Clinical Trials List
Protocol NumberM14-433
NCT Number(ClinicalTrials.gov Identfier)NCT03345849
2018-04-01 - 2019-12-31
Phase III
Recruiting3
ICD-10K50.90
Crohn's disease, unspecified, without complications
A Multicenter, Randomized, Double-Blind, Placebo-Controlled Induction Study of the Efficacy and Safety of Upadacitinib (ABT-494) in Subjects with Moderately to Severely Active Crohn's Disease Who Have Inadequately Responded to or are Intolerant to Conventional Therapies but Have Not Failed Biologic Therapy
-
Trial Applicant
AbbVie
-
Sponsor
AbbVie
-
Trial scale
Multi-Regional Multi-Center
-
Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- Chun-Lung Feng Digestive System Department
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- FAN -FENG CHIANG Division of General Internal Medicine
- 趙德馨 Division of Colorectal Surgery
- 陳家昌 Digestive System Department
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
Audit
None
Principal Investigator
Co-Principal Investigator
- 翁昭旼 Division of General Internal Medicine
- 謝銘鈞 Division of Hematology & Oncology
- SHU-CHEN WEI Digestive System Department
- YEN-HSUAN NI Division of Pediatrics
The Actual Total Number of Participants Enrolled
0 Recruiting
Audit
None
Condition/Disease
Moderately to Severely Active Crohn's Disease
Objectives
The objective of Study M14-433 is to evaluate the efficacy and safety of upadacitinib
compared to placebo as induction therapy in subjects with moderately and severely active Crohn's
disease (CD).
Test Drug
Upadacitinib (ABT-494)
Active Ingredient
Upadacitinib (ABT-494)
Dosage Form
Tablet
Dosage
45mg/30mg
Endpoints
Primary Outcome Measures :
Percentage of Participants with Clinical Remission per Crohn's Disease Activity Index (CDAI) [ Time Frame: Week 12 ]
CDAI is defined as CDAI <150.
Percentage of Participants with Endoscopic Response [ Time Frame: Week 12 ]
Endoscopic response is defined as decrease in Simple Endoscopic Score for Crohn's Disease (SES-CD) from Baseline.
Secondary Outcome Measures :
Percentage of Participants with Clinical Remission per Patient-Reported Outcomes (PROs) [ Time Frame: Week 12 ]
Clinical remission is defined based on average daily stool frequency (SF) AND average daily abdominal pain (AP) score.
Percentage of Participants with Endoscopic Remission [ Time Frame: Week 12 ]
Endoscopic remission is defined per Simplified Endoscopic Score for Crohn's Disease (SES-CD).
Percentage of Participants who Discontinue Corticosteroid Use for Crohn's Disease (CD) and Achieve Clinical Remission per per Crohn's Disease Activity Index (CDAI), in Participants Taking Corticosteroids at Baseline. [ Time Frame: Week 12 ]
CDAI is defined as CDAI <150, in participants taking corticosteroids at Baseline.
Change in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) [ Time Frame: Baseline (Week 0) to Week 12 ]
The FACIT-F questionnaire was developed to assess fatigue.
Change in Inflammatory Bowel Disease Questionnaire (IBDQ) [ Time Frame: Baseline (Week 0) to Week 12 ]
The IBDQ is used to assess the quality of life of patients with inflammatory bowel disease.
Percentage of Participants Achieving Clinical Response 100 (CR-100) [ Time Frame: Up to Week 12 ]
Decrease of at least 100 points in CDAI from Baseline.
Percentage of Participants with Clinical Remission per Crohn's Disease Activity Index (CDAI) [ Time Frame: Week 4 ]
CDAI is defined as CDAI <150.
Percentage of Participants with Hospitalizations due to Crohn's Disease (CD) [ Time Frame: Week 12 ]
This is assessed by reviewing participant's hospitalization data.
Percentage of Participants with Resolution of Extra-Intestinal Manifestation (EIMs) , in Participants with EIMs at Baseline [ Time Frame: Week 12 ]
EIMs are defined as manifestations of Crohn's disease in areas of the body other than the digestive tract, including eyes, skin, joints, mouth, and liver.
Percentage of Participants with Clinical Remission per Crohn's Disease Activity Index (CDAI) [ Time Frame: Week 12 ]
CDAI is defined as CDAI <150.
Percentage of Participants with Endoscopic Response [ Time Frame: Week 12 ]
Endoscopic response is defined as decrease in Simple Endoscopic Score for Crohn's Disease (SES-CD) from Baseline.
Secondary Outcome Measures :
Percentage of Participants with Clinical Remission per Patient-Reported Outcomes (PROs) [ Time Frame: Week 12 ]
Clinical remission is defined based on average daily stool frequency (SF) AND average daily abdominal pain (AP) score.
Percentage of Participants with Endoscopic Remission [ Time Frame: Week 12 ]
Endoscopic remission is defined per Simplified Endoscopic Score for Crohn's Disease (SES-CD).
Percentage of Participants who Discontinue Corticosteroid Use for Crohn's Disease (CD) and Achieve Clinical Remission per per Crohn's Disease Activity Index (CDAI), in Participants Taking Corticosteroids at Baseline. [ Time Frame: Week 12 ]
CDAI is defined as CDAI <150, in participants taking corticosteroids at Baseline.
Change in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) [ Time Frame: Baseline (Week 0) to Week 12 ]
The FACIT-F questionnaire was developed to assess fatigue.
Change in Inflammatory Bowel Disease Questionnaire (IBDQ) [ Time Frame: Baseline (Week 0) to Week 12 ]
The IBDQ is used to assess the quality of life of patients with inflammatory bowel disease.
Percentage of Participants Achieving Clinical Response 100 (CR-100) [ Time Frame: Up to Week 12 ]
Decrease of at least 100 points in CDAI from Baseline.
Percentage of Participants with Clinical Remission per Crohn's Disease Activity Index (CDAI) [ Time Frame: Week 4 ]
CDAI is defined as CDAI <150.
Percentage of Participants with Hospitalizations due to Crohn's Disease (CD) [ Time Frame: Week 12 ]
This is assessed by reviewing participant's hospitalization data.
Percentage of Participants with Resolution of Extra-Intestinal Manifestation (EIMs) , in Participants with EIMs at Baseline [ Time Frame: Week 12 ]
EIMs are defined as manifestations of Crohn's disease in areas of the body other than the digestive tract, including eyes, skin, joints, mouth, and liver.
Inclution Criteria
Main Inclusion:
1. Confirmed diagnosis of CD for at least 3 months prior to Baseline. Appropriate documentation of
biopsy results consistent with the diagnosis of CD, in the assessment of the investigator, must be
available.
2. SES-CD (excluding the presence of narrowing component) ≥ 6 (or ≥ 4 for subjects with isolated
ileal disease), as confirmed by a central reader.
3. Average daily liquid/very soft SF ≥ 4.0 and/or average daily AP ≥ 2.0 at Baseline.
4. Demonstrated an inadequate response or intolerance to one or more conventional therapies, in the
opinion of the investigator, as defined below:
Oral locally acting steroids
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 Inability to taper oral budesonide to below 6 mg/day without recurrent active disease, OR
Intravenous or oral corticosteroids
o Signs and symptoms of persistently active disease despite a history of at least
one induction regimen consisting of a dose equivalent to prednisone (or equivalent)
≥ 40 mg/day orally for at least 3 weeks or intravenously for 1 week, OR
o Inability to taper corticosteroids to below a dose equivalent to prednisone 10 mg/day
without recurrent active disease, OR
Immunosuppressants
o Sign and symptoms of persistently active disease despite a history of at least one 12 weeks
regimen of the following:
AZA: ≥ 2.0 mg/kg/day (≥ 1 mg/kg/day for subjects in Japan, Korea, Taiwan or
China), rounded to the nearest available tablet or half tablet formulation, OR a
documented 6-thioguanine nucleotide (6-TGN) level of > 235 pmol/8 × 108 RBC at a
dose < 2 mg/kg/day OR documentation that a dose reduction was required due to
elevated 6-MP levels (> 5700 pmol/8 ×108
erythrocytes) OR
6-MP: ≥ 1 mg/kg/day (≥ 0.6 mg/kg/day for subjects in Japan, Korea, Taiwan or
China), rounded to the nearest available tablet or half tablet formulation, (or a 6-TGN
level of > 235 pmol/8 × 108 RBC) OR
MTX (≥ 25 mg/week subcutaneous [SC] or intramuscular [IM]), OR
Tacrolimus (for subjects in Japan or Taiwan only: documented trough level of 5 –
10 ng/mL).
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.
Intolerance to corticosteroids may include depression, severe insomnia, osteopenia, cushingoid
features, etc. Intolerance to AZA/6-MP should include elevations of liver enzymes,
pancreatitis, etc. Demonstration of intolerance requires no minimum dose or duration of use
and may include subjects with known thiopurine methyltransferase (TPMT) genetic mutation or
low activity.
Note: Subjects who have received prior biologic for up to 1 year may be enrolled; however,
subjects must have discontinued the biologic for reasons other than inadequate response or
intolerance (e.g., change of insurance, well controlled disease), and must meet the criteria for
intolerance or inadequate response to oral locally acting steroids, systemic steroids (prednisone
or equivalent), and/or immunosuppressants as defined above.
1. Confirmed diagnosis of CD for at least 3 months prior to Baseline. Appropriate documentation of
biopsy results consistent with the diagnosis of CD, in the assessment of the investigator, must be
available.
2. SES-CD (excluding the presence of narrowing component) ≥ 6 (or ≥ 4 for subjects with isolated
ileal disease), as confirmed by a central reader.
3. Average daily liquid/very soft SF ≥ 4.0 and/or average daily AP ≥ 2.0 at Baseline.
4. Demonstrated an inadequate response or intolerance to one or more conventional therapies, in the
opinion of the investigator, as defined below:
Oral locally acting steroids
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 Inability to taper oral budesonide to below 6 mg/day without recurrent active disease, OR
Intravenous or oral corticosteroids
o Signs and symptoms of persistently active disease despite a history of at least
one induction regimen consisting of a dose equivalent to prednisone (or equivalent)
≥ 40 mg/day orally for at least 3 weeks or intravenously for 1 week, OR
o Inability to taper corticosteroids to below a dose equivalent to prednisone 10 mg/day
without recurrent active disease, OR
Immunosuppressants
o Sign and symptoms of persistently active disease despite a history of at least one 12 weeks
regimen of the following:
AZA: ≥ 2.0 mg/kg/day (≥ 1 mg/kg/day for subjects in Japan, Korea, Taiwan or
China), rounded to the nearest available tablet or half tablet formulation, OR a
documented 6-thioguanine nucleotide (6-TGN) level of > 235 pmol/8 × 108 RBC at a
dose < 2 mg/kg/day OR documentation that a dose reduction was required due to
elevated 6-MP levels (> 5700 pmol/8 ×108
erythrocytes) OR
6-MP: ≥ 1 mg/kg/day (≥ 0.6 mg/kg/day for subjects in Japan, Korea, Taiwan or
China), rounded to the nearest available tablet or half tablet formulation, (or a 6-TGN
level of > 235 pmol/8 × 108 RBC) OR
MTX (≥ 25 mg/week subcutaneous [SC] or intramuscular [IM]), OR
Tacrolimus (for subjects in Japan or Taiwan only: documented trough level of 5 –
10 ng/mL).
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.
Intolerance to corticosteroids may include depression, severe insomnia, osteopenia, cushingoid
features, etc. Intolerance to AZA/6-MP should include elevations of liver enzymes,
pancreatitis, etc. Demonstration of intolerance requires no minimum dose or duration of use
and may include subjects with known thiopurine methyltransferase (TPMT) genetic mutation or
low activity.
Note: Subjects who have received prior biologic for up to 1 year may be enrolled; however,
subjects must have discontinued the biologic for reasons other than inadequate response or
intolerance (e.g., change of insurance, well controlled disease), and must meet the criteria for
intolerance or inadequate response to oral locally acting steroids, systemic steroids (prednisone
or equivalent), and/or immunosuppressants as defined above.
Exclusion Criteria
Main Exclusion:
1. Subject with a current diagnosis of ulcerative colitis or indeterminate colitis.
Concomitant Medications and Treatments
2. Subject on CD related antibiotics who:
has not been on stable doses of these medications for at least 14 days prior to Baseline.
has discontinued these medications within 14 days of Baseline.
3. Subject on oral aminosalicylates who:
has not been on stable doses of these medications for at least 14 days prior to Baseline.
has discontinued these medications within 14 days of Baseline.
4. Subject on corticosteroids who meet the following:
prednisone or equivalent dose > 30 mg/day; or
budesonide > 9 mg/day; or
has not been on the current course for at least 14 days prior to Baseline and on a stable dose for
at least 7 days prior to Baseline.
5. Subject on MTX who:
has not been on the current course for ≥ 42 days prior to Baseline, and
has not been on a stable dose for ≥ 28 days prior to Baseline
CD Related
6. Subject with the following known complications of CD:
abscess (abdominal or peri-anal),
symptomatic bowel strictures,
fulminant colitis,
toxic megacolon,
or any other manifestation that might require surgery while enrolled in the study,
7. Subject with ostomy or ileoanal pouch
8. Subject diagnosed with conditions that could interfere with drug absorption including but not
limited to short gut or short bowel syndrome.
9. Subject with surgical bowel resection within the past 3 months prior to Baseline, or a history of
> 3 bowel resections
Safety
10. Laboratory values meeting the following criteria within the Screening period prior to the first dose
of study drug:
Serum aspartate transaminase or alanine transaminase > 2.0 × upper limit of normal;
Total white blood cell count < 2500/µL;
Estimated glomerular filtration rate by simplified 4-variable Modification of Diet in Renal
Disease (MDRD) formula < 40 mL/min/1.73 m2
;
Hemoglobin < 9 g/dL;
Platelet count < 100,000/µL;
Absolute neutrophil count < 1200/µL;
Absolute lymphocytes count < 750/µL.
1. Subject with a current diagnosis of ulcerative colitis or indeterminate colitis.
Concomitant Medications and Treatments
2. Subject on CD related antibiotics who:
has not been on stable doses of these medications for at least 14 days prior to Baseline.
has discontinued these medications within 14 days of Baseline.
3. Subject on oral aminosalicylates who:
has not been on stable doses of these medications for at least 14 days prior to Baseline.
has discontinued these medications within 14 days of Baseline.
4. Subject on corticosteroids who meet the following:
prednisone or equivalent dose > 30 mg/day; or
budesonide > 9 mg/day; or
has not been on the current course for at least 14 days prior to Baseline and on a stable dose for
at least 7 days prior to Baseline.
5. Subject on MTX who:
has not been on the current course for ≥ 42 days prior to Baseline, and
has not been on a stable dose for ≥ 28 days prior to Baseline
CD Related
6. Subject with the following known complications of CD:
abscess (abdominal or peri-anal),
symptomatic bowel strictures,
fulminant colitis,
toxic megacolon,
or any other manifestation that might require surgery while enrolled in the study,
7. Subject with ostomy or ileoanal pouch
8. Subject diagnosed with conditions that could interfere with drug absorption including but not
limited to short gut or short bowel syndrome.
9. Subject with surgical bowel resection within the past 3 months prior to Baseline, or a history of
> 3 bowel resections
Safety
10. Laboratory values meeting the following criteria within the Screening period prior to the first dose
of study drug:
Serum aspartate transaminase or alanine transaminase > 2.0 × upper limit of normal;
Total white blood cell count < 2500/µL;
Estimated glomerular filtration rate by simplified 4-variable Modification of Diet in Renal
Disease (MDRD) formula < 40 mL/min/1.73 m2
;
Hemoglobin < 9 g/dL;
Platelet count < 100,000/µL;
Absolute neutrophil count < 1200/µL;
Absolute lymphocytes count < 750/µL.
The Estimated Number of Participants
-
Taiwan
6 participants
-
Global
501 participants
