Ulcerative Colitis MedDRA version: 20.0 Level: PT Classification code 10009900 Term: Colitis ulcerative System Organ Class: 10017947 - Gastrointestinal disorders
Conditions
Sponsors
AbbVie Deutschland GmbH & Co. KG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female between 16 and 75 years of age at Baseline. o Adolescent subjects at the age of 16 and 17 years old will be enrolled if approved by the country or regulatory/health agency. If these approvals have not been granted, only subjects = 18 years old will be enrolled o Adolescent subjects at the age 16 and 17 years old must weigh = 40 kg and meet the definition of Tanner Stage 5 at screening visit 2. Diagnosis of UC for 90 days or greater prior to Baseline, confirmed by colonoscopy during the Screening Period, with exclusion of current infection, colonic dysplasia and/or malignancy. Appropriate documentation of biopsy results consistent with the diagnosis of UC, in the assessment of the Investigator, must be available. 3. Active UC with an Adapted Mayo score of 5 to 9 points and endoscopic subscore of 2 to 3 (confirmed by central reader). 4. Demonstrated an inadequate response, loss of response, or intolerance to at least one of the following including, oral aminosalicylates, corticosteroids, immunosuppressants, and/or biologic therapies, in the opinion of the investigator, as defined below: NOTE: An inadequate response, loss of response, or intolerance to Oral Aminosalicylates will NOT count towards eligibility criteria in AT, CZ, IE, LV, LT, NO, PL, PT, ES, SE, and UK • Oral aminosalicylates (e.g., mesalamine, sulfasalazine, olsalazine, balsalazide) o Signs and symptoms of persistently active disease, in the opinion of the investigator, during a current or prior course of at least 4 weeks of treatment with 2.4 g/day mesalamine, 4 g/day sulfasalazine, 1 g/day olsalazine, or 6.75 g/day balsalazide. • Corticosteroids o Signs and symptoms of persistently active disease despite a history of at least one induction regimen that included a dose equivalent to prednisone = 40 mg/day orally for at least 3 weeks or intravenously for 1 week, OR o Unable to taper corticosteroids to below a dose equivalent to prednisone 10 mg daily orally without recurrent active disease, OR o Signs and symptoms of persistently active disease during or after a course of at least 4 weeks of treatment with 9 mg/day budesonide or 5 mg/day beclomethasone, OR o Unable to taper oral budesonide to at or below 6 mg/day without recurrent active disease, OR o History of intolerance to corticosteroids (including, but not limited to Cushing's syndrome, osteopenia/osteoporosis, hyperglycemia, insomnia, infection). • Immunosuppressants o Signs and symptoms of persistently active disease despite a history of at least one 90 day regimen of oral azathioprine (= 1.5 mg/kg/day; for subjects in Japan, China, and Taiwan only: = 1.0 mg/kg/day), 6-MP (= 1 mg/kg/day; [for subjects in Japan, China, and Taiwan only: = 0.6 mg/kg/day, rounded to the nearest available tablet of half tablet formulation] or a documented 6-TGN level of 230 – 450 pmol/8 × 108 RBC or higher on the current dosing regimen), injectable MTX (= 15 mg/week subcutaneous [SC] or intramuscular), or tacrolimus (for subjects in Japan and Taiwan only: documented trough level of 5 – 10 ng/mL), OR o History of intolerance to at least one immunosuppressant (including, but not limited to nausea/vomiting, abdominal pain, pancreatitis, liver enzyme abnormalities, lymphopenia, infection) Note: Oral MTX use is allowed during the study, however prior or current use of oral MTX is not sufficient for inclusion into the study unless these subjects were previously treated with aminosalicylates, cortic
Exclusion criteria
Exclusion criteria: 1. Subject with current diagnosis of Crohn's disease (CD) or diagnosis of indeterminate colitis (IC). 2. Current diagnosis of fulminant colitis and/or toxic megacolon. 3. Subject with disease limited to the rectum (ulcerative proctitis) during the Screening endoscopy. 4. Received cyclosporine, tacrolimus, or mycophenolate mofetil within 30 days prior to Baseline. 5. Subject who received azathioprine or 6-MP within 10 days of Baseline. 6. Received intravenous corticosteroids within 14 days prior to Screening or during the Screening Period. 7. Subject with previous exposure to JAK inhibitor (e.g., tofacitinib, baricitinib, filgotinib, upadacitinib). 8. Screening laboratory and other analyses show any of the following abnormal results: • Serum Aspartate Transaminase (AST) or Alanine Transaminase (ALT) > 2.0 × upper limit of the reference range (ULN); • Estimated glomerular filtration rate by simplified 4-variable Modification of Diet in Renal Disease (MDRD) formula < 30 mL/min/1.73 m2; • Total White Blood Cell (WBC) count < 2500/µL; • Absolute neutrophil count (ANC) < 1,200/µL; • Platelet count < 100,000/µL; • Absolute lymphocytes count < 750/µL; • Hemoglobin < 9g/dL.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The objective of Study M14-675 (Phase 3 induction) is to evaluate the efficacy and safety of upadacitinib 45 mg once daily (QD) compared to placebo in inducing clinical remission (per Adapted Mayo score) in subjects with moderately to severely active ulcerative colitis.;Secondary Objective: The secondary objectives of the study are to evaluate the efficacy of upadacitinib 45 mg QD comparing with placebo in ranked secondary endpoints of achieving endoscopic improvement, endoscopic remission, clinical response per Adapted Mayo Score ,clinical response per Partial Adapted Mayo score, no bowel urgency, no abdominal pain, histologic improvement, response in IBDQ Below symptom domain, mucosal healing, UC-related hospitalization, UC-related surgery, and response in IBDQ fatigue item;Primary end point(s): The primary endpoint for Study M14-675 is the proportion of subjects who achieve clinical remission per Adapted Mayo score (defined as SFS = 1 and not greater than baseline, RBS of 0, and endoscopic sub score = 1) at Week 8. ;Timepoint(s) of evaluation of this end point: Part 1: Week 8 and Part 2: Week 16 (Extended Treatment Period; as applicable) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Proportion of subjects with endoscopic improvement at Week 8 2. Proportion of subjects with endoscopic remission at Week 8 3. Proportion of subjects achieving clinical response per Adapted Mayo Score at Week 8 4. Proportion of subjects achieving clinical response per Partial Adapted Mayo score (defined as decrease from Baseline = 1 points and = 30% from Baseline, PLUS a decrease in RBS = 1 or an absolute RBS = 1 )at Week 2 5. Proportion of subjects who reported no bowel urgency at Week 8 6. Proportion of subjects who reported no abdominal pain at Week 8 7. Proportion of subjects who achieved histologic improvement (defined as decrease from Baseline in Geboes score) at Week 8 8. Proportion of subjects achieving response in IBDQ Bowel Symptom domain (increase of IBDQ bowel symptom domain score =6) at Week 8 9. Proportion of subjects with mucosal healing (endoscopic and histologic remission) at Week 8 10. Proportion of subjects with UC-related hospitalizations through Week 8 11. Proportion of subjects with UC-related surgeries through Week 8 12. Proportion of subjects achieving response in IBDQ fatigue item (increase of IBDQ fatigue item score =1) at Week 8. ;Timepoint(s) of evaluation of this end point: For points 1, 2, 3, 5, 6, 7, 8, 9, 10, 11, 12 - week 8 For point 4 - Week 2 | — |
Countries
Argentina, Australia, Austria, Belarus, Bosnia and Herzegovina, Brazil, Canada, Chile, China, Colombia, Croatia, Czech Republic, Finland, France, Germany, Greece, Hungary, Ireland, Israel, Japan, Korea, Republic of, Latvia, Lithuania, Malaysia, Mexico, Netherlands, Norway, Poland, Portugal, Puerto Rico, Russian Federation, Serbia, Singapore, Slovakia, South Africa, Spain, Sweden, Switzerland, Taiwan, Turkey, Ukraine, United Kingdom, United States
Contacts
Public ContactEU Clinical Trials Helpdesk
AbbVie Ltd
Outcome results
None listed