACKGROUND

• Scherl EJ, Pruitt R, Gordon GL, Lamet M, Shaw A, Huang S, Mareya S, Forbes WP. Safety and efficacy of a new 3.3 g b.i.d. tablet formulation in patients with mild-to-moderately-active ulcerative colitis: a multicenter, randomized, double-blind, placebo-controlled study. Am J Gastroenterol. 2009 Jun;104(6):1452-9. doi: 10.1038/ajg.2009.83. Epub 2009 Apr 21.

  PMID: 19491859 BACKGROUND

• Salas A, Hernandez-Rocha C, Duijvestein M, Faubion W, McGovern D, Vermeire S, Vetrano S, Vande Casteele N. JAK-STAT pathway targeting for the treatment of inflammatory bowel disease. Nat Rev Gastroenterol Hepatol. 2020 Jun;17(6):323-337. doi: 10.1038/s41575-020-0273-0. Epub 2020 Mar 19.

  PMID: 32203403 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

blood, fecal, and colonic tissue sampling

MeSH Terms

Conditions

Colitis, Ulcerative

Interventions

Janus Kinase Inhibitors

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Vipul Jairath, MD, PhD

  Alimentiv Inc.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 17, 2020
• First Posted: October 5, 2020
• Study Start: August 25, 2020
• Primary Completion: December 15, 2020
• Study Completion: December 2, 2021
• Last Updated: January 4, 2022

Record last verified: 2021-12

Locations

NL (1)