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Not able to meet recruitment targets
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| Name | Class |
|---|---|
| Alimentiv Translational Research Consortium | UNKNOWN |
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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:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Open-Label Group | Eligible patients will include those who will be prescribed Janus Kinase inhibitor as part of their routine medical care. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Janus Kinase Inhibitor | Drug | Janus Kinase inhibitor induction therapy will be administered according to Standard Of Care (SOC) |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
1.18 years of age or older.
2.Male or nonpregnant, nonlactating females.
3.Diagnosis of Ulcerative Colitis for at least 3 months prior to screening.
4.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.
5.Physician plans to administer Janus Kinase inhibitor for at least 8 weeks of induction therapy as part of Standard of Care (SOC).
6.Documentation of a negative test result for latent tuberculosis within the last 12 months, or according to routine clinical practice.
7.Able to participate fully in all aspects of this clinical trial, including collection of tissue biopsies.
8.Written informed consent must be obtained and documented.
Exclusion Criteria:
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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.
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| Name | Affiliation | Role |
|---|---|---|
| Vipul Jairath, MD, PhD | Alimentiv Inc. | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Amsterdam Medical Center, IBD Center | Amsterdam | North Halland | 1105 AZ | Netherlands |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30343116 | Background | 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. | |
| 26475633 |
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| ID | Term |
|---|---|
| D003093 | Colitis, Ulcerative |
| ID | Term |
|---|---|
| D003092 | Colitis |
| D005759 | Gastroenteritis |
| D005767 | Gastrointestinal Diseases |
| D004066 | Digestive System Diseases |
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| ID | Term |
|---|---|
| D000075242 | Janus Kinase Inhibitors |
| ID | Term |
|---|---|
| D047428 | Protein Kinase Inhibitors |
| D004791 | Enzyme Inhibitors |
| D045504 | Molecular Mechanisms of Pharmacological Action |
| D020228 | Pharmacologic Actions |
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blood, fecal, and colonic tissue sampling
| 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 |
| Identify a tissue biomarker signature as a surrogate measure for change from baseline in UC-100 score | 8 or 10 weeks, 24 weeks |
| Identify whether colonic tissue pSTAT at week 8 and/or 24 correlates with change from baseline in UC-100 score | 8 or 10 weeks, 24 weeks |
| Determine the time-concentration profile of Janus Kinase inhibitor at steady state in stool samples. | 24 weeks |
| Determine the time-concentration profile of Janus Kinase inhibitor at steady state in serum samples. | 24 weeks |
| Determine the time-concentration profile of Janus Kinase inhibitor at steady state in tissue samples. | 24 weeks |
| Evaluate correlation of exposure of Janus Kinase inhibitor between stool samples following SOC induction therapy and at Week 24. | 8 or 10 weeks, 24 weeks |
| Evaluate correlation of exposure of Janus Kinase inhibitor between serum samples following SOC induction therapy and at Week 24. | 8 or 10 weeks, 24 weeks |
| Evaluate correlation of exposure of Janus Kinase inhibitors between tissue samples following SOC induction therapy and at Week 24. | 8 or 10 weeks, 24 weeks |
| Explore the exposure-response relationship of Janus Kinase inhibitors with exposure measured in stool samples and response defined as tissue PD biomarkers following SOC induction therapy and at Week 24. | 8 or 10 weeks, 24 weeks |
| Explore the exposure-response relationship of Janus Kinase inhibitors with exposure measured in serum samples and response defined as tissue PD biomarkers following SOC induction therapy and at Week 24. | 8 or 10 weeks, 24 weeks |
| Explore the exposure-response relationship of Janus Kinase inhibitors with exposure measured in tissue samples and response defined as tissue PD biomarkers following SOC induction therapy and at Week 24. | 8 or 10 weeks, 24 weeks |
| Develop an exposure-response model of Janus Kinase inhibitors to characterize the relationships between local and systemic drug exposure and clinical, endoscopic, histologic, or biologic response to therapy. | 24 weeks |
| Identify potential demographic and disease factors affecting the most relevant JAKi exposure-response relationships and determine target threshold of systemic exposure associated with relevant clinical, endoscopic, histologic, and/or biologic outcomes. | 8 or 10 weeks, 24 weeks |
| Evaluate long-term hospitalization rates, surgery rates, and corticosteroid use after initiation of Janus Kinase inhibitor therapy and identify baseline or early biomarker signatures associated with these long-term healthcare resource use outcomes | 2 years |
| Measure adverse drug reactions, clinical, endoscopic, and histologic response and remission rates to Janus Kinase inhibitors in a "real-world" population | 24 weeks |
| 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. |
| 19491859 | 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. |
| 32203403 | 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. |
| D015212 |
| Inflammatory Bowel Diseases |
| D003108 | Colonic Diseases |
| D007410 | Intestinal Diseases |
| D020164 | Chemical Actions and Uses |