inflammatory bowel disease (IBD) Ulcerative colitis
Conditions
Interventions
Investigational Products: Adalimumab
Mode of administration: Subcutaneous injection (SC)
Induction Study: Double-Blind Induction: Subjects will be randomized to receive
one of 2 double-blind adalimu
Sponsors
AbbVie Deutschland GmbH & Co. KG
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: Main Inclusion: 1. Subject must be able and willing to provide written informed consent and comply with the requirements of this study protocol.;2. Male or female >= 18 and 10 and = 6 mg/day, dose has been stable for at least 7 days prior to Baseline and the duration of the current steroid course has been at least 14 days prior to Baseline. Dose = 1.5 mg/kg/day or 6-MP >= 1 mg/kg/day (rounded to the nearest available tablet or half tablet formulation) or a documented 6-TGN level of at least 230 pmol/8 x 108 RBC to clarify a therapeutic level was achieved on the current dosing regimen or MTX >= 15 mg/week (Subcutaneous [SC]/Intramuscular [IM]), or a dose that is the highest tolerated by the subject (e.g., due to leukopenia, elevated liver enzymes, nausea) during that time. Note: If a subject is taking (both an oral corticosteroid and an immunosuppressant listed above)BOTH of the drugs need to meet the above dosing and duration of use criteria. Oral MTX use is allowed during the study (at a stable dose for 28 days prior to Baseline), however prior or current use of oral MTX is not sufficient for inclusion into the study. or, Concurrent therapy with oral corticosteroids or immunosuppressants (azathioprine, 6-MP or SC/IM MTX) is not required for subjects not currently taking these medications who were previously treated during the past 1 year and have confirmed documentation of failure to respond, or were previously treated during the past 5 years and have confirmed documentation indicating lack of tolerability.;5. Subject may be included if they have previously experience
Exclusion criteria
Exclusion criteria: Main Exclusion: 1. Subject with diagnosis and/or history 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 therapeutic enema or suppository, other than required for endoscopy, within 7 days prior to the Screening endoscopy and during the remainder of the Screening Period.;5. History of subtotal colectomy with ileorectostomy or colectomy with ileoanal pouch, Kock pouch, or ileostomy or is planning bowel surgery.;6. Received cyclosporine, tacrolimus, or mycophenolate mofetil within 30 days prior to Baseline. 7. Positive pregnancy test at Screening (serum) or Baseline (urine). 8. Female who is breast-feeding or considering becoming pregnant during the study. 9. History of clinically significant drug or alcohol abuse in the last 12 months. 10. Subject on azathioprine, 6-MP, MTX, or another immunosuppressant (e.g., thalidomide) who: - Has not been on these medications for at least 42 days prior to Baseline; or - Has not been on stable doses of these medications for at least 28 days prior to Baseline; or - Has discontinued these medications within 14 days of Baseline. - Has not been on these medications for at least 42 days prior to Baseline; or - Has not been on stable doses of these medications for at least 28 days prior to Baseline; or - Has discontinued these medications within 14 days of Baseline.;11. Subject on oral aminosalicylates who: - Has not been on stable doses of these medications for at least 14 days prior to Baseline; or - Has discontinued use of aminosalicylates within 14 days of Baseline.;12. Subject on oral corticosteroid > 40 mg/day (prednisone or equivalent) or subject on oral budesonide > 9 mg/day; or subject on oral beclomethasone > 5 mg/day; or - Subject taking an oral corticosteroid (excluding budesonide): dose > 10 mg/day, but has not been on a stable dose for at least 7 days prior to Baseline; or dose > 10 mg/day, but has not been on a current steroid course of at least 14 days in duration prior to Baseline; or dose = 6 mg/day, but has not been on a stable dose for at least 7 days prior to Baseline; or dose >= 6 mg/day, but has not been on a current steroid course of at least 14 days in duration prior to Baseline; or dose < 6 mg/day dose but has not been on a stable dose of at least 10 days prior to Baseline; or dose < 6 mg/day but has not been a current steroid course of at least 14 days in duration prior to Baseline; or;Has been taking both oral budesonide (or oral becomethasone) and oral prednisone (or equivalent) simultaneously and/or has discontinued use of corticosteroids within 14 days of Baseline.;13. Received intravenous corticosteroids within 14 days prior to Screening or during the Screening Period.;14. Positive Clostridium difficile (C. difficile) toxin stool assay during the Screening Period.;15. Currently receiving total parenteral nutrition (TPN).;16. Subject who received any investigational agent or procedure (i
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Efficacy: The primary efficacy endpoint for the Induction Study is: • Proportion of subjects achieving clinical remission (defined as a Full Mayo score 1) at Week 8. The primary efficacy endpoint for the Maintenance Study is: • Proportion of Week 8 responders (per Full Mayo score, defined as a decrease in Full Mayo score of >= 3 points and >= 30% from Baseline Plus a decrease in the rectal bleeding subscore [RBS] >= 1 or an absolute RBS of 0 or 1) achieving clinical remission (per Full Mayo score) at Week 52. Pharmacokinetics: Blood samples will be collected for the measurement of serum adalimumab concentrations just prior to dosing at Baseline and Weeks 2, 4, 8, 10, 12, 16, 22, 24, 29, 35, 37, 42, 48, 52 (or at the PD visit if the subject discontinues prior to Week 52), and unscheduled visits. Pre-dosing serum samples for HACAs and infliximab concentrations will be collected at Week 0. Blood samples will be collected for the measurement of AAA just prior to dosing at Baseline and Weeks 4, 8, 12, 24, 37, 52 (or at the PD visit if the subject discontinues prior to Week 52), and unscheduled visits. Safety: Safety analyses will be performed on all subjects who receive at least one dose of study drug. Incidence of adverse events, changes in vital signs, physical examination results, and clinical laboratory data will be assessed. | — |
Secondary
| Measure | Time frame |
|---|---|
| Ranked secondary efficacy variables (ranked hierarchically in decreasing order) for the Induction Study are: 1. Proportion of subjects achieving endoscopic improvement (endoscopic subscore of 0 or 1) at Week 8. 2. Proportion of subjects with fecal calprotectin below 150 mg/kg at Week 8. 3. Proportion of subjects with IBDQ response (increase of IBDQ >= 16 from Baseline) at Week 8. 4. Proportion of subjects achieving clinical response (per Full Mayo score) at Week 8. 5. Proportion of subjects achieving endoscopic subscore of 0 at Week 8. Additional pre-specified endpoints in the Induction Study include but are not limited to the following: • Assessment of the relationship between adalimumab serum concentrations and efficacy during the Induction Study • All-cause and UC-related hospitalization and surgery rates during Weeks 0 - 8. • Change from Baseline in histologic score at Week 8. • Proportion of subjects achieving clinical remission per Adapted Mayo Score (defined as stool frequency subscore 1 at Week 8. • Relationship between histologic scores and endoscopic improvement (endoscopy subscore of 0 or 1) at Week 8. • Relationship between histologic scores and endoscopic subscore of 0 at Week 8. Ranked secondary efficacy variables (ranked hierarchically in decreasing order) for the Maintenance Study are: 1. Proportion of Week 8 responders (per Full Mayo score) achieving endoscopic improvement (endoscopic subscore of 0 or 1) at Week 52. 2. Proportion of Week 8 responders (per Full Mayo score) taking steroids at Baseline who are steroid free for at least 90 days at Week 52. 3. Proportion of Week 8 responders (per Full Mayo score) taking steroids at Baseline who are steroid free for at least 90 days and in clinical remission (per Full Mayo score) at Week 52. 4. Proportion of Week 8 remitters (per Full Mayo score) achieving clinical remission (per Full Mayo score) at Week 52. Proportion of Week 8 remitters (per Full Mayo score) achieving en | — |
Countries
Netherlands
Outcome results
None listed