Clinical Trials List
Protocol NumberM14-431
NCT Number(ClinicalTrials.gov Identfier)NCT03345836
2018-04-01 - 2020-01-31
Phase III
Recruiting1
Terminated1
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 Biologic Therapy
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Trial Applicant
AbbVie
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Sponsor
AbbVie
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Trial scale
Multi-Regional Multi-Center
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Update
2023/03/10
Investigators and Locations
Co-Principal Investigator
- 翁昭旼 Division of General Internal Medicine
- 謝銘鈞 Division of Hematology & Oncology
- YEN-HSUAN NI Division of Pediatrics
The Actual Total Number of Participants Enrolled
0 Recruiting
Audit
None
Co-Principal Investigator
- Cheng-Tang Chiu Digestive System Department
- Ming-Yao Su Digestive System Department
- Ming-Wei Lai Division of Pediatrics
- Puo-Hsien Le Digestive System Department
- 林偉彬 Digestive System Department
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Condition/Disease
Moderately to Severely Active Crohn's Disease
Objectives
The objective of Study M14-431 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 SES-CD.
Percentage of Participants who Discontinue Corticosteroid Use for Crohn's Disease (CD) and Achieve Clinical Remission [ Time Frame: Week 12 ]
This is assessed in participants taking corticosteroids at Baseline. Clinical remission is defined as CDAI < 150.
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 during 12 week double-blind induction period by reviewing participant's hospitalization data.
Percentage of Participants with Resolution of Extra-Intestinal Manifestation (EIM) , in Participants with EIM 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 SES-CD.
Percentage of Participants who Discontinue Corticosteroid Use for Crohn's Disease (CD) and Achieve Clinical Remission [ Time Frame: Week 12 ]
This is assessed in participants taking corticosteroids at Baseline. Clinical remission is defined as CDAI < 150.
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 during 12 week double-blind induction period by reviewing participant's hospitalization data.
Percentage of Participants with Resolution of Extra-Intestinal Manifestation (EIM) , in Participants with EIM 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, as determined by 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 score ≥ 2.0 at Baseline.
4. Demonstrated an inadequate response or intolerance to one or more of the following biologic
agents:
At least one 6-week induction regimen of infliximab (≥ 5 mg/kg intravenous [IV] at Baseline
and Weeks 2, and 6),
At least one 4-week induction regimen of adalimumab (one 160 mg subcutaneous [SC] dose at
Baseline, followed by one 80 mg SC dose at Week 2 [or one 80 mg SC dose at Baseline,
followed by one 40 mg SC dose at Week 2, in countries where this dosing regimen is
approved]),
At least one 4-week induction regimen of certolizumab pegol (400 mg SC at Baseline and
Weeks 2, and 4),
At least one 6-week induction regimen of vedolizumab (300 mg IV at Baseline and Weeks 2,
and 6),
At least one 8-week induction regimen of ustekinumab [260 mg (≤ 55 kg) or 390 mg (> 55 to
≤ 85 kg) or 520 mg (> 85 kg) IV, followed by 90 mg SC at Week 8],
Recurrence of symptoms during scheduled maintenance dosing following prior clinical benefit
of the above biologics,
Intolerance to a biologic may include, but not limited to infusion-related reaction, rash, serum
sickness, anaphylaxis, elevated liver enzymes, demyelination, congestive heart failure,
infection. Demonstration of intolerance requires no minimum dose or duration of use.
1. Confirmed diagnosis of CD for at least 3 months prior to Baseline. Appropriate documentation of
biopsy results consistent with the diagnosis of CD, as determined by 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 score ≥ 2.0 at Baseline.
4. Demonstrated an inadequate response or intolerance to one or more of the following biologic
agents:
At least one 6-week induction regimen of infliximab (≥ 5 mg/kg intravenous [IV] at Baseline
and Weeks 2, and 6),
At least one 4-week induction regimen of adalimumab (one 160 mg subcutaneous [SC] dose at
Baseline, followed by one 80 mg SC dose at Week 2 [or one 80 mg SC dose at Baseline,
followed by one 40 mg SC dose at Week 2, in countries where this dosing regimen is
approved]),
At least one 4-week induction regimen of certolizumab pegol (400 mg SC at Baseline and
Weeks 2, and 4),
At least one 6-week induction regimen of vedolizumab (300 mg IV at Baseline and Weeks 2,
and 6),
At least one 8-week induction regimen of ustekinumab [260 mg (≤ 55 kg) or 390 mg (> 55 to
≤ 85 kg) or 520 mg (> 85 kg) IV, followed by 90 mg SC at Week 8],
Recurrence of symptoms during scheduled maintenance dosing following prior clinical benefit
of the above biologics,
Intolerance to a biologic may include, but not limited to infusion-related reaction, rash, serum
sickness, anaphylaxis, elevated liver enzymes, demyelination, congestive heart failure,
infection. Demonstration of intolerance requires no minimum dose or duration of use.
Exclusion Criteria
Main Exclusion:
1. Subject with a current diagnosis of ulcerative colitis (UC) 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 (AST) or alanine transaminase > 2.0 × upper limit of the
reference range (ULN);
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 lymphocyte count < 750/µL.
1. Subject with a current diagnosis of ulcerative colitis (UC) 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 (AST) or alanine transaminase > 2.0 × upper limit of the
reference range (ULN);
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 lymphocyte count < 750/µL.
The Estimated Number of Participants
-
Taiwan
8 participants
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Global
625 participants
